Study on the application value of fluorescent laparoscopy in pancreatic tumor surgery

Fetched: November 30th, 2023, 5:00am GMT by Shihang Xi

Gland Surg. 2023 Oct 30;12(10):1403-1413. doi: 10.21037/gs-23-331. Epub 2023 Oct 26.

ABSTRACT

BACKGROUND: Fluorescent laparoscopy is rarely used in pancreatic surgery. The aim of this study was to investigate the value of fluorescent laparoscopy in pancreatic tumor surgery.

METHODS: A total of 19 patients with pancreatic tumors who were treated in the Department of Hepatobiliary Surgery at the First Affiliated Hospital of Wannan Medical College from January 2021 to August 2022 were selected. Fluorescent laparoscopy was used intraoperatively, and the imaging characteristics of different tumors were recorded and analyzed.

RESULTS: Among the 19 participants, postoperative pathology confirmed 12 cases of pancreatic cancer (8 cases of moderately differentiated adenocarcinoma, 3 cases of moderately-poorly differentiated adenocarcinoma, and 1 case of acinar cell carcinoma), 4 cases of pancreatic cystic tumors (1 case of microcystic serous cystadenoma, 1 case of serous cystadenoma, 1 case of solid pseudopapillary tumor, and 1 case of solid-cystic pseudopapillary tumor), 1 case of pancreatic neuroendocrine tumor (G1 stage), and 2 cases of inflammatory lesions. There were 8 cases of pancreaticoduodenectomy, 6 cases of distal pancreatectomy, 3 cases of middle pancreatectomy, 1 case of local pancreatectomy, and 1 case of duodenum-preserving pancreatic head resection. One minute after intravenous injection of indocyanine green (ICG), 10 of the 12 patients with pancreatic cancer showed tumor peritumor imaging; 2 cases of pancreatic serous cystic tumors did not show imaging; 2 cases of solid pseudopapillary tumors had tumor body imaging; 1 case of neuroendocrine tumor had tumor body imaging, with complete fluorescence imaging after specimen dissection; there were 2 cases pathologically confirmed as inflammatory lesions, 1 case with tumor body imaging, and 1 case with capsule imaging.

CONCLUSIONS: By reasonably controlling the administration time and dose of ICG during surgery, some pancreatic tumors can be fluorescently imaged, which is beneficial for intraoperative tumor localization and margin determination.

PMID:38021196 | PMC:PMC10660181 | DOI:10.21037/gs-23-331
Primary synovial sarcoma and acinar adenocarcinoma of prostate rarely occur simultaneously: A case report

Fetched: November 30th, 2023, 5:00am GMT by Qichong Shi

Medicine (Baltimore). 2023 Nov 24;102(47):e36151. doi: 10.1097/MD.0000000000036151.

ABSTRACT

RATIONALE: Primary synovial sarcoma of the prostate is an extremely rare mesenchymal malignant soft tissue tumor with unique morphological features. Synovial sarcoma often occurs in the pararticular tissues of limbs in young people, but rarely occurs in prostate. Because it is very rare, it is easily misdiagnosed as benign prostatic hyperplasia or prostate cancer clinically. A case of synchronous acinar adenocarcinoma of the prostate has not been reported. In this article, we report a unique case of primary prostatic synovial sarcoma with acinar adenocarcinoma.

PATIENT CONCERNS: A 58-year-old male patient was found to have a prostate mass during physical examination. Prostate ultrasound examination showed an increase in prostate volume of 5.2 × 3.3 × 3.3 cm, mixed echo mass can be seen on the left side of the prostate, with a size of approximately 4.9 × 4.3 cm, left seminal vesicle compressed.

DIAGNOSES: Prostatic synovial sarcoma (biphasic type) combined with prostatic acinar adenocarcinoma (Gleason 3 + 3).

INTERVENTION: The patient received radical prostatectomy, followed by adjuvant chemotherapy and radiotherapy.

OUTCOME: After 2 months of follow-up, at the time of writing this article, the patient received a comprehensive treatment plan of adjuvant chemotherapy and radiotherapy for 2 months, and no recurrence or metastasis was found.

LESSONS: Primary prostatic synovial sarcoma (biphasic type) combined with prostatic acinar adenocarcinoma is a very unique and rare case, and effective treatment guidelines are not yet clear, posing new challenges to clinical treatment. Making full use of pathological and imaging examinations, early diagnosis and radical surgery combined with multidisciplinary treatment seem to be still a positive method.

PMID:38013382 | PMC:PMC10681603 | DOI:10.1097/MD.0000000000036151
Analysis of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance

Fetched: November 29th, 2023, 5:00am GMT by Juliana Mota Siqueira

Mod Pathol. 2023 Oct 28;37(1):100371. doi: 10.1016/j.modpat.2023.100371. Online ahead of print.

ABSTRACT

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.

PMID:38015043 | DOI:10.1016/j.modpat.2023.100371
Acinar cystic transformation in the pancreatic tail

Fetched: November 28th, 2023, 5:00am GMT by Makiko Tatsumi

Clin J Gastroenterol. 2023 Dec;16(6):919-924. doi: 10.1007/s12328-023-01838-2. Epub 2023 Jul 31.

ABSTRACT

Pancreatic acinar cystic transformation (ACT) is a rare non-neoplastic cystic lesion that is predominantly located at the pancreatic head in females. Preoperative definitive diagnosis of ACT remains challenging despite advances in radiologic imaging methods. A 25-year-old male patient presented with abdominal discomfort and a 50-mm cystic lesion in the pancreatic tail. The patient underwent laparoscopic distal pancreatectomy, because branch duct intraductal papillary mucinous neoplasm cannot be ruled out and the presence of abdominal symptoms. The resected specimen revealed a collection of small and large cysts lined by a single cuboidal epithelium layer with scattered pancreatic tissue exhibiting fibrosis in the septal wall. The cystic lesion was epithelial, trypsin-positive, B cell lymphoma 10-positive, cytokeratin 19-positive, mucin 1-positive, and MUC6-negative with a differentiated lobular central conduit causing to an adeno-cystic cell, thereby supporting the ACT diagnosis. Distinguishing ACT from other pancreatic cystic tumors remains a diagnostic challenge despite improvements in radiologic imaging methods. Surgical resection may be justified when other cystic neoplasms cannot be excluded because of its heterogeneous nature, although the ACT is a non-neoplastic lesion, and cases of malignant transformation have never been reported to date.

PMID:37523124 | DOI:10.1007/s12328-023-01838-2
A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland

Fetched: November 26th, 2023, 5:00am GMT by Pietro De Luca

Cancers (Basel). 2023 Nov 17;15(22):5456. doi: 10.3390/cancers15225456.

ABSTRACT

BACKGROUND: The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence.

METHODS: A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution's local head and neck pathologist.

RESULTS: The patients' age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2-61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones.

CONCLUSION: AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical-epidemiological-histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism.

PMID:38001716 | PMC:PMC10669973 | DOI:10.3390/cancers15225456
A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists

Fetched: November 25th, 2023, 5:00am GMT by Ingrid Garajová

Curr Oncol. 2023 Oct 31;30(11):9587-9601. doi: 10.3390/curroncol30110694.

ABSTRACT

Pancreatic cancer (PDAC) is one of the most aggressive solid tumors and is showing increasing incidence. The aim of our review is to provide practical help for all clinical oncologists and to summarize the current management of PDAC using a simple "ABC method" (A-anatomical resectability, B-biological resectability and C-clinical conditions). For anatomically resectable PDAC without any high-risk factors (biological or conditional), the actual standard of care is represented by surgery followed by adjuvant chemotherapy. The remaining PDAC patients should all be treated with initial systemic therapy, though the intent for each is different: for borderline resectable patients, the intent is neoadjuvant; for locally advanced patients, the intent is conversion; and for metastatic PDAC patients, the intent remains just palliative. The actual standard of care in first-line therapy is represented by two regimens: FOLFIRINOX and gemcitabine/nab-paclitaxel. Recently, NALIRIFOX showed positive results over gemcitabine/nab-paclitaxel. There are limited data for maintenance therapy after first-line treatment, though 5-FU or FOLFIRI after initial FOLFIRINOX, and gemcitabine, after initial gemcitabine/nab-paclitaxel, might be considered. We also dedicate space to special rare conditions, such as PDAC with germline BRCA mutations, pancreatic acinar cell carcinoma and adenosquamous carcinoma of the pancreas, with few clinically relevant remarks.

PMID:37999114 | PMC:PMC10669959 | DOI:10.3390/curroncol30110694
Identification of a novel RSRC1-ALK (R6: A20) fusion using next-generation sequencing technique

Fetched: November 21st, 2023, 5:00am GMT by Jingjing Xia

Cancer Genet. 2023 Nov;278-279:18-23. doi: 10.1016/j.cancergen.2023.08.003. Epub 2023 Aug 9.

ABSTRACT

Non-small-cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) fusion showed promising responses to ALK tyrosine kinase inhibitors (TKIs). In this study, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next generation sequencing (NGS) and Sanger sequencing were performed to identify the presence of ALK fusion, to investigate whether the patient may benefit from TKI therapy. Postoperative pathological analysis indicated invasive adenocarcinoma with mainly mucinous type and partial micropapillary type in left lower lung. Minimally invasive adenocarcinoma was seen in left upper lung, with mainly acinar type. NGS detected a novel RSRC1-ALK (R6: A20) fusion in left lower lobe sample, which was presented as the fusion of exon 6 of RSRC1 and exon 20 of ALK gene. Sanger sequencing validated the fusion. Break rearrangement signal of ALK gene was detected in 80% of tumor cells. Immunohistochemistry showed ALK positive expression in lung. For the treatment, the patient received ensartinib hydrochloride with a dose of 225 mg per day. He was in a state of progression-free survival for at least 24 months in follow-up with no complications. NGS can be used for exploring treatment options for NSCLC patients with ALK fusion.

PMID:37572583 | DOI:10.1016/j.cancergen.2023.08.003
Defining the relationship of salivary gland malignancies to novel cell subpopulations in human salivary glands using single nucleus RNA-sequencing

Fetched: November 18th, 2023, 5:00am GMT by Takuya Nakagawa

Int J Cancer. 2023 Nov 16. doi: 10.1002/ijc.34790. Online ahead of print.

ABSTRACT

Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin. By single nucleus RNA-seq, salivary gland cells were stratified into four clusters: acinar cells, ductal cells 1, ductal cells 2 and myoepithelial cells/stromal cells. The localization of each cell group was verified by IHC of each cluster marker gene, and one group of ductal cells was found to represent intercalated ductal cells labeled with HES1. Furthermore, in comparison with SGC RNA-seq data, acinar cell markers were upregulated in AciCC, but downregulated in ACC and ductal cell markers were upregulated in SDC but downregulated in MECA, suggesting that markers of origin are highly expressed in some SGC. Cell type expressions in specific SGC histology are similar to those found in normal salivary gland populations, indicating a potential etiologic relationship.

PMID:37971144 | DOI:10.1002/ijc.34790
Advances in targeted therapy for pancreatic cancer

Fetched: November 16th, 2023, 5:00am GMT by Lin Xing

Biomed Pharmacother. 2023 Dec;168:115717. doi: 10.1016/j.biopha.2023.115717. Epub 2023 Oct 18.

ABSTRACT

Pancreatic cancer (PC) represents a group of malignant tumours originating from pancreatic duct epithelial cells and acinar cells, and the 5-year survival rate of PC patients is only approximately 12%. Molecular targeted drugs are specific drugs designed to target and block oncogenes, and they have become promising strategies for the treatment of PC. Compared to traditional chemotherapy drugs, molecular targeted drugs have greater targeting precision, and they have significant therapeutic effects and minimal side effects. This article reviews several molecular targeted drugs that are currently in the experimental stage for the treatment of PC; these include antibody-drug conjugates (ADCs), aptamer-drug conjugates (ApDCs) and peptide-drug conjugates (PDCs). ADCs can specifically recognize cell surface antigens and reduce systemic exposure and toxicity of chemotherapy drugs. By delivering nucleic acid drugs to target cells, the targeting RNA of ApDCs can inhibit the expression or translation of mutated genes, thereby inhibiting tumour development. Moreover, PDCs can effectively penetrate tumour cells, and the peptide groups in PDCs preferentially target tumour cells with minimal side effects. In the targeted therapy of PC, molecular targeted drugs have very broad prospects, which provides new hope for the clinical treatment of PC patients and is worth further research.

PMID:37862965 | DOI:10.1016/j.biopha.2023.115717
Secretory carcinoma of parotid gland masquerading as acinic cell carcinoma on cytology: Case report and review of literature

Fetched: November 12th, 2023, 5:00am GMT by G Anju

Diagn Cytopathol. 2023 Nov 11. doi: 10.1002/dc.25251. Online ahead of print.

ABSTRACT

Secretory carcinoma is a relatively recently discovered low-grade salivary gland carcinoma with morphological similarities to its breast counterpart. The histopathological features of this entity are well established; however, the cytomorphological features are not well evaluated, leading to diagnostic challenges and pitfalls. We report a case of secretory carcinoma (SC) of the parotid gland, which was misdiagnosed as acinic cell carcinoma (ACC) on fine-needle aspiration cytology, to describe the cytological features.

PMID:37950566 | DOI:10.1002/dc.25251
PDL1 and molecular biomarkers expression in non-small cell lung cancer in Tunisian patients

Fetched: November 7th, 2023, 5:00am GMT by Yoldez Houcine

Monaldi Arch Chest Dis. 2023 Nov 3. doi: 10.4081/monaldi.2023.2778. Online ahead of print.

ABSTRACT

In cancer treatment, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors are thriving. Activated T lymphocytes expressed PD-1, it works with its ligand PD-L1 to limit T lymphocyte activation and prevent autoimmune disease. The expression of molecular biomarkers and PD-L1 in lung cancer determines the appropriate treatment strategy for patients with lung cancer. The purpose of this study was to look at the prevalence of molecular biomarkers and PD-L1 expression in a large group of Tunisian patients with advanced non-small cell lung cancer. We conducted an observational retrospective study in which medical/treatment history data were extracted retrospectively from medical records and archived tissue samples between January 1st 2019 and December 31st 2021. We gathered 157 patients who had recently been diagnosed with non-small cell lung carcinoma. In 36.9%of the cases, there was no molecular genotyping. EGFR (28.6%), KRAS (5.73%), and ALK gene rearrangement were the most common genotyping mutations (3.8%). ROS1 rearrangement was not present. There was a link between EGFR and gender, HER and age, and KRAS and biopsy tissue origin. Six of the tested cases with PD-L1 met the cut-off (³50%). PD-L1 positivity was more common in solid type adenocarcinoma (1.9%) than in acinar or papillary adenocarcinoma. There were no significant differences in PD-L1 expression across clinical and demographic parameters. High PD-L1 expression and molecular abnormalities were found in 1 case of EGFR, 1 case of BRAF, and 1 case of KRAS (3 cases). All of the other specimens with abnormalities had a PD-L1 <50%. ALK, ROS1, BRAF, KRAS, and MET were found to be significantly associated with PD-L1 expression. Our study is one of the country's largest, describing a large panel of biomarkers and their clinicopathologic/histopathologic associations in Tunisian lung cancer patients. We have the same molecular profile as European patients with an EGFR mutation, which is not the most common genotype abnormality in Tunisian patients. There is only one mutation at any given time. The expression of PD-L1 is determined by the histologic type and the origin of the biopsy tissue.

PMID:37930659 | DOI:10.4081/monaldi.2023.2778
Pancreatic mixed acinar-neuroendocrine carcinoma with intraductal growth: A case report with radiologic-pathologic correlations

Fetched: November 7th, 2023, 5:00am GMT by Hiroshi Baba

Radiol Case Rep. 2023 Oct 9;18(12):4422-4430. doi: 10.1016/j.radcr.2023.09.032. eCollection 2023 Dec.

ABSTRACT

Pancreatic mixed acinar-neuroendocrine carcinomas are rare malignant tumors of the pancreas. They are composed histologically of both acinar and neuroendocrine cells. The pancreatic duct is known to be an important site of tumor growth for acinar cell carcinomas, neuroendocrine tumors, and intraductal tubulopapillary neoplasms. To the best of our knowledge, there has been only 1 report of a mixed acinar-neuroendocrine carcinoma growing into the pancreatic duct and no reports detailing imaging findings with this tumor. We here report a 69-year-old man who presented with worsening glycemic control. Multiphase contrast-enhanced computed tomography and magnetic resonance imaging revealed a well-circumscribed mass with poor contrast enhancement in the pancreatic tail region of the pancreatic duct. The intraductal mass showed diffusion restriction on magnetic resonance imaging. These imaging findings are consistent with the expansive, smooth-surfaced polypoid tumor of low vascularity and high cellularity that was diagnosed pathologically. Mixed acinar-neuroendocrine carcinomas should be included in the differential diagnosis of intraductal tumors of the pancreas with poor contrast enhancement and diffusion restriction.

PMID:37929047 | PMC:PMC10624768 | DOI:10.1016/j.radcr.2023.09.032
Pancreatic ductal adenocarcinoma with acinar-to-ductal metaplasia-like cancer cells shows increased cellular proliferation

Fetched: November 7th, 2023, 5:00am GMT by Reiji Nishimon

Pancreatology. 2023 Nov;23(7):811-817. doi: 10.1016/j.pan.2023.08.007. Epub 2023 Aug 26.

ABSTRACT

BACKGROUND/OBJECTIVES: Acinar-to-ductal metaplasia (ADM) has been shown to contribute to the development of pancreatic ductal adenocarcinoma (PDAC) in genetically engineered mouse models, but little is known about whether acinar cell plasticity contributes to carcinogenesis in human PDAC. We aimed to assess whether cancer cells that stain positive for amylase and CK19 (ADM-like cancer cells) are present in human resected PDAC and to investigate their role in tumor progression.

METHODS: We immunohistochemically investigated the presence of ADM-like cancer cells, and compared the clinical and histological parameters of PDAC patients with and without ADM-like cancer cells.

RESULTS: ADM-like cancer cells were detected in 16 of 60 (26.7%) PDAC specimens. Positive staining for anterior gradient protein 2 (AGR2) was observed in 14 of 16 (87.5%) PDAC specimens with ADM-like cancer cells. On the other hand, the intensity of AGR2 expression (negative, low/moderate or high) was lower in PDAC with ADM-like cancer cells (9/7) than in PDAC without these cells (11/33) (P = 0.032). The presence of ADM-like cancer cells was significantly correlated with increased cell proliferation (P = 0.012) and tended to be associated with MUC1 expression (P = 0.067).

CONCLUSIONS: These results indicated that acinar cells may act as the origin of human PDAC, and that their presence may be useful for the stratification of human PDAC to predict prognosis.

PMID:37659916 | DOI:10.1016/j.pan.2023.08.007
Utility of MUC4 in the diagnosis of secretory carcinoma of salivary glands

Fetched: November 5th, 2023, 5:00am GMT by Saira Fatima

Ann Diagn Pathol. 2023 Dec;67:152220. doi: 10.1016/j.anndiagpath.2023.152220. Epub 2023 Oct 28.

ABSTRACT

Salivary gland tumors are diverse in morphology and both benign and malignant tumors may pose diagnostic challenges especially in small biopsies. Secretory carcinoma (SC) is histologically characterized by microcysts, follicles, solid growth pattern and occasional papillary structures, and absence of zymogen granules. SC is molecularly defined by the presence of novel gene fusion ETV6::NTRK3. Among the positive stains (S100 and mammaglobin), MUC4 is now another promising marker for the diagnosis of SC, that would enable the pathologists to exclude other morphologically close simulators. Aim of this study was to report clinicopathological features and assess utility of MUC4 in the diagnosis of SC. MUC4 was performed on 22 cases of SC. Glass slides were reviewed to record morphological patterns and staining of S100, mammaglobin, DOG1 and MUC4. Age ranged from 9 to 63 years with mean age of 34.41 ± 16.28 years. The male: female ratio was 72.7 %:27.3 %. The majority occurred in major salivary glands. A combination of patterns was seen; microfollicles were the most prevalent (90 %) followed by papillary-cystic and macrofollicles. MUC4 was positive in 19/21 (90 %) cases with almost equal number of 2+ and 3+ staining. MUC4 was negative in all cases of acinic cell carcinoma, polymorphous adenocarcinoma, adenoid cystic carcinoma, salivary duct carcinoma, myopepithelioma and myoeithelial carcinoma, cystadenoma and cribriform adenocarcinoma and all except 3 cases of mucoepidermoid carcinoma tested. Overall sensitivity of MUC4 was 95.4 %, specificity 90 %, p-value being <0.01, positive predictive value 87.5 % and negative predictive value 96.4 %. A characteristic cytoplasmic granular pattern was observed in 76.1 % tumors. S100 and mammaglobin were positive in all the performed cases. DOG1 was positive in 6/11 (28.5 %) tumors. In conclusion, MUC4 is a useful addition to a diagnostic immunohistochemical panel for SC, and to distinguish it from close potential mimickers such as acinic cell carcinoma, especially in practice settings where molecular testing is unavailable.

