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Diagn Cytopathol. 2024 Dec 7. doi: 10.1002/dc.25428. Online ahead of print.
ABSTRACT
INTRODUCTION: In this study we aim to analyze the TRPS1 immunostaining of salivary gland tumors (SGT) on cytology cell blocks and compare the staining pattern on subsequent surgical resections.
METHODS: Malignant SGTs, oncocytomas and basal cell adenomas diagnosed on fine needle aspiration were retrieved from 2019 to 2021 database. Cases with surgical follow-up were selected. TRPS1 staining was performed on cytology cell blocks and surgical specimens. Scoring was interpreted by two pathologists independently.
RESULTS: Our cohort comprised of 58 cases: 45 malignant and 13 benign. TRPS1 scoring was interpreted for 44 cytology and 51 surgical cases. 14 cytology cases lacked tumor cells on deeper levels. For 7 cases, surgical blocks were not retrievable. TRPS1 positivity for cytology and surgical cases were 52% and 47% respectively. In the malignant cohort, TRPS1 was positive in 21/32 (66%) cytology cases and 21/43 (56%) surgical cases. All cases of basal cell adenocarcinoma, carcinoma ex pleomorphic adenoma and salivary duct carcinoma were TRPS1 positive on cytology. All cases of adenoid cystic carcinoma and acinic cell carcinoma were TRPS1 positive on surgical resections. In the benign cohort, TRPS1 was positive in 2/12 (17%) cytology cases; however, none of the surgically resected benign cases showed reactivity (0/8). Cytology-surgical correlation of TRPS1 staining was done in 37 cases. We found 21 concordant and 16 discordant cases. Discordance was highest in mucoepidermoid carcinoma.
CONCLUSION: TRPS1 is not an entirely specific marker for breast carcinoma. TRPS1 positivity was noted in a substantial number of salivary gland malignant neoplasms. Cases demonstrating discordance in TRPS1 staining pattern on cytology-surgical correlation warrant further exploration.
PMID:39644132 | DOI:10.1002/dc.25428
Thorax. 2024 Nov 29:thorax-2024-221426. doi: 10.1136/thorax-2024-221426. Online ahead of print.
NO ABSTRACT
PMID:39613457 | DOI:10.1136/thorax-2024-221426
Diagn Cytopathol. 2024 Nov 27. doi: 10.1002/dc.25423. Online ahead of print.
ABSTRACT
Clear cell tumors of parotid gland encompass a wide spectrum of neoplasms, including benign and malignant epithelial neoplasms. Additionally, tumors from adjacent structures such as paraganglioma, and metastatic neoplasms may also show clear cells. Overlapping cytological features may cause difficulty in diagnosis. This 50-year-old female presented with inability to close the right eye for 4 years, and with an infra-auricular swelling. Fine-needle aspiration cytology (FNAC) done outside was submitted for review with a diagnosis of neuroendocrine tumor. Smears showed clusters of tumor cells with abundant vacuolated cytoplasm and uniform round to ovoid nuclei. Features were those of salivary gland neoplasm of uncertain malignant potential, that is Milan category IVB: cellular neoplasm with clear cell features, with differential diagnoses of myoepithelial cell neoplasms, acinic cell carcinoma and paraganglioma. FNAC repeated for better characterization showed similar polygonal cells, accompanied by few spindle-shaped cells with ovoid nuclei, suggestive of paraganglioma. However, DOTANOC uptake was absent. Patient underwent radical parotidectomy; intraoperative frozen section showed a spindle cell tumor. Final histopathology revealed an intraparotid facial nerve schwannoma. The tumor was multi-nodular, with some nodules being composed almost entirely of polygonal cells with clear cytoplasm, that is, Antoni B areas, and others showing typical Antoni A areas admixed with Antoni B areas. Parotid FNAC has high accuracy for diagnosis of epithelial lesions; however, mesenchymal tumors often pose a diagnostic difficulty. Intraparotid schwannoma is not uncommon and may be diagnosed easily on FNAC when morphology is classical. However, intra-tumoral heterogeneity and less common histological subtypes may present a pitfall in cytodiagnosis.
PMID:39601052 | DOI:10.1002/dc.25423
Medicina (Kaunas). 2024 Oct 28;60(11):1766. doi: 10.3390/medicina60111766.
ABSTRACT
Rare pancreatic tumors and non-neoplastic tumor-like lesions present a diagnostic challenge due to their uncommon occurrence and overlapping imaging characteristics with more prevalent pancreatic neoplasms. Advances in imaging technologies and diagnostic criteria have contributed to increased detection of these rare entities in clinical practice. This pictorial review focuses on the radiologic-pathologic correlation of rare pancreatic tumors, including colloid carcinoma, acinar cell carcinoma, pancreatoblastoma, primary pancreatic lymphoma, and non-neoplastic tumor-like lesions such as hamartomas and inflammatory pseudotumors. Detailed imaging features, such as signal intensities on MRI and enhancement patterns on CT, are correlated with pathological findings to assist in the differential diagnosis. Familiarity with these characteristics is crucial for radiologists to ensure accurate diagnosis and guide appropriate treatment strategies, as management and prognosis significantly differ from common pancreatic neoplasms.
PMID:39596951 | PMC:PMC11596154 | DOI:10.3390/medicina60111766
Ann Surg Oncol. 2024 Nov 22. doi: 10.1245/s10434-024-16331-4. Online ahead of print.
ABSTRACT
BACKGROUND: Pancreatic acinar cell carcinoma (pACC) is a rare neoplasm of the exocrine pancreas. There is a dearth of information about tumor characteristics and patient outcomes. This study describes the clinical characteristics, genetic alterations, and survival outcomes of resected pACC.
PATIENTS AND METHODS: Consecutive patients undergoing pancreatectomy for pathologically confirmed pACC from 1999 to 2022 across three high-volume pancreas surgery centers were analyzed. Patient demographics, tumor characteristics, treatment data, and genetic sequencing were obtained through retrospective abstraction.
RESULTS: A total of 61 patients with resected pACC were identified. Median overall survival (OS) was 73 months and median recurrence free survival was 22 months. Nine patients underwent resection for oligometastatic disease; median OS was not reached after a median follow-up of 31 months from date of metastasectomy. Adjuvant chemotherapy was administered in 67% of patients with FOLFOX/FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, ± irinotecan) the most common regimen (58%). Sequencing data were obtained in 47 (77%) patients. A mutation in at least one of three core genes associated with the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, or PALB2) occurred in 26% (n = 12) with BRCA2 the most frequently identified. A mutation in any other "non-core" gene associated with DNA damage repair or the HRR pathway was identified in 45% (n = 21) with a high tumor mutational burden of > 10 mutations per megabase in 13%.
CONCLUSIONS: Resection of pACC is associated with favorable survival outcomes, even in the setting of oligometastatic disease. Mutations in the HRR pathway are common, providing opportunities for potential targeted therapeutic options.
PMID:39576455 | DOI:10.1245/s10434-024-16331-4
Indian J Otolaryngol Head Neck Surg. 2024 Dec;76(6):5470-5477. doi: 10.1007/s12070-024-05007-w. Epub 2024 Sep 11.
ABSTRACT
AIMS: This study aimed to investigate the relationship between human papillomavirus (HPV) infection and the development of salivary gland tumour (SGT) by evaluating the expression of p16 and the oncoproteins HPV16-L1 and HPV18-E6 using immunohistochemical (IHC) staining. Additionally, we assess the agreement between these oncoproteins and p16 in diagnosing HPV-infected SGT.
METHODS: This cross-sectional study included all SGT cases undergoing surgical resection at Hospital Universiti Sains Malaysia (HUSM) and Hospital Raja Perempuan Zainab II (HRPZ) in Malaysia from April 2022 to April 2023. IHC staining was performed on paraffin-embedded tissues at the Pathology Laboratory, HUSM, to evaluate the expression of p16, HPV16-L1, and HPV18-E6 oncoproteins. The clinicopathological data were correlated with the staining results.
RESULTS: 49 SGT cases were identified, mainly in middle-aged Malay women, with most tumours originating from the parotid gland. Malignant tumours included mucoepidermoid carcinoma (22.4%), adenoid cystic carcinoma (4.1%), acinic cell carcinoma (4.1%), and adenocarcinoma (2%). Benign tumours primarily consisted of pleomorphic adenoma (49%) and Warthin tumours (16.3%). Positive p16 expression was detected in 67% of cases, while HPV16 and HPV18 were detected in 65% and 90% of tumours, respectively. HPV16-L1 exhibited 75.8% sensitivity and 56.3% specificity, while HPV18-E6 showed 100% sensitivity and 31.2% specificity compared to p16.
CONCLUSION: The study findings suggest a correlation between the presence of high-risk HPV types 16 and 18 and the development of SGT, as evidenced by the overexpression of p16, HPV16-L1, and HPV18-E6 oncoproteins. Both HPV16-L1 and HPV18-E6 tests are acceptable, reliable, and sensitive for detecting high-risk HPV in SGT.
PMID:39559137 | PMC:PMC11569377 | DOI:10.1007/s12070-024-05007-w
Ann Diagn Pathol. 2025 Feb;74:152406. doi: 10.1016/j.anndiagpath.2024.152406. Epub 2024 Nov 9.
ABSTRACT
Recent studies suggest that trichorhinophalangeal syndrome type 1 (TRPS1) is sensitive immunomarker for breast carcinoma (BC). Salivary duct carcinoma (SDC) of salivary gland can share similar morphologic and immunophenotypic features with BC. This study aimed to assess the expression of TRPS1 in SDC and other salivary gland tumors (SGTs). Cytology cases and selected surgical specimens of SGTs were retrieved. Forty-three cases were selected and TRPS1 immunohistochemistry (IHC) was performed on cell blocks and some histologic specimens. Of those 43 cases, all 13 SDC cases showed TRPS1 expression except for one case. The remaining 30 cases include pleomorphic adenoma (n = 7), Warthin tumor (n = 4), basal cell adenoma (n = 3), adenoid cystic carcinoma (n = 2), secretory carcinoma (n = 5), mucoepidermoid carcinoma (n = 4), and acinic cell carcinoma (n = 5). Three of thirty cases were negative for TRPS1 while the remainder showed variable expression of TRPS1 ranging from focal weak to diffuse strong staining. The three negative cases include a case of secretory carcinoma, mucoepidermoid carcinoma and Warthin tumor. Our study confirmed that TRPS1 expression is present in SDC and other SGTs, indicating an overlapping immunoprofile with breast cancer. Additionally, it may not help differentiate SDC or SGTs from each other. Further studies with larger cohorts are needed.
PMID:39547127 | DOI:10.1016/j.anndiagpath.2024.152406
Cancer Prev Res (Phila). 2024 Oct 1;17(10):457-470. doi: 10.1158/1940-6207.CAPR-24-0200.
ABSTRACT
Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; PdxCre1 (KC) genetically engineered mouse model and tested the utility of AB-680, a small molecule inhibitor targeting CD73, to inhibit PanIN progression. AB-680, or vehicle control, was administered using oral gavage delivery 3 days/week at 10 mg/kg, beginning when the mice were 2 months old and lasting 3 months. We euthanized the mice at 5 months old. In the KC model, we quantified significantly less pancreatitis, early and advanced PanIN, and quantified a significant increase in M1 macrophages in AB-680-treated mice. Single-cell RNA sequencing (scRNA-seq) of pancreata of AB-680-treated mice revealed increased infiltration of CD4+ T cells, CD8+ T cells, and mature B cells. The scRNA-seq analysis showed that CD73 inhibition reduced M2 macrophages, acinar, and PanIN cell populations. CD73 inhibition enhanced immune surveillance and expanded unique clonotypes of TCR and BCR, indicating that inhibition of CD73 augments adaptive immunity early in the neoplastic microenvironment. Prevention Relevance: Previous studies found PanIN lesions in healthy pancreata. Not all progress to PDAC, suggesting a window for enhanced antitumor immunity through immunoprevention therapy. CD73 inhibition in our study prevents PanIN progression, reduces immune-suppressive macrophages and expands TCR and BCR unique clonotypes, highlighting an encouraging therapeutic avenue for high-risk individuals.
PMID:39099209 | PMC:PMC11443214 | DOI:10.1158/1940-6207.CAPR-24-0200
Semin Diagn Pathol. 2024 Oct 5:S0740-2570(24)00088-1. doi: 10.1053/j.semdp.2024.10.003. Online ahead of print.
ABSTRACT
Salivary gland-like tumors of the breast are rare neoplasms that share morphologic, immunophenotypic, and/or genetic features with their salivary gland counterparts, highlighting a shared underlying histopathogenesis in most cases. Salivary gland-like carcinomas included in the World Health Organization classification of breast tumors are adenoid cystic carcinoma, secretory carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, and the exceedingly rare polymorphous adenocarcinoma. These carcinomas are usually triple negative for estrogen receptor and progesterone receptor expression and HER2 overexpression, yet generally have favorable prognosis, in contrast to high-grade triple negative carcinomas of no special type. On the other hand, a small subset, such as solid-basaloid adenoid cystic carcinoma, rare high-grade carcinomas, and those associated with transformation to other types of high-grade invasive carcinoma can behave more aggressively. Other salivary gland-like tumors of the breast, such as pleomorphic adenoma and adenomyoepithelioma, are usually benign but can rarely undergo malignant transformation. Although clinical experience with salivary gland-like breast tumors is overall limited, their recognition and accurate classification has important implications for prognosis and clinical management, especially to avoid overtreatment of salivary gland-like carcinomas. The identification of characteristic genetic alterations and/or immunohistochemical surrogates in many of these tumors has practical applications to establishing an accurate diagnosis and directing clinical management. This review highlights the histopathologic and genetic characteristics of salivary gland-like breast tumors and the implications of the diagnosis for current clinical management.
PMID:39389890 | DOI:10.1053/j.semdp.2024.10.003
Lung Cancer. 2024 Oct 5;197:107987. doi: 10.1016/j.lungcan.2024.107987. Online ahead of print.
ABSTRACT
Recognizing non-invasive growth patterns is necessary for correct diagnosis, invasive size determination and pT-stage in resected non-small cell lung carcinoma. Due to iatrogenic collapse after resection, the distinction between adenocarcinoma in-situ (AIS) and invasive adenocarcinoma may be difficult. The aim of this study is to investigate the complex morphology of non-mucinous non-invasive patterns of AIS in resection specimen with iatrogenic collapse, and to relate this to follow-up. The effects of iatrogenic collapse on the morphology of collapsed AIS were simulated in a mathematical model. Three dimensional related criteria applied in a modified classification, using also cytokeratin 7 and elastin as additional stains, in two independent retrospective cohorts of primary pulmonary adenocarcinomas ≤3 cm resection specimen with available follow-up information. The model demonstrated that infolding of alveolar walls occurs during iatrogenic collapse and lead to a significant increase in tumor cell heights in maximal collapse areas, compared to less collapsed areas. The morphology of infolded AIS overlaps with patterns described as papillary and acinar adenocarcinoma according to the WHO classification, necessitating an adaptation. The modified classification incorporates recognition of iatrogenic and biologic collapse, tangential cutting effect true invasion and surrogate markers of invasion i.e. grey zone, covering a multilayering falling short of micropapillary, cribriform and solid alveolar filling growth. The use of elastin and CK7 staining aids in the morphologic recognition of iatrogenic collapsed AIS and the distinction from invasive adenocarcinoma. Out of a total of 70 resection specimens 1 case was originally classified as AIS and 9 were reclassified as iatrogenic collapsed AIS. Patients with collapsed AIS showed a 100 % recurrence-free survival after a mean follow-up time of 69.5 months. With the current WHO classification, AIS is overdiagnosed as invasive adenocarcinoma due to infolding. The modified classification facilitates the diagnosis of AIS.
PMID:39388963 | DOI:10.1016/j.lungcan.2024.107987
Indian J Otolaryngol Head Neck Surg. 2024 Oct;76(5):4153-4162. doi: 10.1007/s12070-024-04807-4. Epub 2024 Jun 20.
ABSTRACT
OBJECTIVE: the study aimed to characterize the novel entity referred to as secretory carcinoma of the salivary glands.
METHODS: we comprehensively evaluated 150 patients afflicted by malignant salivary gland tumors who had been under treatment at the University of Verona. Inclusion criteria primarily focused on the availability of paraffin block materials and adequate follow-up data. Subsequently, we conducted a comprehensive Fluorescent In Situ Hybridization (FISH) analysis, utilizing probes targeting NTRK-3, MALM-2, EWRS-1, HER-2, MDM-2, and NTRK1-2.