PMID:37924657 | DOI:10.1016/j.anndiagpath.2023.152220
ST6GAL1 sialyltransferase promotes acinar to ductal metaplasia and pancreatic cancer progression

Fetched: November 4th, 2023, 5:00am GMT by Nikita Bhalerao

JCI Insight. 2023 Oct 9;8(19):e161563. doi: 10.1172/jci.insight.161563.

ABSTRACT

The role of aberrant glycosylation in pancreatic ductal adenocarcinoma (PDAC) remains an under-investigated area of research. In this study, we determined that ST6 β-galactoside α2,6 sialyltransferase 1 (ST6GAL1), which adds α2,6-linked sialic acids to N-glycosylated proteins, was upregulated in patients with early-stage PDAC and was further increased in advanced disease. A tumor-promoting function for ST6GAL1 was elucidated using tumor xenograft experiments with human PDAC cells. Additionally, we developed a genetically engineered mouse (GEM) model with transgenic expression of ST6GAL1 in the pancreas and found that mice with dual expression of ST6GAL1 and oncogenic KRASG12D had greatly accelerated PDAC progression compared with mice expressing KRASG12D alone. As ST6GAL1 imparts progenitor-like characteristics, we interrogated ST6GAL1's role in acinar to ductal metaplasia (ADM), a process that fosters neoplasia by reprogramming acinar cells into ductal, progenitor-like cells. We verified ST6GAL1 promotes ADM using multiple models including the 266-6 cell line, GEM-derived organoids and tissues, and an in vivo model of inflammation-induced ADM. EGFR is a key driver of ADM and is known to be activated by ST6GAL1-mediated sialylation. Importantly, EGFR activation was dramatically increased in acinar cells and organoids from mice with transgenic ST6GAL1 expression. These collective results highlight a glycosylation-dependent mechanism involved in early stages of pancreatic neoplasia.

PMID:37643018 | PMC:PMC10619436 | DOI:10.1172/jci.insight.161563
Supratentorial Collision Tumor of Hemangioblastoma and Metastatic Clear Cell Renal Cell Carcinoma in a Patient with von Hippel-Lindau Disease

Fetched: October 31st, 2023, 5:00am GMT by Wenjun Luo

Case Rep Oncol. 2023 Sep 18;16(1):919-929. doi: 10.1159/000531876. eCollection 2023 Jan-Dec.

ABSTRACT

Collision tumors are rarely reported in patients with von Hippel-Lindau (VHL) disease, even though VHL patients often present with multi-organ tumor syndromes, like hemangioblastoma and renal cell carcinoma (RCC). Hemangioblastoma is rarely located in a supratentorial location, and intracranial lateral ventricular is also not a common site of metastasis for RCC. It is extremely rare for the two tumors to collide in the supratentorial area. We report a 64-year-old man with a history of clear cell RCC who presented with a sudden headache. The brain magnetic resonance imaging revealed that there was a cystic-solid mass in the intracranial lateral ventricular trigone. Histopathologically, the tumor consisted of two distinct components, most of which showed the typical morphology of hemangioblastoma. However, there were a few acinar structures composed of clear cells scattered in hemangioblastoma, and these acinar structures were subsequently confirmed as clear cell RCC. The genetic testing confirmed that the patient had VHL disease with de novo somatic mutation. Based on our case report, we systematically reviewed the characteristics of collision tumor composed of hemangioblastoma and metastatic RCC in VHL patients. The special growth site of our case is the first report of this kind of collision tumor, and can also help enrich our understanding of VHL disease and collision tumor.

PMID:37900808 | PMC:PMC10601739 | DOI:10.1159/000531876
RBPJ Deficiency Sensitizes Pancreatic Acinar Cells to KRAS-Mediated Pancreatic Intraepithelial Neoplasia Initiation

Fetched: October 24th, 2023, 5:00am GMT by Leiling Pan

Cell Mol Gastroenterol Hepatol. 2023;16(5):783-807. doi: 10.1016/j.jcmgh.2023.07.013. Epub 2023 Aug 4.

ABSTRACT

BACKGROUND AND AIMS: Development of pancreatic ductal adenocarcinoma (PDAC) is a multistep process intensively studied; however, precocious diagnosis and effective therapy still remain unsatisfactory. The role for Notch signaling in PDAC has been discussed controversially, as both cancer-promoting and cancer-antagonizing functions have been described. Thus, an improved understanding of the underlying molecular mechanisms is necessary. Here, we focused on RBPJ, the receiving transcription factor in the Notch pathway, examined its expression pattern in PDAC, and characterized its function in mouse models of pancreatic cancer development and in the regeneration process after acute pancreatitis.

METHODS: Conditional transgenic mouse models were used for functional analysis of RBPJ in the adult pancreas, initiation of PDAC precursor lesions, and pancreatic regeneration. Pancreata and primary acinar cells were tested for acinar-to-ductal metaplasia together with immunohistology and comprehensive transcriptional profiling by RNA sequencing.

RESULTS: We identified reduced RBPJ expression in a subset of human PDAC specimens. Ptf1α-Cre^ERT-driven depletion of RBPJ in transgenic mice revealed that its function is dispensable for the homeostasis and maintenance of adult acinar cells. However, primary RBPJ-deficient acinar cells underwent acinar-to-ductal differentiation in ex vivo. Importantly, oncogenic KRAS expression in the context of RBPJ deficiency facilitated the development of pancreatic intraepithelial neoplasia lesions with massive fibrotic stroma formation. Interestingly, RNA-sequencing data revealed a transcriptional profile associated with the cytokine/chemokine and extracellular matrix changes. In addition, lack of RBPJ delays the course of acute pancreatitis and critically impairs it in the context of KRAS^G12D expression.

CONCLUSIONS: Our findings imply that downregulation of RBPJ in PDAC patients derepresses Notch targets and promotes KRAS-mediated pancreatic acinar cells transformation and desmoplasia development.

PMID:37543088 | PMC:PMC10520364 | DOI:10.1016/j.jcmgh.2023.07.013
Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate

Fetched: October 18th, 2023, 5:00am GMT by Jinge Zhao

Cancer Res. 2023 Oct 17. doi: 10.1158/0008-5472.CAN-23-1176. Online ahead of print.

ABSTRACT

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally co-exists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared to concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathological heterogeneity between IDC-P and PAC. Compared to co-existing PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 metastatic prostate cancer patients revealed that IDC-P carriers with lower risk ISUP grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P.

PMID:37847513 | DOI:10.1158/0008-5472.CAN-23-1176
Primary Lung Adenocarcinoma With ALK Gene Rearrangement Mostly Occupied by the Signet-Ring Cell Carcinoma Component: A Case Report

Fetched: October 17th, 2023, 5:00am GMT by Akira Okimura

Cureus. 2023 Sep 11;15(9):e45068. doi: 10.7759/cureus.45068. eCollection 2023 Sep.

ABSTRACT

Primary lung carcinoma tumors possessing a signet-ring cell carcinoma (SRCC) component at varying proportions are rare, while those primarily composed of an SRCC component are much rarer. Reported here is a case of primary lung adenocarcinoma primarily composed of an SRCC component with a scant acinar component that developed in an 81-year-old male. Approximately 95% of the adenocarcinoma was occupied by an SRCC component that was shown to be diastase-resistant based on positive periodic acid-Schiff staining. Immunostaining for ALK and fluorescence in situ hybridization analysis (break-apart assay) showed the presence of an ALK gene rearrangement. Findings in this case indicated a primary lung adenocarcinoma with ALK gene rearrangement, in which an SRCC component accounted for approximately 95% of the tumor.

PMID:37842503 | PMC:PMC10568040 | DOI:10.7759/cureus.45068
Selinexor for the treatment of recurrent or metastatic salivary gland tumors: Results from the GEMS-001 clinical trial

Fetched: October 12th, 2023, 5:00am GMT by Alberto Hernando-Calvo

Cancer Med. 2023 Oct;12(20):20299-20310. doi: 10.1002/cam4.6589. Epub 2023 Oct 11.

ABSTRACT

OBJECTIVES: We aimed to evaluate the activity of selinexor, an oral selective inhibitor of nuclear export, in patients with recurrent or metastatic salivary gland tumors (SGT).

METHODS: GEMS-001 is an open-label Phase 2 study for patients with recurrent or metastatic SGT with two parts. In Part 1 of the protocol, patients had tumor samples profiled with targeted next generation sequencing as well as immunohistochemistry for androgen receptor, HER-2 and ALK. For Part 2, patients with no targeted therapies available were eligible to receive selinexor 60 mg given twice weekly every 28 days. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival (PFS) and prevalence of druggable alterations across SGT.

RESULTS: One hundred patients were enrolled in GEMS-001 and underwent genomic and immunohistochemistry profiling. A total of 21 patients who lacked available matched therapies were treated with selinexor. SGT subtypes (WHO classification) included adenoid cystic carcinoma (n = 10), salivary duct carcinoma (n = 3), acinic cell carcinoma (n = 2), myoepithelial carcinoma (n = 2), carcinoma ex pleomorphic adenoma (n = 2) and other (n = 2). Of 18 evaluable patients, stable disease (SD) was observed in 17 patients (94%) (SD ≥6 months in 7 patients (39%)). However, no objective responses were observed. The median PFS was 4.9 months (95% confidence interval, 3.4-10). The most common treatment-related Grade 1-2 adverse events were nausea [17 patients (81%)], fatigue [16 patients (76%)], and dysgeusia [12 patients (57%)]. Most common treatment-related Grade 3-4 adverse events were hyponatremia [3 patients (14%)], neutrophil count decrease [3 patients (14%)] and cataracts [2 patients (10%)]. No treatment-related deaths were observed.

CONCLUSIONS: Although tumor reduction was observed across participants, single agent selinexor anti-tumor activity was limited.

PMID:37818869 | PMC:PMC10652322 | DOI:10.1002/cam4.6589
Primary acinic cell carcinoma of the breast: A case report and literature review

Fetched: October 10th, 2023, 5:00am GMT by Zhi-Min Deng

Heliyon. 2023 Sep 14;9(9):e20160. doi: 10.1016/j.heliyon.2023.e20160. eCollection 2023 Sep.

ABSTRACT

Acinic cell carcinoma (ACCA), a type of malignant epithelial neoplasm, tends to occur in the parotid gland, and is occasionally found within the breast. Published literature regarding primary ACCA of the breast is scarce, and the number of reports may be fewer than 100. At present, full clinical details have not been published. As an extremely rare disorder, ACCA cannot be definitively diagnosed depending on microscopic structure alone and often requires the assistance of immunohistochemistry. Currently, universal therapies are not available. Here, we present a 47-year-old patient with a history of a palpable mass in the outer upper quadrant of the left breast for more than 2 years, which had obviously increased in size in the last half year. This patient was definitively diagnosed with primary ACCA of the breast. Neoadjuvant chemotherapy was performed preoperatively, and drug sensitivity tests based on primary tumor cells were conducted after surgery and successfully screened chemotherapy schemes for the patient's greater benefit. The whole treatment course followed the guidelines for invasive breast cancer. The patient was free of symptoms for 14 months after surgery. Long-term follow-up is in progress. Altogether, to further broaden the understanding of primary ACCA of the breast, we detail the diagnosis and treatment of one patient and review the relevant literature.

PMID:37809983 | PMC:PMC10559923 | DOI:10.1016/j.heliyon.2023.e20160
Differential expression of LLGL2 in prostate ductal adenocarcinoma and acinar adenocarcinoma and its significance

Fetched: October 10th, 2023, 5:00am GMT by W Zhang

Zhonghua Bing Li Xue Za Zhi. 2023 Oct 8;52(10):1012-1016. doi: 10.3760/cma.j.cn112151-20230216-00138.

ABSTRACT

Objective: To investigate the expression differences of LLGL2 between prostatic ductal adenocarcinoma (PDA) and prostatic acinar adenocarcinoma, and its potential clinical significance. Methods: Eighteen patients diagnosed of PDA or prostatic acinar adenocarcinoma with PDA component by histopathology during January 2015 and December 2019 in the Beijing Hospital, China were retrospectively studied. The transcriptome analysis was conducted using the tissue of PDA and prostatic acinar adenocarcinoma. Differentially expressed genes and the differences in expression profiles were identified. Further, differentially expressed proteins were verified by immunohistochemistry. Results: The tissue from 8 of the 18 patients were used for transcriptome analysis, the results of which were compared with data from public databases. 129 differentially expressed genes were identified. 45 of them were upregulated while 84 were downregulated. The results of gene enrichment analysis and gene oncology (GO) analysis revealed that the differentially expressed genes were mostly enriched in the hypertrophic cardiomyopathy and interleukin-17 related pathways. GPAT2, LLGL2, MAMDC4, PCSK9 and SMIM6 were differentially expressed between PDA and prostatic acinar adenocarcinoma. Moreover, LLGL2 was more likely expressed in the cytoplasm (P=0.04) than the nucleus (P<0.01) in PDA, compared with prostatic acinar adenocarcinoma. Conclusions: The gene expression profiling indicates that PDA are very similar to prostatic acinar adenocarcinoma. Among the differentially expressed proteins screened and verified in this study, the expression of GPAT2, LLGL2, MAMDC4 and PCSK9 is increased in PDA, while that of SMIM6 is reduced in PDA. The expression of LLGL2 shows significantly different patterns between PDA and prostatic acinar carcinoma, and thus may help differentiate PDA from prostatic acinar adenocarcinoma in clinical practice.

PMID:37805392 | DOI:10.3760/cma.j.cn112151-20230216-00138
Single-cell mapping identifies MSI+ cells as a common origin for diverse subtypes of pancreatic cancer

Fetched: October 7th, 2023, 5:00am GMT by Nirakar Rajbhandari

Cancer Cell. 2023 Nov 13;41(11):1989-2005.e9. doi: 10.1016/j.ccell.2023.09.008. Epub 2023 Oct 5.

ABSTRACT

Identifying the cells from which cancers arise is critical for understanding the molecular underpinnings of tumor evolution. To determine whether stem/progenitor cells can serve as cells of origin, we created a Msi2-Cre^ERT2 knock-in mouse. When crossed to CAG-LSL-Myc^T58A mice, Msi2-Cre^ERT2 mice developed multiple pancreatic cancer subtypes: ductal, acinar, adenosquamous, and rare anaplastic tumors. Combining single-cell genomics with computational analysis of developmental states and lineage trajectories, we demonstrate that MYC preferentially triggers transformation of the most immature MSI2⁺ pancreas cells into multi-lineage pre-cancer cells. These pre-cancer cells subsequently diverge to establish pancreatic cancer subtypes by activating distinct transcriptional programs and large-scale genomic changes, and enforced expression of specific signals like Ras can redirect subtype specification. This study shows that multiple pancreatic cancer subtypes can arise from a common pool of MSI2⁺ cells and provides a powerful model to understand and control the programs that shape divergent fates in pancreatic cancer.

PMID:37802055 | DOI:10.1016/j.ccell.2023.09.008
Bronchial oncocytic carcinoma in an adult: a case report and literature review

Fetched: October 7th, 2023, 5:00am GMT by Yi-Fan Shen

BMC Pulm Med. 2023 Oct 6;23(1):375. doi: 10.1186/s12890-023-02669-0.

ABSTRACT

BACKGROUND: Lung salivary-type tumors originating from bronchial submucosal glands are rare, only four types of salivary gland-type tumors are listed in 2015 WHO classification of lung tumors. Here, we report a rare case of oncocytic carcinoma (OC) in the right main bronchus.

CASE PRESENTATION: A 34-year-old man presented to our hospital with a two-month history of recurrent hemoptysis and with one month of inspiratory dyspnea. Pulmonary function tests showed mild restrictive ventilatory dysfunction and severe diffusion dysfunction. Furthermore, the flow volume loop showed a variable extra-thoracic obstruction. Computed tomography (CT) of the chest revealed that a polypiform nodule of 13 mm in diameter was at the proximal right main bronchus. Testing for purified protein derivative was positive (category 2). The nodule was resected under bronchoscopy. The bronchial aspirate was negative for mycobacterium tuberculosis and tumor cells. The biopsy sample showed a solid and acinar predominant pattern with abundant eosinophilic cytoplasm. The bronchial mucosa was destroyed and replaced by tumor cells. The loose edematous stromal reaction could be seen in a local area. Immunohistochemically, tumor cells were positive for CK, EMA, Vimentin, CD117, CK7, S100, Mammaglobin and SOX10. Only scattered tumor cells were stained by basal cell markers, including CK5/6, P40 and P63. Electron microscopy revealed numerous swelling mitochondria with lacking mitochondrial cristae in tumor cells. Fluorescence in situ hybridization (FISH) testing for MAML2 and ETV6 rearrangement were negative. Next-generation sequencing analysis of 520 genes in the tissue biopsy specimen showed no somatic mutation. The diagnosis of OC was made. Subsequently, the patient underwent a right upper lobectomy with sleeve resection of the main bronchus and lymph dissection. No recurrent evidence was seen during two years of chest CT follow-up.

CONCLUSIONS: To our knowledge, this is the first case of primary OC in the bronchus. This patient has no recurrence during two years of follow-up, indicating that primary OC in the bronchus has the same favorable prognosis as in salivary glands. Moreover, complete excision and thorough sampling to know the invasive growth pattern is important to reach the correct diagnosis.

PMID:37803309 | PMC:PMC10559420 | DOI:10.1186/s12890-023-02669-0
Acinic cell carcinoma mimicking Warthin's tumor: A diagnostic challenge on fine-needle cytology

Fetched: October 7th, 2023, 5:00am GMT by Busra Yaprak Bayrak

Diagn Cytopathol. 2023 Oct 6. doi: 10.1002/dc.25233. Online ahead of print.

ABSTRACT

The cytologic diagnosis of acinic cell carcinoma (ACC) can be challenging due to its polymorphous appearance and sharing cytomorphologic characteristics with other benign and malignant neoplasms as well as non-neoplastic diseases, even though various histomorphological aspects of ACC have been documented. We presented a 39-year-old female patient applied with right pre-auricular parotid swelling spreading infra-auricular region which was gradually increased in size for 3 months. Ultrasonographic examination revealed hypoechoic well-circumscribed mass with 17 × 22 × 29 mm size. Magnetic resonance imaging revealed intra-parotid solid lesion with cystic areas, slightly hypointense on T1 and hyperintense on T2 weighted images. The mass was pushing the retromandibular vein medially, still lateral to it in the caudal images, but in dumbbell-shape spreading through parapharyngeal space in superiorly cranial images. Fine-needle aspiration cytology was also performed with guidance of ultrasonography. The cytological examination of the lesion was characterized by the predominance of heterogeneous lymphoid cells, clusters of epithelial cells with a variety of cytologic appearances, including granular, transparent, vacuolated, and oncocytic, and the presence of numerous naked nuclei with a protein-like foamy background. Due to intense lymphocytic inflammation, it was considered as benign primary parotid tumor such as Warthin's tumor. The excision material was examined histopathologically. Immunohistochemical analysis showed that this carcinoma was positive for DOG1, SOX10, cytokeratin 7 and negative for mammaglobin. This salivary gland tumor was reported as a rare variant of ACC with lymphoid-rich stroma. To improve the diagnostic accuracy, various morphological aspects of ACC should be considered in the pathological practice.

PMID:37800395 | DOI:10.1002/dc.25233
Small Cell Neuroendocrine Carcinoma of the Parotid Gland: An Uncommon Example of Incompletely Encapsulated Tumor Including S100 Protein-Positive Clear Cells

Fetched: October 5th, 2023, 5:00am GMT by Hiroshi Harada

Kurume Med J. 2023 Nov 30;69(1.2):103-109. doi: 10.2739/kurumemedj.MS6912009. Epub 2023 Oct 3.