RESULTS: out of the initial cohort, 37 patients met the eligibility criteria for our study. We identified NTRK3 gene rearrangements in four patients (11%), two of whom had mucoepidermoid carcinoma, and the remaining two had acinic cell carcinoma. Notably, none of these patients had initially received a secretory carcinoma diagnosis. The primary treatment approach for all patients entailed surgical parotid gland resection. The overall survival (OS) for patients with NTRK3 rearrangements amounted to 78 months, with a corresponding progression-free survival (PFS) of 73 months.
CONCLUSION: in summary, our case series suggests that secretory carcinomas exhibit a favorable clinical course and underscores the pivotal importance of distinguishing secretory carcinomas from other histological subtypes.
PMID:39376339 | PMC:PMC11455849 | DOI:10.1007/s12070-024-04807-4
Folia Med (Plovdiv). 2024 Jun 30;66(3):441-444. doi: 10.3897/folmed.66.e114880.
ABSTRACT
Pancreatic acinar cell carcinoma (PACC) is a rare subgenre of pancreatic adenocarcinoma, where the cells show acinar architecture. Specified causes of this neoplasia have not yet been deduced and it usually appears with nonspecific symptoms. Diagnosis is based on its characteristics in various imaging techniques, on its histological characteristics and the expression of specific immunohistochemical biomarkers. Surgical excision of the tumor is usually performed with high chances of recurrence, whereas the benefits of radiotherapy and chemotherapy are still ambiguous. In this paper, a 51-year-old female patient with a mass in the head of the pancreas was taken as a case study. She presented with icterus and imaging showed a defined mass in the head of the pancreas accompanied by dilation of the biliary tree. Biopsy and histological assessment done after the surgical excision showed components of PACC differentiation. The patient was regulated after surgery, especially regarding endocrinology and immunology.
PMID:39365627 | DOI:10.3897/folmed.66.e114880
NPJ Precis Oncol. 2024 Oct 3;8(1):221. doi: 10.1038/s41698-024-00708-5.
ABSTRACT
Acinar cell carcinoma (ACC) and pancreatoblastoma (PBL) are rare pancreatic malignancies with acinar differentiation. Proteogenomic profiling of ACC and PBL revealed distinct protein expression patterns compared to pancreatic ductal adenocarcinoma (PDAC) and benign pancreas. ACC and PBL exhibited similarities, with enrichment in proteins related to RNA processing, chromosome organization, and the mitoribosome, while PDACs overexpressed proteins associated with actin-based processes, extracellular matrix, and immune-active stroma. Pathway activity differences in metabolic adaptation, epithelial-to-mesenchymal transition, and DNA repair were characterized between these diseases. PBL showed upregulation of Wnt-CTNNB1 and IGF2 pathways. Seventeen ACC-specific proteins suggested connections to metabolic diseases with mitochondrial dysfunction, while 34 PBL-specific proteins marked this pediatric cancer with an embryonic stem cell phenotype and alterations in chromosomal proteins and the cell cycle. This study provides novel insights into the proteomic landscapes of ACC and PBL, offering potential targets for diagnostic and therapeutic development.
PMID:39363045 | PMC:PMC11449907 | DOI:10.1038/s41698-024-00708-5
Front Oncol. 2024 Sep 13;14:1466255. doi: 10.3389/fonc.2024.1466255. eCollection 2024.
ABSTRACT
Pancreatic cancer (PC) is the sixth leading cause of cancer-related deaths worldwide, primarily due to late-stage diagnosis and limited treatment options. While novel biomarkers and immunotherapies are promising, further research into specific molecular targets is needed. Glycans, which are carbohydrate structures mainly found on cell surfaces, play crucial roles in health and disease. The Thomsen-Friedenreich-related carbohydrate antigen Sialyl-Tn (STn), a truncated O-glycan structure, is selectively expressed in epithelial tumors, including PC. In this study, we performed a comprehensive analysis of STn expression patterns in normal, premalignant, and malignant pancreatic lesions. Additionally, we analyzed the association between STn expression and various clinicopathological features. STn expression was statistically associated with pathological diagnosis; it was absent in normal pancreatic tissue but prevalent in pancreatic carcinoma lesions, including pancreatic ductal adenocarcinoma (PDAC), pancreatic acinar cell carcinoma, and pancreatic adenosquamous carcinoma. Moreover, we found a significant association between STn expression and tumor stage, with higher STn levels observed in stage II tumors compared to stage I. However, STn expression did not correlate with patient survival or outcomes. Furthermore, STn expression was assessed in PDAC patient-derived xenograft (PDX) models, revealing consistent STn levels throughout engraftment and tumor growth cycles. This finding supports the PDX model as a valuable tool for testing new anti-STn therapeutic strategies for PC in clinical setting.
PMID:39346741 | PMC:PMC11427427 | DOI:10.3389/fonc.2024.1466255
J Exp Clin Cancer Res. 2024 Sep 28;43(1):265. doi: 10.1186/s13046-024-03189-3.
ABSTRACT
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) features KRAS mutations in approximately 90% of human cases and excessive stromal response, termed desmoplastic reaction. Oncogenic KRAS drives pancreatic carcinogenesis by acting on both epithelial cells and tumor microenvironment (TME). We have previously shown that Homeodomain-Interacting Protein Kinase 2 (HIPK2) cooperates with KRAS in sustaining ERK1/2 phosphorylation in human colorectal cancers. Here, we investigated whether HIPK2 contributes to oncogenic KRAS-driven tumorigenesis in vivo, in the onset of pancreatic cancer.
METHODS: We employed an extensively characterized model of KRASG12D-dependent preinvasive PDAC, the Pdx1-Cre;LSL-KRasG12D/+ (KC) mice. In these mice, HIPK2 was inhibited by genetic knockout in the pancreatic epithelial cells (KCH-/-) or by pharmacologic inactivation with the small molecule 5-IodoTubercidin (5-ITu). The development of preneoplastic acinar-to-ductal metaplasia (ADM), intraepithelial neoplasia (PanIN), and their associated desmoplastic reaction were analyzed.
RESULTS: In Hipk2-KO mice (KCH-/-), ERK phosphorylation was lowered, the appearance of ADM was slowed down, and both the number and pathologic grade of PanIN were reduced compared to Hipk2-WT KC mice. The pancreatic lesion phenotype in KCH-/- mice was characterized by abundant collagen fibers and reduced number of αSMA+ and pSTAT3+ desmoplastic cells. These features were reminiscent of the recently described human "deserted" sub-TME, poor in cells, rich in matrix, and associated with tumor differentiation. In contrast, the desmoplastic reaction of KC mice resembled the "reactive" sub-TME, rich in stromal cells and associated with tumor progression. These observations were confirmed by the pharmacologic inhibition of HIPK2 in KC mice.
CONCLUSION: This study demonstrates that HIPK2 inhibition weakens oncogenic KRAS activity and pancreatic tumorigenesis providing a rationale for testing HIPK2 inhibitors to mitigate the incidence of PDAC development in high-risk individuals.
PMID:39342278 | PMC:PMC11437985 | DOI:10.1186/s13046-024-03189-3
Asian J Endosc Surg. 2024 Oct;17(4):e13388. doi: 10.1111/ases.13388.
ABSTRACT
Solitary fibrous tumor (SFT) is a spindle cell tumor driven by the NAB2-STAT6 fusion gene. While it can originate from any soft tissue, primary SFT of the pancreas is rare with limited reports. A 36-year-old man came to our department due to abdominal pain. Computed tomography revealed a circular mass with weak peripheral enhancement and an internal cyst in the pancreatic tail. Diagnosis was not confirmed through endoscopic ultrasound-guided biopsy, and differential diagnoses included acinar cell carcinoma and pancreatic neuroendocrine tumor. A robotic distal pancreatectomy with splenectomy was performed, and the patient was discharged 11 days postoperatively. Histopathological examination showed an irregular arrangement of spindle cells, and immunohistochemical staining was positive for CD34 and STAT6, confirming an SFT diagnosis with low metastatic risk. Robotic surgery effectively managed this tumor.
PMID:39340122 | DOI:10.1111/ases.13388
Case Rep Oncol Med. 2024 Sep 17;2024:7998149. doi: 10.1155/2024/7998149. eCollection 2024.
ABSTRACT
Introduction: Neuroendocrine/small-cell prostate cancer (NEPC) is a rare and aggressive subtype of prostate cancer, which typically develops after prolonged treatment for metastatic castration-resistant disease, but can, less commonly, occur de novo. Case Presentation: We describe a case of de novo NEPC in a tumor with mixed pathology including acinar adenocarcinoma and neuroendocrine/small-cell carcinoma with rapid progression of metastatic disease. Despite initiation of treatment with androgen deprivation therapy (ADT) and chemotherapy, the patient continued to exhibit progression leading to multiple complications including a large bowel obstruction and ultimately progressive hepatic metastases resulting in liver failure. Conclusion: This case illustrates the clinical presentation and highly aggressive nature of de novo NEPC. Recognizing atypical clinical progression in prostate cancer is critical for the detection of NEPC; however, despite early identification and initiation of treatment, the prognosis remains poor, thus highlighting the need for further study into NEPC biology and novel therapeutic approaches.
PMID:39318975 | PMC:PMC11421938 | DOI:10.1155/2024/7998149
Endosc Ultrasound. 2024 May-Jun;13(3):129-144. doi: 10.1097/eus.0000000000000056. Epub 2024 Apr 30.
ABSTRACT
Rare malignant pancreatic lesions are systematically reported in this review. The focus is on the imaging appearance of the rare epithelial pancreatic tumors such as the solid pseudopapillary neoplasm, acinar cell carcinoma, rare subtypes of adenocarcinoma, and pancreatoblastoma as seen on ultrasound, EUS, and contrast-enhanced ultrasound or EUS. The present overview summarizes the data and shows that not every pancreatic tumor is likely to be the most common entities of ductal adenocarcinoma or neuroendocrine tumor.
PMID:39318646 | PMC:PMC11419495 | DOI:10.1097/eus.0000000000000056
Kidney Med. 2024 Aug 10;6(10):100887. doi: 10.1016/j.xkme.2024.100887. eCollection 2024 Oct.
ABSTRACT
Paraneoplastic cast nephropathy, a rare cause of acute kidney injury, is most commonly observed in cases of multiple myeloma and is characterized by the formation of intratubular casts composed of monoclonal light chains. Nonmonoclonal paraneoplastic cast nephropathy has also been reported in patients with pancreatic acinar cell carcinoma or prolactinoma. In this case report, we present a case of polyclonal cast nephropathy in a patient with metastatic acinar cell carcinoma. We aim to emphasize the significance of recognizing this uncommon complication in patients with solid tumors and to discuss the diagnostic challenges and potential pathophysiology of this unique condition.
PMID:39310118 | PMC:PMC11415795 | DOI:10.1016/j.xkme.2024.100887
Front Oncol. 2024 Sep 2;14:1438179. doi: 10.3389/fonc.2024.1438179. eCollection 2024.
ABSTRACT
Acinic cell carcinoma (AciCC) of the breast is a rare malignant epithelial neoplasm, with approximately 60 cases reported in the literature. It predominantly affects women and exhibits significant histological heterogeneity. The diagnosis of breast AciCC is primarily based on the presence of eosinophilic and/or basophilic granular cytoplasm and markers of serous acinar differentiation. Despite being considered a low-grade variant of conventional triple-negative breast cancer (TNBC), over 25% of patients with breast AciCC have adverse clinical outcomes. Additionally, in early research, microglandular adenosis (MGA) and atypical MGA were considered potential precursors for various breast cancers, including intraductal carcinoma, invasive ductal carcinoma, adenoid cystic carcinoma, metaplastic carcinoma, and AciCC. Similarly, some studies have proposed that breast AciCC should be considered a type of carcinoma developing in MGA with acinic cell differentiation rather than a distinct entity. Therefore, the pathogenesis of breast AciCC has not yet been clarified. Moreover, to the best of our knowledge, the literature has not summarized the latest prognosis and treatment of breast AciCC. In this review, we synthesized the current literature and the latest developments, aiming at exploring the clinicopathology, histological origin, molecular features, prognosis, and treatment of breast AciCC from a novel perspective.
PMID:39286022 | PMC:PMC11402605 | DOI:10.3389/fonc.2024.1438179
Ann Afr Med. 2024 Oct 1;23(4):752-755. doi: 10.4103/aam.aam_72_24. Epub 2024 Sep 14.
ABSTRACT
Acinic cell carcinoma (ACC) arising in the salivary glands is a rare tumor. It is a low-grade malignant salivary gland tumor. It is predominantly seen in females and occurs in the fifth and sixth decades of life. It is mostly located in the parotid gland. ACC has a significant potential for recurrence and metastasis. Therefore, long-term follow-up is necessary after treatment. Here, a 28-year-old male presented with right preauricular swelling for 9 months. Ultrasound of the head-and-neck region and fine-needle aspiration cytology of preauricular swelling suggest the diagnosis of neoplasm in the parotid gland, most probably a benign tumor. After that, a total parotidectomy with facial nerve preservation was performed. On histopathological and immunohistochemical study was consistent with the diagnosis of ACC in the parotid gland.
PMID:39279180 | DOI:10.4103/aam.aam_72_24
Surg Oncol Clin N Am. 2024 Oct;33(4):747-760. doi: 10.1016/j.soc.2024.04.008. Epub 2024 Jul 16.
ABSTRACT
Salivary gland carcinoma is a rare form of head and neck carcinoma, but it comprises a variety of subsites and histologic subtypes that each present with unique clinical courses and management challenges. Preoperative work-up generally consists of fine-needle aspiration cytology and MRI. However, because of the large variety of subtypes, there are often challenges obtaining a histologic diagnosis before surgery. Upfront surgery at the primary site leads to the greatest improvement in survival. Posttreatment surveillance of these patients is important. This article discusses some of the current controversies in the management of salivary gland carcinomas.
PMID:39244292 | DOI:10.1016/j.soc.2024.04.008
Zhonghua Bing Li Xue Za Zhi. 2024 Sep 8;53(9):910-915. doi: 10.3760/cma.j.cn112151-20240201-00074.
ABSTRACT
Objective: To investigate the clinicopathological features and differential diagnosis of eosinophilic vacuolated tumor (EVT). Methods: Seven cases of EVT with characteristic morphology and unequivocal diagnosis from the Affiliated Hospital of Qingdao University (6 cases), Qingdao, China and the 971 Hospital of PLA Navy (1 case), Qingdao, China between January 2010 and December 2021 were subject to morphological and immunohistochemical analyses. Additionally, whole exome sequencing (WES) was performed in two cases. Twenty-two cases of renal oncocytoma (RO) and 17 cases of eosinophilic chromophobe renal cell carcinoma (eChRCC) diagnosed at the same time were used as controls. Results: Four males and three females with a mean age of 42 years (range: 29-61 years) were included in the study. The tumors were nodular and well-circumscribed, with sizes ranging from 1.5 to 4.5 cm. On cross-section, they appeared gray-red or gray-white, solid, and soft. Tumor cells were arranged in nests, solid sheets, and acinar or small vesicular structures. These cells exhibited eosinophilic cytoplasm with large, prominent clear vacuoles and round nuclei with prominent nucleoli. Perinuclear halos were focally present in four cases, while small tumor cells with sparse cytoplasm and hyperchromatic nuclei were seen in one case. No necrosis or mitosis was noted. Edematous stroma was detected in three cases. All tumors were positive for CD117 and Cathepsin K, but negative for vimentin and CK7. CK20 was positive in scattered individual cells, and Ki-67 positivity ranged from 1% to 4%. Point mutations in MTOR were identified in both patients who were subject to the molecular analysis. Statistical differences in the expression of Cathepsin K, CD10, S-100A1, and Cyclin D1 between EVT and RO (P<0.05) were significant, so were the differences in the expression of Cathepsin K, CD10, CK7 and claudin 7 between EVT and eChRCC (P<0.001). Seven patients were followed up for 4 to 96 months (mean, 50 months), with no recurrences or metastases. Conclusions: EVT is a rare renal tumor that shares morphological and immunophenotypic features with RO and eChRCC, and it is closely linked to the TSC/MTOR pathway. The presence of large prominent transparent vacuoles in eosinophilic cytoplasm along with conspicuous nucleoli is its key morphological characteristics. The use of combined immunohistochemical stains greatly aids in its diagnosis. Typically, the tumor exhibits indolent biological behaviors with a favorable prognosis.
PMID:39231743 | DOI:10.3760/cma.j.cn112151-20240201-00074
Biochem Biophys Res Commun. 2024 Nov 12;733:150603. doi: 10.1016/j.bbrc.2024.150603. Epub 2024 Aug 24.