ABSTRACT

Small cell carcinoma is rare in salivary glands and has recently been termed small cell neuroendocrine carcinoma. We herein describe an uncommon example arising in the parotid gland. The patient was a 75 yearold Japanese male who had swelling in the right parotid area. He underwent a superficial lobectomy and, after a histological diagnosis was made, a total parotidectomy. Histologically, the tumor had a thick hyalinized capsule that was incomplete, beyond which the tumor invaded into the surrounding parotid parenchyma. The tumor consisted of typical small basophilic cells intermingled with bland clear cells, between which a gradual transition was observed both inside and outside the capsule. Small basophilic cells were immunoreactive for chromograninA as well as synaptophysin, while clear cells were positive for S100 protein. The Ki-67 labeling rate reached 30-40% at the high points of small basophilic cells, but clear cells were minimally labelled. The present case was considered a dedifferentiated carcinoma of the parotid gland, possibly with acinic cell carcinoma as a precursor. This tumor could also be considered a "mixed exocrine-endocrine carcinoma," which may explain the histogenesis of neuroendocrine carcinomas in non-endocrine organs that are not included in the diffuse (dispersed) neuroendocrine system, such as the parotid gland.

PMID:37793887 | DOI:10.2739/kurumemedj.MS6912009
Secretory carcinoma of salivary gland: A rare tumor masquerading as acinic cell carcinoma on cytology

Fetched: October 4th, 2023, 5:00am GMT by Charu Agarwal

Diagn Cytopathol. 2023 Oct 3. doi: 10.1002/dc.25232. Online ahead of print.

ABSTRACT

Secretory carcinoma (SC) was originally described as mammary analogue secretory carcinoma (MASC). We present here a case of 33 years old male who came to ENT outpatient department with a complaint of swelling over the left side of his neck for 8 months. On Fine-needle aspiration cytology, an impression of cytomorphological features suggestive of acinic cell carcinoma (Milan category V) was given. Left functional endoscopic sinus surgery was done. On histopathology, a final impression of Secretory carcinoma, the left submandibular gland was given with pathological stage classification as pT2N0Mx. SC of the salivary gland is a rare entity that may pose diagnostic challenges. Awareness of its cytologic features is paramount to achieve an accurate diagnosis. Morphologic interpretation must be supported by an immunohistochemical profile and molecular studies to confirm a diagnosis of SC.

PMID:37786377 | DOI:10.1002/dc.25232
Clinicopathological features and prognostic significance of pulmonary adenocarcinoma with signet ring cell components: meta-analysis and SEER analysis

Fetched: October 2nd, 2023, 5:00am GMT by Yang Tan

Clin Exp Med. 2023 Oct 1. doi: 10.1007/s10238-023-01200-3. Online ahead of print.

ABSTRACT

Pulmonary adenocarcinoma is a common type of lung cancer that has been on the rise in recent years. Signet ring cell components (SRCC) can be present in various patterns of pulmonary adenocarcinoma, including papillary, acinar, and solid patterns. "Signet ring cell carcinoma" is a distinct subtype in the 2014 WHO classification of lung neoplasms, subsequent WHO classifications in 2015 and 2021 have deemed signet ring cells as accompanying morphological features with no clinical significance. The prognostic and clinical implications of SRCC in pulmonary adenocarcinoma remain controversial. Therefore, we conducted a meta-analysis to investigate the clinicopathological features and prognostic factors of SRCC in pulmonary adenocarcinoma. We conducted a comprehensive search in PubMed, EMBASE, and Web of Science to identify studies that examined the clinicopathological features and prognostic implications of pulmonary adenocarcinoma with SRCC. We used both fixed- and random-effects models to analyze the data and calculate the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). Additionally, we explored the prognostic significance of SRCC in pulmonary adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database. Our meta-analysis included 29 studies with pulmonary adenocarcinoma and SRCC components. The results showed that pulmonary adenocarcinoma with SRCC was associated with larger tumor size (OR = 1.99; 95% CI, 1.62-2.44, p < 0.001), advanced overall stage (OR = 5.18, 95% CI, 3.28-8.17, p < 0.00001) and lymph node stage (OR = 5.79, 95% CI, 1.96-17.09, p = 0.001), and worse overall survival (OS) compared to those without SRCC (HR = 1.80, 95% CI, 1.50-2.16, p < 0.00001). Analysis using the SEER dataset confirmed these findings. Our meta-analysis provides evidence that pulmonary adenocarcinoma with SRCC is associated with distinct clinicopathological features and a poorer prognosis. These findings have important implications for the management and treatment of patients. However, further studies are needed to validate these findings and explore the significance of SRCC in various subtypes of pulmonary adenocarcinoma.

PMID:37779169 | DOI:10.1007/s10238-023-01200-3
Rare ROS1-CENPW gene in pancreatic acinar cell carcinoma and the effect of crizotinib plus AG chemotherapy: A case report

Fetched: September 21st, 2023, 5:00am GMT by Tao Wang

World J Clin Cases. 2023 Aug 26;11(24):5823-5829. doi: 10.12998/wjcc.v11.i24.5823.

ABSTRACT

BACKGROUND: This is the first report of an ROS1-CENPW fusion gene in pancreatic malignancies.

CASE SUMMARY: A 77-year-old woman with a pancreatic tumor and multiple liver metastases was admitted to our hospital. Genetic testing revealed the presence of the ROS1-CENPW fusion gene, a rare fusion gene that has not been previously reported in the field of pancreatic cancer. The patient received crizotinib plus AG (albumin paclitaxel plus gemcitabine) chemotherapy. After treatment, the patient's condition stabilized, and her prognosis was good.

CONCLUSION: The ROS1-CENPW gene treatment regimen used in this case is an excellent treatment option that provides new hope for patients with advanced pancreatic cancer and similar genetic mutations. To date, owing to the rarity of the ROS1-CENPW fusion gene, our team has encountered only a single case. Therefore, the efficacy of crizotinib plus AG chemotherapy in patients with pancreatic acinar cell carcinoma harboring the ROS1-CENPW fusion gene requires further validation.

PMID:37727713 | PMC:PMC10506013 | DOI:10.12998/wjcc.v11.i24.5823
Immunohistological profiling confirms salivary gland-like nature of the tubarial glands and suggests closest resemblance to the palatal salivary glands

Fetched: September 16th, 2023, 5:00am GMT by Sarah Pringle

Radiother Oncol. 2023 Oct;187:109845. doi: 10.1016/j.radonc.2023.109845. Epub 2023 Aug 4.

ABSTRACT

BACKGROUND AND PURPOSE: High label uptake in 68 Ga-PSMA-11 PET/CT recently identified a bilateral nasopharyngeal structure as a salivary gland (SG)-like additional 'area of interest', to be considered in conditions affecting SGs. These structures were termed 'tubarial glands'. We aimed to further characterize their histological and immunohistochemical position compared to established SGs.

METHODS: Tubarial gland tissue was compared with parotid, submandibular, sublingual, palatal and labial SGs tissue using immunohistological techniques.

RESULTS: Expression of acinar cell-associated aquaporin-5 (AQP5) was detected in tubarial glands, in an apical location associated in control, established SGs with polarized, secretory acinar cells. Keratin14 (KRT14) expression in cells peripheral to AQP5⁺ clusters also suggested presence of myoepithelial cells. α-amylase, prolactin-induced protein, proline rich protein Haelll subfamily 2, and Muc5B expression suggests mucous acinar cell presence, and presence of muco-serous acinar cells peripheral to putative mucous acinar cells. Expression of adrenergic receptor-β1 by acinar-like cells of the tubarial gland suggests ability to transduce sympathetic neuronal signaling. In terms of ductal architecture, tubarial glands contained large excretory-like ducts (similar to all other SGs), and squamous ducts, comprised of intermingled KRT14⁺ and KRT7⁺ cells. These squamous ducts were also observed in palatal, sublingual and labial SGs. No striated or intercalated ducts were observed, similar to palatal SGs.

CONCLUSION: Based on histological and immunohistochemical analyses, the tubarial glands resemble SGs. They most convincingly echo characteristics of the palatal SGs in terms of ductal cells, and both the palatal and labial SGs when considering acinar cells.

PMID:37543053 | DOI:10.1016/j.radonc.2023.109845
Pancreatic adenocarcinoma arising from an ectopic pancreas in a cat

Fetched: September 15th, 2023, 5:00am GMT by Hyun Cho

Vet Radiol Ultrasound. 2023 Sep;64(5):E50-E54. doi: 10.1111/vru.13263. Epub 2023 Jun 20.

ABSTRACT

An 8-year-old male neutered Korean shorthair cat presented with chronic vomiting. Radiographically, an oval-shaped soft tissue abdominal mass caudoventral to the left kidney was detected. On ultrasonography, the hypoechoic mass was well-defined with thick, irregular, and hyperechoic margins and had no continuity with the pancreas or other adjacent organs. The mass was surgically excised. Areas of atypical pancreatic acinar epithelial cells were identified histopathologically. Postoperative CT demonstrated a normal pancreas in the expected anatomical region. Based on diagnostic imaging, surgical and histopathology findings, the mass was diagnosed as a well-differentiated pancreatic acinar cell adenocarcinoma arising from ectopic pancreatic tissue.

PMID:37340693 | DOI:10.1111/vru.13263
SECRETORY CARCINOMA OF SALIVARY GLANDS WITH NTRK3 BREAK-APART MOLECULAR REARRANGEMENT: POTENTIAL MISDIAGNOSIS WITH MUCOEPIDERMOID CARCINOMA

Fetched: September 15th, 2023, 5:00am GMT by Riccardo Nocini

J Stomatol Oral Maxillofac Surg. 2023 Dec;124(6S):101635. doi: 10.1016/j.jormas.2023.101635. Epub 2023 Sep 12.

ABSTRACT

A woman presented a right submandibular gland lesion with cytologic diagnosis of mucoepidermoid carcinoma. Patient underwent sialoadenectomy en bloc with supraomohyoid neck dissection. Positivity for ETV6-NTRK3 genes fusion on surgical sample led to final diagnosis of secretory carcinoma (SC). Secretory carcinoma has been renamed by WHO in 2017 from mammary-analogue-secretory carcinoma (MASC). Only 649 have been reported until 2019. While cytologic alteration are shared with other neoplasms as the acinic cell and mucoepidermoid carcinomas, ETV6-NTRK3 rearrangement is pathognomonic of SC. Although usually indolent and with low-stage presentation, SC has higher rate of local recurrences and nodal involvement than ACC. Surgical treatment represent the gold standard. Real prevalence of SC is probably underestimated due to the recent WHO 2017 reclassification. While cytologic analysis does not allow to discriminate SC from other malignancies, chromosomal examination is recommended. When low-grade SC is diagnosed, complete surgical resection assures good prognosis.

PMID:37709146 | DOI:10.1016/j.jormas.2023.101635
Recent developments in the pathology of primary pulmonary salivary gland-type tumours

Fetched: September 12th, 2023, 5:00am GMT by Julia R Naso

Histopathology. 2023 Sep 11. doi: 10.1111/his.15039. Online ahead of print.

ABSTRACT

Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland-type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland-type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland-type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type-tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high-grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland-type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland-type tumours of the lung and those primary to other sites.

PMID:37694812 | DOI:10.1111/his.15039
Fibrolamellar carcinomas-growth arrested by paracrine signals complexed with synthesized 3-O sulfated heparan sulfate oligosaccharides

Fetched: September 9th, 2023, 5:00am GMT by Wencheng Zhang

Matrix Biol. 2023 Aug;121:194-216. doi: 10.1016/j.matbio.2023.06.008. Epub 2023 Jul 2.

ABSTRACT

Fibrolamellar carcinomas (FLCs), lethal tumors occurring in children to young adults, have genetic signatures implicating derivation from biliary tree stem cell (BTSC) subpopulations, co-hepato/pancreatic stem cells, involved in hepatic and pancreatic regeneration. FLCs and BTSCs express pluripotency genes, endodermal transcription factors, and stem cell surface, cytoplasmic and proliferation biomarkers. The FLC-PDX model, FLC-TD-2010, is driven ex vivo to express pancreatic acinar traits, hypothesized responsible for this model's propensity for enzymatic degradation of cultures. A stable ex vivo model of FLC-TD-2010 was achieved using organoids in serum-free Kubota's Medium (KM) supplemented with 0.1% hyaluronans (KM/HA). Heparins (10 ng/ml) caused slow expansion of organoids with doubling times of ∼7-9 days. Spheroids, organoids depleted of mesenchymal cells, survived indefinitely in KM/HA in a state of growth arrest for more than 2 months. Expansion was restored with FLCs co-cultured with mesenchymal cell precursors in a ratio of 3:7, implicating paracrine signaling. Signals identified included FGFs, VEGFs, EGFs, Wnts, and others, produced by associated stellate and endothelial cell precursors. Fifty-three, unique heparan sulfate (HS) oligosaccharides were synthesized, assessed for formation of high affinity complexes with paracrine signals, and each complex screened for biological activity(ies) on organoids. Ten distinct HS-oligosaccharides, all 10-12 mers or larger, and in specific paracrine signal complexes elicited particular biological responses. Of note, complexes of paracrine signals and 3-O sulfated HS-oligosaccharides elicited slowed growth, and with Wnt3a, elicited growth arrest of organoids for months. If future efforts are used to prepare HS-oligosaccharides resistant to breakdown in vivo, then [paracrine signal-HS-oligosaccharide] complexes are potential therapeutic agents for clinical treatments of FLCs, an exciting prospect for a deadly disease.

PMID:37402431 | DOI:10.1016/j.matbio.2023.06.008
Primary renal malignant epithelioid angiomyolipoma with distant metastasis: a case report and literature review

Fetched: September 8th, 2023, 5:00am GMT by Jun Zhang

Front Oncol. 2023 Aug 22;13:1207536. doi: 10.3389/fonc.2023.1207536. eCollection 2023.

ABSTRACT

Epithelioid angiomyolipoma (EAML) is a rare type of mesenchymal angiomyolipoma with potential malignancy in the kidney that can cause lymph node metastases, local recurrence, and distant metastases. Herein, we describe a case of EAML in the right kidney of a 51-year-old man who was admitted to the hospital with a right abdominal mass. Computed tomography revealed a heterogeneously enhanced mass with blurred margins, which was considered a malignant tumor. A radical nephrectomy was then performed. Two years later, the patient developed liver metastases from EAML and was administered sintilimab combined with bevacizumab. The patient survived after 6 months of follow-up. Histologically, the tumors showed clear boundaries and no obvious capsules. The tumor tissue mainly consisted of epithelioid tumor cells, thick-walled blood vessels, and a small amount of adipose tissue. Tumor cells with lipid vacuoles and acinar areas were large, round, polygonal, eosinophilic, or transparent in the cytoplasm. The enlarged and hyperchromatic nuclei were accompanied by distinct nucleoli and pathological mitosis. These histopathological findings resembled those of renal cell carcinoma, and immunohistochemical analysis was performed. The tumor cells were diffusely positive for HMB45, Melan-A, CK20, vimentin antibodies, and TFE3, suggesting that the tumor originated from perivascular epithelioid cells, excluding renal cell carcinoma. The Ki-67 index was 10%. These histopathological features were observed in liver mass puncture tissues. We also summarized 46 cases of EAML with distant metastasis and explored the clinicopathological features of EAML to improve the treatment of the disease. EAML is often ignored in the clinical setting, leading to metastasis and recurrence. Therefore, EAMLs require long-term follow-up, and timely detection of recurrent disease can improve the prognosis.

PMID:37675231 | PMC:PMC10477911 | DOI:10.3389/fonc.2023.1207536
Chaotic transformation of parotid acinic cell carcinoma to metastatic dedifferentiated high-grade pathology - A rare case with clinical and emotional challenge

Fetched: September 7th, 2023, 5:00am GMT by Faiza Ahmed

Int J Surg Case Rep. 2023 Sep;110:108784. doi: 10.1016/j.ijscr.2023.108784. Epub 2023 Sep 2.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Acinic cell carcinoma (AciCC) is a rare entity in which high-grade transformation (HGT), formerly dedifferentiation, is uncommon. This case report presents a rare case of AciCC, with rapid transformation to metastatic high-grade dedifferentiated pathology after initial curative treatment.

CASE PRESENTATION: A 58-year-old woman presented in the medical oncology clinic with a progressive swelling on the right side of her face. Magnetic resonance imaging revealed a 5 × 5 cm lobulated parotid gland lesion, and fine needle aspiration biopsy was consistent with carcinoma. After informed consent, a Modified-Blair incision was given as a standard approach to the right preauricular area under general anaesthesia, and a right superficial parotidectomy with the removal of the tumor and selective lymph node dissection was performed. Histopathology of the resected mass was reported as parotid AciCC. She was given adjuvant radiation therapy. A repeat PET CT scan ten weeks after the completion of her adjuvant radiation treatment showed local disease recurrence as well as multiple pulmonary deposits. A repeat biopsy was reported as DOG-1 positive dedifferentiated (high-grade) acinic cell carcinoma, and she was offered platinum-based palliative systemic chemotherapy.

CLINICAL DISCUSSION: Parotid acinic cell carcinomas with high-grade transformation are rare. This case highlights its critical diagnostic markers, curative and palliative management and long-term follow-up.

CONCLUSION: The transformation of parotid AciCC to high-grade, dedifferentiated pathology is unusual and belligerent. Hence, these tumors need intense treatment with a multimodality approach. Close follow-ups with history and physical examination, along with periodic imaging, should be considered for these patients.

PMID:37672826 | PMC:PMC10510077 | DOI:10.1016/j.ijscr.2023.108784
Germline BRCA2 Mutations Are Prevalent in Pancreatic Acinar Cell Carcinoma

Fetched: September 2nd, 2023, 5:00am GMT

Cancer Discov. 2023 Nov 1;13(11):OF3. doi: 10.1158/2159-8290.CD-RW2023-138.

ABSTRACT

Pancreatic acinar cell carcinoma (PACC) has a high prevalence of BRCA2 germline pathogenic variants.

PMID:37655853 | DOI:10.1158/2159-8290.CD-RW2023-138
Systematic Review of Management and Survival Outcome of Parotid Cancers with Lateral Skull Base Invasion

Fetched: August 29th, 2023, 5:00am GMT by Pietro De Luca

Indian J Otolaryngol Head Neck Surg. 2023 Sep;75(3):2713-2721. doi: 10.1007/s12070-023-03787-1. Epub 2023 May 3.

ABSTRACT

Lateral skull base involvement from parotid cancers is a rare condition and is considered a poor prognostic indicator. The aim of this study was to systematically review the literature of parotid tumors with temporal bone invasion to analyze the survival outcome. A systematic literature review was performed in August 2022, without time limits, and 289 patients affected by parotid gland cancers and lateral skull base involvement were included. The most common symptoms in parotid tumors at the onset were indolent mass, facial weakness, pain, and hearing loss; the chi-square value is 23.1063, with a statistically significance (p = < 0.000121). The five most common histologies were adenoid cystic carcinoma, acinic cell carcinoma, mucoepidermoid carcinoma, adenocarcinoma, and squamous cell carcinoma. The facial nerve function after surgery showed statistically significance (functional vs. non-functional; chi-square was 91.7698, p = < 0.00001). Mean follow-up was 36.2 months (range 0.3-192). At the last follow-up, more patients died of disease (DOD; 60/289, 21%) than other causes (DOOC; 5/289, 2%). There is a statistically significant correlation between patients died for tumor (DOD) and patients died for other causes (DOOC) (p = < 0.0001), suggesting that the lateral skull base invasion negatively impacts on survival. Basing on the results of our systematic review, lateral skull base involvement from parotid recurrent/advance tumors should be considered a poor prognostic factor, as the majority of patients die due to this condition. It also would be necessary to have "clear"works, with full data (demographic, clinical, surgical data), and with a longer follow up, in order to assess the best treatment modality of these patients.

PMID:37636674 | PMC:PMC10447298 | DOI:10.1007/s12070-023-03787-1
Fibrosis induced by resident macrophages has divergent roles in pancreas inflammatory injury and PDAC

Fetched: August 29th, 2023, 5:00am GMT by John M Baer

Nat Immunol. 2023 Sep;24(9):1443-1457. doi: 10.1038/s41590-023-01579-x. Epub 2023 Aug 10.

ABSTRACT

Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs. Pancreas TRMs had an extracellular matrix remodeling phenotype that was important for maintaining tissue homeostasis during inflammation. Loss of TRMs led to exacerbation of severe pancreatitis and death, due to impaired acinar cell survival and recovery. During pancreatitis, TRMs elicited protective effects by triggering the accumulation and activation of fibroblasts, which was necessary for initiating fibrosis as a wound healing response. The same TRM-driven fibrosis, however, drove pancreas cancer pathogenesis and progression. Together, these findings indicate that TRMs play divergent roles in the pathogenesis of pancreatitis and cancer through regulation of stromagenesis.