ABSTRACT
Serine proteases are among the important groups of enzymes having significant roles in cell biology. Trypsin is a representative member of the serine superfamily of enzymes, produced by acinar cells of pancreas. It is a validated drug target for various ailments including pancreatitis and colorectal cancer. Premature activation of trypsin is involved in the lysis of pancreatic tissues, which causes pancreatitis. It is also reported to be involved in colorectal carcinoma by activating other proteases, such as matrix metalloproteinase (MMPs). The development of novel trypsin inhibitors with good pharmacokinetic properties could play important roles in pharmaceutical sciences. This study reports the crystal structures of bovine pancreatic trypsin with four molecules; cimetidine, famotidine, pimagedine, and guanidine. These compounds possess binding affinity towards the active site (S1) of trypsin. The structures of all four complexes provided insight of the binding of four different ligands, as well as the dynamics of the active site towards the bind with different size ligands. This study might be helpful in designing of new potent inhibitors of trypsin and trypsin like serine proteases.
PMID:39216203 | DOI:10.1016/j.bbrc.2024.150603
Cancer Rep (Hoboken). 2024 Aug;7(8):e70007. doi: 10.1002/cnr2.70007.
ABSTRACT
BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Recently, molecular analysis revealed that PACC shows a high frequency of the BRCA1/2 mutation and is likely to be considered a cancer associated with hereditary breast and ovarian cancer (HBOC). Hereditary cancers, including HBOC, are characterized by multifocal and/or metachronous tumors. However, no case reports exist of germline BRCA1-mutated synchronous and metachronous PACC.
CASE: A 58-year-old man was diagnosed with synchronous and metachronous PACC at the age of 56 and underwent two surgeries. Ten months after the second surgery, the patient developed multiple liver metastases. Gemcitabine plus nab-paclitaxel therapy was administered as first-line chemotherapy. After seven cycles, computed tomography examination revealed progressive disease (PD). Therefore, modified FOLFIRINOX (mFFX) was administered as second- line chemotherapy. After 19 cycles of mFFX, comprehensive cancer genomic profiling (CGP) identified a BRCA1 pathogenic variant that was confirmed to be germline origin. Accordingly, we treated the patient with olaparib; however, he was diagnosed with PD after 4 months. He subsequently died 5 years and 9 months after the initial surgery, and 3 years and 10 months after chemotherapy. Based on the genetic data of the patients, his family members received genetic counseling followed by cascade testing. Consequently, the same gBRCA1 pathogenic variant was detected in the son and his surveillance for HBOC-related cancers was initiated.
CONCLUSION: We diagnosed a 58-year-old man with a synchronous and metachronous PACC with germline BRCA1 pathogenic variant. Considering that PACC is likely to have BRCA1/2 mutations responsible for HBOC, we need to be aware of the possible presence of multifocal and/or metachronous tumors in patients with PACC. Additionally, patients with PACC should undergo genetic examinations, which would be beneficial in determining treatment strategies and health care for blood relatives.
PMID:39188100 | PMC:PMC11347749 | DOI:10.1002/cnr2.70007
Clin Respir J. 2024 Aug;18(8):e70006. doi: 10.1111/crj.70006.
ABSTRACT
INTRODUCTION: Lung adenocarcinoma (LUAD) is one of the major histopathological types of non-small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined.
METHODS: A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole-exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA-LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined.
RESULTS: The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA-LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)-ERK and p-AKT (Ser473), and the reduced protein level of p-ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group.
CONCLUSION: Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.
PMID:39188060 | PMC:PMC11347615 | DOI:10.1111/crj.70006
Gastroenterology. 2024 Sep;167(4):718-732.e18. doi: 10.1053/j.gastro.2024.04.031. Epub 2024 May 9.
ABSTRACT
BACKGROUND & AIMS: Acinar-to-ductal metaplasia (ADM) is crucial in the development of pancreatic ductal adenocarcinoma. However, our understanding of the induction and resolution of ADM remains limited. We conducted comparative transcriptome analyses to identify conserved mechanisms of ADM in mouse and human.
METHODS: We identified Sox4 among the top up-regulated genes. We validated the analysis by RNA in situ hybridization. We performed experiments in mice with acinar-specific deletion of Sox4 (Ptf1a: CreER; Rosa26-LSL-YFPLSL-YFP; Sox4fl/fl) with and without an activating mutation in Kras (KrasLSL-G12D/+). Mice were given caerulein to induce pancreatitis. We performed phenotypic analysis by immunohistochemistry, tissue decellularization, and single-cell RNA sequencing.
RESULTS: We demonstrated that Sox4 is reactivated in ADM and pancreatic intraepithelial neoplasias. Contrary to findings in other tissues, Sox4 actually counteracts cellular dedifferentiation and helps maintain tissue homeostasis. Moreover, our investigations unveiled the indispensable role of Sox4 in the specification of mucin-producing cells and tuft-like cells from acinar cells. We identified Sox4-dependent non-cell-autonomous mechanisms regulating the stromal reaction during disease progression. Notably, Sox4-inferred targets are activated upon KRAS inactivation and tumor regression.
CONCLUSIONS: Our results indicate that our transcriptome analysis can be used to investigate conserved mechanisms of tissue injury. We demonstrate that Sox4 restrains acinar dedifferentiation and is necessary for the specification of acinar-derived metaplastic cells in pancreatic injury and cancer initiation and is activated upon Kras ablation and tumor regression in mice. By uncovering novel potential strategies to promote tissue homeostasis, our findings offer new avenues for preventing the development of pancreatic ductal adenocarcinoma.
PMID:38729450 | DOI:10.1053/j.gastro.2024.04.031
J Surg Oncol. 2024 Aug 19. doi: 10.1002/jso.27808. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas demonstrates an indolent disease course; however, some patients present with a "malignant" phenotype, including distant metastases resistant to chemotherapy. This analysis identifies molecular drivers of metastatic SPN using the world's largest clinicogenomics database.
METHODS: The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange was queried for primary and metastatic SPN samples. Sample-level genomic alterations were compared. A pan-pancreatic cancer analysis assessed relevant mutations among all metastatic pancreatic malignancies.
RESULTS: Among 28 SPN samples identified (n = 17 primary, n = 11 metastatic), the most commonly mutated gene was CTNNB1, (24/28 samples; 85.7%). Most mutations were missense (21/24; 87.5%) or in-frame deletions (3/24; 12.5%). The most common CTNNB1 mutations in primary SPN were exon 3 S37F/C missense mutations (6/16 profiled patients, 37.5%), contrasting exon 3 D32N/Y/H missense mutations in metastatic samples (6/11 profiled patients, 54.5%). Metastatic SPN had higher rates of CTNNB1 mutations than metastases from pancreatic ductal adenocarcinoma (72.7% vs. 1.1%; q < 0.0001), pancreatic neuroendocrine tumor (72.7% vs. 2.5%; q < 0.0001), and pancreatic acinar cell carcinoma (72.7% vs. 11.5%; q = 0.0254).
CONCLUSIONS: Missense mutations along exon 3 of CTNNB1 predominate metastatic SPN, differentiating these patients from those with metastases from analogous pancreatic malignancies.
PMID:39155692 | DOI:10.1002/jso.27808
Cesk Patol. 2024;60(2):81-89.
ABSTRACT
The current WHO classification of digestive system tumours (2019) has presented the concept of diagnostics of intraductal and cystic neoplasms of the pancreas mostly based on integrated molecular data and evaluations of their malignant potential. Intraductal pancreatic neoplasms with ductal phenotype include microscopic precursor lesions of pancreatic ductal adenocarcinoma - the pancreatic intraepithelial neoplasia and macroscopic precursor lesions of pancreatic cancer, where intraductal papillary mucinous neoplasm represents the most common neoplasm of the pancreas with cystic appearance. Both intraductal oncocytic papillary neoplasm and intraductal tubulopapillary neoplasm are now classified as separate entities associated with less aggressive subtypes of pancreatic carcinoma and better prognosis. Clinical significance of microscopic pancreatic intraepithelial neoplasias is limited, in contrast to other intraductal neoplasms, which are presented as cystic and/or solid tumours by imaging methods with important consequences for further treatment and indication of surgical therapy (resection versus "watch and wait" strategies). Neoplasms of nonductal origin, such as acinar cell carcinomas and neuroendocrine neoplasms, can uncommonly display an intraductal growth and their correct classification has a great clinical importance. Moreover, differential diagnostics of cystic pancreatic lesions include not only cystic and pseudocystically transformed neoplasms, but also a large spectrum of reactive, inflammatory and dysontogenetic cystic lesions.
PMID:39138010
Curr Opin Gastroenterol. 2024 Sep 1;40(5):431-438. doi: 10.1097/MOG.0000000000001051. Epub 2024 Jun 25.
ABSTRACT
PURPOSE OF REVIEW: The burdens of pancreatic ductal adenocarcinoma (PDAC) and acute pancreatitis are increasing globally. We reviewed current literature on whether acute pancreatitis is a causal factor for PDAC and examined clinical manifestations of PDAC-associated acute pancreatitis.
RECENT FINDINGS: Recent findings detail the timing of acute pancreatitis before and after PDAC occurrence, further solidifying the evidence for PDAC-associated acute pancreatitis and for acute pancreatitis as a causal risk factor for PDAC. The risk of PDAC remains elevated above the general population in patients with distant history of acute pancreatitis. PDAC risk also increases with recurrent acute pancreatitis episodes, independent of smoking and alcohol. Mechanisms linking acute pancreatitis to PDAC include inflammation and neutrophil infiltration, which can be attenuated by suppressing inflammation and/or epigenetic modulation, thus slowing the progression of acinar-to-ductal metaplasia. Clinical presentation and management of acute pancreatitis in the context of PDAC are discussed, including challenges acute pancreatitis poses in the diagnosis and treatment of PDAC, and novel interventions for PDAC-associated acute pancreatitis.
SUMMARY: PDAC risk may be reduced with improved acute pancreatitis prevention and treatment, such as antiinflammatories or epigenetic modulators. Increased acute pancreatitis and PDAC burden warrant more research on better diagnosis and management of PDAC-associated acute pancreatitis.
PMID:38935270 | PMC:PMC11305936 | DOI:10.1097/MOG.0000000000001051
Head Neck Pathol. 2024 Aug 5;18(1):66. doi: 10.1007/s12105-024-01673-y.
ABSTRACT
BACKGROUND: ETV6 gene rearrangement is the molecular hallmark of secretory carcinoma (SC), however; the nature, frequency, and clinical implications of atypical ETV6 signal patterns by fluorescence in situ hybridization (FISH) has not yet been systematically evaluated in salivary gland neoplasms.
METHODS: The clinical, histopathologic, immunohistochemical and molecular features of seven salivary SCs, including four cases with atypical ETV6 FISH patterns, were retrospectively analyzed along with a critical appraisal of the literature on unbalanced ETV6 break-apart in SCs.
RESULTS: The patients were four males and three females (31-70 years-old). Five presented with a painless neck mass and two patients with recurrent disease had a history of a previously diagnosed acinic cell carcinoma of the buccal mucosa. Histologically, there were varied combinations of microcystic, papillary, tubular, and solid patterns. All tumors were diffusely positive for S100 and/or SOX10, while 2 cases also showed luminal DOG1 staining. Rearrangement of the ETV6 locus was confirmed in 5/7 cases, of which 3 cases showed classic break-apart signals, 1 case further demonstrated duplication of the ETV6 5`end and the other loss of one copy of ETV6. Two cases harbored ETV6 deletion without rearrangement. Two of the 4 cases with atypical ETV6 FISH patterns represented recurrent tumors, one with widespread skeletal muscle involvement, bone and lymphovascular invasion. Surgical treatment resulted in gross-total resection in all 7 cases, with a median follow up of 9.5 months post-surgery for primary (n = 3) and recurrent disease (n = 1).
CONCLUSION: Duplication of the distal/telomeric ETV6 probe represented the most common (26/40; 65%) variant ETV6 break-apart FISH pattern in salivary SC reported in the literature and appears indicative of an aggressive clinical course.
PMID:39101978 | PMC:PMC11300731 | DOI:10.1007/s12105-024-01673-y
Am J Otolaryngol. 2024 Jul 31;45(6):104446. doi: 10.1016/j.amjoto.2024.104446. Online ahead of print.
ABSTRACT
OBJECTIVES: Acinic cell carcinoma (ACC) most frequently arises in the parotid gland. Treatment consists of surgical resection and sometimes adjuvant therapy. ACC is most often a low-grade malignancy with good prognosis. Higher-grade tumors are often treated aggressively with total parotidectomy, neck dissection, and adjuvant therapy; however, the effect of parotid gland resection extent on oncologic outcomes has not been studied. Herein, we examine predictors of oncologic outcomes, including the effect of extent of resection.
METHODS: Patients with diagnosis of parotid ACC treated at our institution were included in this retrospective study. Patient factors were examined, and patients were grouped by extent of resection and tumor grade.
RESULTS: 58 patients, including 32 low-grade, 7 intermediate-grade, and 14 high-grade were included. Patients with low-grade tumors were more likely to undergo lesser extent of parotidectomy and less likely to undergo neck dissection. Two patients with low grade tumors developed recurrence, one local and one regional. Recurrence rate did not differ with resection extent in low-grade tumors. High tumor grade was found to be associated with disease progression. There was no association with adjuvant treatment and outcomes. Across all tumor grades advanced AJCC stage was found to be associated with disease progression.
CONCLUSIONS: In ACC patients with low-grade tumors and lower disease stage who undergo lesser extent of surgical resection oncologic outcomes were favorable. Patients with high-grade tumors carry a high risk of recurrence, despite aggressive treatment. AJCC stage and histopathologic grade may predict outcomes and guide treatment.
PMID:39096567 | DOI:10.1016/j.amjoto.2024.104446
Vet Pathol. 2024 Jul 30:3009858241266943. doi: 10.1177/03009858241266943. Online ahead of print.
ABSTRACT
Large-scale retrospective studies allow for identification of disease trends, such as predisposing factors, typical clinical signs, and range of histologic lesions, which cannot be determined in individual case reports. Lesions of the endocrine pancreas of ferrets are extensively reported; however, there are no in-depth investigations of lesions in the exocrine pancreas. This retrospective analysis presents the histologic features, clinical signs, and concurrent diseases of lesions in the exocrine pancreas of ferrets. Seventy-seven lesions were reported and included acinar cell hyperplasia (n = 32), chronic pancreatitis (n = 16), acute pancreatitis (n = 13), acinar cell adenoma (n = 5), acinar cell carcinoma (n = 4), acinar cell atrophy (n = 3), presumptive acinar cell hypoplasia (n = 2), and lymphoma (n = 2). Our results demonstrate that acinar cell hyperplasia and chronic pancreatitis can both cause grossly visible pancreatic nodules. Hyperplasia was not associated with neoplastic transformation. In addition, acinar cell adenoma was slightly more common than carcinoma, which is contrary to most reports of neoplasia in ferrets. Our findings also suggest that acute pancreatitis can be a sequela to pancreatic biopsy and that there may be an association between chronic pancreatitis and diabetes mellitus in ferrets. Finally, zinc toxicosis was found to be an unlikely cause of pancreatitis in these ferrets based on zinc tissue concentration testing in a subset of cases.
PMID:39078021 | DOI:10.1177/03009858241266943
Cureus. 2024 Jun 25;16(6):e63159. doi: 10.7759/cureus.63159. eCollection 2024 Jun.
ABSTRACT
Introduction Lung cancer diagnosis faces challenges due to morphological heterogeneity and limited biopsy tissue. This study evaluates the efficacy of a minimal panel immunostaining technique using immunohistochemical markers like napsin A, thyroid transcription factor 1 (TTF-1), p63, and synaptophysin to improve the precision of lung carcinoma subclassification. Methods A retrospective analytical study was conducted at the Histopathology Laboratory of Saveetha Medical College and Hospital, Chennai, from January 2018 to February 2024. A total of 64 lung carcinoma cases were analyzed. Inclusion criteria included biopsy samples from lung lesions with a confirmed diagnosis of lung carcinoma based on histomorphological examination, covering all age groups and both genders. Non-carcinomatous lung lesions were excluded. Clinical data were obtained from the Medical Information Archiving Software (MIAS) database and histopathological examination request forms. Under a light microscope, tissue samples were examined after being fixed in formalin, processed, and stained with hematoxylin and eosin (H&E). Additionally, a minimal panel of immunohistochemical markers, including napsin A, TTF-1, p63, and synaptophysin, was used to subclassify lung carcinomas. Results The age group older than 50 years was the most affected, with a higher incidence in males. Histologically, 49% of cases were adenocarcinoma, 42% were squamous cell carcinoma, and 9% were small cell carcinoma. Immunohistochemistry (IHC) results adjusted these proportions to 54.6% adenocarcinoma, 31.2% squamous cell carcinoma, and 14% small cell carcinoma, showing a 5.6% increase in adenocarcinoma cases. The most common adenocarcinoma pattern was mixed, followed by acinar. TTF-1 and napsin A were crucial for identifying adenocarcinoma, while p63 was key for squamous cell carcinoma. Synaptophysin confirmed neuroendocrine differentiation in small cell carcinoma. Conclusion Incorporating a minimal panel of IHC markers significantly enhances the accuracy of lung carcinoma subclassification, addressing diagnostic challenges posed by morphological heterogeneity and limited sample size. This approach supports more precise and efficient clinical care for patients with lung cancer. Further validation in diverse clinical settings is recommended.
PMID:39070322 | PMC:PMC11272665 | DOI:10.7759/cureus.63159
Cureus. 2024 Jun 25;16(6):e63134. doi: 10.7759/cureus.63134. eCollection 2024 Jun.
ABSTRACT
INTRODUCTION: Acinic cell carcinoma (AciCC) is a rare clinical entity and a salivary gland malignancy. It is associated with wide histological variations in the cytomorphological patterns.
METHODS: Sixty cases diagnosed as AciCC from 2002 to 2023 were assessed for diverse cytomorphological patterns.
RESULTS: The mean age of patients at the time of diagnosis was 44.35±16.8 years ranging from 15 to 81 years. Females comprised 58.3% for a F: M ratio of 1.4:1. Fifty three cases (88.3%) occurred in the parotid gland, two cases in the nasal region (3.3%), and one case each in the soft plate and upper lip (1.7%). The location of the remaining three cases was not specified. The most common presenting complaint was a well-defined facial swelling associated with pain. The average tumor size was 3.8±1.9 cm. The most predominant architectural pattern was solid (83.3%) followed by microcystic (60%), then follicular (41.7%), papillary cystic (14.3%), and tubulocystic (28.6%), and AciCC with de-differentiation/high-grade transformation was reported in three cases (5%). In 83.3% of the cases (50 out of 60), we noticed a mixture of two or more growth patterns. Other degenerative changes included prominent lymphoid stroma, hemorrhage, and cystic change.
CONCLUSION: Awareness and recognition of diverse cytomorphological patterns of AciCC, especially in institutions of a developing country where there is limited availability of highly specific and sensitive immunohistochemical stains or molecular diagnostics, are crucial and essential.
PMID:39055445 | PMC:PMC11271973 | DOI:10.7759/cureus.63134
Diagn Pathol. 2024 Jul 24;19(1):100. doi: 10.1186/s13000-024-01521-1.
ABSTRACT
BACKGROUND: Acinic cell carcinoma (AciCC) of the breast is a rare subtype of breast cancer. It was considered a low-grade triple-negative breast cancer (TNBC) with the potential to progress or transform into a high-grade lesion because of the molecular similarities with conventional aggressive TNBC in several genetic studies. Microscopically, the coexistence of classical low-grade and high-grade triple-negative components in breast AciCC is not uncommon. However, there is a scarcity of research on the comparative histopathological and genetic aspects of both components.
CASE PRESENTATION: A 34-year-old woman with a nontender mass in the upper outer quadrant of the left breast was initially diagnosed with a malignant small round cell tumor (undifferentiated or poorly differentiated carcinoma) based on a preoperative biopsy, which was later identified as breast AciCC with a high-grade solid component. Left breast-conserving surgery with sentinel lymph node biopsy was performed. Microscopically, the breast AciCC consisted of a classical acinic component and a high-grade component. The latter demonstrated a solid sheet-like pattern characterized by large, round, pleomorphic or vesicular nuclei, prominent nucleoli, and frequent mitotic activities. Classical acinic architectures focally merged together to form solid nests and transited into high-grade areas. Remarkably, in the high-grade lesion, conventional immunochemical markers for breast AciCC, such as α1-antitrypsin (AAT), Lysozyme (LYS), Epithelial membrane antigen (EMA), S100 protein (S100), and cytokeratin (CK) were negative, whereas cell cycle protein D1 (cyclin D1) and vimentin showed diffuse expression. Next‑generation sequencing (NGS) revealed that 43.5% of variants were identical in both components. Furthermore, PAK5 mutation; copy number (CN) loss of CDH1, CHEK1, and MLH1; and CN gains of CDK6, HGF, and FOXP1 were identified in the high-grade lesion. The patient was treated with eight cycles of adjuvant chemotherapy (epirubicin combined with cyclophosphamide) and radiotherapy after surgery, and she is currently alive for 43 months with no metastases or recurrences.
CONCLUSIONS: This case demonstrates a comparative analysis of the histopathological and genetic characteristics of classical low-grade and high-grade components of AciCC within the same breast. This information may serve as a morphological and molecular basis for further investigation into the molecular mechanisms underlying high-grade lesions in breast AciCC.
PMID:39049123 | PMC:PMC11267969 | DOI:10.1186/s13000-024-01521-1
Prostate. 2024 Sep;84(12):1146-1156. doi: 10.1002/pros.24751. Epub 2024 May 27.
ABSTRACT
BACKGROUND: Thanks to technological advances, prostate cancer (PCa) can be diagnosed at a younger age. It is known that most of these patients are in the low-intermediate risk group, and the histological grade of the tumor increases in half of those undergoing radical prostatectomy (Rp) compared to their diagnostic biopsies. This is especially important in terms of active surveillance (AS) and/or the timely evaluation of curative treatment options in patients diagnosed at an early age. Our aim was to investigate clinical and histopathological parameters that may be associated with an increase in the histological grade of the tumor in patients with acinar adenocarcinoma who were diagnosed by transrectal ultrasound-guided biopsy (TRUS-Bx) and underwent Rp.
METHODS: A total of 205 patients with classical acinar adenocarcinoma diagnosed by TRUS-Bx without metastasis and who underwent Rp were grouped according to the D'Amico risk classification. Age at diagnosis, serum prostate-specific antigen (PSA), PSA density, prostate volume, Prostate Imaging Reporting and Data System (PI-RADS) score, clinical stage, Gleason Grade Group (GGG), high-grade intraepithelial neoplasia in tumor-free cores (HGPIN) (single and ≥2 cores), perineural invasion (PNI), and lymphovascular invasion (LVI) was obtained. Additionally, GGG, pathological stage, lymph node metastasis, surgical margin positivity, and tumor volume obtained from Rp were evaluated. Comparisons were made between the case groups in which the tumor grade increased and remained the same, in terms of age, serum PSA, PSA density, HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI in all biopsies (with or without tumors), as well as risk groups. In addition, the relationships of HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI on TRUS-Bx with age, serum PSA and PSA density, tumor volume, surgical margin positivity, pathological stage, lymph node metastasis, and risk groups were examined separately.
RESULTS: Of the patients, 72 (35.1%) were in the low-risk group, 95 (46.3%) in the intermediate-risk group, and 38 (18.5%) in the high-risk group. Most of the patients with an increased histological grade (n = 38, 48.1%) were in the low-risk group (p < 0.05) and had an advanced median age. HGPIN in single and ≥2 tumor-free cores and PNI were more common in these patients (p < 0.01, p < 0.001, and p < 0.05, respectively). According to the multivariable analysis, advanced age (odds ratio [OR]: 1.087, 95% confidence interval [CI]: 1.029-1.148, p < 0.05), high serum PSA (OR: 1.047, 95% CI: 1.006-1.090, p < 0.05), HGPIN in ≥2 tumor-free cores (OR: 6.346, 95% CI: 3.136-12.912, p < 0.001), and PNI (OR: 3.138, 95% CI: 1.179-8.356, p < 0.05) were independent risk factors for a tumor upgrade. Furthermore, being in the low-risk group was an independent risk factor when compared to the intermediate- and high-risk groups (OR: 0.187, 95% CI: 0.080-0.437, p < 0.001 and OR: 0.054, 95% CI: 0.013-0.230, p < 0.001, respectively). The HGPIN diagnosis was more common in the low- and intermediate-risk groups. Advanced age at diagnosis, high serum PSA and PSA density values were associated with PNI on TRUS-Bx. High serum PSA and PSA density values were associated with LVI on TRUS-Bx. Surgical margin positivity was higher in cases with PNI and LVI detected by TRUS-Bx. HGPIN in ≥2 tumor-free cores, PNI, and LVI on TRUS-Bx were associated with a higher rate of lymph node metastases.
CONCLUSIONS: In patients diagnosed with acinar adenocarcinoma, the presence of HGPIN even in a single tumor-free core on TRUS-Bx was found to be significant in terms of showing an increase in the histological tumor grade in Rp. The diagnosis of HGPIN in ≥2 tumor-free cores on TRUS-Bx was determined as an independent risk factor for an increased Gleason score after Rp. Furthermore, an advanced age, a high serum PSA value, being in the low-risk group, and the presence of PNI were associated with a tumor upgrade. HGPIN in ≥2 tumor-free cores, PNI, and LVI were also associated with lymph node metastasis. Therefore, the diagnosis of HGPIN should be signed out on pathological reports.
PMID:38798171 | DOI:10.1002/pros.24751
Cancer Res. 2024 Jul 15;84(14):2225-2226. doi: 10.1158/0008-5472.CAN-24-0874.
ABSTRACT
Pancreatic cancer is usually detected at a late stage, when tumors have already metastasized; therefore, it has a poor prognosis with a 5-year survival rate of 11% to 12%. A key to targeting this high mortality is to develop methods for detecting the disease at a stage in which it is still local to the pancreas. However, this needs a better understanding of the events that govern pancreatic cancer oncogenesis. In this issue of Cancer Research, Neuß and colleagues report metabolic changes associated with acinar-to-ductal metaplasia (ADM), an initiating event that leads to the formation of precursor lesions for pancreatic ductal adenocarcinoma (PDAC). Their findings reveal a switch to aerobic glycolysis, increased c-MYC signaling, and increased serine metabolism as driving factors for the ADM process. These findings are important as they demonstrate that metabolic changes that drive the proliferation and metastasis of full-blown PDAC begin in the earliest lesions. The data not only provide insights into how PDAC develops but also a potential explanation for previously described findings, such as circulating lesion cells can be detected even when no carcinoma in situ is present. In summary, this article is highly relevant for furthering our understanding of how metabolic reprogramming drives the earliest events leading to PDAC development and could lay the groundwork for developing methods for early detection or intervention. See related article by Neuß et al., p. 2297.
PMID:39005051 | DOI:10.1158/0008-5472.CAN-24-0874
Hepatobiliary Pancreat Dis Int. 2024 Jul 6:S1499-3872(24)00101-2. doi: 10.1016/j.hbpd.2024.07.005. Online ahead of print.
NO ABSTRACT
PMID:39004574 | DOI:10.1016/j.hbpd.2024.07.005
J Cancer Res Clin Oncol. 2024 Jul 11;150(7):347. doi: 10.1007/s00432-024-05841-z.
ABSTRACT
BACKGROUND: Therapeutic approach used for pancreatic ductal adenocarcinoma is usually translated also for the rarer acinar counterpart, which shows a different mutational landscape nevertheless. While dMMR/MSI-H status is rare in the ductal histotype, it appears to be more prevalent in pancreatic acinar cell carcinoma (PACC).
CASE PRESENTATION: We report the case of a patient with locally advanced MSI-H PACC in whom the treatment with the anti-PD-1 pembrolizumab, administered as third line, made possible surgical resection, achieving even an exceptional pathological complete response.
CONCLUSIONS: Treatment of PACC should be tailored based on the peculiar molecular features that distinguish PACC from ductal adenocarcinoma. Evaluation of potentially therapeutically targetable alterations should be mandatory in case of PACC diagnosis.
PMID:38990367 | PMC:PMC11239721 | DOI:10.1007/s00432-024-05841-z
World J Urol. 2024 Jul 11;42(1):404. doi: 10.1007/s00345-024-05109-8.
ABSTRACT
BACKGROUND: Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions.
PATIENTS AND METHODS: We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues.
RESULTS: Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively).
CONCLUSIONS: Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.
PMID:38990246 | DOI:10.1007/s00345-024-05109-8
Prostate Cancer Prostatic Dis. 2024 Jul 10. doi: 10.1038/s41391-024-00866-4. Online ahead of print.
ABSTRACT
BACKGROUND: To assess cancer-specific mortality (CSM) and other-cause mortality (OCM) rates in patients with rare histological prostate cancer subtypes.
METHODS: Using the Surveillance, Epidemiology, and End Results database (2004-2020), we applied smoothed cumulative incidence plots and competing risks regression (CRR) models.
RESULTS: Of 827,549 patients, 1510 (0.18%) harbored ductal, 952 (0.12%) neuroendocrine, 462 (0.06%) mucinous, and 95 (0.01%) signet ring cell carcinoma. In the localized stage, five-year CSM vs. OCM rates ranged from 2 vs. 10% in acinar and 3 vs. 8% in mucinous, to 55 vs. 19% in neuroendocrine carcinoma patients. In the locally advanced stage, five-year CSM vs. OCM rates ranged from 5 vs. 6% in acinar, to 14 vs. 16% in ductal, and to 71 vs. 15% in neuroendocrine carcinoma patients. In the metastatic stage, five-year CSM vs. OCM rates ranged from 49 vs. 15% in signet ring cell and 56 vs. 16% in mucinous, to 63 vs. 9% in ductal and 85 vs. 12% in neuroendocrine carcinoma. In multivariable CRR, localized neuroendocrine (HR 3.09), locally advanced neuroendocrine (HR 9.66), locally advanced ductal (HR 2.26), and finally metastatic neuroendocrine carcinoma patients (HR 3.57; all p < 0.001) exhibited higher CSM rates relative to acinar adenocarcinoma patients.
CONCLUSIONS: Compared to acinar adenocarcinoma, patients with neuroendocrine carcinoma of all stages and locally advanced ductal carcinoma exhibit higher CSM rates. Conversely, CSM rates of mucinous and signet ring cell adenocarcinoma do not differ from those of acinar adenocarcinoma.
PMID:38987307 | DOI:10.1038/s41391-024-00866-4
J Am Soc Cytopathol. 2024 Jun 8:S2213-2945(24)00058-9. doi: 10.1016/j.jasc.2024.06.001. Online ahead of print.
ABSTRACT
INTRODUCTION: There is a lack of documentation regarding cytopathology of renal neuroendocrine neoplasms (NENs) due to their rarity.
MATERIALS AND METHODS: Five cytology cases were gathered from 3 institutes.
RESULTS: Cohort consisted of 4 females and 1 male. Fine needle aspiration biopsy and touch preparation slides of core needle biopsy revealed cellular samples, composed of round, plasmacytoid, or columnar cells. Tumor cells were present in nested, acinar, 3D cluster, and individual cell patterns. Tumor cells in 3 cases exhibited uniformly round to oval small nuclei with inconspicuous nucleoli, finely granular chromatin, and smooth nuclear membranes, whereas 2 other cases showed pleomorphic nuclei with conspicuous nucleoli, nuclear molding, and irregular nuclear membranes. Tumor cells displayed pale or granular cytoplasm, with 1 case showing small vacuoles. Examination of cores and cell blocks demonstrated tumor cells in sheets, nests, or acini. All tumor cells were positive for neuroendocrine immunomarkers. Based on mitotic count, Ki-67 index and morphology, 3 tumors were graded as well-differentiated neuroendocrine tumor (WDNET) (1 grade [G] 3, 1 G2, 1 G1) and 2 as large cell neuroendocrine carcinoma. Deletion of 7q, 10q, and 19q was detected in WDNETs. Two patients with large cell neuroendocrine carcinoma and 1 with WDNET G3 underwent chemotherapy due to aggressiveness, whereas nephrectomy was performed for patients with WDNET G1 and 2 without metastasis.
CONCLUSIONS: Cytopathological characteristics of renal NENs closely resemble those affecting other organs. Despite its rarity, renal NENs should be kept in mind when confronted with morphological resemblances to NENs, to prevent misdiagnosis and inappropriate therapeutic interventions.
PMID:38981825 | DOI:10.1016/j.jasc.2024.06.001
Cancer Discov. 2024 Jul 8. doi: 10.1158/2159-8290.CD-24-0137. Online ahead of print.
ABSTRACT
Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor Pdx1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in mouse and human. We have identified the receptor tyrosine kinase Ror2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition.
PMID:38975886 | DOI:10.1158/2159-8290.CD-24-0137
J Pathol Transl Med. 2024 Jul;58(4):182-190. doi: 10.4132/jptm.2024.06.25. Epub 2024 Jul 9.