PMID:37563309 | DOI:10.1038/s41590-023-01579-x
Microfluidic coaxial 3D bioprinting of cell-laden microfibers and microtubes for salivary gland tissue engineering

Fetched: August 28th, 2023, 5:00am GMT by Yu Yin

Biomater Adv. 2023 Nov;154:213588. doi: 10.1016/j.bioadv.2023.213588. Epub 2023 Aug 14.

ABSTRACT

Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar death caused by radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC). Currently, only palliative treatments exist for xerostomia, and many patients endure deteriorated oral health and poor quality of life. Tissue engineering could offer a permanent solution for SG replacement by isolating healthy SG tissues prior to RT, expanding its cells in vitro, and recreating a functional salivary neogland for implantation post-RT. 3D bioprinting methods potentiate spatial cell deposition into defined hydrogel-based architectures, mimicking the thin epithelia developed during the complex branching morphogenesis of SG. By leveraging a microfluidics-based bioprinter with coaxial polymer and crosslinker streams, we fabricated thin, biocompatible, and reproducible hydrogel features that recapitulate the thin epithelia characteristics of SG. This flexible platform enabled two modes of printing: we produced solid hydrogel fibers, with diameters <100 μm, that could be rastered to create larger mm-scale structures. By a second method, we generated hollow tubes with wall thicknesses ranging 45-80 μm, total tube diameters spanning 0.6-2.2 mm, and confirmed tube patency. In both cases, SG cells could be printed within the thin hydrogel features, with preserved phenotype and high viability, even at high density (5.0 × 10⁶ cells/mL). Our work demonstrates hydrogel feature control across multiple length scales, and a new paradigm for addressing SG restoration by creating microscale tissue engineered components.

PMID:37634337 | DOI:10.1016/j.bioadv.2023.213588
Genomic Evolution and Transcriptional Changes in the Evolution of Prostate Cancer into Neuroendocrine and Ductal Carcinoma Types

Fetched: August 27th, 2023, 5:00am GMT by Srinivasa R Rao

Int J Mol Sci. 2023 Aug 12;24(16):12722. doi: 10.3390/ijms241612722.

ABSTRACT

Prostate cancer is typically of acinar adenocarcinoma type but can occasionally present as neuroendocrine and/or ductal type carcinoma. These are associated with clinically aggressive disease, and the former often arises on a background of androgen deprivation therapy, although it can also arise de novo. Two prostate cancer cases were sequenced by exome capture from archival tissue. Case 1 was de novo small cell neuroendocrine carcinoma and ductal adenocarcinoma with three longitudinal samples over 5 years. Case 2 was a single time point after the development of treatment-related neuroendocrine prostate carcinoma. Case 1 showed whole genome doubling in all samples and focal amplification of AR in all samples except the first time point. Phylogenetic analysis revealed a common ancestry for ductal and small cell carcinoma. Case 2 showed 13q loss (involving RB1) in both adenocarcinoma and small cell carcinoma regions, and 3p gain, 4p loss, and 17p loss (involving TP53) in the latter. By using highly curated samples, we demonstrate for the first time that small-cell neuroendocrine and ductal prostatic carcinoma can have a common ancestry. We highlight whole genome doubling in a patient with prostate cancer relapse, reinforcing its poor prognostic nature.

PMID:37628903 | PMC:PMC10454593 | DOI:10.3390/ijms241612722
Rare Solid Pancreatic Lesions on Cross-Sectional Imaging

Fetched: August 27th, 2023, 5:00am GMT by Ana Veron Sanchez

Diagnostics (Basel). 2023 Aug 21;13(16):2719. doi: 10.3390/diagnostics13162719.

ABSTRACT

Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most common subtype is pancreatic ductal adenocarcinoma (PDAC), to a point that pancreatic cancer and PDAC are used interchangeably. But, in addition to PDAC, and to the other most common and well-known solid lesions, either related to benign conditions, such as pancreatitis, or not so benign, such as pancreatic neuroendocrine neoplasms (pNENs), there are solid pancreatic lesions considered rare due to their low incidence. These lesions may originate from a cell line with a differentiation other than exocrine/endocrine, such as from the nerve sheath as for pancreatic schwannoma or from mesenchymal cells as for solitary fibrous tumour. These rare solid pancreatic lesions may show a behaviour that ranges in a benign to highly aggressive malignant spectrum. This review includes cases of an intrapancreatic accessory spleen, pancreatic tuberculosis, solid serous cystadenoma, solid pseudopapillary tumour, pancreatic schwannoma, purely intraductal neuroendocrine tumour, pancreatic fibrous solitary tumour, acinar cell carcinoma, undifferentiated carcinoma with osteoclastic-like giant cells, adenosquamous carcinoma, colloid carcinoma of the pancreas, primary leiomyosarcoma of the pancreas, primary and secondary pancreatic lymphoma and metastases within the pancreas. Therefore, it is important to determine the correct diagnosis to ensure optimal patient management. Because of their rarity, their existence is less well known and, when depicted, in most cases incidentally, the correct diagnosis remains challenging. However, there are some typical imaging features present on cross-sectional imaging modalities that, taken into account with the clinical and biological context, contribute substantially to achieve the correct diagnosis.

PMID:37627978 | PMC:PMC10453474 | DOI:10.3390/diagnostics13162719
A resected case of acinar cell carcinoma of the pancreas with liver metastasis following chemotherapy using modified FOLFIRINOX

Fetched: August 24th, 2023, 5:00am GMT by Shuhei Yamada

Surg Case Rep. 2023 Aug 23;9(1):147. doi: 10.1186/s40792-023-01729-1.

ABSTRACT

BACKGROUND: Acinar cell carcinoma of the pancreas is a rare exocrine malignancy representing less than 1% of all pancreatic neoplasms. It has been reported that it responds to treatment differently from pancreatic ductal adenocarcinoma and the treatment algorithm for acinar cell carcinoma usually depends on the stage of the respective tumor and the patient's current status.

CASE PRESENTATION: A 60-year-old man presented with upper abdominal pain and anorexia. Abdominal ultrasonography showed a large-sized hepatic mass and he was referred to our hospital. Contrast-enhanced computed tomography demonstrated a 110-mm low-density area occupying the right hemi-liver and an enhanced mass of 70 × 56 mm in the tail of the pancreas, which seemed to directly infiltrate into the spleen. The case was diagnosed as acinar cell carcinoma with a simultaneous liver metastasis identified by liver biopsy. Upfront resection of pancreatic cancer with distant metastasis might not be considered as an optimal choice, and in this case chemotherapy was administered prior to curative resection. Chemotherapy using the modified FOLFIRINOX regimen was undertaken, resulting in a partial remission; the liver tumor reduced in size from 110 to 47 mm and the pancreatic tumor from 70 to 40 mm. The patient then safely underwent curative hepatic resection with distal pancreato-splenectomy. Histological examinations revealed small-sized atypical cells with large nuclei that had formed acinar patterns, and immunostaining with trypsin was positive in tumor cells, which was in accordance with acinar cell carcinoma. More than 3 years later, the patient is doing well without any recurrence.

CONCLUSION: Aggressive and curative surgery in combination with chemotherapy such as FOLFIRINOX could be a treatment option to achieve long-term survival in cases of acinar cell carcinoma with liver metastases.

PMID:37610633 | PMC:PMC10447704 | DOI:10.1186/s40792-023-01729-1
Genomic Profiling Reveals Germline Predisposition and Homologous Recombination Deficien cy in Pancreatic Acinar Cell Carcinoma

Fetched: August 23rd, 2023, 5:00am GMT by Diana Mandelker

J Clin Oncol. 2023 Nov 20;41(33):5151-5162. doi: 10.1200/JCO.23.00561. Epub 2023 Aug 22.

ABSTRACT

PURPOSE: To determine the genetic predisposition underlying pancreatic acinar cell carcinoma (PACC) and characterize its genomic features.

METHODS: Both somatic and germline analyses were performed using an Food and Drug Administration-authorized matched tumor/normal sequencing assay on a clinical cohort of 28,780 patients with cancer, 49 of whom were diagnosed with PACC. For a subset of PACCs, whole-genome sequencing (WGS; n = 12) and RNA sequencing (n = 6) were performed.

RESULTS: Eighteen of 49 (36.7%) PACCs harbored germline pathogenic variants in homologous recombination (HR) and DNA damage response (DDR) genes, including BRCA1 (n = 1), BRCA2 (n = 12), PALB2 (n = 2), ATM (n = 2), and CHEK2 (n = 1). Thirty-one PACCs displayed pure, and 18 PACCs harbored mixed acinar cell histology. Fifteen of 31 (48%) pure PACCs harbored a germline pathogenic variant affecting HR-/DDR-related genes. BRCA2 germline pathogenic variants (11 of 31, 35%) were significantly more frequent in pure PACCs than in pancreatic adenocarcinoma (86 of 2,739, 3.1%; P < .001), high-grade serous ovarian carcinoma (67 of 1,318, 5.1%; P < .001), prostate cancer (116 of 3,401, 3.4%; P < .001), and breast cancer (79 of 3,196, 2.5%; P < .001). Genomic features of HR deficiency (HRD) were detected in 7 of 12 PACCs undergoing WGS, including 100% (n = 6) of PACCs with germline HR-related pathogenic mutations and 1 of 6 PACCs lacking known pathogenic alterations in HR-related genes. Exploratory analyses revealed that in PACCs, the repertoire of somatic driver genetic alterations and the load of neoantigens with high binding affinity varied according to the presence of germline pathogenic alterations affecting HR-/DDR-related genes and/or HRD.

CONCLUSION: In a large pan-cancer cohort, PACC was identified as the cancer type with the highest prevalence of both BRCA2 germline pathogenic variants and genomic features of HRD, suggesting that PACC should be considered as part of the spectrum of BRCA-related malignancies.

PMID:37607324 | PMC:PMC10667000 | DOI:10.1200/JCO.23.00561
Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma

Fetched: August 17th, 2023, 5:00am GMT by Qiqi Ye

J Clin Pathol. 2023 Aug 16:jcp-2023-208989. doi: 10.1136/jcp-2023-208989. Online ahead of print.

ABSTRACT

AIMS: Secretory carcinoma of breast (SCB) typically harbours ETV6-NTRK3 gene fusion. Pan-Trk immunohistochemistry analysis (IHC) has been shown to be sensitive for SCB diagnosis. However, weak focal pan-Trk nuclear staining was previously found in 10% of non-secretory breast carcinomas. To further examine pan-Trk IHC specificity, we evaluated pan-Trk staining in various breast carcinoma subtypes.

METHODS: The study cohort consisted of 346 invasive breast carcinomas (IBCs), including 8 SCBs and 48 triple-negative histological mimickers (36 metaplastic carcinomas, including 12 matrix-producing carcinomas; 5 adenoid cystic carcinomas; 5 apocrine carcinomas; 2 acinic cell carcinomas), 101 triple-negative IBCs of no special type, 101 estrogen receptor (ER)-positive/HER2-negative IBCs and 88 HER2-positive IBCs. Six salivary gland secretory carcinomas were also included. Pan-Trk IHC was performed on tumours using a rabbit monoclonal pan-Trk antibody. Any nuclear staining in the invasive carcinoma cells was considered positive.

RESULTS: All 14 secretory carcinomas from breast and salivary gland exhibited moderate to strong pan-Trk nuclear staining. In contrast, no pan-Trk nuclear staining was identified in any of the 338 non-secretory IBCs. Focal cytoplasmic pan-Trk staining was observed in nine non-secretory IBCs (2.7%), and was considered nonspecific and negative.

CONCLUSIONS: Our results indicate that pan-Trk nuclear staining is highly specific for SCB. In low-grade to intermediate-grade IBCs that share histological features with SCB, adding pan-Trk to a routing panel of estrogen receptor/progesterone receptor/HER2 is highly diagnostic. Our results also support using pan-Trk IHC to differentiate SCB from its triple-negative histological mimickers, such as adenoid cystic carcinoma, matrix-producing carcinoma, apocrine carcinoma and acinic cell carcinoma.

PMID:37586834 | DOI:10.1136/jcp-2023-208989
Driver Mutations of Pancreatic Cancer Affect Ca2+ Signaling and ATP Production

Fetched: August 16th, 2023, 5:00am GMT by Kinga B Stopa

Function (Oxf). 2023 Jul 4;4(5):zqad035. doi: 10.1093/function/zqad035. eCollection 2023.

ABSTRACT

Glandular pancreatic epithelia of the acinar or ductal phenotype may seem terminally differentiated, but they are characterized by remarkable cell plasticity. Stress-induced trans-differentiation of these cells has been implicated in the mechanisms of carcinogenesis. Current consensus links pancreatic ductal adenocarcinoma with onco-transformation of ductal epithelia, but under the presence of driver mutations in Kras and Trp53, also with trans-differentiation of pancreatic acini. However, we do not know when, in the course of cancer progression, physiological functions are lost by mutant acinar cells, nor can we assess their capacity for the production of pancreatic juice components. Here, we investigated whether two mutations-Kras^G12D and Trp53^R172H-present simultaneously in acinar cells of KPC mice (model of oncogenesis) influence cytosolic Ca²⁺ signals. Since Ca²⁺ signals control the cellular handling of digestive hydrolases, any changes that affect intracellular signaling events and cell bioenergetics might have an impact on the physiology of the pancreas. Our results showed that physiological doses of acetylcholine evoked less regular Ca²⁺ oscillations in KPC acinar cells compared to the control, whereas responses to supramaximal concentrations were markedly reduced. Menadione elicited Ca²⁺ signals of different frequencies in KPC cells compared to control cells. Finally, Ca²⁺ extrusion rates were significantly inhibited in KPC cells, likely due to the lower basal respiration and ATP production. Cumulatively, these findings suggest that driver mutations affect the signaling capacity of pancreatic acinar cells even before the changes in the epithelial cell morphology become apparent.

PMID:37575483 | PMC:PMC10413928 | DOI:10.1093/function/zqad035
Case Report: Analysis of four cases of metastatic bladder masses after radical prostatectomy

Fetched: August 15th, 2023, 5:00am GMT by Hao Wang

Front Oncol. 2023 Jul 28;13:1211027. doi: 10.3389/fonc.2023.1211027. eCollection 2023.

ABSTRACT

OBJECTIVE: The aim of this study is to investigate the clinical characteristics and diagnostic and therapeutic methods of bladder metastasis after radical prostatectomy and to improve its diagnosis and treatment.

METHODS: The clinical data of four patients with bladder metastasis after radical prostatectomy were retrospectively analyzed from January 2011 to December 2021. Three cases suffered from intermittent gross hematuria, and only one case was found to have an elevated prostate-specific antigen (PSA) value. Transurethral resection of bladder tumor was performed in four cases, in which one case also underwent resection of urethral mass. Three cases received endocrine therapy, one of which added intravesical instillation and radiation therapy. Another case received chemotherapy based on comprehensive treatment.

RESULTS: According to the pathological and immunohistochemical results, three cases were acinar adenocarcinoma of the prostate with Gleason score of 9, and all cases were PSA positive and negative for cytokeratin 7 (CK7) and GATA binding protein 3 (GATA-3). One case was small cell neuroendocrine carcinoma of the prostate and was positive for chromogranin A (CGA), synaptophysin (SYN), and cluster of differentiation 56 (CD56). During the follow-up period of 4 to 13 months, one case was lost to follow-up and three cases were alive.

CONCLUSION: Bladder metastasis after radical prostatectomy is rare, and pathology combined with immunohistochemistry is the gold standard for its diagnosis. Pathological type determines its treatment. Systemic treatment is essential, and local treatment is the most palliative means. Early diagnosis and treatment is significant for better prognosis.

PMID:37576903 | PMC:PMC10417713 | DOI:10.3389/fonc.2023.1211027
TRPS1 immunohistochemical expression in salivary gland tumors: A pilot study

Fetched: August 12th, 2023, 5:00am GMT by Youley Tjendra

Am J Clin Pathol. 2023 Aug 11:aqad100. doi: 10.1093/ajcp/aqad100. Online ahead of print.

ABSTRACT

OBJECTIVES: TRPS1 is a new, sensitive marker for breast carcinoma (BC). Salivary glands and breasts are both exocrine glands; thus, their tumors may share similar morphology and immunophenotype. Among salivary gland-type BC, TRPS1 is reported to be positive in secretory carcinomas (SCs) but negative in acinic cell carcinomas (AciCCs) and most adenoid cystic carcinomas (AdCCs). A subset of salivary duct carcinomas (SDCs) is positive for TRPS1. Herein, we investigate TRPS1 immunohistochemical expression in salivary gland tumors (SGTs).

METHODS: A retrospective search yielded 110 SGTs (97 primary and 13 metastatic). TRPS1 immunohistochemistry was scored as negative, low positive, intermediate positive, or strongly positive.

RESULTS: TRPS1 was expressed in 78% (14/18) of pleomorphic adenoma (PA) cases but negative/low positive in all Warthin tumors (6/6 [100%]). In basal cell adenoma (BCA), TRPS1 expression was intermediate to strong (13/14 [92%]) in the stromal cells, whereas ductal or basal cells showed low expression. TRPS1 expression varied in malignant SGTs, with intermediate to strong staining in 100% (15/15) of AdCCs, 100% (5/5) of basal cell adenocarcinoma, 100% (3/3) of intraductal carcinoma, 89% (8/9) of polymorphous adenocarcinoma, and 89% (7/8) of SDCs; negative/low positive expression was observed in 100% (3/3) of SCs, 89% (8/9) of AciCCs, and 50% (3/3) of mucoepidermoid carcinomas. In addition, strong and intermediate TRPS1 expression was observed in metastatic SGT to the lungs, lymph nodes, and soft tissue.

CONCLUSIONS: Overall, TRPS1 is strongly expressed in PA as well as malignant and metastatic SGT. In addition, TRPS1 is positive in stromal cells of BCA but negative or low positive in ductal and basal cells.

PMID:37565763 | DOI:10.1093/ajcp/aqad100
Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients

Fetched: August 11th, 2023, 5:00am GMT by Ruben Bellotti

HPB (Oxford). 2023 Nov;25(11):1411-1419. doi: 10.1016/j.hpb.2023.07.897. Epub 2023 Jul 27.

ABSTRACT

BACKGROUND: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC.

METHODS: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols.

RESULTS: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy.

DISCUSSION: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting.

PMID:37563033 | DOI:10.1016/j.hpb.2023.07.897
Farnesoid X receptor activation inhibits pancreatic carcinogenesis

Fetched: August 8th, 2023, 5:00am GMT by Zhen Xu

Biochim Biophys Acta Mol Basis Dis. 2023 Oct;1869(7):166811. doi: 10.1016/j.bbadis.2023.166811. Epub 2023 Jul 27.

ABSTRACT

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily that controls bile acid (BA) homeostasis, has also been proposed as a tumor suppressor for breast and liver cancer. However, its role in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis remains controversial. We recently found that FXR attenuates acinar cell autophagy in chronic pancreatitis resulting in reduced autophagy and promotion of pancreatic carcinogenesis. Feeding Kras-p48-Cre (KC) mice with the BA chenodeoxycholic acid (CDCA), an FXR agonist, attenuated pancreatic intraepithelial neoplasia (PanIN) progression, reduced cell proliferation, neoplastic cells and autophagic activity, and increased acinar cells, elevated pro-inflammatory cytokines and chemokines, with a compensatory increase in the anti-inflammatory response. Surprisingly, FXR-deficient KC mice did not show any response to CDCA, suggesting that CDCA attenuates PanIN progression and decelerate tumorigenesis in KC mice through activating pancreatic FXR. FXR is activated in pancreatic cancer cell lines in response to CDCA in vitro. FXR levels were highly increased in adjuvant and neoadjuvant PDAC tissue compared to healthy pancreatic tissue, indicating that FXR is expressed and potentially activated in human PDAC. These results suggest that BA exposure activates inflammation and suppresses autophagy in KC mice, resulting in reduced PanIN lesion progression. These data suggest that activation of pancreatic FXR has a protective role by reducing the growth of pre-cancerous PDAC lesions in response to CDCA and possibly other FXR agonists.

PMID:37515840 | DOI:10.1016/j.bbadis.2023.166811
True Oncocytic Acinic Cell Carcinoma: A Case Image

Fetched: August 6th, 2023, 5:00am GMT by Matthew G Romanish

Head Neck Pathol. 2023 Sep;17(3):883-885. doi: 10.1007/s12105-023-01578-2. Epub 2023 Aug 4.