ABSTRACT
BACKGROUND: Acinar cell carcinoma (ACC) is a rare malignant epithelial neoplasm, which shares many cytomorphological features with other non-ductal pancreatic neoplasms such as pancreatic neuroendocrine neoplasm (PanNEN) and solid-pseudopapillary neoplasm (SPN). Due to the relative rarity of these tumors, pathologists are less familiar with the cytological features, especially on liquid-based cytology (LBC) which has been relatively recently introduced for endoscopic ultrasound-guided fine needle aspiration specimens.
METHODS: We evaluated the detailed cytological features of 15 histologically confirmed ACC (7 conventional smears [CS], 8 LBC), and compared them with the LBC features of SPN (n = 9) and PanNEN (n = 9).
RESULTS: Compared with CS, LBCs of ACC demonstrated significantly less bloody background. All ACCs demonstrated prominent nucleoli and macronucleoli on LBC. On comparison with the LBC features of SPN and PanNEN, most ACCs demonstrated a necrotic background with apoptotic debris while PanNEN and SPN did not show these features. Acinar structures were predominantly observed in ACC, while frequent pseudopapillary structures were seen only in SPN. Prominent nucleoli and macronucleoli were only seen in ACC.
CONCLUSIONS: ACC had characteristic cytological features that could be observed on LBC preparations, such as high cellularity, necrotic/apoptotic background, nuclear tangles, acinar arrangement of cells, and macronucleoli. These findings also help distinguish ACC from PanNEN and SPN on LBC. It is important to be familiar with these features, as an accurate diagnosis on endoscopic ultrasound-guided fine needle aspiration cytology would have impact on the management of the patient.
PMID:38973328 | PMC:PMC11261172 | DOI:10.4132/jptm.2024.06.25
J Pathol. 2024 Aug;263(4-5):466-481. doi: 10.1002/path.6298. Epub 2024 Jun 25.
ABSTRACT
The E3 ubiquitin ligase thyroid hormone receptor interacting protein 12 (TRIP12) has been implicated in pancreatic adenocarcinoma (PDAC) through its role in mediating the degradation of pancreas transcription factor 1a (PTF1a). PTF1a is a transcription factor essential for the acinar differentiation state that is notably diminished during the early steps of pancreatic carcinogenesis. Despite these findings, the direct involvement of TRIP12 in the onset of pancreatic cancer has yet to be established. In this study, we demonstrated that TRIP12 protein was significantly upregulated in human pancreatic preneoplastic lesions. Furthermore, we observed that TRIP12 overexpression varied within PDAC samples and PDAC-derived cell lines. We further demonstrated that TRIP12 was required for PDAC-derived cell growth and for the expression of E2F-targeted genes. Acinar-to-ductal cell metaplasia (ADM) is a reversible process that reflects the high plasticity of acinar cells. ADM becomes irreversible in the presence of oncogenic Kras mutations and leads to the formation of preneoplastic lesions. Using two genetically modified mouse models, we showed that a loss of TRIP12 prevented acini from developing ADM in response to pancreatic injury. With two additional mouse models, we further discovered that a depletion of TRIP12 prevented the formation of KrasG12D-induced preneoplastic lesions and impaired metastasis formation in the presence of mutated KrasG12D and Trp53R172H genes. In summary our study identified an overexpression of TRIP12 from the early stages of pancreatic carcinogenesis and proposed this E3 ubiquitin ligase as a novel regulator of acinar plasticity with an important dual role in initiation and metastatic steps of PDAC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
PMID:38924548 | DOI:10.1002/path.6298
Int Cancer Conf J. 2024 Apr 22;13(3):281-288. doi: 10.1007/s13691-024-00679-1. eCollection 2024 Jul.
ABSTRACT
Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor type, and ruptured pancreatic tumors are rarer. Computed tomography (CT) in a 48-year-old man incidentally revealed a raptured pancreatic tail tumor. The patient was treated conservatively because he was asymptomatic, and his general condition was stable. After a detailed examination, the pancreatic tumor was diagnosed as raptured PACC. Considering the potential infiltration of tumor cells into the hematoma within the omental sac, our decision is to initiate chemotherapy as the primary course of action. A liquid biopsy was performed, and comprehensive genomic profiling of circulating tumor DNA showed a tumor BRCA2 mutation. Chemotherapy with modified FOLFIRINOX (mFFX) was selected as the first treatment. After seven courses of mFFX, the primary tumor diminished remarkably. At this time, the radical resection was performed via distal pancreatectomy with simultaneous resection of the gastric wall and colon, which had adhered strongly to the tumor. Histopathological examination revealed that the tumor had shrunk to less than 5% of its original size due to chemotherapy (Grade 3 of Evans Classification). Devising treatment strategies for ruptured pancreatic malignant tumors is challenging due to the worsening general condition caused by severe abdominal symptoms and intra-abdominal bleeding. In this context, this case-report documents a rare instance of raptured PACC with a tumor BRCA2 mutation that underwent radical resection following mFFX treatment.
PMID:38962046 | PMC:PMC11217244 | DOI:10.1007/s13691-024-00679-1
Medicina (Kaunas). 2024 May 27;60(6):877. doi: 10.3390/medicina60060877.
ABSTRACT
Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively. Primary signet-ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical Case: In June of 2023, a 54-year-old Caucasian male presented with a complaint of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups, including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma stage IV. Unfortunately, due to the advanced stage of the disease, PE, and third-degree thrombocytopenia, the patient was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results, which may contribute to its late diagnosis. Inconsistent immunohistochemical findings and an unpredictable response to hormonal treatment together pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusions: This study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease, which may positively influence the prognosis.
PMID:38929494 | PMC:PMC11205309 | DOI:10.3390/medicina60060877
Int J Mol Sci. 2024 Jun 16;25(12):6619. doi: 10.3390/ijms25126619.
ABSTRACT
Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.
PMID:38928326 | PMC:PMC11204091 | DOI:10.3390/ijms25126619
Diagn Cytopathol. 2024 Nov;52(11):E256-E259. doi: 10.1002/dc.25377. Epub 2024 Jun 24.
ABSTRACT
Mammary analogue secretory carcinoma (MASC) is a rare salivary gland tumor which shares its histologic, immunohistochemical, and genetic features with the secretory carcinoma (SC) of breast. In this case report, we describe a case of MASC in a young adolescent male with swelling in the right angle of mandible which is a relatively rare site to present along with its correlation of cytological, histological, and immunohistochemical features. A 16-year-old male came with the complaint of swelling in the right angle of mandible since 2 years. Contrast-enhanced computed tomography (CECT) neck revealed differential diagnosis of nerve sheath tumor, pleomorphic adenoma, and adenoid cystic neoplasm was kept, and subsequently fine-needle aspiration cytology (FNAC) was done. FNAC was done in which differential diagnosis of myoepithelial neoplasm, acinic cell carcinoma, and SC was given. Surgical excision was done followed by histopathological examination. Immunohistochemistry panel was also applied, and final diagnosis of SC was rendered. SC has distinct cytological, histological, and immunohistochemical features which should be recognized by the pathologists for the appropriate management of the patient.
PMID:38923370 | DOI:10.1002/dc.25377
Clin Cancer Res. 2024 Sep 3;30(17):3812-3823. doi: 10.1158/1078-0432.CCR-23-3981.
ABSTRACT
PURPOSE: Even though BRAF fusions are increasingly detected in standard multigene next-generation sequencing panels, few reports have explored their structure and impact on clinical course.
EXPERIMENTAL DESIGN: We collected data from patients with BRAF fusion-positive cancers identified through a genotyping protocol of 97,024 samples. Fusions were characterized and reviewed for oncogenic potential (in-frame status, non-BRAF partner gene, and intact BRAF kinase domain).
RESULTS: We found 241 BRAF fusion-positive tumors from 212 patients with 82 unique 5' fusion partners spanning 52 histologies. Thirty-nine fusion partners were not previously reported, and 61 were identified once. BRAF fusion incidence was enriched in pilocytic astrocytomas, gangliogliomas, low-grade neuroepithelial tumors, and acinar cell carcinoma of the pancreas. Twenty-four patients spanning multiple histologies were treated with MAPK-directed therapies, of which 20 were evaluable for RECIST. Best response was partial response (N = 2), stable disease (N = 11), and progressive disease (N = 7). The median time on therapy was 1 month with MEK plus BRAF inhibitors [(N = 11), range 0-18 months] and 8 months for MEK inhibitors [(N = 14), range 1-26 months]. Nine patients remained on treatment for longer than 6 months [pilocytic astrocytomas (N = 6), Erdheim-Chester disease (N = 1), extraventricular neurocytoma (N = 1), and melanoma (N = 1)]. Fifteen patients had acquired BRAF fusions.
CONCLUSIONS: BRAF fusions are found across histologies and represent an emerging actionable target. BRAF fusions have a diverse set of fusion partners. Durable responses to MAPK therapies were seen, particularly in pilocytic astrocytomas. Acquired BRAF fusions were identified after targeted therapy, underscoring the importance of postprogression biopsies to optimize treatment at relapse in these patients.
PMID:38922339 | PMC:PMC11371517 | DOI:10.1158/1078-0432.CCR-23-3981
Pathology. 2024 Oct;56(6):786-794. doi: 10.1016/j.pathol.2024.04.002. Epub 2024 Jun 4.
ABSTRACT
KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant. KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.
PMID:38918148 | DOI:10.1016/j.pathol.2024.04.002
Arkh Patol. 2024;86(3):30-37. doi: 10.17116/patol20248603130.
ABSTRACT
OBJECTIVE: The purpose of this work was to evaluate c-MYC gene amplification in the substrate of prostate acinar adenocarcinoma at various Gleason scores and various stages of the disease, taking into account the morphological characteristics of the tumor.
MATERIAL AND METHODS: The number of cases in the study was 82, including the control group - 12 cases. Morphological assessment included: determination of the total Gleason score, grading group, assessment of lymphovascular/perineural invasion, and architectural characteristics of the tumor. Gene amplification was assessed by FISH using the c-MYC (8q24)/SE8 probe.
RESULTS: In all cases of the study group, amplification of the c-MYC gene was detected in the tumor, with a significant difference from the control group (p<0.05). When assessing cases with 4-6 fold copies of the gene, significant differences were established between patients with stages II and III of the disease and stage IV (10.0 and 13.5 versus 30.0) (p<0.05). Cluster amplification of the c-MYC gene was detected with equal frequency in groups of patients with stages III and IV of the disease, while in stage II of the disease, the event almost did not occur (p<0.05). A significant increase in the level of c-MYC gene amplification was found in groups with advanced stages of the disease (p<0.02). Non-cluster amplification significantly distinguishes T4M0 and T4M1 stage patients from the rest with a significant increase in the score (p<0.05). In the metastatic stage of the disease, there was an increase c-MYC gene amplification compared to the non-metastatic stage (p<0.02). The copy number of the c-MYC gene was significantly higher in cases with perineural and lymphovascular invasion, as well as in cases of cribriform tumor organization (p<0.05).
CONCLUSION: Amplification of the c-MYC gene in prostate tumor cells is associated with advanced stages of the disease (T4M0 and T4M1) with an increase in the copy number of the gene during the metastatic stage of the process. It was found that increased amplification of the c-MYC gene distinguishes groups of patients whose tumors exhibit perineural and lymphovascular invasion, as well as a cribriform pattern of tumor organization.
PMID:38881003 | DOI:10.17116/patol20248603130
Am J Pathol. 2024 Jul;194(7):1346-1373. doi: 10.1016/j.ajpath.2024.02.023. Epub 2024 Apr 15.
ABSTRACT
Because the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and phosphorylated Ser-139 residue of the histone variant H2AX (γH2AX) foci linked to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+;Trp53flox/flox;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3-μm micropores. To search for pancreatic cancer cell-of-origin, analysis of single-cell data sets revealed that the extracellular matrix shaped an alternate route of acinar-ductal transdifferentiation of acinar cells into topoisomerase II α (TOP2A)-overexpressing cancer cells and derived subclusters with copy number amplifications in MYC-PTK2 (protein tyrosine kinase 2) locus and PIK3CA. High-PTK2 expression is associated with 171 differentially methylated CpG loci, 319 differentially expressed genes, and poor overall survival in The Cancer Genome Atlas-Pancreatic Adenocarcinoma cohort. Abolished RGD-integrin signaling by disintegrin KG blocked the PTK2 phosphorylation, increased cancer apoptosis, decreased vav guanine nucleotide exchange factor 1 (VAV1) expression, and prolonged overall survival in the KPC mice. Reduction of α-smooth muscle actin deposition in the CD248 knockout KPC mice remodeled the tissue stroma and down-regulated TOP2A expression in the epithelium. In summary, stromal stiffness induced the onset of cancer cells-of-origin by ectopic TOP2A expression, and the genomic amplification of MYC-PTK2 locus via alternative transdifferentiation of pancreatic progenitor cells is the vulnerability useful for disintegrin KG treatment.
PMID:38631549 | DOI:10.1016/j.ajpath.2024.02.023
J Korean Soc Radiol. 2024 May;85(3):643-648. doi: 10.3348/jksr.2023.0126. Epub 2024 May 23.
ABSTRACT
Acinic cell carcinoma is a rare malignant tumor that accounts for 2%-3% of salivary gland tumors. Acinic cell carcinoma arising from the breast is extremely rare, with only approximately 70 cases reported to date. Owing to its rarity, previous studies have primarily focused on pathological findings. Herein, we present the clinical and radiological features of acinic cell carcinoma of the breast in a 33-year-old woman.
PMID:38873389 | PMC:PMC11166594 | DOI:10.3348/jksr.2023.0126
Auris Nasus Larynx. 2024 Aug;51(4):755-760. doi: 10.1016/j.anl.2024.05.007. Epub 2024 Jun 8.
ABSTRACT
OBJECTIVE: While several studies reported epidermal growth factor receptor (EGFR) expression in salivary gland cancer (SGC), results varied due to a lack of unified definition of EGFR positivity. In this study, we assessed the EGFR expression level using both EGFR positive score and cumulative EGFR score in the patients with SGC.
METHODS: Between January 2010 and April 2021, 102 patients with SGC who underwent surgical resection were reviewed retrospectively by immunohistochemistry. The membrane staining intensity was scored as follows: no staining (0), weak staining (1+), intermediate staining (2+), and strong staining (3+). The cumulative EGFR score was determined on a continuous scale of 0-300 using the formula:1 × (1+: percentage of weakly stained cells) + 2 × (2+: percentage of moderately stained cells) + 3 × (3+: percentage of strongly stained cells).
RESULTS: EGFR expression in SGC varied widely even among the same as well as different histopathological types. The average EGFR positive scores were 46.0 %, 55.7 %, 51.6 %, 1.0 %, 26.8 %, 50 %, and 76.8 % for mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (AcCC), adenocarcinoma NOS (ACNOS), carcinoma ex pleomorphic adenoma (CAexPA), and squamous cell carcinoma (SqCC), respectively. The average cumulative EGFR scores were 82, 91, 80, 1, 52, 93, and 185 for MEC, SDC, AdCC, AcCC, ACNOS, CAexPA, and SqCC, respectively.
CONCLUSIONS: EGFR positive scores and cumulative EGFR scores in SGCs varied among the various histological types, and even in the same histological type. These scores may predict the clinical outcome of SGC treated with EGFR-targeting therapies, such as head and neck photoimmunotherapy, and need to be evaluated in future studies.
PMID:38852332 | DOI:10.1016/j.anl.2024.05.007
Appl Immunohistochem Mol Morphol. 2024 Jul 1;32(6):264-271. doi: 10.1097/PAI.0000000000001209. Epub 2024 Jun 7.
ABSTRACT
There is a limited amount of data on the role of programmed cell death ligand (PD-L) -1 and PD-L2 in salivary gland carcinomas. We aimed to evaluate the prognostic value of PD-L1 and PD-L2 expressions, which are closely related to immune mechanisms, with respect to salivary gland tumor types and stages. Data from patients with salivary gland masses surgically removed between 2006 and 2021, diagnosed with a malignant salivary gland neoplasm, were retrospectively analyzed. Immunoreactivity for PD-L1 and PD-L2 was performed on resection materials. The mean age of 90 patients was 52.1±18.8 and 46.7% were male. Overall, 55.6% of patients were diagnosed with adenoid cystic carcinoma (ACC), 23.3% with mucoepidermoid carcinoma (MEC), 16.7% with acinic cell carcinoma (AciCC), 3.3% with ductal carcinoma (DC), and 1 patient with pleomorphic adenoma ex carcinoma (PA-ex-CA). In all, 52% of ACC, 12% of AciCC, 24% of MEC, and 12% of DC cases were at stage IV. The tumor diameter, frequencies of lymphovascular invasion, metastasis, positive surgical margin, recurrence, and mortality rates of patients at stages III and IV were significantly larger than those at stages I and II ( P <0.05). The percentages of tumor cell score (TCS) and immune cell score (ICS) for PD-L1 were significantly higher among patients with MEC compared with those with other types of tumors ( P =0.0011). However, the percentages of combined score (CS) for PD-L1 and tumor cell score for PD-L2 were comparable among tumor types ( P >0.05). No significant difference was found in these scores for PD-L1 between tumor stages ( P >0.05), but for PD-L2, all patients at stage I had TCS <1% for PD-L2, while all patients at stages II and III, and 92% of patients at stage IV had TCS ≥1% ( P <0.0001). High expression of PD-L1 was mostly observed in MEC cases ( P =0.0016), while all patients with AciCC had a low PD-L1 expression level ( P =0.0206). The mean tumor diameter, rate of lymphovascular invasion, perineural invasion, metastasis, positive surgical margin, recurrence, type of treatment, mortality, and TILs ratio did not differ significantly according to PD-L1 expression level ( P >0.05). The percentage of tumor-infiltrating lymphocytes was comparable among negative and positive PD-L1 scores according to both 1% and 5% threshold values ( P >0.05). High PD-L1 expression is rare in AciCC, while PD-L1 expression is high in MEC. Our findings underline the importance of future screening for PD-L1 and PD-L2 before patients undergoing immunotherapies in all salivary gland tumors.
PMID:38847110 | DOI:10.1097/PAI.0000000000001209
Clin J Gastroenterol. 2024 Oct;17(5):970-975. doi: 10.1007/s12328-024-01992-1. Epub 2024 Jun 5.
ABSTRACT
Pancreatic acinar cell carcinoma (PACC) is a rare type of pancreatic cancer; further, its pathogenesis and treatment strategies remain unclear. We report the case of a 70-year-old man who presented with a chief complaint of abdominal distention. Computed tomography scans revealed a large lobulated mass (tumor diameter: 150 mm) in the pancreatic body tail, which was diagnosed as a PACC through endoscopic ultrasonography fine needle aspiration. The other imaging modalities did not reveal distant metastases, and the tumor was classified as resectable. Neoadjuvant chemotherapy was planned after staging laparoscopy ruled out microscopic distant metastasis. First-line chemotherapy with gemcitabine + nab-paclitaxel failed due to tumor growth and worsening abdominal distention. Evaluation using the BRACAnalysis® device indicated that the patient was positive for BRCA1 mutation. Second-line modified FOLFIRINOX (mFFX) resulted in a marked decrease in elastase 1 levels; moreover, a partial antitumor response was observed, which prompted radical resection. After distal pancreatectomy, the patient has survived for 3.5 years without recurrence. BRCA-mutated pancreatic cancer is more likely to respond to mFFX, including platinum, and BRCA mutations have been reported to be highly prevalent in PACC. It is important to evaluate the presence of BRCA mutations in patients with PACC prior to treatment.
PMID:38836973 | DOI:10.1007/s12328-024-01992-1
Virchows Arch. 2024 Jun 1. doi: 10.1007/s00428-024-03830-8. Online ahead of print.
ABSTRACT
Paediatric pancreatic acinar cell carcinoma (PACC) presents a diagnostic challenge, often confused with pancreatoblastoma (PB) due to its rarity. It is crucial to differentiate between PB and PACC, given their distinct therapeutic strategies and prognoses. Histologically, the absence of squamoid nests and scarcity of tumor mesenchyme support PACC. Conversely, the identification of a BRAF alteration leans towards PACC. Here, we present the case of an 8-year-old girl with a well-defined mass in the pancreas. The tumor exhibited a SEC31A-BRAF fusion gene and amplification of 18p, showcasing unequivocal acinar differentiation and a minor degree of neuroendocrine differentiation. Additionally, the tumor displayed scant fibrous stroma, and an absence of squamoid nests, further supporting PACC. Notably, this is the first reported instance of a solid tumor featuring a SEC31A-BRAF gene fusion. The discovery of this novel fusion gene expands our understanding of BRAF fusion partner profiles, particularly in the context of paediatric PACC.
PMID:38822175 | DOI:10.1007/s00428-024-03830-8
J Oral Maxillofac Pathol. 2024 Jan-Mar;28(1):134-137. doi: 10.4103/jomfp.jomfp_332_23. Epub 2024 Apr 15.
ABSTRACT
Oncocytic mucoepidermoid carcinoma (OMEC) is an uncommon variant of mucoepidermoid carcinoma. Histopathologically, it is characterised by the predominance of cells with large polygonal morphology and with an abundance of eosinophilic granules. We present a rare case of OMEC manifested as painless palatal swelling in a 25-year-old young male. The overlying mucosa was normal in appearance, with no evidence of ulceration or discharge. Histopathology examination showed the presence of sheets of mucous and intermediate cells along with cystic areas of variable sizes and shapes. On high power magnification, oncocytes were evident, showing abundant granular eosinophilic cytoplasm with central dark round nuclei. Around 75-80% tumour cell population was composed of oncocytic cells. The predominant presence of oncocytes can present diagnostic difficulties to pathologists due to overlapping features with adenoid cystic carcinoma, oncocytoma, acinic cell carcinoma, Warthin's tumour, and other oncocyte tumours. Although the presence of oncocytes is a pathognomonic feature, the role of immunohistochemistry and genetic analysis in diagnosis is discussed in the present paper. Moreover, considering its behaviour as a low-grade MEC, it is prudent to avoid an aggressive treatment strategy and prevent unwarranted morbidity. We recommend prospective studies to better understand the factors that influence the prognosis of OMEC.
PMID:38800424 | PMC:PMC11126252 | DOI:10.4103/jomfp.jomfp_332_23
BMJ Case Rep. 2024 May 24;17(5):e260385. doi: 10.1136/bcr-2024-260385.
ABSTRACT
Cancer-associated stroke is an evolving subgroup of embolic strokes of undetermined source. A man in his mid-20s with progressive follicular variant acinic cell carcinoma of the parotid was admitted because of new onset left-sided weakness. Neuroimaging confirmed a right middle cerebral artery infarction. After extensive diagnostics, stroke aetiology was deemed from cancer-induced hypercoagulability. Questions which arose regarding his management included (1) What was the best antithrombotic for secondary stroke prevention? (2) What was his risk for intracranial or tumorous bleeding once antithrombotics had been started? (3) How many days post-stroke could the antithrombotic be initiated? and (4) When could he be cleared for palliative chemotherapy and whole brain irradiation? The approach to address the abovementioned questions in the management of a rare cancer complicated by stroke is presented. Although treatments are guided by known pathomechanisms, additional studies are needed to further support current treatment strategies for this subgroup of patients.
PMID:38789271 | DOI:10.1136/bcr-2024-260385
Head Neck Pathol. 2024 May 22;18(1):44. doi: 10.1007/s12105-024-01650-5.
ABSTRACT
While acinic cell carcinoma (AciCC) can undergo high-grade transformation (HGT) to high-grade adenocarcinoma or poorly differentiated carcinoma, other morphologies such as spindle cell/sarcomatoid carcinoma are rare and not well-characterized. We herein report a novel case of AciCC with squamoglandular and chondrosarcomatous HGT mimicking a so-called 'carcinosarcoma ex-pleomorphic adenoma'. The patient is an 81-year-old male with a two-month history of neck swelling and referred otalgia who presented with a left parapharyngeal space mass extending into retropharyngeal space and pterygoid muscles. On resection, the tumor showed considerable morphologic diversity with high-grade serous and mucous acinar components as well as cribriform to solid apocrine-like components with comedonecrosis and squamous differentiation, all of which were embedded in a chondromyxoid background ranging from paucicellular and bland to a high-grade chondrosarcoma/pleomorphic sarcoma-like appearance. Only a minor conventional AciCC component was noted. Immunostains were negative for AR and only focally positive for GCDFP-15 arguing against a true apocrine phenotype, while PLAG1 and HMGA2 were negative arguing against an antecedent pleomorphic adenoma. On the other hand, SOX-10, DOG-1 and PAS after diastase highlighted serous acinar differentiation, and mucicarmine, and NKX3.1 highlighted mucous acinar differentiation. NR4A3 immunohistochemical staining and NR4A3 fluorescence in situ hybridization were positive in the carcinomatous and sarcomatoid components while sequencing analysis of both components revealed identical alterations involving TP53, PIK3CB, ARID1A, and STK11. This unique case warrants caution in designating all salivary sarcomatoid carcinomas with heterologous elements as part of the 'carcinoma ex-pleomorphic adenoma' family.
PMID:38775845 | PMC:PMC11111628 | DOI:10.1007/s12105-024-01650-5
Dev Cell. 2024 May 20;59(10):1317-1332.e5. doi: 10.1016/j.devcel.2024.03.018. Epub 2024 Apr 3.
ABSTRACT
UBE2F, a neddylation E2, neddylates CUL5 to activate cullin-RING ligase-5, upon coupling with neddylation E3 RBX2/SAG. Whether and how UBE2F controls pancreatic tumorigenesis is previously unknown. Here, we showed that UBE2F is essential for the growth of human pancreatic cancer cells with KRAS mutation. In the mouse KrasG12D pancreatic ductal adenocarcinoma (PDAC) model, Ube2f deletion suppresses cerulein-induced pancreatitis, and progression of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia. Mechanistically, Ube2f deletion inactivates the Mapk-c-Myc signals via blocking ubiquitylation of Diras2, a substrate of CRL5Asb11 E3 ligase. Biologically, DIRAS2 suppresses growth and survival of human pancreatic cancer cells harboring mutant KRAS, and Diras2 deletion largely rescues the phenotypes induced by Ube2f deletion. Collectively, Ube2f or Diras2 plays a tumor-promoting or tumor-suppressive role in the mouse KrasG12D PDAC model, respectively. The UBE2F-CRL5ASB11 axis could serve as a valid target for pancreatic cancer, whereas the levels of UBE2F or DIRAS2 may serve as prognostic biomarkers for PDAC patients.
PMID:38574733 | DOI:10.1016/j.devcel.2024.03.018
Am J Surg Pathol. 2024 Jul 1;48(7):901-908. doi: 10.1097/PAS.0000000000002242. Epub 2024 May 20.
ABSTRACT
Pseudosquamous adenocarcinoma of the lung is an unusual morphologic variant of poorly differentiated non-small cell lung carcinoma that superficially resembles a squamous cell carcinoma. We have examined 10 cases of these tumors in 4 women and 6 men, aged 47 to 93 years. The tumors were all peripheral and measured from 1.5 to 5.5 cm. All cases were characterized by solid nests of large polygonal tumor cells containing atypical nuclei with abundant cytoplasm and sharp cell borders, adopting a pavement-like architecture that simulated squamous cell carcinoma. Some cases demonstrated intracytoplasmic hyaline inclusions suggestive of keratinization. The nests of tumor cells often showed central comedo-like areas of necrosis. Intercellular bridges were not seen in any of the cases. The tumors often displayed marked clearing of the cytoplasm enhancing their epidermoid appearance. In 4 cases, the solid pseudosquamous areas were seen to merge with a focal lepidic adenocarcinoma component, and in 1 case, abortive microscopic foci of acinar differentiation were also noted within the tumor. One case showed focal sarcomatoid spindle cell areas. The tumor cells were negative for p40 and CK5/6 and labeled with TTF1 or Napsin-A, confirming an adenocarcinoma phenotype. Clinical follow-up information was available in 8 patients; 6 patients died of their tumors between 6 months to 11 years after diagnosis (mean: 3.1 y). One patient died of complications related to surgery and one patient with a low-stage tumor died at 27 years from other causes. Solid pattern adenocarcinomas can be confused for squamous cell carcinoma and may require immunohistochemistry to determine their true phenotype.
PMID:38764378 | DOI:10.1097/PAS.0000000000002242
Clin J Gastroenterol. 2024 Aug;17(4):776-781. doi: 10.1007/s12328-024-01983-2. Epub 2024 May 18.
ABSTRACT
Pancreatic acinar cell carcinoma (PACC) is a very rare subtype of pancreatic cancer. Due to small number of patients, no standard chemotherapy protocol has been established. We experienced an extremely rare case of PACC with liver metastasis that showed a pathological complete response after modified FOLFIRINOX (mFFX) therapy. A 42-year-old man who underwent distal pancreatectomy for an 80 mm tumor at the pancreatic tail 3 years ago was referred to our hospital in September 2017 for the treatment of a recurrent liver tumor. Percutaneous biopsy revealed an acinar-neuroendocrine carcinoma, similar to the surgical specimen. He received eight cycles of irinotecan plus cisplatin chemotherapy. However, the tumor increased in size, and treatment was switched to mFFX therapy. The tumor in the liver shrank remarkably after nine cycles of mFFX therapy. Conversion surgery was selected, and the patient underwent hepatic left and caudate lobectomy 8 months after administration of mFFX. The resected specimen showed no viable tumor cells, indicating a pathological complete response. The histological diagnosis was reconsidered, and PACC was finally diagnosed via an additional immunohistological review. The patient has remained well with no recurrence for 6 years after surgery. This study is the first to report a case of pathological complete response with mFFX therapy for the recurrence of PACC.
PMID:38761340 | DOI:10.1007/s12328-024-01983-2
2024 Feb 24. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–.
ABSTRACT
Bronchoalveolar carcinoma (BAC) is a variant of non-small cell lung cancer (NSCLC) that, in recent years, has received a new identity and nomenclature from the histology perspective. The orphan among lung cancers has found a family, albeit with some newfound stepbrothers and sisters. The overhaul in the classification system of solitary adenocarcinomas has been driven by the purpose of identifying tumors that have an indolent clinical course and can be treated with a more conservative approach and a higher success rate. BAC is now consisting of five types based on histology: adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant nonmucinous adenocarcinoma, invasive mucinous adenocarcinoma, and invasive adenocarcinoma with its subtypes.
Until the previous decade, strict pathologic criteria defined BAC as a tumor arising from terminal bronchiolar and alveolar acinar epithelia with an absence of invasion through the alveolar basement membrane into the pulmonary parenchyma. A growing consensus has been to subclassify adenocarcinoma with radiologic features of ground-glass opacities, with no or minimal extrathoracic spread, and histology demonstrating a lepidic growth pattern in the presence or absence of associated minimally invasive or invasive disease. These types of lung cancers are seen more often in younger patients who are typically non-smokers and with an almost equal 1:1 gender predisposition, or with a slight female predominance.
Clin J Gastroenterol. 2024 Aug;17(4):771-775. doi: 10.1007/s12328-024-01981-4. Epub 2024 May 14.
ABSTRACT
Pancreatic acinar cell carcinoma (PACC) is a rare cancer with no specific treatment. The treatment and chemotherapy for PACC are selected according to pancreatic ductal adenocarcinoma (PDAC). Herein, we describe a recurrent PACC case of an older adult patient. The patient was treated with systemic chemotherapy, chemoradiotherapy, and maintenance therapy based on the pathologic germline BRCA2 variant, resulting in long-term survival. The pathogenic BRCA variant is detected more frequently in patients with PACC than in those with PDAC. The BRCA variant significantly impacts treatment selection and prognosis; therefore, early genomic analysis is recommended when treating PACC.
PMID:38743170 | DOI:10.1007/s12328-024-01981-4
Fam Cancer. 2024 Aug;23(3):393-398. doi: 10.1007/s10689-024-00390-3. Epub 2024 May 11.
ABSTRACT
A 73-year-old Japanese man with a history of distal biliary cancer treated by pancreatoduodenectomy developed pancreatic acinar cell carcinoma (PACC) treated by remnant pancreatectomy and adjuvant chemotherapy. Thirteen months after surgery, multiple liver metastases developed and FOLFOX chemotherapy was initiated. Based on the PACC diagnosis and a positive family history for breast and ovarian cancer genetic testing was performed which revealed a pathogenic germline BRCA2 variant (c.8629G > T, p.Glu2877Ter). Olaparib therapy was initiated and the metastases responded well (partial response). PACC is a BRCA2-associated cancer which may respond well to PARP inhibitors.
PMID:38733420 | DOI:10.1007/s10689-024-00390-3
Quintessence Int. 2024 May 30;55(5):392-398. doi: 10.3290/j.qi.b5282467.