ABSTRACT

A 67-year-old female with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) presented with right sided otalgia and a 2-3 cm firm, tender right posterior parotid mass. Fine needle aspiration biopsy (FNAB) established a diagnosis of acinic cell carcinoma (AciCC). Further workup demonstrated lung nodules which were confirmed by FNAB to represent metastatic AciCC. A right radical parotidectomy with sacrifice of the facial nerve, segmental mandibulectomy, and selective neck dissection (levels II-IV) was performed. Microscopically, the tumor displayed an infiltrative border with a solid multinodular growth pattern and fibrosclerotic septation. The tumor was composed mainly of uniform cells with abundant eosinophilic granular cytoplasm with round nuclei with prominent nucleoli. Nuclei were fairly monomorphic, mitotic counts were 3-4 per 2mm² and there was no necrosis despite the aggressive growth pattern. An anti-mitochondrial immunohistochemical stain showed strong reactivity in the tumor cells, with an internal positive control of adjacent striated ducts. An immunohistochemical stain for NR4A3 demonstrated strong nuclear reactivity in the tumor cells. Electron microscopy highlighted the tumor cells with numerous mitochondria and distinctive electron dense intramitochondrial inclusions. Concurrent CLL/SLL was identified on histologic examination of the lymph nodes, but they were free of AciCC. After eight weeks of follow-up, she tolerated the surgery well and is currently receiving radiation therapy to the parotid and neck. In this illustrative case, we justify the oncocytic designation of AciCC by morphology, immunohistochemistry, and electron microscopy.

PMID:37541995 | PMC:PMC10513996 | DOI:10.1007/s12105-023-01578-2
Tff2 defines transit-amplifying pancreatic acinar progenitors that lack regenerative potential and are protective against Kras-driven carcinogenesis

Fetched: August 6th, 2023, 5:00am GMT by Zhengyu Jiang

Cell Stem Cell. 2023 Aug 3;30(8):1091-1109.e7. doi: 10.1016/j.stem.2023.07.002.

ABSTRACT

While adult pancreatic stem cells are thought not to exist, it is now appreciated that the acinar compartment harbors progenitors, including tissue-repairing facultative progenitors (FPs). Here, we study a pancreatic acinar population marked by trefoil factor 2 (Tff2) expression. Long-term lineage tracing and single-cell RNA sequencing (scRNA-seq) analysis of Tff2-DTR-CreER^T2-targeted cells defines a transit-amplifying progenitor (TAP) population that contributes to normal homeostasis. Following acute and chronic injury, Tff2⁺ cells, distinct from FPs, undergo depopulation but are eventually replenished. At baseline, oncogenic Kras^G12D-targeted Tff2⁺ cells are resistant to PDAC initiation. However, Kras^G12D activation in Tff2⁺ cells leads to survival and clonal expansion following pancreatitis and a cancer stem/progenitor cell-like state. Selective ablation of Tff2⁺ cells prior to Kras^G12D activation in Mist1⁺ acinar or Dclk1⁺ FP cells results in enhanced tumorigenesis, which can be partially rescued by adenoviral Tff2 treatment. Together, Tff2 defines a pancreatic TAP population that protects against Kras-driven carcinogenesis.

PMID:37541213 | PMC:PMC10414754 | DOI:10.1016/j.stem.2023.07.002
Two rare cancers of the exocrine pancreas: to treat or not to treat like ductal adenocarcinoma?

Fetched: August 5th, 2023, 5:00am GMT by Nebojsa Skorupan

J Cancer Metastasis Treat. 2023;9:5. doi: 10.20517/2394-4722.2022.106. Epub 2023 Mar 7.

ABSTRACT

Pancreatic cancer is an aggressive malignancy with increasing incidence. Pancreatic ductal adenocarcinoma (PDAC) accounts for > 90% of pancreatic cancer diagnoses, while other exocrine tumors are much rarer. In this review, we have focused on two rare cancers of the exocrine pancreas: adenosquamous carcinoma of the pancreas (ASCP) and pancreatic acinar cell carcinoma (PACC). The latest findings regarding their cellular and molecular pathology, clinical characteristics, prognosis, and clinical management are discussed. New genetic and transcriptomic data suggest that ASCP is related to or overlaps with the basal transcriptomic subtype of PDAC. These tumors are highly aggressive and driven by activated KRAS and MYC expression. Clinical outcomes remain poor and effective treatments are limited. PACC has no morphologic or genetic resemblance to PDAC and more favorable outcomes. Early stage PACC patients have improved survival with surgical resection and patients with advanced disease benefit most from platinum- or fluoropyrimidine-containing chemotherapy. Frequency of actionable genetic mutations is high in this disease and case reports suggest good outcomes when matched therapy is given. Dedicated clinical studies examining ASCP and PACC are limited and difficult to accrue. Further research is needed to define optimal clinical management for these rare diseases.

PMID:37538977 | PMC:PMC10400043 | DOI:10.20517/2394-4722.2022.106
Expression and significance of INSM1 and SOX11 in pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm

Fetched: August 4th, 2023, 5:00am GMT by Z Cao

Beijing Da Xue Xue Bao Yi Xue Ban. 2023 Aug 18;55(4):575-581. doi: 10.19723/j.issn.1671-167X.2023.04.001.

ABSTRACT

OBJECTIVE: To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine tumor (PNET) and solid pseudopapillary neoplasm (SPN).

METHODS: To detect the expression of INSM1, SOX11, Syn, CgA, CD56, β-catenin, and CD99 in 56 cases of PNET, 42 cases of SPN, 16 cases of ductal adenocarcinoma (DACC) and 8 cases of acinar cell carcinoma (ACC) by immunohistochemistry. The application value of combination of INSM1 and SOX11 was compared with conventional markers (Syn, CgA, CD56, β-catenin, and CD99) in diagnosis and differential diagnosis of PNET and SPN.

RESULTS: (1) In the 56 cases of PNET, the positive signals of INSM1 were located in the tumor and islet nucleus, the positive expression rate in the tumor tissues was 91.07% (51/56), whereas the signal was absent in 42 cases of SPN, 16 cases of DACC and 8 cases of ACC, and there were significant statistical difference between PNET with SPN, DACC, and ACC respectively (P < 0.001). (2) The positive signals of SOX11 were located in the tumor nucleus, with the positive expression rate was 92.86% (39/42) in SPN, however, the positive expression rate of SOX11 was 8.93% (5/56) in PNET, which included 3 cases of G1 and 2 cases of G3 types of PNET, the SOX11 positive signal was absent in 16 cases of DACC, 8 cases of ACC and peritumoral nomal pancreatic tissue, and the differences were statistically significant of positive rate between SPN with PNET, DACC and ACC, respectively (P < 0.001). (3) The sensitivity of INSM1(+)/SOX11(-) immunophenotype for PNET was 85.71%, vs. CD56 (57.14%), the difference was statistically significant (P=0.001); vs. Syn (80.36%) and CgA (71.43%), the difference was no statistically significant (P>0.05). The specificity of INSM1(+)/SOX11(-) for PNET was 100.00%, vs. Syn (42.86%) and CD56 (47.62%), the difference was statistically significant (P < 0.001); vs. CgA (92.86%), the difference was no statistically significant (P>0.05). The sensitivity of INSM1(-)/SOX11(+) immunophenotype for SPN was 92.86%, vs. β-catenin (90.48%) and CD99 (85.71%), the difference was no statistically significant (P>0.05). The specificity of INSM1(-)/SOX11(+) for SPN was 96.43%, vs. CD99 (48.21%), the difference was statistically significant (P < 0.001); vs. β-catenin (100.00%), the difference was no statistically significant (P>0.05). (4) The positive expression of INSM1 and SOX11 in PNET and SOX11 were not correlated with clinicopathological parameters (age, gender, tumor size, location, grade, and metastasis) (P>0.05).

CONCLUSION: The positive expression patterns of INSM1 and SOX11 in PNET and SPN respectively are conductive to distinguish the both tumors. The combination of both take precedence over some corresponding conventional immunohistochemical markers in terms of sensitivity and specificity.

PMID:37534634 | PMC:PMC10398779 | DOI:10.19723/j.issn.1671-167X.2023.04.001
Exploring the Epidemiology and Survival Trends in Pediatric Major Salivary Gland Malignancies: Insights from the National Cancer Database

Fetched: July 29th, 2023, 5:00am GMT by Madison Coleman

Curr Oncol. 2023 Jun 25;30(7):6134-6147. doi: 10.3390/curroncol30070456.

ABSTRACT

OBJECTIVE: To investigate the clinicopathological, therapeutic, and survival data on pediatric major salivary gland cancers.

MATERIALS AND METHODS: National Cancer Database (NCDB) query from 2004 to 2018.

RESULTS: In total, 967 cases of individuals under the age of 21 were identified. Most cancers affected the parotid gland (86%). Mucoepidermoid carcinoma (41.3%) and acinic cell adenocarcinoma (33.6%) were the most common. Tumors occurred more often from age 11 to 21, and females were more affected. Histology varied by age, gender, and race. In the 0-5 age group, mucoepidermoid carcinoma and myoepithelial carcinoma/sarcoma/rhabdomyosarcoma were the most common pathologies. In patients over 5 years old, mucoepidermoid carcinoma was the most frequent tumor in boys, while acinic cell adenocarcinoma was more common in girls. African American patients had a higher incidence of mucoepidermoid carcinoma, while White patients in the 0-5 age group had a higher incidence of myoepithelial carcinoma/sarcoma/rhabdomyosarcoma tumors. Low-grade tumors were commonly diagnosed at stage I, but the 0-5 age group had a high frequency of stage IV tumors. The overall 5-year survival rate was 94.9%, with 90% for the 0-5 years age group and 96% for the 11-15 years age group. Negative margins were associated with higher 5-year survival rates in high-stage tumors (93%) compared to positive margins (80%). Submandibular malignancies had worse 5-year survival rates across all age groups.

CONCLUSIONS: Major salivary gland malignancies in pediatric patients exhibit variations in histopathologic characteristics by age, gender, and race. Negative margins impact 5-year survival rates, especially in high-stage tumors.

PMID:37504316 | PMC:PMC10378439 | DOI:10.3390/curroncol30070456
Ectopic Cushing's Syndrome Secondary to Acinic Cell Carcinoma of the Parotid Gland: A Case Report

Fetched: July 28th, 2023, 5:00am GMT by Pedro Miguel Antunes Meireles

Case Rep Oncol. 2023 Jul 13;16(1):532-536. doi: 10.1159/000530445. eCollection 2023 Jan-Dec.

ABSTRACT

We present a case report of a patient with a rare high-grade transformation of an acinic cell carcinoma (ACC) of the parotid gland, who developed Cushing's syndrome (CS) as a result of ectopic secretion of adrenocorticotropic hormone by the tumour. The hypercortisolism was successfully treated with metyrapone, and the ACC was treated with local radiotherapy and a combined six cycles of gemcitabine and cisplatin, having achieved a partial response to the tumour. A multidisciplinary approach and combined medical treatment with radiotherapy and were essential for disease control and CS management. ACC should be considered in the differential diagnosis of ectopic CS.

PMID:37497425 | PMC:PMC10368098 | DOI:10.1159/000530445
Heparanase 2 (Hpa2)- a new player essential for pancreatic acinar cell differentiation

Fetched: July 28th, 2023, 5:00am GMT by Yasmin Kayal

Cell Death Dis. 2023 Jul 25;14(7):465. doi: 10.1038/s41419-023-05990-y.

ABSTRACT

Heparanase 2 (Hpa2, HPSE2) is a close homolog of heparanase. Hpa2, however, lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase enzymatic activity. Mutations of HPSE2 were identified in patients diagnosed with urofacial syndrome (UFS), a rare genetic disorder that exhibits abnormal facial expression and bladder voiding dysfunction, leading to renal damage and eventually renal failure. In order to reveal the role of HPSE2 in tissue homeostasis, we established a conditional Hpa2-KO mouse. Interestingly, the lack of Hpa2 was associated with a marked decrease in the expression of key pancreatic transcription factors such as PTF1, GATA6, and Mist1. This was associated with a two-fold decrease in pancreas weight, increased pancreatic inflammation, and profound morphological alterations of the pancreas. These include massive accumulation of fat cells, possibly a result of acinar-to-adipocyte transdifferentiation (AAT), as well as acinar-to-ductal metaplasia (ADM), both considered to be pro-tumorigenic. Furthermore, exposing Hpa2-KO but not wild-type mice to a carcinogen (AOM) and pancreatic inflammation (cerulein) resulted in the formation of pancreatic intraepithelial neoplasia (PanIN), lesions that are considered to be precursors of invasive ductal adenocarcinoma of the pancreas (PDAC). These results strongly support the notion that Hpa2 functions as a tumor suppressor. Moreover, Hpa2 is shown here for the first time to play a critical role in the exocrine aspect of the pancreas.

PMID:37491420 | PMC:PMC10368643 | DOI:10.1038/s41419-023-05990-y
Recurrent acinic cell carcinoma of the parotid gland with lateral skull base invasion: Case report and discussion of the literature

Fetched: July 21st, 2023, 5:00am GMT by Pietro De Luca

Clin Case Rep. 2023 Jul 17;11(7):e7512. doi: 10.1002/ccr3.7512. eCollection 2023 Jul.

ABSTRACT

Medical records of a 76-year-old woman with a recurrent acinic cell carcinoma of the left parotid gland with lateral skull base invasion were reviewed. She underwent subtotal petrosectomy followed by radiation therapy. After surgery, she remained disease-free for more than 16 months.

PMID:37469364 | PMC:PMC10352549 | DOI:10.1002/ccr3.7512
Cytomorphologic, immunophenotypical and molecular features of pancreatic acinar cell carcinoma

Fetched: July 21st, 2023, 5:00am GMT by Tong Sun

Diagn Cytopathol. 2023 Nov;51(11):674-683. doi: 10.1002/dc.25196. Epub 2023 Jul 19.

ABSTRACT

OBJECTIVES: As a rare tumor in pancreas, pancreatic acinar cell carcinoma (PACC) possesses a distinct molecular feature from pancreatic ductal carcinoma (PDAC). Though the diagnosis of PACC is often established based on cytology specimens, its cytologic diagnosis can be challenging. Furthermore, the correlation between PACC cytomorphology and its unique different molecular alterations have not been fully explored.

METHODS: Cytology features were analyzed in 8 histologically proven PACC and cytohistological correlation was performed. Immunocytochemistry for trypsin, chymotrypsin, BCL10, synaptophysin, chromogranin A, INSM1, β-catenin, and Ki-67 was assessed. Comprehensive molecular profiling and additional targetable treatment biomarker assessment were also performed.

RESULTS: The cohort included 4 mixed acinar-neuroendocrine carcinomas, 3 pure PACCs, and 1 mixed acinar-ductal carcinoma. Immunophenotypical features are consistent with diagnoses of PACC or PACC with neuroendocrine features. Identified genetic alterations included somatic mutations of CTNNB1, TP53, MAP2K1, PTEN, RAC1, germline mutations of NBN and BRAC2, and gene fusion of CCDC6-RET.

CONCLUSIONS: The current study is the first attempt to explore the correlation between the cytomorphology characteristics and molecular features of PACC and a few intriguing findings were observed. Further validation in larger cohorts is warranted.

PMID:37469257 | DOI:10.1002/dc.25196
New treatment insights into pancreatic acinar cell carcinoma: case report and literature review

Fetched: July 20th, 2023, 5:00am GMT by Fangrui Zhao

Front Oncol. 2023 Jul 3;13:1210064. doi: 10.3389/fonc.2023.1210064. eCollection 2023.

ABSTRACT

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic malignancy with unique clinical, molecular, and morphologic features. The long-term survival of patients with PACC is substantially better than that of patients with ductal adenocarcinoma of the pancreas. Surgical resection is considered the first choice for treatment; however, there is no standard treatment option for patients with inoperable disease. The patient with metastatic PACC reported herein survived for more than 5 years with various treatments including chemotherapy, radiotherapy, antiangiogenic therapy and combined immunotherapy.

PMID:37465113 | PMC:PMC10351044 | DOI:10.3389/fonc.2023.1210064
Intrapancreatic fat, pancreatitis, and pancreatic cancer

Fetched: July 18th, 2023, 5:00am GMT by Anna C Lilly

Cell Mol Life Sci. 2023 Jul 15;80(8):206. doi: 10.1007/s00018-023-04855-z.

ABSTRACT

Pancreatic cancer is typically detected at an advanced stage, and is refractory to most forms of treatment, contributing to poor survival outcomes. The incidence of pancreatic cancer is gradually increasing, linked to an aging population and increasing rates of obesity and pancreatitis, which are risk factors for this cancer. Sources of risk include adipokine signaling from fat cells throughout the body, elevated levels of intrapancreatic intrapancreatic adipocytes (IPAs), inflammatory signals arising from pancreas-infiltrating immune cells and a fibrotic environment induced by recurring cycles of pancreatic obstruction and acinar cell lysis. Once cancers become established, reorganization of pancreatic tissue typically excludes IPAs from the tumor microenvironment, which instead consists of cancer cells embedded in a specialized microenvironment derived from cancer-associated fibroblasts (CAFs). While cancer cell interactions with CAFs and immune cells have been the topic of much investigation, mechanistic studies of the source and function of IPAs in the pre-cancerous niche are much less developed. Intriguingly, an extensive review of studies addressing the accumulation and activity of IPAs in the pancreas reveals that unexpectedly diverse group of factors cause replacement of acinar tissue with IPAs, particularly in the mouse models that are essential tools for research into pancreatic cancer. Genes implicated in regulation of IPA accumulation include KRAS, MYC, TGF-β, periostin, HNF1, and regulators of ductal ciliation and ER stress, among others. These findings emphasize the importance of studying pancreas-damaging factors in the pre-cancerous environment, and have significant implications for the interpretation of data from mouse models for pancreatic cancer.

PMID:37452870 | PMC:PMC10349727 | DOI:10.1007/s00018-023-04855-z
Epidemiological, Clinical, and Histopathological Features of Salivary Gland Tumors among 150 Sudanese Patients: 10 Years' Experience

Fetched: July 15th, 2023, 5:00am GMT by Somaya T S Hamid

J Microsc Ultrastruct. 2022 Nov 9;11(2):92-96. doi: 10.4103/jmau.jmau_113_20. eCollection 2023 Apr-Jun.

ABSTRACT

BACKGROUND AND OBJECTIVES: Salivary gland tumors (SGTs) are serious challenges to pathologists. Herein, we aimed to assess epidemiological and histopathological characteristics of SGTs among Sudanese patients.

MATERIALS AND METHODS: This retrospective descriptive study was undertaken at The pathology department in Khartoum State between 2008 and 2018. Patient records, histopathological reports, and slides were retrieved; and re-examined by two histopathologists. Diagnoses were reclassified according to the 2017 WHO classification of SGTs.

RESULTS: Overall, 150 cases of Sudanese patients with SGT were included (90 [60%] males and 60 [40%] females). Among these, 105 were benign (70%) and 45 were malignant (30%). The parotid glands were the most common site for both benign and malignant tumors (77/150; 51%: 59 benign (76.6%) and 18 malignant [23.4%]). The next common site was the submandibular gland (54 [36%]: 38 benign [70.3%] and 16 malignant [29.7%]), followed by minor salivary glands (19 [12.7%]: 8 benign and 11 malignant [57.9%]). Benign gland entities included pleomorphic adenoma (88/105; 83.7%), oncocytoma (5/105; 4.8%), myoepithelioma (4/105; 3.8%), Whartin tumors (3/105; 2.9%), basal cell adenoma (3/105; 2.9%), and sialolipoma (2/105; 1.9%). Malignant gland entities included adenoid cystic carcinoma (12; 26.7%), mucoepidermoid carcinoma (10; 22,2%), acinic cell carcinoma (6; 13.3%), poorly differentiated carcinoma (4; 8.9%), adenocarcinoma NOS (not otherwise specified) (4; 8.9%), basal cell adenocarcinoma (3; 6.7%), carcinoma ex pleomorphic adenoma (3; 6.7%), polymorphous adenocarcinoma (2; 4.4%), salivary duct carcinoma (1; 2.2%), and epithelial-myoepithelial carcinoma (2.2%).

CONCLUSIONS: SGTs shared several epidemiological and histopathological features, exhibiting high incidence in the parotid and submandibular glands, lower prevalence in minor glands, and greater male predominance.

PMID:37448823 | PMC:PMC10337678 | DOI:10.4103/jmau.jmau_113_20
Acinic Cell Carcinoma in the 21st Century: A Population-Based Study from the SEER Database and Review of Recent Molecular Genetic Advances

Fetched: July 15th, 2023, 5:00am GMT by Jaffar Khan

Cancers (Basel). 2023 Jun 27;15(13):3373. doi: 10.3390/cancers15133373.

ABSTRACT

BACKGROUND: Acinic cell carcinoma (AciCC) comprises 6-7% of all salivary gland neoplasms and is the second most common salivary gland malignancy in children. Like many salivary gland carcinomas, it is considered low grade but occasionally it behaves aggressively. Understanding the risk factors associated with recurrence, metastasis, and death is important to determine the counseling and management of individual patients. Older population-based studies are presumed to have been confounded by the misclassification of other neoplasms as AciCC, in particular secretory carcinoma and cystadenocarcinoma. Since diagnostic tools to reliably separate these entities have been available for over a decade, reevaluation of epidemiologic data limited to the 21st century should allow a better characterization of the clinicopathological characteristics of AciCC.

METHODS: Our study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2000 to 2018. Cox regression model analysis was performed to identify risk factors independently affecting survival.

RESULTS: Data for 2226 patients with AciCC were extracted from the database. Most patients were females: 59%, and white: 80.5%, with a mean age at diagnosis of 51.2 (SD ± 18.7) years. Most cases (81%) were localized at presentation. Tumor size was less than 2 cm in 42%, 2-4 cm in 47%, and >4 cm in 11%. Low-grade tumors had 5-year survival > 90%, whereas high-grade tumors had survival < 50%. Of the patients with known lymph node status only 7.3% had nodal metastases. Distant metastases were documented in 1.1%, involving lungs 44%, bone 40%, liver 12%, and brain 4%. The most common treatment modality was surgery alone: 63.6% followed by surgery and adjuvant radiation: 33%. A few received chemotherapy (1.8%) or multimodality therapy (1.2%). The 5-year overall survival rate was 90.6% (95%CI 89.1-91.9), and disease-specific survival was 94.6% (95%CI 93.3-95.6). Multivariable cox regression analysis showed that undifferentiated (HR = 8.3) and poorly differentiated tumor grade (HR = 6.4), and metastasis (HR = 5.3) were the worst independent prognostic factors. Other poor risk factors included age > 50 (HR = 3.5) and tumor size > 4 cm (HR = 2.5).

CONCLUSIONS: In the US, AciCC is more common in middle age white females, and most tumors are less than 4 cm and localized at diagnosis. The most relevant negative prognostic factor was high tumor grade which was associated with higher hazard ratios for death than all other variables, including regional or distant metastases at presentation.

PMID:37444484 | PMC:PMC10340722 | DOI:10.3390/cancers15133373
Nomogram Models for Distinguishing Intraductal Carcinoma of the Prostate From Prostatic Acinar Adenocarcinoma Based on Multiparametric Magnetic Resonance Imaging

Fetched: July 8th, 2023, 5:00am GMT by Ling Yang

Korean J Radiol. 2023 Jul;24(7):668-680. doi: 10.3348/kjr.2022.1022.

ABSTRACT

OBJECTIVE: To compare multiparametric magnetic resonance imaging (MRI) features of intraductal carcinoma of the prostate (IDC-P) with those of prostatic acinar adenocarcinoma (PAC) and develop prediction models to distinguish IDC-P from PAC and IDC-P with a high proportion (IDC ≥ 10%, hpIDC-P) from IDC-P with a low proportion (IDC < 10%, lpIDC-P) and PAC.

MATERIALS AND METHODS: One hundred and six patients with hpIDC-P, 105 with lpIDC-P and 168 with PAC, who underwent pretreatment multiparametric MRI between January 2015 and December 2020 were included in this study. Imaging parameters, including invasiveness and metastasis, were evaluated and compared between the PAC and IDC-P groups as well as between the hpIDC-P and lpIDC-P subgroups. Nomograms for distinguishing IDC-P from PAC, and hpIDC-P from lpIDC-P and PAC, were made using multivariable logistic regression analysis. The discrimination performance of the models was assessed using the receiver operating characteristic area under the curve (ROC-AUC) in the sample, where the models were derived from without an independent validation sample.

RESULTS: The tumor diameter was larger and invasive and metastatic features were more common in the IDC-P than in the PAC group (P < 0.001). The distribution of extraprostatic extension (EPE) and pelvic lymphadenopathy was even greater, and the apparent diffusion coefficient (ADC) ratio was lower in the hpIDC-P than in the lpIDC-P group (P < 0.05). The ROC-AUCs of the stepwise models based solely on imaging features for distinguishing IDC-P from PAC and hpIDC-P from lpIDC-P and PAC were 0.797 (95% confidence interval, 0.750-0.843) and 0.777 (0.727-0.827), respectively.

CONCLUSION: IDC-P was more likely to be larger, more invasive, and more metastatic, with obviously restricted diffusion. EPE, pelvic lymphadenopathy, and a lower ADC ratio were more likely to occur in hpIDC-P, and were also the most useful variables in both nomograms for predicting IDC-P and hpIDC-P.

PMID:37404109 | PMC:PMC10323418 | DOI:10.3348/kjr.2022.1022
The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative

Fetched: July 5th, 2023, 5:00am GMT by Grégoire B Morand

Cancer. 2023 Oct 15;129(20):3263-3274. doi: 10.1002/cncr.34932. Epub 2023 Jul 4.

ABSTRACT

BACKGROUND: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands.

METHODS: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution.

RESULTS: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins.

CONCLUSIONS: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

PMID:37401841 | DOI:10.1002/cncr.34932
Prostate-Specific Membrane Antigen Uptake Heterogeneity in Mixed Ductal-Acinar Adenocarcinoma of the Prostate

Fetched: July 4th, 2023, 5:00am GMT by Qian Zhao

Clin Nucl Med. 2023 Aug 1;48(8):750-752. doi: 10.1097/RLU.0000000000004742. Epub 2023 Jun 8.

ABSTRACT

Prostate-specific membrane antigen (PSMA) PET findings of mixed ductal-acinar adenocarcinoma of the prostate are rarely reported. We describe 18 F-PSMA-1007 PET/CT and delayed pelvic 18 F-PSMA-1007 PET/MRI findings in a case of prostatic mixed ductal-acinar adenocarcinoma with multiple lymph node and bone metastases. The primary tumor showed heterogeneous PSMA uptake. The metastases in the right ilium and acetabulum showed intense PSMA uptake, but the pelvic lymph node and left iliac bone metastases showed no significant PSMA uptake. Knowledge of the intraprimary and intermetastatic heterogeneity of PSMA uptake in mixed ductal-acinar adenocarcinoma of the prostate may be helpful for accurate interpretation.

PMID:37290403 | DOI:10.1097/RLU.0000000000004742
p53 inhibitor iASPP is an unexpected suppressor of KRAS and inflammation-driven pancreatic cancer

Fetched: July 1st, 2023, 5:00am GMT by Paul Miller

Cell Death Differ. 2023 Jul;30(7):1619-1635. doi: 10.1038/s41418-023-01168-3. Epub 2023 Jun 3.

ABSTRACT

Oncogenic KRAS activation, inflammation and p53 mutation are key drivers of pancreatic cancer (PC) development. Here we report iASPP, an inhibitor of p53, as a paradoxical suppressor of inflammation and oncogenic KRAS^G12D-driven PC tumorigenesis. iASPP suppresses PC onset driven by KRAS^G12D alone or KRAS^G12D in combination with mutant p53^R172H. iASPP deletion limits acinar-to-ductal metaplasia (ADM) in vitro but accelerates inflammation and KRAS^G12D-induced ADM, pancreatitis and PC tumorigenesis in vivo. KRAS^G12D/iASPP^Δ8/Δ8 tumours are well-differentiated classical PCs and their derivative cell lines form subcutaneous tumours in syngeneic and nude mice. Transcriptomically, either iASPP deletion or p53 mutation in the KRAS^G12D background altered the expression of an extensively overlapping gene set, comprised primarily of NF-κB and AP1-regulated inflammatory genes. All these identify iASPP as a suppressor of inflammation and a p53-independent oncosuppressor of PC tumorigenesis.

PMID:37270580 | PMC:PMC10307949 | DOI:10.1038/s41418-023-01168-3
Mixed acinar-neuroendocrine carcinoma of the pancreas with positive for microsatellite instability: a case report and review of the literature

Fetched: June 30th, 2023, 5:00am GMT by Kenji Yoshino

Surg Case Rep. 2023 Jun 30;9(1):122. doi: 10.1186/s40792-023-01709-5.

ABSTRACT

BACKGROUND: Mixed acinar-neuroendocrine carcinoma (MANEC) of the pancreas is a rare tumor. We report a case of successful surgical resection of expansively growing MANEC of the pancreas with microsatellite instability (MSI)-high.

CASE PRESENTATION: The patient was an asymptomatic 65-year-old male. A computed tomography (CT) scan for a follow-up after treatment of pneumonia incidentally revealed a hypoenhancing 12-cm expansively growing tumor in the pancreatic body. An endoscopic ultrasound-guided fine-needle aspiration of the tumor suggested the diagnosis of MANEC. We performed distal pancreatectomy with combined resection of the spleen, left adrenal gland, transverse colon, small bowel, and stomach. The intraoperative findings showed that the tumor was capsular and was in contact with the SMA, SMV, and CA; however, obvious infiltration of these vessels was not observed..Pathological findings indicated MANEC with MSI-high. Among mismatch repair (MMR) gene proteins, PMS2 was lost and MLH1, MSH2, and MSH6 were retained. The tumor recurred 5 months after surgery. The patient was treated with gemcitabine plus nab-paclitaxel followed by pembrolizumab, which did not show objective response.

DISCUSSION: This is the first report investigating MSI and MMR in MANEC. Standard chemotherapy has not been established for MANEC. Detection of MSI-high is essential since PD-1 monoclonal antibodies for MSI-high cases might be one of the good treatment options. Herein, we discuss the various cytomorphologic and clinical features of MANEC and present a brief review of the literatures.

CONCLUSIONS: The accumulation of data from additional cases is necessary to further evaluate this type of carcinoma and provide a standardized optimal therapy for MANEC.

PMID:37386324 | PMC:PMC10310609 | DOI:10.1186/s40792-023-01709-5
TERT Promoter Mutation in Benign and Malignant Salivary Gland Tumors; A Cross-Sectional Study

Fetched: June 30th, 2023, 5:00am GMT by Ali Zare-Mirzaie

Iran J Pathol. 2023;18(1):64-74. doi: 10.30699/IJP.ijp.2023.556651.2927. Epub 2023 Mar 23.

ABSTRACT

BACKGROUND & OBJECTIVE: Telomere-related tumorigenesis mechanisms in the salivary gland, including mutation in the promoter region of TERT, have been rarely investigated. Therefore, the present study aimed to investigate the mutation in the promoter region of TERT in benign and malignant salivary gland tumors.

METHODS: This was a descriptive-analytical cross-sectional study. Tissue samples of 54 patients with primary salivary gland tumors sent to the pathology department of Rasool-e-Akram Hospital from September 2017 to September 2021 were examined. Fifteen samples including two groups of the most common benign tumors (n=5; 3 pleomorphic adenomas and 2 Warthin tumors) and four groups of the most common malignant tumors (n=10; 3 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas, 2 acinic cell carcinoma, and 2 salivary duct carcinoma) were selected. The promoter region of TERT, including well-known hot spot regions, is sequenced using the Sanger sequencing method. Data were analyzed using statistical software R version 4.1.2.

RESULTS: Of 15 salivary gland tumor specimens, consisting of 5 benign tumors and 10 malignant tumors after DNA sequencing, TERT promoter region mutation was only seen in one of the adenoid cystic carcinoma samples, located at -146 bp upstream from ATG (chr5: 1,295,250 C>T).

CONCLUSION: TERT promoter mutation was not different in malignant and benign salivary tumors. Nonetheless, there are a few studies that report TERT promoter mutation in adenoid cystic carcinoma of the salivary gland, necessitating the need for further investigations.

PMID:37383158 | PMC:PMC10293604 | DOI:10.30699/IJP.ijp.2023.556651.2927
CELA3B immunostaining is a highly specific marker for acinar cell carcinoma of the pancreas

Fetched: June 29th, 2023, 5:00am GMT by Ria Uhlig

PLoS One. 2023 Jun 28;18(6):e0287528. doi: 10.1371/journal.pone.0287528. eCollection 2023.

ABSTRACT

Chymotrypsin-like elastase family member 3B (CELA3B, elastase-3B) is a pancreatic enzyme with digestive function in the intestine. Since RNA analyses of normal tissues suggest that CELA3B expression is limited to the pancreas, the potential diagnostic utility of CELA3B immunohistochemistry for the distinction of pancreatic from extrapancreatic cancers and in the distinction of acinar cell carcinoma from ductal adenocarcinoma was assessed. CELA3B expression was successfully analyzed in 13,223 tumor samples from 132 different tumor types and subtypes as well as 8 samples each of 76 different normal tissue types by immunohistochemistry in a tissue microarray format (TMA). In normal tissues, CELA3B immunostaining was only seen in acinar cells and in a fraction of ductal cells of the pancreas as well as on some apical membranes of surface epithelial cells of the intestine. Among tumors, CELA3B immunostaining was seen in 12 of 16 (75%) acinar cell carcinoma of the pancreas including 6 cases with strong staining (37.5%) as well as in 5 of 13,207 other tumors (0.04%). These included 1.2% of 91 adenoid cystic carcinomas, 1.2% of 246 mucoepidermoid carcinomas and 0.8% of 127 acinic cell carcinomas of salivary glands. Our data show a good sensitivity (75%) and a high specificity (99.9%) of CELA3B immunohistochemistry for diagnosing acinar cell carcinoma of the pancreas.

PMID:37379306 | PMC:PMC10306197 | DOI:10.1371/journal.pone.0287528
A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review

Fetched: June 29th, 2023, 5:00am GMT by Nektarios Koufopoulos

J Pers Med. 2023 Jun 19;13(6):1016. doi: 10.3390/jpm13061016.

ABSTRACT

Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.

PMID:37374005 | PMC:PMC10303679 | DOI:10.3390/jpm13061016
Analysis of survival and prognostic factors of clear cell adenocarcinoma of the prostate: a case-control study for a rare cancer entity

Fetched: June 27th, 2023, 5:00am GMT by Sijin Chen

Sci Rep. 2023 Jun 26;13(1):10317. doi: 10.1038/s41598-023-37092-2.

ABSTRACT

Clear cell adenocarcinoma of the prostate (CCPC) is a rare entity compared to acinar carcinoma of the prostate (APC). The survival rate and prognostic factors of CCPC are still unclear and deserve further study. We downloaded data on prostate cancer from the Surveillance, Epidemiology, and End Results database for 1975-2019. After inclusion and exclusion criteria, we compared APC and analyzed cancer-specific mortality (CSM) and overall mortality (OM) in CCPC patients and prognostic risk factors using a propensity score matching (PSM) study and multivariate Cox regression. We included 408,004 cases of APC as a control group and 130 cases of CCPC as a case group. Compared with APC patients, the incidence of CCPC was extremely low, and the median age of diagnosis was older (72.00 years vs. 69.00 years, p < 0.01). In addition, more rates were diagnosed at an earlier stage (1975-1998, 93.1% vs. 50.2%, p < 0.001), more unstaged or unknown stage ratios (87.7% vs. 42.7%, p < 0.001), and more surgical treatments (66.2% vs. 47.6%, p < 0.001), but the prognosis of CCPC patients was worse. After PSM, the median survival time of CCPC patients was shorter (57.50 month vs. 88.00 month, p < 0.01), the rate of CSM was higher (41.5% vs. 27.7%, p < 0.05), and the rate of OM was higher (99.2% vs. 90.8%, p < 0.01). In the adjusted model 2 after PSM, the CSM risk of CCPC patients reached HR 1.76 (95%CI 1.13-2.72), which was 76% higher than that of APC patients (p < 0.05). It was further found that surgical treatment might benefit CSM in CCPC patients (HR 0.39, 95%CI 0.18-0.82, p < 0.05) in Univariate analysis, but it was insignificant in further multivariate analysis. This is the first large-scale case-control report on the survival risk and prognostic factors of CCPC patients. We found that the prognosis of CCPC patients was significantly worse than that of APC. Surgery might be an effective treatment that may improve its prognosis. Clear cell adenocarcinoma, prostate, acinar carcinoma, survival rate, rare cancer, propensity score matching, case-control study.

PMID:37365217 | PMC:PMC10293167 | DOI:10.1038/s41598-023-37092-2
Brg1 controls stemness and metastasis of pancreatic cancer through regulating hypoxia pathway

Fetched: June 27th, 2023, 5:00am GMT by Osamu Araki

Oncogene. 2023 Jun;42(26):2139-2152. doi: 10.1038/s41388-023-02716-4. Epub 2023 May 18.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. We previously reported that chromatin remodeler Brg1 is essential for acinar cell-derived PDAC formation in mice. However, the functional role of Brg1 in established PDAC and its metastasis remains unknown. Here, we investigated the importance of Brg1 for established PDAC by using a mouse model with a dual recombinase system. We discovered that Brg1 was a critical player for the cell survival and growth of spontaneously developed PDAC in mice. In addition, Brg1 was essential for metastasis of PDAC cells by inhibiting apoptosis in splenic injection and peritoneal dissemination models. Moreover, cancer stem-like property was compromised in PDAC cells by Brg1 ablation. Mechanistically, the hypoxia pathway was downregulated in Brg1-deleted mouse PDAC and BRG1-low human PDAC. Brg1 was essential for HIF-1α to bind to its target genes to augment the hypoxia pathway, which was important for PDAC cells to maintain their stem-like properties and to metastasize to the liver. Human PDAC cells with high BRG1 expression were more susceptible to BRG1 suppression. In conclusion, Brg1 plays a critical role for cell survival, stem-like property and metastasis of PDAC through the regulation of hypoxia pathway, and thus could be a novel therapeutic target for PDAC.

PMID:37198398 | DOI:10.1038/s41388-023-02716-4
Role of Adjuvant Radiotherapy in Acinic Cell Carcinoma of the Salivary Glands: A Systematic Review

Fetched: June 25th, 2023, 5:00am GMT by R Patil

Clin Oncol (R Coll Radiol). 2023 Sep;35(9):e489-e497. doi: 10.1016/j.clon.2023.06.011. Epub 2023 Jun 16.

ABSTRACT

A systematic review was carried out to evaluate if adjuvant radiotherapy for acinic cell carcinomas (ACCs) of salivary glands improves survival. Twelve retrospective studies published between 2000 and 2020 that analysed the effect of radiotherapy on salivary gland neoplasms and ACCs of salivary glands and met the inclusion criteria were included in the review. The overall quality of the studies was moderate to low. There was no high-quality evidence for improved survival with radiotherapy for ACCs of the salivary gland. Some evidence suggests that there may be an advantage for patients with high-grade tumours, but these data should be interpreted with caution due to the small number of patients and low-quality evidence. Good quality of evidence is lacking. Recommendation for adjuvant radiotherapy for tumours with poor prognostic factors will require discussion and shared decision-making with the patients.

PMID:37355414 | DOI:10.1016/j.clon.2023.06.011
Pediatric primary salivary gland tumors

Fetched: June 24th, 2023, 5:00am GMT by Parker Jesberg

Am J Otolaryngol. 2023 Sep-Oct;44(5):103948. doi: 10.1016/j.amjoto.2023.103948. Epub 2023 Jun 8.

ABSTRACT

OBJECTIVES: To characterize the presentation and treatment of children presenting with primary salivary gland neoplasms.

METHODS: A retrospective review of primary salivary tumor patients presenting to Children's Hospital Colorado between January 2000 and August 2020.

RESULTS: Fifty children were identified with primary salivary gland tumors, comprising of 39 (78 %) benign and 11 (22 %) malignant lesions. Pleomorphic adenoma was the most common benign tumor (36/39, 92 %), while acinic cell carcinoma was the most common malignancy (7/11, 64 %). The parotid gland was the most common site, followed by the submandibular gland (66 % vs. 34 %). No tumors were found in the sublingual glands. Benign neoplasms accounted for 70 % of parotid lesions and 94 % of submandibular tumors. No significant differences in age (13.6 years, SD 4 vs. 13.0 years, SD 4.3) were noted between patients with benign and malignant disease, but tumors in females were more frequently malignant (M:F 1:1.3 vs. 1:2.7 for benign and malignant tumors, respectively). Neck dissection and/or facial nerve sacrifice were required in 27 % (3/11) and 9.1 % (1/11) of malignancies, respectively. Local recurrence was observed in 7.7 % (3/39) of benign cases and 9.1 % (1/11) of malignant cases. No salivary malignancies required chemotherapy, though one patient with neurofibromatosis received imatinib prior to resection. Two patients with locoregional malignancy received adjunctive radiation. The average duration of follow up for benign and malignant disease were 12.6 ± 25 and 45.1 ± 32 months, respectively.