ABSTRACT
Secretory carcinoma is a malignant salivary gland tumor, which typically presents as an indolent painless mass within the parotid gland. Involvement of the minor gland is reported but less common. Secretory carcinoma was often misclassified as other salivary gland mimics, particularly acinic cell carcinoma, prior to 2010. It was first recognized as a molecularly distinct salivary gland tumor harboring the same fusion gene as well as histologic and cytogenetic features seen in juvenile breast cancer. Secretory carcinoma is generally managed in the same way as other low-grade salivary gland neoplasms and has a favorable prognosis; however, high-grade transformation requiring aggressive therapeutic interventions have been documented. Recent studies of biologic agents targeting products of this fusion gene offer the promise of a novel therapeutic option for treatment of this malignancy. Due to the limited number of reported cases, the spectrum of clinical behavior, best practices for management, and long-term treatment outcomes for secretory carcinoma remain unclear. A long-standing secretory carcinoma involving minor salivary glands of the mucobuccal fold, which was detected years after it was first noted by the patient, is reported. This case brings to light the importance of a thorough clinical exam during dental visits and reviews diagnostic differentiation of this malignancy from other mimics and discusses decision making for its management.
PMID:38695062 | DOI:10.3290/j.qi.b5282467
Mol Cancer Res. 2024 May 2;22(5):440-451. doi: 10.1158/1541-7786.MCR-23-0199.
ABSTRACT
The study identifies an opportunity to discover a PKA-independent pathway downstream of oncogene GNAS for managing IPMN lesions and their progression to PDAC.
PMID:38319286 | PMC:PMC10906748 | DOI:10.1158/1541-7786.MCR-23-0199
Am J Surg Pathol. 2024 Jun 1;48(6):681-690. doi: 10.1097/PAS.0000000000002219. Epub 2024 Apr 29.
ABSTRACT
Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.
PMID:38682454 | DOI:10.1097/PAS.0000000000002219
Zhonghua Bing Li Xue Za Zhi. 2024 May 8;53(5):501-503. doi: 10.3760/cma.j.cn112151-20231026-00315.
ABSTRACT
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PMID:38678337 | DOI:10.3760/cma.j.cn112151-20231026-00315
J Gastroenterol Hepatol. 2024 Apr 23. doi: 10.1111/jgh.16573. Online ahead of print.
NO ABSTRACT
PMID:38653582 | DOI:10.1111/jgh.16573
Eur Arch Otorhinolaryngol. 2024 Aug;281(8):4305-4313. doi: 10.1007/s00405-024-08650-9. Epub 2024 Apr 23.
ABSTRACT
BACKGROUND: The preoperative diagnosis of salivary gland cancer (SGC) is crucial for the application of appropriate treatment, particularly involving the extension of the resection.
METHODS: Retrospective search of medical database identified 116 patients treated surgically with malignant tumors of salivary gland between 2010 and 2020. Analysis included the demographical data, clinical course, type of surgical and adjuvant treatment, histology type and margin status, perivascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LN). Facial nerve function, recurrence-free and overall survival were evaluated. Adequate statistics were used for data analysis.
RESULTS: The final cohort included 63 SGC patients, with adenoid cystic carcinoma the most common pathological type (27%, n = 17), followed by adenocarcinoma (17.4% n = 11). T1 and T2 patients accounted for majority cases (n = 46). The lymph node metastases were confirmed with the histopathology in 31.7% (n = 20). Distant metastases were observed in 4.8% of cases (n = 3). 38% (n = 24) of SGC were treated selectively with surgery, 49.2% (n = 31) had postoperative radiotherapy and 15.9% (n = 10)-radio-chemotherapy. The final facial nerve function was impaired in 38% of patients. Mean overall survival (OS) for all patients was 108.7 (± 132.1) months, and was the most favorable for acinar cell carcinoma (118.9 ± 45.4) and the poorest for squamous cell carcinoma (44 ± 32). Cox regression analysis of disease-free survival and OS identified significant association only with patients' age over 65 years, the hazard ratio of 7.955 and 6.486, respectively.
CONCLUSIONS: The efficacy of treatment modalities for SGC should be verified with regard to the histopathological type, but also the patients' age should be taken into account.
PMID:38649542 | PMC:PMC11266216 | DOI:10.1007/s00405-024-08650-9
Acta Cytol. 2024;68(3):219-226. doi: 10.1159/000538687. Epub 2024 Apr 17.
ABSTRACT
INTRODUCTION: The advances of minimally invasive endoscopy-guided procedures that usually yield limited diagnostic material changed pancreaticobiliary cytopathology into one of the most challenging areas of cytopathology given the abundance of differential diagnoses to be considered when dealing with limited specimens.
CASE PRESENTATION: We describe a few challenging examples of potential pitfalls in pancreatobiliary cytopathology evaluation collected from a busy academic hospital (tertiary) center. Case 1 illustrates the challenges in handling paucicellular specimens from pancreatic solid lesions in which differential diagnoses may include acinar cell carcinoma, neuroendocrine tumors, adenocarcinoma, or even benign pancreatic tissue, among others. Case 2 illustrates the pitfalls in evaluating limited specimens from patients with chronic pancreatitis, specially when distinguishing exuberant reactive atypia from dysplastic changes is mandatory. Case 3 illustrates pitfalls in distinguishing malignancy from reactive changes in biliary brushing specimens from patients with primary sclerosing cholangitis. Finally, cases 4 and 5 highlight the importance of including the possibility of pancreatic metastasis in the differential diagnoses of some pancreatic lesions.
CONCLUSION: Over time, there has been an increasing demand for pathologists to render diagnoses on limited specimens obtained through minimally invasive procedures which can be frequently challenging even for the most experienced professionals. In many difficult cases, salvaging additional material for a cell block can turn out to be extremely helpful given the possibility of utilizing additional ancillary tests for diagnostic confirmation.
PMID:38631319 | PMC:PMC11305519 | DOI:10.1159/000538687
Surg Case Rep. 2024 Apr 16;10(1):87. doi: 10.1186/s40792-024-01872-3.
ABSTRACT
CASE PRESENTATION: A 61-year-old female was referred to our hospital with a neoplastic lesion in the duodenum. Computed tomography with contrast enhancement revealed a 10-mm tumor in the duodenum. Upper gastrointestinal endoscopy revealed a submucosal tumor-like lesion in the descending part of the duodenum. Endoscopic ultrasound revealed a well-defined hypoechoic tumor. Biopsy and immunohistochemical findings including negative Synaptophysin and Chromogranin A staining and positive Trypsin and BCL10 staining suggested a carcinoma with acinar cell differentiation. Pancreatoduodenectomy was performed, and the resected specimen had a 15-mm solid nodule in the submucosal layer of the duodenum. Pancreatogram of the resected specimen revealed a tumor localized in the accessory papilla region. In histopathological examination, the tumor was found in the submucosa of the duodenum with pancreatic tissue present nearby, and these were separated from the pancreatic parenchyma by the duodenal muscle layer. These findings led to a diagnosis of acinar cell carcinoma originating from the accessory papilla of the duodenum.
CONCLUSION: Acinar cell carcinoma originating from the accessory papilla of the duodenum is exceptionally rare, with no reported cases to date. The origin was considered to be pancreatic tissue located in the accessory papilla region.
PMID:38625458 | PMC:PMC11019189 | DOI:10.1186/s40792-024-01872-3
EMBO Rep. 2024 Apr;25(4):1886-1908. doi: 10.1038/s44319-024-00104-x. Epub 2024 Feb 27.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a dismal prognosis that arises from precursor lesions called pancreatic intraepithelial neoplasias (PanINs). Progression from low- to high-grade PanINs is considered as tumor initiation, and a deeper understanding of this switch is needed. Here, we show that synaptic molecule neuroligin-2 (NLGN2) is expressed by pancreatic exocrine cells and plays a crucial role in the regulation of contact inhibition and epithelial polarity, which characterize the switch from low- to high-grade PanIN. NLGN2 localizes to tight junctions in acinar cells, is diffusely distributed in the cytosol in low-grade PanINs and is lost in high-grade PanINs and in a high percentage of advanced PDACs. Mechanistically, NLGN2 is necessary for the formation of the PALS1/PATJ complex, which in turn induces contact inhibition by reducing YAP function. Our results provide novel insights into NLGN2 functions outside the nervous system and can be used to model PanIN progression.
PMID:38413734 | PMC:PMC11014856 | DOI:10.1038/s44319-024-00104-x
Cancer Metastasis Rev. 2024 Mar;43(1):393-408. doi: 10.1007/s10555-023-10164-5. Epub 2024 Jan 9.
ABSTRACT
Cellular plasticity and therapy resistance are critical features of pancreatic cancer, a highly aggressive and fatal disease. The pancreas, a vital organ that produces digestive enzymes and hormones, is often affected by two main types of cancer: the pre-dominant ductal adenocarcinoma and the less common neuroendocrine tumors. These cancers are difficult to treat due to their complex biology characterized by cellular plasticity leading to therapy resistance. Cellular plasticity refers to the capability of cancer cells to change and adapt to different microenvironments within the body which includes acinar-ductal metaplasia, epithelial to mesenchymal/epigenetic/metabolic plasticity, as well as stemness. This plasticity allows heterogeneity of cancer cells, metastasis, and evasion of host's immune system and develops resistance to radiation, chemotherapy, and targeted therapy. To overcome this resistance, extensive research is ongoing exploring the intrinsic and extrinsic factors through cellular reprogramming, chemosensitization, targeting metabolic, key survival pathways, etc. In this review, we discussed the mechanisms of cellular plasticity involving cellular adaptation and tumor microenvironment and provided a comprehensive understanding of its role in therapy resistance and ways to overcome it.
PMID:38194153 | DOI:10.1007/s10555-023-10164-5
J Pathol. 2024 Jul;263(3):338-346. doi: 10.1002/path.6287. Epub 2024 Apr 9.
ABSTRACT
Necrotising sialometaplasia (NSM) is a non-neoplastic lesion mainly arising in the minor salivary glands of the oral cavity. In the clinical features, NSM shows swelling with or without ulceration, and can mimic a malignant disease such as squamous cell carcinoma. Histopathologically, NSM usually shows the lobular architecture that is observed in the salivary glands. Additionally, acinar infarction and squamous metaplasia of salivary ducts and acini are observable. The aetiology of this lesion remains unknown, although it has a characteristic feature that sometimes requires clinical and histopathological differentiation from malignancy. In this study, we investigated upregulated genes in NSM compared with normal salivary glands, and focused on the TGF-β3 (TGFB3) gene. The results of the histopathological studies clarified that fibroblasts surrounding the lesion express TGF-β3. Moreover, in vitro studies using mouse salivary gland organoids revealed that TGF-β3 suppressed salivary gland cell proliferation and induced squamous metaplasia. We demonstrated a possible aetiology of NSM by concluding that increased TGF-β3 expression during wound healing or tissue regeneration played a critical role in cell proliferation and metaplasia. © 2024 The Pathological Society of Great Britain and Ireland.
PMID:38594209 | DOI:10.1002/path.6287
Gut. 2024 Apr 5;73(5):770-786. doi: 10.1136/gutjnl-2023-330941.
ABSTRACT
OBJECTIVE: Epidemiological studies highlight an association between pancreatic ductal adenocarcinoma (PDAC) and oral carriage of the anaerobic bacterium Porphyromonas gingivalis, a species highly linked to periodontal disease. We analysed the potential for P. gingivalis to promote pancreatic cancer development in an animal model and probed underlying mechanisms.
DESIGN: We tracked P. gingivalis bacterial translocation from the oral cavity to the pancreas following administration to mice. To dissect the role of P. gingivalis in PDAC development, we administered bacteria to a genetically engineered mouse PDAC model consisting of inducible acinar cell expression of mutant Kras (Kras +/LSL-G12D; Ptf1a-CreER, iKC mice). These mice were used to study the cooperative effects of Kras mutation and P. gingivalis on the progression of pancreatic intraepithelial neoplasia (PanIN) to PDAC. The direct effects of P. gingivalis on acinar cells and PDAC cell lines were studied in vitro.
RESULTS: P. gingivalis migrated from the oral cavity to the pancreas in mice and can be detected in human PanIN lesions. Repetitive P. gingivalis administration to wild-type mice induced pancreatic acinar-to-ductal metaplasia (ADM), and altered the composition of the intrapancreatic microbiome. In iKC mice, P. gingivalis accelerated PanIN to PDAC progression. In vitro, P. gingivalis infection induced acinar cell ADM markers SOX9 and CK19, and intracellular bacteria protected PDAC cells from reactive oxygen species-mediated cell death resulting from nutrient stress.
CONCLUSION: Taken together, our findings demonstrate a causal role for P. gingivalis in pancreatic cancer development in mice.
PMID:38233197 | DOI:10.1136/gutjnl-2023-330941
J Gastrointest Surg. 2024 Jul;28(7):1208-1209. doi: 10.1016/j.gassur.2024.03.034. Epub 2024 Apr 2.
NO ABSTRACT
PMID:38574961 | DOI:10.1016/j.gassur.2024.03.034
Am J Surg Pathol. 2024 May 1;48(5):511-520. doi: 10.1097/PAS.0000000000002205. Epub 2024 Apr 3.
ABSTRACT
The diagnosis of solid pseudopapillary neoplasm of the pancreas (SPN) can be challenging due to potential confusion with other pancreatic neoplasms, particularly pancreatic neuroendocrine tumors (NETs), using current pathological diagnostic markers. We conducted a comprehensive analysis of bulk RNA sequencing data from SPNs, NETs, and normal pancreas, followed by experimental validation. This analysis revealed an increased accumulation of peroxisomes in SPNs. Moreover, we observed significant upregulation of the peroxisome marker ABCD1 in both primary and metastatic SPN samples compared with normal pancreas and NETs. To further investigate the potential utility of ABCD1 as a diagnostic marker for SPN via immunohistochemistry staining, we conducted verification in a large-scale patient cohort with pancreatic tumors, including 127 SPN (111 primary, 16 metastatic samples), 108 NET (98 nonfunctional pancreatic neuroendocrine tumor, NF-NET, and 10 functional pancreatic neuroendocrine tumor, F-NET), 9 acinar cell carcinoma (ACC), 3 pancreatoblastoma (PB), 54 pancreatic ductal adenocarcinoma (PDAC), 20 pancreatic serous cystadenoma (SCA), 19 pancreatic mucinous cystadenoma (MCA), 12 pancreatic ductal intraepithelial neoplasia (PanIN) and 5 intraductal papillary mucinous neoplasm (IPMN) samples. Our results indicate that ABCD1 holds promise as an easily applicable diagnostic marker with exceptional efficacy (AUC=0.999, sensitivity=99.10%, specificity=100%) for differentiating SPN from NET and other pancreatic neoplasms through immunohistochemical staining.
PMID:38567813 | PMC:PMC11020129 | DOI:10.1097/PAS.0000000000002205
Pathol Int. 2024 May;74(5):295-297. doi: 10.1111/pin.13423. Epub 2024 Apr 2.
NO ABSTRACT
PMID:38563588 | DOI:10.1111/pin.13423
NPJ Precis Oncol. 2024 Apr 1;8(1):82. doi: 10.1038/s41698-024-00497-x.
ABSTRACT
Pancreatic acinar cell carcinoma (PACC) is a rare form of pancreatic cancer that commonly harbors targetable alterations, including activating fusions in the MAPK pathway and loss-of-function (LOF) alterations in DNA damage response/homologous recombination DNA repair-related genes. Here, we describe a patient with PACC harboring both somatic biallelic LOF of NBN and an activating NTRK1 fusion. Upon disease progression following 13 months of treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), genomic analysis of a metastatic liver biopsy revealed the emergence of a novel reversion mutation restoring the reading frame of NBN. To our knowledge, genomic reversion of NBN has not been previously reported as a resistance mechanism in any tumor type. The patient was treated with, but did not respond to, targeted treatment with a selective NTRK inhibitor. This case highlights the complex but highly actionable genomic landscape of PACC and underlines the value of genomic profiling of rare tumor types such as PACC.
PMID:38561473 | PMC:PMC10985087 | DOI:10.1038/s41698-024-00497-x
Breast Cancer. 2024 May;31(3):496-506. doi: 10.1007/s12282-024-01564-8. Epub 2024 Mar 28.
ABSTRACT
BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST).
METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST.
RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p < 0.05). Nonetheless, tumor grade 3 and higher AJCC stage groups remained as significant independent prognostic factors in multivariate analysis (p < 0.05). The apparent better breast cancer-specific survival of salivary gland-type carcinoma as compared to that of invasive carcinoma, NST, was diminished following adjustment for differences in baseline clinicopathological features and treatment-related variables.