CONCLUSIONS: This study presents one of the larger single institutional experiences of pediatric primary salivary neoplasms in the past 20 years, identifying pleomorphic adenoma and acinic cell carcinoma as the most common benign and malignant etiologies, respectively. While this review found most neoplasms presented as a localized mass effectively managed with conservative surgical resection, aggressive tumors required multidisciplinary care.

PMID:37352681 | DOI:10.1016/j.amjoto.2023.103948
Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system

Fetched: June 23rd, 2023, 5:00am GMT by Allen S Ho

Head Neck. 2023 Aug;45(8):2028-2039. doi: 10.1002/hed.27429. Epub 2023 Jun 22.

ABSTRACT

BACKGROUND: The comparative impact of histologic variants and grade has not been well described.

METHODS: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival.

RESULTS: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73).

CONCLUSION: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.

PMID:37345665 | DOI:10.1002/hed.27429
Advances in tuft cells, a chemosensory cell in sequential diseases of the pancreas

Fetched: June 20th, 2023, 5:00am GMT by Wanzhen Wei

Biochim Biophys Acta Rev Cancer. 2023 Jul;1878(4):188911. doi: 10.1016/j.bbcan.2023.188911. Epub 2023 May 12.

ABSTRACT

Tuft cells are solitary chemosensory cells distributed mainly in hollow organs and detected in human and mouse pancreas precursor lesions of pancreatic cancer. Induced by inflammation and KRAS mutation, pancreatic acinar cell-derived tuft cells play a protective role in epithelium injury. The tumour suppression of tuft cells has been indicated in some studies. However, the function of tuft cells in pancreatic cancer remains unclear. In this review, we first introduce the definition of tuft cells and then review the relationship between tuft cells and pancreatic inflammation. In addition, we emphasized the role of tuft cells in the genesis and development of pancreatic cancers, especially the part of markers for tuft cell's doublecortin-like kinase 1 (DCLK1). Finally, we turn to the microscopic perspective and review the interactions between tuft cells and the microbiome in the pancreatic microenvironment. Overall, we describe the role of tuft cells in response to tissue damage and tumour progression in the pancreas. Nevertheless, the specific formation principle and the more detailed mechanism of action of tuft cells in the pancreas remain to be further explored.

PMID:37182665 | DOI:10.1016/j.bbcan.2023.188911
Hematopoietic progenitor kinase 1 inhibits the development and progression of pancreatic intraepithelial neoplasia

Fetched: June 17th, 2023, 5:00am GMT by Hua Wang

J Clin Invest. 2023 Jun 15;133(12):e163873. doi: 10.1172/JCI163873.

ABSTRACT

Ras plays an essential role in the development of acinar-to-ductal metaplasia (ADM) and pancreatic ductal adenocarcinoma (PDAC). However, mutant Kras is an inefficient driver for PDAC development. The mechanisms of the switching from low Ras activity to high Ras activity that are required for development and progression of pancreatic intraepithelial neoplasias (PanINs) are unclear. In this study, we found that hematopoietic progenitor kinase 1 (HPK1) was upregulated during pancreatic injury and ADM. HPK1 interacted with the SH3 domain and phosphorylated Ras GTPase-activating protein (RasGAP) and upregulated RasGAP activity. Using transgenic mouse models of HPK1 or M46, a kinase-dead mutant of HPK1, we showed that HPK1 inhibited Ras activity and its downstream signaling and regulated acinar cell plasticity. M46 promoted the development of ADM and PanINs. Expression of M46 in KrasG12D Bac mice promoted the infiltration of myeloid-derived suppressor cells and macrophages, inhibited the infiltration of T cells, and accelerated the progression of PanINs to invasive and metastatic PDAC, while HPK1 attenuated mutant Kras-driven PanIN progression. Our results showed that HPK1 plays an important role in ADM and the progression of PanINs by regulating Ras signaling. Loss of HPK1 kinase activity promotes an immunosuppressive tumor microenvironment and accelerates the progression of PanINs to PDAC.

PMID:37140994 | PMC:PMC10266776 | DOI:10.1172/JCI163873
Histopathological evaluation of minor salivary gland aberrations in oral squamous cell carcinoma

Fetched: June 15th, 2023, 5:00am GMT by Ridhi Bhola

J Cancer Res Ther. 2023 Jan-Mar;19(2):299-303. doi: 10.4103/jcrt.jcrt_1832_21.

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most established oral cancers in India, with high morbidity and mortality. The most common etiological agent associated with it is tobacco (in any form), which releases chemical carcinogens that affect not only the oral epithelial lining but also deep stromal structures such as minor salivary glands. They may cause changes in ductal or acinar part of gland depending on tumor grade, thus providing a fertile soil for tumor growth and recurrence.

AIMS AND OBJECTIVE: To observe the frequency of minor salivary gland changes associated with tobacco as well as to measure the length and depth of ductal involvement in routine tissue sections of OED and OSCC.

MATERIALS AND METHODS: A total of 94 hematoxylin and eosinstained archival slides which included cases of well, moderate, and poorly differentiated OSCC and oral epithelial dysplasia were histopathologically evaluated to observe changes in different components of minor salivary gland. Ductal hyperplasia, ductal metaplasia, mucous pooling within duct, acinar degeneration, pattern of malignant cell invasion (single/clusters), inflammatory infiltrate, eosinophilic cuffing around the gland, and glandular/vascular involvement were evaluated in each slide and correlated with different grades of OSCC.

RESULTS: Ductal hyperplasia, inflammatory cell infiltrate, mucous pooling, and pattern of malignant cell infiltration came out to be statistically significant with the highest percentage of changes being observed in poorly differentiated squamous cell carcinoma > moderately differentiated squamous cell carcinoma> well differentiated squamous cell carcinoma>oral epithelial dysplasia. Further, the results of this study suggest that extension of dysplasia or squamous cell carcinoma from overlying oral epithelium along salivary gland ducts is an uncommon finding. Conclusion: Hence, histopathological interpretation for OED and OSCC should also include changes related to associated minor salivary gland tissue as detection and eradication of the putative precursors are the best way of decreasing the overall morbidity caused by tumors.

PMID:37313908 | DOI:10.4103/jcrt.jcrt_1832_21
KRAS-Dependency in Pancreatic Ductal Adenocarcinoma: Mechanisms of Escaping in Resistance to KRAS Inhibitors and Perspectives of Therapy

Fetched: June 13th, 2023, 5:00am GMT by Enrico Gurreri

Int J Mol Sci. 2023 May 26;24(11):9313. doi: 10.3390/ijms24119313.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is still one of the deadliest cancers in oncology because of its increasing incidence and poor survival rate. More than 90% of PDAC patients are KRAS mutated (KRASmu), with KRASG12D and KRASG12V being the most common mutations. Despite this critical role, its characteristics have made direct targeting of the RAS protein extremely difficult. KRAS regulates development, cell growth, epigenetically dysregulated differentiation, and survival in PDAC through activation of key downstream pathways, such as MAPK-ERK and PI3K-AKT-mammalian target of rapamycin (mTOR) signaling, in a KRAS-dependent manner. KRASmu induces the occurrence of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) and leads to an immunosuppressive tumor microenvironment (TME). In this context, the oncogenic mutation of KRAS induces an epigenetic program that leads to the initiation of PDAC. Several studies have identified multiple direct and indirect inhibitors of KRAS signaling. Therefore, KRAS dependency is so essential in KRASmu PDAC that cancer cells have secured several compensatory escape mechanisms to counteract the efficacy of KRAS inhibitors, such as activation of MEK/ERK signaling or YAP1 upregulation. This review will provide insights into KRAS dependency in PDAC and analyze recent data on inhibitors of KRAS signaling, focusing on how cancer cells establish compensatory escape mechanisms.

PMID:37298264 | PMC:PMC10253344 | DOI:10.3390/ijms24119313
Secretory carcinoma of minor salivary glands of buccal mucosa: A case report and review of the literature

Fetched: June 6th, 2023, 5:00am GMT by Noshad Ali Langah

Int J Surg Case Rep. 2023 Jun;107:108357. doi: 10.1016/j.ijscr.2023.108357. Epub 2023 May 26.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Secretory carcinoma (SC) is an uncommon salivary gland neoplasm of the oral cavity that microscopically may mimic acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC). Secretory carcinoma (SC) of the salivary gland has been recently added in fourth edition of the head and neck world health organization. Most of these tumors are located on the parotid gland with very few cases reported in the minor salivary glands of the buccal mucosa. This work has been reported in line with the SCARE criteria.

PRESENTATION OF CASE: A 42 years old hypertensive male, shop keeper by occupation, with no prior addiction history, no dental extraction or trauma, presented with complaint of nodular lesion on left buccal mucosa for five years. On Clinical examination, adequate mouth opening, dentulous patient with 2.4 × 2 cm well circumscribed, nodular, non-tender, benign looking lesion was observed on left buccal mucosa near upper alveolus. Overlying mucosa appeared normal with no clinically palpable cervical lymphadenopathy. Histopathology revealed salivary gland neoplasm favoring secretory carcinoma. MRI scan showed lobulated enhancing nodular lesion arising from left buccal mucosa of size 2.3 ∗ 1.3 ∗ 1.7 cm, close to left superior alveolus without involving any cortical areas of marrow infiltration, with bilateral symmetrical level IIa reactive cervical nodes. Wide local excision and ipsilateral selective neck dissection [level 1, 2, 3] was done. Post-operative period was smooth with no complain of paresthesia observed. The final histopathology report showed secretory carcinoma. Two out of six lymph nodes from level I were positive for metastatic carcinoma with no extra nodal extension. Final stage of the tumor was pT1N2bMx. Patient underwent post-operative adjuvant radiotherapy for period of 6 weeks, received total 30 fractions and total dose of 6000 centigray.

CLINICAL DISCUSSION: SC behaved clinically an indolent being painless and having long duration of symptoms with normal overlying mucosa. But histopathologically there was cervical node metastasis. That changed final staging and added adjuvant treatment for this patient. The discrepancy in clinical and pathological diagnosis might be due to the indolent clinical behavior of SC arising in the minor salivary gland of buccal mucosa. In the present case, the absence of zymogen granules and presence of microcytic pattern with eosinophilic cytoplasm and eosinophilic secretory material were suggestive of SC.

CONCLUSION: This case report represents a rare case of SC of minor salivary glands of buccal mucosa, which was indolent as per clinical presentation but on final histopathological report it had cervical nodal metastasis that changed the final stage of the disease, for which adjuvant radiotherapy was needed. Although Secretory carcinomas are generally considered having a favorable prognosis and are regarded as low- grade carcinomas with limited number of recurrence and cervical nodal metastasis, but sometimes they do metastasize to cervical nodes for which accurate and timely intervention in the form of neck dissection may be performed to establish final staging and start additional treatment modality if required for better outcome of the disease.

PMID:37276758 | PMC:PMC10258499 | DOI:10.1016/j.ijscr.2023.108357
Notch signaling pathway in pancreatic tumorigenesis

Fetched: June 6th, 2023, 5:00am GMT by Wen-Cheng Chung

Adv Cancer Res. 2023;159:1-36. doi: 10.1016/bs.acr.2023.02.001. Epub 2023 Feb 28.

ABSTRACT

The Notch signaling pathway is an evolutionary conserved signal transduction cascade that is critical to embryonic and postnatal development, but aberrant Notch signaling is also implicated in tumorigenesis of many organs including the pancreas. Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy in the pancreas, with a dismally low survival rate due to the late-stage diagnosis and peculiar therapeutic resistance. Upregulation of the Notch signaling pathway has been found in preneoplastic lesions as well as PDACs in genetically engineered mouse models and human patients, and inhibition of the Notch signaling suppresses tumor development and progression in mice as well as patient-derived xenograft tumor growth, suggesting a critical role for Notch in PDAC. However, the role of Notch signaling pathway remains contentious, exemplified by differential functions of Notch receptors and contrasting outcomes of abolishing Notch signaling in murine PDAC models with distinct cell-of-origin or at different stages. Glycosylation of Notch receptors represents a powerful regulatory mechanism of Notch signaling, and its functional significance in PDAC has begun to emerge. Beyond its impact on tumor cells, Notch signaling is an important regulator of the components of pancreatic tumor microenvironment, including blood vasculature, stellate cells, fibroblasts, and immune cells. Finally, Notch may act as a tumor suppressor in pancreatic neuroendocrine tumor, the second most common pancreatic neoplasm with the incidence on rise. This review summarizes the research on the complex roles of Notch signaling in pancreatic tumorigenesis and the development of potential Notch-targeting therapies for pancreatic cancer.

PMID:37268393 | DOI:10.1016/bs.acr.2023.02.001
Comprehensive DNA Methylation Analysis Indicates That Pancreatic Intraepithelial Neoplasia Lesions Are Acinar-Derived and Epigenetically Primed for Carcinogenesis

Fetched: June 6th, 2023, 5:00am GMT by Emily K W Lo

Cancer Res. 2023 Jun 2;83(11):1905-1916. doi: 10.1158/0008-5472.CAN-22-4052.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is believed to arise from the accumulation of a series of somatic mutations and is also frequently associated with pancreatic intraepithelial neoplasia (PanIN) lesions. However, there is still debate as to whether the cell type-of-origin of PanINs and PDACs in humans is acinar or ductal. As cell type identity is maintained epigenetically, DNA methylation changes during pancreatic neoplasia can provide a compelling perspective to examine this question. Here, we performed laser-capture microdissection on surgically resected specimens from 18 patients to isolate, with high purity, DNA for whole-genome bisulfite sequencing from four relevant cell types: acini, nonneoplastic ducts, PanIN lesions, and PDAC lesions. Differentially methylated regions (DMR) were identified using two complementary analytical approaches: bsseq, which identifies any DMRs but is particularly useful for large block-like DMRs, and informME, which profiles the potential energy landscape across the genome and is particularly useful for identifying differential methylation entropy. Both global methylation profiles and block DMRs clearly implicated an acinar origin for PanINs. At the gene level, PanIN lesions exhibited an intermediate acinar-ductal phenotype resembling acinar-to-ductal metaplasia. In 97.6% of PanIN-specific DMRs, PanIN lesions had an intermediate methylation level between normal and PDAC, which suggests from an information theory perspective that PanIN lesions are epigenetically primed to progress to PDAC. Thus, epigenomic analysis complements histopathology to define molecular progression toward PDAC. The shared epigenetic lineage between PanIN and PDAC lesions could provide an opportunity for prevention by targeting aberrantly methylated progression-related genes.

SIGNIFICANCE: Analysis of DNA methylation landscapes provides insights into the cell-of-origin of PanIN lesions, clarifies the role of PanIN lesions as metaplastic precursors to human PDAC, and suggests potential targets for chemoprevention.

PMID:36989344 | PMC:PMC10239363 | DOI:10.1158/0008-5472.CAN-22-4052
Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC)Unveils New Actionable Genomic Aberrations in PACC

Fetched: June 3rd, 2023, 5:00am GMT by Vaia Florou

Clin Cancer Res. 2023 Sep 1;29(17):3408-3417. doi: 10.1158/1078-0432.CCR-22-3724.

ABSTRACT

PURPOSE: Pure pancreatic acinar cell carcinomas (PACC) are rare malignancies with no established treatment. PACC demonstrates significant genetic intertumoral heterogeneity with multiple pathways involved, suggesting using targeted cancer therapeutics to treat this disease. We aggregated one of the largest datasets of pure PACC to examine the genomic variability and explore patient-specific therapeutic targets.

EXPERIMENTAL DESIGN: PACC specimens (n = 51) underwent next-generation sequencing of DNA (n = 29) or whole exome (n = 22) and RNA (whole transcriptome, n = 29) at a commercial laboratory. We performed comparative analyses of a genomic cohort of pancreatic ductal adenocarcinomas (PDAC; n = 4,205). In parallel, we conducted a retrospective review of patients with PACC treated at Huntsman Cancer Institute (HCI).

RESULTS: The real-world dataset included samples from 51 patients with PACC. We found key molecular differences between pure PACC and PDAC, highlighting the unique characteristics of pure PACC. Major differences in PACC include lower MAPK signaling and less stromal cell abundance compared with PDAC. Pure PACC showed genomic loss-of-heterozygosity to largely coincide with mutations in BRCA1, BRCA2, and PALB2. Of the 7 patients treated at HCI, one had a tumor that harbored a BRAF-V600E mutation. Leveraging precision oncology, this patient is being treated with encorafenib plus binimetinib, achieving an exceptionally durable and ongoing complete response of more than 3 years.

CONCLUSIONS: There are major differences between PACC and PDAC, including downregulation of the MAPK signaling pathway, and less stromal cell abundance. In addition, genomic characterization of pure PACC revealed frequent targetable alterations, which can guide patient treatment.

PMID:37266563 | DOI:10.1158/1078-0432.CCR-22-3724
Metastatic Pancreatic Acinar Cell Carcinoma: An Unlikely Culprit

Fetched: June 1st, 2023, 5:00am GMT by Alena Bashinskaya

Cureus. 2023 Apr 29;15(4):e38288. doi: 10.7759/cureus.38288. eCollection 2023 Apr.

ABSTRACT

Although acinar cells comprise a large volume of the pancreas, they rarely transform into malignant neoplasms. Once they arise, they rapidly metastasize via hematogenous spread to other organs such as the brain, liver, lung, and skeletal system. Cutaneous involvement, however, is rarely seen in all patients with primary pancreatic neoplasms. The most frequently reported site of cutaneous manifestations is the umbilicus, with the other sites including the trunk, lower extremities, head, and neck. Here, we report a case of metastatic pancreatic acinar cell carcinoma with cutaneous involvement of the patient's scalp.

PMID:37255915 | PMC:PMC10226385 | DOI:10.7759/cureus.38288
Acinic cell carcinoma of the oral and maxillofacial region: an international multicenter study

Fetched: June 1st, 2023, 5:00am GMT by Laura Borges Kirschnick

Braz Oral Res. 2023 May 29;37:e050. doi: 10.1590/1807-3107bor-2023.vol37.0050. eCollection 2023.

ABSTRACT

The aim of this study was to describe the prevalence, clinicopathological, and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial region. AciCC cases were retrospectively retrieved from 11 pathology centers of three different countries. Medical records were examined to extract demographic, clinical, pathologic, and follow-up information. A total of 75 cases were included. Females (65.33%) with a mean age of 45.51 years were mostly affected. The lesions usually presented as an asymptomatic (64.28%) nodule (95.66%) in the parotid gland (70.68%). The association of two histopathological patterns was the most common finding (48.93%) and the tumors presented mainly conventional histopathological grades (86.11%). Surgical treatment was performed in the majority of the cases (59.19%). Local recurrence was observed in 20% of the informed cases, regional metastasis in 30.43%, and distant metastasis in 12.50%. The statistical analysis showed that the cases with a solid histopathological pattern (p=0.01), high-grade transformation (p=0.008), recurrence (p=0.007), and regional metastasis (p=0.03) were associated with poor survival. In conclusion, high histopathological transformation, presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region.

PMID:37255070 | DOI:10.1590/1807-3107bor-2023.vol37.0050
Gastric Amphicrine Carcinoma Showing Neuroendocrine and Pancreatic Acinar Cell Differentiation. Lesson from a Challenging Case Opening New Perspectives in the Diagnostic Work-Up of Gastric Neuroendocrine Neoplasms

Fetched: May 31st, 2023, 5:00am GMT by Amedeo Sciarra

Endocr Pathol. 2023 May 30. doi: 10.1007/s12022-023-09773-1. Online ahead of print.

ABSTRACT

Amphicrine carcinomas are epithelial neoplasms composed of cells with co-existing exocrine-neuroendocrine phenotype and are challenging lesions from both diagnostic and therapeutic perspectives.Here, we report the case of a 63-year-old male patient with a gastric nodule that was endoscopically biopsied, revealing histological features of a type 3 well-differentiated gastric neuroendocrine tumor (NET). At imaging, the lesion was single and limited to the stomach, but did not present ^In-111Octreotide uptake, despite SSTR2A immunohistochemical expression. The patient underwent a wedge resection of the gastric wall, with a final pathological diagnosis of amphicrine carcinoma with pancreatic acinar cell and neuroendocrine features (pT1b). Predictive immunohistochemistry showed microsatellite stability and negative HER2 status. Hotspot targeted deep sequencing of 57 genes showed no somatic mutation, in agreement with the low mutational burden reported for gastric amphicrine carcinomas. Due to a low stage of the tumor and the poor performance status of the patient, no additional oncological treatment was administered. The patient was disease-free after 18 months.This unusual case highlights the importance of considering amphicrine carcinoma in the diagnostic work-up of gastric type 3 NET. This can be done by including in the immunohistochemical panel non-neuroendocrine markers, such as the pancreatic acinar cell and glandular ones. Correct pathological diagnosis is pivotal to determine the appropriate staging (NET vs exocrine one) for surgical and oncological management.

PMID:37249796 | DOI:10.1007/s12022-023-09773-1
HER2/ERBB2 overexpression in advanced gallbladder carcinoma: comprehensive evaluation by immunocytochemistry and fluorescence in situ hybridisation on fine-needle aspiration cytology samples

Fetched: May 24th, 2023, 5:00am GMT by Pragya Verma

J Clin Pathol. 2023 May 23:jcp-2023-208940. doi: 10.1136/jcp-2023-208940. Online ahead of print.

ABSTRACT

AIMS: Advanced gallbladder carcinoma (AGBC) carries a poor prognosis with dismal survival. There are no data regarding HER2/ERBB2 expression in AGBC. This study evaluated the overexpression of HER2/ERBB2 in cytological aspirates from AGBCs to identify potential patients for whom anti-HER2 targeted therapies can benefit.

METHODS: This prospective, case-control study was performed on 50 primary AGBC cases. A detailed cytomorphological assessment, followed by immunocytochemistry (ICC) for HER2/ERBB2, was performed on AGBC cell blocks. A similar number of age-matched and gender-matched resected chronic cholecystitis specimens were included as controls. Fluorescence in situ hybridisation (FISH) was performed in equivocal cases.

RESULTS: A total of 10 (20%) cases showed positive (3+), 19 (38%) equivocal (2+) expression and 21 (42%) were negative on HER2/ERBB2 ICC. None of the equivocal cases demonstrated HER2 amplification by FISH. Among the controls, none showed positive (3+) immunoexpression, 23 (46%) demonstrated equivocal expression and 27 (54%) were negative. On statistical analysis, HER2/ERBB2 overexpression was significantly associated with AGBC compared with the controls. Of all the clinical, radiological and cytomorphological parameters, the predominant papillary or acinar arrangements of the tumour cells were significantly associated with HER2/ERBB2 overexpression.

CONCLUSIONS: This is the first study to evaluate the expression of HER2/ERBB2 on cytological aspirates in AGBC using ICC and FISH. HER2/ERBB2 overexpression(20%) was significantly associated with AGBC. Furthermore, predominant papillary or acinar arrangements of tumour cells in the cytological smears were significantly associated with HER2/ERBB2 overexpression. They can serve as potential predictors of HER2/ERBB2 overexpression to select AGBC patients for anti-HER2 targeted therapies.

PMID:37221046 | DOI:10.1136/jcp-2023-208940
A rare pancreatic neoplasm in a 40-year-old male patient

Fetched: May 24th, 2023, 5:00am GMT by Faten Limaiem

Clin Case Rep. 2023 May 20;11(5):e7387. doi: 10.1002/ccr3.7387. eCollection 2023 May.

ABSTRACT

KEY CLINICAL MESSAGE: The differential diagnoses of solid pseudopapillary neoplasm of the pancreas include cystic pancreatic neuroendocrine tumor, acinar cell carcinoma, and pancreatoblastoma.

ABSTRACT: Solid pseudopapillary neoplasm (SPN) is a low-grade malignant pancreatic tumor which accounts for 0.9%-2.7% of all exocrine pancreatic neoplasms. It predominantly affects young females (90%) and less frequently occurs in male patients. Its prognosis after surgical resection remains excellent. Herein, we report a case of SPN in a male patient.

PMID:37220514 | PMC:PMC10199812 | DOI:10.1002/ccr3.7387
Visualization of Intermetastatic Heterogeneity in Mixed Neuroendocrine Carcinoma-Acinar Adenocarcinoma of the Prostate by 68Ga-PSMA, 68Ga-FAPI, and 18F-FDG PET/CT

Fetched: May 24th, 2023, 5:00am GMT by Jiayu Cai

Clin Nucl Med. 2023 Aug 1;48(8):743-745. doi: 10.1097/RLU.0000000000004719. Epub 2023 May 23.

ABSTRACT

Mixed neuroendocrine carcinoma-acinar carcinoma is an uncommon histological type of neuroendocrine prostate cancer. It has been rarely reported in de novo prostate malignancies. In this case, we present 68 Ga-PSMA (prostate-specific membrane antigen), 68 Ga-FAPI, and 18 F-FDG PET/CT findings in the de novo form of mixed large-cell neuroendocrine carcinoma-acinar adenocarcinoma of the prostate. Different levels of radiotracer uptake were observed in different metastatic sites on 68 Ga-PSMA, 68 Ga-FAPI, and 18 F-FDG PET/CT. This case demonstrates that the multitracer PET/CT strategy may be used for the noninvasive detection of the intermetastatic heterogeneity in metastatic neuroendocrine prostate cancer.

PMID:37220226 | DOI:10.1097/RLU.0000000000004719
Blindness Following Endoscopic Excision of Acinic Cell Carcinoma of Sphenoid Sinus: A Case Report

Fetched: May 20th, 2023, 5:00am GMT by Aswathi K V

Indian J Otolaryngol Head Neck Surg. 2023 Apr;75(Suppl 1):751-754. doi: 10.1007/s12070-022-03190-2. Epub 2022 Dec 8.

ABSTRACT

Acinic cell carcinoma (A.C.C.) is a low-grade malignancy involving salivary glands. A.C.C. accounts for only 1-4% of all sinonasal malignancies. We report the case of a 45-year-old female who presented with A.C.C. of paranasal sinus who developed loss of vision after Endoscopic sinus surgery (E.S.S.). Blindness, though rare, is a devastating complication of E.S.S. In this report, the rare occurrence of a papillary cystic variant of A.C.C. in the sphenoid sinus is reported. The causes that may lead to blindness during E.S.S. are analyzed in the absence of direct neural trauma.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12070-022-03190-2.

PMID:37206856 | PMC:PMC10188821 | DOI:10.1007/s12070-022-03190-2
Evaluating Autophagy Levels in Two Different Pancreatic Cell Models Using LC3 Immunofluorescence

Fetched: May 18th, 2023, 5:00am GMT by Felipe J Renna

J Vis Exp. 2023 Apr 28;(194). doi: 10.3791/65005.

ABSTRACT

Autophagy is a specialized catabolic process that selectively degrades cytoplasmic components, including proteins and damaged organelles. Autophagy allows cells to physiologically respond to stress stimuli and, thus, maintain cellular homeostasis. Cancer cells might modulate their autophagy levels to adapt to adverse conditions such as hypoxia, nutrient deficiency, or damage caused by chemotherapy. Ductal pancreatic adenocarcinoma is one of the deadliest types of cancer. Pancreatic cancer cells have high autophagy activity due to the transcriptional upregulation and post-translational activation of autophagy proteins. Here, the PANC-1 cell line was used as a model of pancreatic human cancer cells, and the AR42J pancreatic acinar cell line was used as a physiological model of highly differentiated mammalian cells. This study used the immunofluorescence of microtubule-associated protein light chain 3 (LC3) as an indicator of the status of autophagy activation. LC3 is an autophagy protein that, in basal conditions, shows a diffuse pattern of distribution in the cytoplasm (known as LC3-I in this condition). Autophagy induction triggers the conjugation of LC3 to phosphatidylethanolamine on the surface of newly formed autophagosomes to form LC3-II, a membrane-bound protein that aids in the formation and expansion of autophagosomes. To quantify the number of labeled autophagic structures, the open-source software FIJI was utilized with the aid of the "3D Objects Counter" tool. The measure of the autophagic levels both in physiological conditions and in cancer cells allows us to study the modulation of autophagy under diverse conditions such as hypoxia, chemotherapy treatment, or the knockdown of certain proteins.

PMID:37184277 | DOI:10.3791/65005
Rare Non-Neuroendocrine Pancreatic Tumours

Fetched: May 17th, 2023, 5:00am GMT by Agata Mormul

Cancers (Basel). 2023 Apr 9;15(8):2216. doi: 10.3390/cancers15082216.

ABSTRACT

The most common tumour of the pancreas is ductal adenocarcinoma (PDAC). It remains one of the most lethal non-neuroendocrine solid tumours despite the use of a multi-approach strategy. Other, less-common neoplasms, which are responsible for 15% of pancreatic lesions, differ in treatment and prognosis. Due to the low incidence rate, there is a lack of information about the rarest pancreatic tumours. In this review, we described six rare pancreatic tumours: intraductal papillary mucinous neoplasm (IPMN), mucinous cystadenoma (MCN), serous cystic neoplasm (SCN), acinar cell carcinoma (ACC), solid pseudopapillary neoplasm (SPN) and pancreatoblastoma (PB). We distinguished their epidemiology, clinical and gross features, covered the newest reports about courses of treatment and systematised differential diagnoses. Although the most common pancreatic tumour, PDAC, has the highest malignant potential, it is still essential to properly classify and differentiate less-common lesions. It is vital to continue the search for new biomarkers, genetic mutations and the development of more specific biochemical tests for determining malignancy in rare pancreatic neoplasms.

PMID:37190144 | PMC:PMC10136980 | DOI:10.3390/cancers15082216
A rare case of pancreatic acinar cell carcinoma presenting a submucosal tumor

Fetched: May 7th, 2023, 5:00am GMT by Ryo Sugiura

Endosc Ultrasound. 2023 Mar-Apr;12(2):300-302. doi: 10.4103/EUS-D-22-00078.

NO ABSTRACT

PMID:37148142 | PMC:PMC10237617 | DOI:10.4103/EUS-D-22-00078
Pancreatic acinar cell carcinoma with pleomorphic and spindle cells: An autopsy-proven case

Fetched: May 4th, 2023, 5:00am GMT by Hironori Uruga

Pathol Int. 2023 Jun;73(6):255-260. doi: 10.1111/pin.13326. Epub 2023 May 3.

ABSTRACT

Pancreatic acinar cell carcinomas are glandular and have amphophilic/eosinophilic cytoplasm, presenting acinar, solid, and trabecular structures. Unusual histological features of acinar cell carcinoma are known, such as oncocytic, pleomorphic, spindle, and clear cell variants, but their clinical significance has not been well described. A man in his 70s was referred to our hospital because of elevated serum pancreatic enzymes. Contrast-enhanced abdominal computed tomography revealed slight swelling of the pancreatic head and suspension of the main pancreatic duct in the pancreatic body. He died only 14 days after admission. Gross findings at autopsy showed an ill-defined tumor located in the pancreatic head, involving the gastric and duodenal walls. Peritoneal dissemination, liver metastases, and lymph node metastases were also observed. Microscopically, tumor cells had moderate-to-severe nuclear atypia and amphophilic cytoplasm showing pleomorphism, and diffusely proliferated in solid pattern without lumina, were admixed with spindle cells. Immunohistochemically, tumor cells including pleomorphic and spindle cells were positive for B-cell lymphoma/leukemia 10 and trypsin. Consequently, the diagnosis was pancreatic acinar cell carcinoma with pleomorphic and spindle cells. We encountered a rare variant of pancreatic acinar cell carcinoma with pleomorphic and spindle cells. Clinically, our case showed rapid progression.

PMID:37133201 | DOI:10.1111/pin.13326
Metastasis to the penis from a bladder carcinoma invading only the lamina propria: case report and description of the morphological aspects

Fetched: May 4th, 2023, 5:00am GMT by Marius Stanimir

Rom J Morphol Embryol. 2023 Jan-Mar;64(1):89-94. doi: 10.47162/RJME.64.1.11.

ABSTRACT

INTRODUCTION: Data shows that bladder cancer (BC) takes the seventh place as the most commonly diagnosed when it comes to the male population. Whereas when both genders considered, it moves down the tenth place. Although 75% of patients with BC present with the disease confined to the mucosa or submucosa, rarely secondary metastasis to the penis occurs.

CASE PRESENTATION: A 73-year-old male was referred for gross hematuria in May 2018. A cystoscopy was performed detecting a bladder tumor. The resection of the tumor revealed an invasive high-grade (HG) papillary transitional carcinoma of the bladder with nest variants and lamina propria invasion. The histological examination of the second-look resection disclosed the same tumor characteristics. The patient was scheduled for bacillus Calmette-Guérin (BCG) instillations. Meanwhile, he was diagnosed and treated for a primitive lung acinar adenocarcinoma. Seven months after the first diagnosis, the patient progressed to cT4 at the level of the bladder. He underwent four cycles of Methotrexate, Vinblastine, Doxorubicin (Adriamycin) and Cisplatin (MVAC) chemotherapy followed by a cystoprostatectomy. The histological result was fibrosis and ypT0pN0 classification. Due to pain and solid mass in the penis, a total penectomy was performed and the histological result showed a transitional carcinoma suggesting a metastasis of the urothelial carcinoma of the bladder. Three months following the penectomy, a positron emission tomography∕computed tomography (PET∕CT) scan results showed multiple metastases and positive lymph nodes. Hence, Pembrolizumab treatment was started, providing very good clinical and radiological evolution. At the time of publishing, the patient is alive, and the radiological exams show stability of the disease.

CONCLUSIONS: The detailed descriptions of all histological variants of carcinoma of the bladder in the specimen has great importance and significant impact on the management of the disease.

PMID:37128796 | PMC:PMC10257781 | DOI:10.47162/RJME.64.1.11
Diagnosis and Management of Parotid Gland Cancer with Focus on the Role of Preoperative Fine-Needle Aspiration Cytology: A 10-Year-Long Retrospective Study with 5-Year Follow-Up

Fetched: May 2nd, 2023, 5:00am GMT by Andrea Varazzani

J Maxillofac Oral Surg. 2023 Jun;22(2):373-380. doi: 10.1007/s12663-023-01849-z. Epub 2023 Jan 18.

ABSTRACT

INTRODUCTION: Salivary gland cancers represent a rare heterogeneous group of neoplasms with complex clinicopathological characteristics and distinct biological behaviour. The appropriate diagnosis and management of parotid gland cancer are challenging and should be based on the clinical, imaging, cytological, and histological features. The present study analysed the use of preoperative fine-needle aspiration cytology (FNAC) and intraoperative frozen section (FS) to guide the appropriate surgical and postoperative treatment of parotid gland cancers.

MATERIALS AND METHODS: We selected 48 patients with primary malignancy of the parotid gland surgically treated between 1 January 2008 and 30 June 2017 at the Maxillo-Facial Surgery Division, University Hospital of Parma, Italy. The patients had postoperative histological diagnosis of malignant parotid cancer and were followed up for longer than 5 years.

RESULTS: The 48 patients included in this study had a mean age of 56.7 years. The most frequent type of parotid gland cancer was carcinoma ex pleomorphic adenoma (22.9%), followed by mucoepidermoid carcinoma (16.7%) and acinic cell carcinoma (14.6%). All 48 patients underwent preoperative FNAC: 29 (60.4%) and 19 (39.6%) were suggestive of malignant and benign lesions, respectively. In 31 patients, intraoperative FS was performed.

DISCUSSION: Compared to previous studies, the present study showed significantly lower diagnostic sensitivity of FNAC for parotid gland cancers. The preoperative diagnostic accuracy for suspected malignant cases may be improved by repeat analysis of the cytological specimen by experts, preoperative core needle biopsy, and/or intraoperative FS analysis of the suspected mass.

PMID:37122797 | PMC:PMC10130240 | DOI:10.1007/s12663-023-01849-z
Can Echinococcus Granulosus Infestation Prevent Pancreatic Cancer? An invivo Experimental Study

Fetched: May 2nd, 2023, 5:00am GMT by Serhat Doğan

Asian Pac J Cancer Prev. 2023 Apr 1;24(4):1307-1312. doi: 10.31557/APJCP.2023.24.4.1307.

ABSTRACT

Hydatid cyst is a zoonotic infestation caused by Echinococcus granulosus, and it is known that some parasites found in humans cause cancer in humans or some may have a protective effect against cancer. Cancer is one of the most serious health problems of today and it has been shown in some studies that parasites such as Echinococcus granulosus can have an inhibitory effect. The aim of this study was determined as whether Echinococcus granulosus has an inhibitory effect on exocrine pancreatic cancer with the help of the azaserine-rat model used in different cancer studies. Material and Methods: During experimental process a total of 45 male Wistar rats used, 14-day-old male Wistar rats were divided into groups according to the experimental protocol, administered azaserine injection protocol or kept as a control group without azaserine injection. Animals are grouped as Group 1, Control Group (group not treated with Azaserine and not injected with protoscolex.) (E-A-) (n=7); Group 2, Group injected with (IP) Azaserine only (30mg/kg) (E-A+) (n=8);Group 3, Group injected (IP) with protoscolex suspension of 1 cc only (E+A-) (n=15);Group 4, Group injected both Azaserine (IP) and protoscolex suspension (IP) (E+A+) (n=15). Atypical Acinar Cell Foci (AACF) load in the exocrine pancreas of each rat was measured quantitatively with the help of a video image analyzer and the AACF load was calculated with the help of a mathematical model. Results: Findings showed that the Atypical Acinar Cell Foci (AACF) burden was statistically significantly lower in the Azaserine+ protoscolex (Azaserine-injected-protoscolex-implanted) rat group compared to the other groups, suggesting that Echinococcosis in the azaserine-rat model could inhibit the development of precursor foci of neoplastic changes in the exocrine pancreas. Conclusion: The most significant aspect of our study is that it contributes new insights into the controversy that Echinococcosis suppresses pancreatic cancer.

PMID:37116153 | PMC:PMC10352762 | DOI:10.31557/APJCP.2023.24.4.1307
Mammary analogue secretory carcinoma of the salivary glands

Fetched: April 29th, 2023, 5:00am GMT by Lucas Avondet

Ecancermedicalscience. 2023 Feb 23;17:1511. doi: 10.3332/ecancer.2023.1511. eCollection 2023.

ABSTRACT

BACKGROUND: Mammary analogue secretory carcinoma (MASC) is a new disease among tumours affecting the salivary glands. It was first reported in 2010, and few cases have been reported worldwide. MASC is often incorrectly diagnosed as salivary gland acinic cell carcinoma. We present here the case of a patient with an asymptomatic parotid tumour who underwent a parotidectomy of the superficial lobe.

CASE REPORT: A 78-year-old female patient came to the clinic for a tumour of approximately 2.5 × 2.5 cm and a hard, elastic consistency that had grown insidiously in the right preauricular region. Magnetic resonance imaging of the head and neck showed a heterogeneous ovoid lesion located in the lower part of the superficial lobe of the right parotid gland, measuring 29 × 27 × 27 mm. A superficial parotidectomy was performed with the facial nerve identified and preserved. Immunohistochemistry was positive for S100, mammaglobin, periodic acid Schiff (PAS) and GATA-3. Fluorescence in situ hybridisation analysis was subsequently performed and Translocation-ETS-Leukemia Virus (ETV6) gene rearrangement observed. These findings were consistent with diagnosis of a MASC. The patient then required no new interventions or adjuvant therapy. At publication, she was free of disease and continues in clinical follow-up.

CONCLUSION: MASC is a tumour of the saliva glands that is recently described and rare. There are no studies that describe its biological behaviour or prognosis precisely.

PMID:37113723 | PMC:PMC10129378 | DOI:10.3332/ecancer.2023.1511
Ectopic pancreatic acinar cell carcinoma in the thoracic cavity of F344 rat

Fetched: April 28th, 2023, 5:00am GMT by Chinatsu Fujiwara

J Toxicol Pathol. 2023 Apr;36(2):139-143. doi: 10.1293/tox.2022-0114. Epub 2023 Jan 20.

ABSTRACT

Ectopic pancreatic tissue can occasionally cause inflammation, hemorrhage, stenosis, and invagination, similar to normal pancreatic tissue; however, tumorigenesis is rare. This case report describes an ectopically observed pancreatic acinar cell carcinoma in the thoracic cavity of a female Fischer (F344/DuCrlCrlj) rat. Histopathologically, polygonal tumor cells with periodic acid-Schiff-positive cytoplasmic eosinophilic granules showed solid proliferation and infrequently formed acinus-like structures. Immunohistochemically, the tumor cells were positive for cytokeratin, trypsin, and human B-cell leukemia/lymphoma 10, which specifically reacted with pancreatic acinar cells, and negative for vimentin and human α-smooth muscle actin. Ectopic pancreas develops in the submucosa of the gastrointestinal tract; however, there are few reports of its development and neoplasia in the thoracic cavity. To the best of our knowledge, this is the first report of ectopic pancreatic acinar cell carcinoma in the thoracic cavity of a rat.

PMID:37101959 | PMC:PMC10123294 | DOI:10.1293/tox.2022-0114

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