CONCLUSIONS: This study suggests that when managing primary breast salivary gland-type carcinoma, greater emphasis should be given to the tumor grade and AJCC stage group in addition to acinic cell carcinoma histological type and HER2 overexpression. Conventional prognostic factors are important as salivary gland-type carcinoma had similar prognosis as invasive carcinoma, NST, following adjustment for confounding variables.
PMID:38546966 | DOI:10.1007/s12282-024-01564-8
Curr Oncol. 2024 Mar 19;31(3):1556-1561. doi: 10.3390/curroncol31030118.
ABSTRACT
Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy. Herein, we report a case of DAP with novel genetic alterations (BCOR P1153S, ERG M219I, KDR A750E, POLE S1896P, and RAD21 T461del).
PMID:38534951 | PMC:PMC10968787 | DOI:10.3390/curroncol31030118
Anal Chem. 2024 Mar 26;96(12):4918-4924. doi: 10.1021/acs.analchem.3c05741. Epub 2024 Mar 12.
ABSTRACT
Pancreatic cancer is a highly aggressive and rapidly progressing disease, often diagnosed in advanced stages due to the absence of early noticeable symptoms. The KRAS mutation is a hallmark of pancreatic cancer, yet the underlying mechanisms driving pancreatic carcinogenesis remain elusive. Cancer cells display significant metabolic heterogeneity, which is relevant to the pathogenesis of cancer. Population measurements may obscure information about the metabolic heterogeneity among cancer cells. Therefore, it is crucial to analyze metabolites at the single-cell level to gain a more comprehensive understanding of metabolic heterogeneity. In this study, we employed a 3D-printed ionization source for metabolite analysis in both mice and human pancreatic cancer cells at the single-cell level. Using advanced machine learning algorithms and mass spectral feature selection, we successfully identified 23 distinct metabolites that are statistically significantly different in KRAS mutant human pancreatic cancer cells and mouse acinar cells bearing the oncogenic KRAS mutation. These metabolites encompass a variety of chemical classes, including organic nitrogen compounds, organic acids and derivatives, organoheterocyclic compounds, benzenoids, and lipids. These findings shed light on the metabolic remodeling associated with KRAS-driven pancreatic cancer initiation and indicate that the identified metabolites hold promise as potential diagnostic markers for early detection in pancreatic cancer patients.
PMID:38471062 | DOI:10.1021/acs.analchem.3c05741
Front Oncol. 2024 Mar 11;14:1357233. doi: 10.3389/fonc.2024.1357233. eCollection 2024.
ABSTRACT
This case report details a patient with Pancreatic Acinar Cell Carcinoma (PACC), a rare malignancy with distinctive biological and imaging features. In the absence of standardized treatment protocols for PACC, we embarked on a diagnostic journey that led to the adoption of an innovative therapeutic regimen in our institution. A 45-year-old female patient presented with a pancreatic mass, which was histologically confirmed as PACC following a biopsy. Subsequent genomic profiling revealed a high tumor mutational burden (21.4/Mb), prompting the initiation of combined immunotherapy and targeted therapy. Notably, the patient experienced a unique adverse reaction to the immunotherapy-recurrent subcutaneous soft tissue nodules, particularly in the gluteal and lower limb regions, accompanied by pain, yet resolving spontaneously. Following six cycles of the dual therapy, radiological evaluations indicated a decrease in tumor size, leading to a successful surgical excision. Over a 20-month post-surgical follow-up, the patient showed no signs of disease recurrence. This narrative adds to the existing knowledge on PACC and highlights the potential efficacy of immunotherapy in managing this challenging condition, emphasizing the importance of close monitoring for any adverse reactions.
PMID:38529379 | PMC:PMC10961464 | DOI:10.3389/fonc.2024.1357233
Rare Tumors. 2024 Mar 23;16:20363613241242397. doi: 10.1177/20363613241242397. eCollection 2024.
ABSTRACT
Mucoepidermoid carcinoma (MEC) is a common malignancy arising in the parotid gland. The diagnosis of MEC is typically based on its morphological features alone, characteristically containing mucocytes, intermediate cells and epidermoid cells. However, when cystic degeneration is diffuse, it is challenging to distinguish MEC from other benign cystic tumors. This is a case report of a 58-year-old Caucasian man who presented with a parotid mass. H&E sections of the mass reveal multiloculated cysts lined by bland-looking epithelium with only rare papillary architectures. The papillary proliferation contains mucocytes, and epidermoid cells highlighted by the p63 immunohistochemistry study. The diagnosis was confirmed by FISH result of positive MAML2 (11q21) rearrangement. Patient underwent parotidectomy and is disease-free 6 months post-surgery. MEC with cystic degeneration is a common diagnostic pitfall which can mimic many benign lesions in the salivary gland. We present a rare case with MEC with extensive cystic change, its molecular and pathologic findings and review the diagnostic features of MEC, its benign mimickers and useful tools for distinguishing these entities.
PMID:38525087 | PMC:PMC10960343 | DOI:10.1177/20363613241242397
Zhonghua Yi Xue Za Zhi. 2024 Mar 26;104(12):950-955. doi: 10.3760/cma.j.cn112137-20231008-00675.
ABSTRACT
Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.
PMID:38514344 | DOI:10.3760/cma.j.cn112137-20231008-00675
Oral Oncol. 2024 Apr;151:106762. doi: 10.1016/j.oraloncology.2024.106762. Epub 2024 Mar 20.
ABSTRACT
BACKGROUND: Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database.
METHODS: Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions.
RESULTS: A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis.
CONCLUSION: Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.
PMID:38513311 | DOI:10.1016/j.oraloncology.2024.106762
Sci Rep. 2024 Mar 19;14(1):6582. doi: 10.1038/s41598-024-57294-6.
ABSTRACT
Although pancreatic precancerous lesions are known to be related to obesity and fatty pancreatic infiltration, the mechanisms remain unclear. We assessed the role of fatty infiltration in the process of pancreatic oncogenesis and obesity. A combined transcriptomic, lipidomic and pathological approach was used to explore neoplastic transformations. Intralobular (ILF) and extralobular (ELF) lipidomic profiles were analyzed to search for lipids associated with pancreatic intraepithelial neoplasia (PanINs) and obesity; the effect of ILF and ELF on acinar tissue and the histopathological aspects of pancreatic parenchyma changes in obese (OB) and non-obese patients. This study showed that the lipid composition of ILF was different from that of ELF. ILF was related to obesity and ELF-specific lipids were correlated to PanINs. Acinar cells were shown to have different phenotypes depending on the presence and proximity to ILF in OB patients. Several lipid metabolic pathways, oxidative stress and inflammatory pathways were upregulated in acinar tissue during ILF infiltration in OB patients. Early acinar transformations, called acinar nodules (AN) were linked to obesity but not ELF or ILF suggesting that they are the first reversible precancerous pancreatic lesions to occur in OB patients. On the other hand, the number of PanINs was higher in OB patients and was positively correlated to ILF and ELF scores as well as to fibrosis. Our study suggests that two types of fat infiltration must be distinguished, ELF and ILF. ILF plays a major role in acinar modifications and the development of precancerous lesions associated with obesity, while ELF may play a role in the progression of PDAC.
PMID:38503902 | PMC:PMC10951200 | DOI:10.1038/s41598-024-57294-6
Mod Pathol. 2024 Mar 18:100474. doi: 10.1016/j.modpat.2024.100474. Online ahead of print.
ABSTRACT
Recurrent gene fusions have been observed in epithelioid and myxoid variants of uterine leiomyosarcoma. PGR::NR4A3 fusion was recently described in a subset of epithelioid leiomyosarcomas exhibiting rhabdoid morphology. In this study, we sought to expand the clinical, morphologic, immunohistochemical, and genetic features of gynecologic leiomyosarcomas harboring NR4A3 rearrangement with PGR and novel fusion partners. We identified 9 gynecologic leiomyosarcomas harboring PGR::NR4A3, CARMN::NR4A3, ACTB::NR4A3, and possible SLCO5A1::NR4A3 fusions by targeted RNA sequencing. Tumors frequently affected premenopausal women, involving the uterine corpus, uterine cervix, or pelvis. All were similarly characterized by lobules of monomorphic epithelioid and/or spindled cells arranged in sheets, cords, trabeculae, and micro-and macro-cysts associated with abundant myxoid matrix and hemorrhage, creating a labyrinth-like or pulmonary edema-like architecture. Myogenic differentiation with frequent ER and PR staining and no CD10 expression characterized all tumors. All cases showed high NR4A3 RNA expression levels and NOR1 (NR4A3) nuclear staining similar to salivary gland acinic cell carcinoma and a subset of extraskeletal myxoid chondrosarcomas harboring NR4A3 rearrangement. NOR1 (NR4A3) immunohistochemistry may serve as a useful diagnostic marker of NR4A3 fusion-positive gynecologic leiomyosarcomas.
PMID:38508521 | DOI:10.1016/j.modpat.2024.100474
Head Neck Pathol. 2024 Mar 19;18(1):20. doi: 10.1007/s12105-024-01622-9.
ABSTRACT
BACKGROUND: Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma (AciCC), oncocytic mucoepidermoid carcinoma (OMEC), intraductal carcinoma, and epithelial myoepithelial carcinoma (EMC). This review investigates the differential diagnosis of oncocytoid salivary tumors and explore the role of newly described immunostains as valuable tools for their diagnosing and potentially guiding treatment options.
METHODS: We assess the utility of incorporating new immunohistochemical markers in routine practice to aid in diagnosing oncocytoid salivary tumors and potentially provide treatment options.
RESULTS: In SDC, AR and Her2 immunostains are utilized as diagnostic tools and biomarkers for selecting patients who might benefit from Androgen-deprivation therapy (ADT) and HER2-targeted therapy. Furthermore, nuclear Pan-Trk immunostaining can aid in diagnosing SC. Additionally, NR4A3 immunostaining has been shown high sensitivity and specificity in identifying AciCC in both surgical and cytologic specimens. Similarly, RAS Q61R mutant-specific immunostaining, detected in EMC, may offer a cost-effective diagnostic marker for this tumor. Although further studies are required to evaluate the role of BSND, this marker has been reported to be positive in Warthin tumor and oncocytoma, aiding in differentiating them from other oncocytoid tumors, particularly OMEC. In addition, BRAFV600E mutant-specific immunostaining can serve as a diagnostic and potentially therapeutic marker for oncocytic intraductal carcinoma in mutation positive cases.
CONCLUSION: Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.
PMID:38502259 | PMC:PMC10951193 | DOI:10.1007/s12105-024-01622-9
Int J Clin Oncol. 2024 Jun;29(6):755-763. doi: 10.1007/s10147-024-02505-3. Epub 2024 Mar 16.
ABSTRACT
BACKGROUND: Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited.
METHODS: We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx.
RESULTS: We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC.
CONCLUSIONS: This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.
PMID:38492066 | PMC:PMC11130055 | DOI:10.1007/s10147-024-02505-3
Urol Oncol. 2024 May;42(5):144-154. doi: 10.1016/j.urolonc.2024.01.037. Epub 2024 Mar 13.
ABSTRACT
Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.
PMID:38485644 | DOI:10.1016/j.urolonc.2024.01.037
Cancer Lett. 2024 Apr 1;586:216611. doi: 10.1016/j.canlet.2024.216611. Epub 2024 Feb 1.
ABSTRACT
Pancreatic cancer (PC) is one of the most malignant and deadly tumors of digestive system with complex etiology and pathogenesis. Dysregulations of oncogenes and tumor suppressors due to epigenetic modifications causally affect tumorogenesis; however the key tumor suppressors and their regulations in PC are only partially defined. In this study, we found that Claudin-1 (encoded by CLDN1 gene) was significantly suppressed in PC that correlated with a poor clinical prognosis. Claudin-1 knockdown enhanced PC cell proliferation, migration, and stemness. Pancreatic specific Cldn1 knockout in KPC (LSLKrasG12D/Pdx1-Cre/Trp53R172H+) and KC (LSLKrasG12D/Pdx1-Cre) mice reduced mouse survival, promoted acinar-to-ductal metaplasia (ADM) process, and accelerated the development of pancreatic intraepithelial neoplasia (PanIN) and PC. Further investigation revealed that Claudin-1 suppression was mainly caused by aberrant DNA methylatransferase 1 (DNMT1) and DNMT3A elevations and the resultant CLDN1 promoter hypermethylation, as a DNMT specific inhibitor SGI-1027 effectively reversed the Claudin-1 suppression and inhibited PC progression both in vitro and in vivo in a Claudin-1 preservation-dependent manner. Together, our data suggest that Claudin-1 functions as a tumor suppressor in PC and its epigenetic suppression due to DNMT aberrations is a crucial event that promotes PC development and progression.
PMID:38309617 | DOI:10.1016/j.canlet.2024.216611
J Neurosurg Case Lessons. 2024 Mar 11;7(11):CASE2476. doi: 10.3171/CASE2476. Print 2024 Mar 11.
ABSTRACT
BACKGROUND: Acinic cell carcinomas (AcCCs), rare malignancies of the salivary glands, often recur and metastasize, particularly in the skull base. Conventional radical resection can be invasive for skull base AcCCs adjacent to cranial nerves and major vasculature, and the effectiveness of stereotactic radiosurgery (SRS) as an alternative is not well established.
OBSERVATIONS: This case report details the application of SRS for recurrent skull base AcCCs. A 71-year-old male with a history of resection for a right mandibular AcCC 23 years earlier experienced tumor recurrence involving the right cavernous sinus and nasal cavity. He underwent endoscopic transnasal surgery followed by SRS targeting different tumor locations-the cavernous sinus to the pterygopalatine fossa, maxillary sinus, and clivus-each with a prescribed dose of 20 Gy to the 40% to 50% isodose line. After the first skull base metastasis, additional sessions of localized SRS after endoscopic surgery led to a 12-year survival without sequela.
LESSONS: This is a report indicating that SRS for skull base AcCCs can achieve favorable local control, functional preservation, and long-term survival. SRS may be suitable for skull base AcCC given the lesion's tendency toward multiple local recurrences. Further investigation is needed to validate the treatment's efficacy.
PMID:38467040 | PMC:PMC10936940 | DOI:10.3171/CASE2476
Pathol Res Pract. 2024 Apr;256:155175. doi: 10.1016/j.prp.2024.155175. Epub 2024 Jan 28.
ABSTRACT
Cadherin-17 (CDH17) is a membranous cell adhesion protein predominantly expressed in intestinal epithelial cells. CDH17 is therefore considered a possible diagnostic and therapeutic target. This study was to comprehensively determine the expression of CDH17 in cancer and to further assess the diagnostic utility of CDH17 immunohistochemistry (IHC). A tissue microarray containing 14,948 interpretable samples from 150 different tumor types and subtypes as well as 76 different normal tissue types was analyzed by IHC. In normal tissues, a membranous CDH17 staining was predominantly seen in the epithelium of the intestine and pancreatic excretory ducts. In tumors, 53 of 150 analyzed categories showed CDH17 positivity including 26 categories with at least one strongly positive case. CDH17 positivity was most common in epithelial and neuroendocrine colorectal neoplasms (50.0%-100%), other gastrointestinal adenocarcinomas (42.7%-61.6%), mucinous ovarian cancer (61.1%), pancreatic acinar cell carcinoma (28.6%), cervical adenocarcinoma (52.6%), bilio-pancreatic adenocarcinomas (40.5-69.8%), and other neuroendocrine neoplasms (5.6%-100%). OnIy 9.9% of 182 pulmonary adenocarcinomas were CDH17 positive. In colorectal adenocarcinomas, reduced CDH17 staining was linked to high pT (p = 0.0147), nodal metastasis (p = 0.0041), V1 (p = 0.0025), L1 (p = 0.0054), location in the right colon (p = 0.0033), and microsatellite instability (p < 0.0001). The CDH17 expression level was unrelated to tumor phenotype in gastric and pancreatic cancer. In summary, our comprehensive overview on CDH17 expression in human tumors identified various tumor entities that might often benefit from anti-CDH17 therapies and suggest utility of CDH17 IHC for the distinction of metastatic gastrointestinal or bilio-pancreatic adenocarcinomas (often positive) from primary pulmonary adenocarcinomas (mostly negative).
PMID:38452580 | DOI:10.1016/j.prp.2024.155175
Ann Diagn Pathol. 2024 Jun;70:152283. doi: 10.1016/j.anndiagpath.2024.152283. Epub 2024 Feb 24.
ABSTRACT
INTRODUCTION: Primary pulmonary salivary gland-type tumours (PPSGT) are rare lung neoplasms arising from submucosal seromucinous glands in the central airway.
METHODS AND RESULTS: We retrospectively analysed the clinicopathological features of 111 PPSGTs diagnosed at our institute between 2003 and 2021. The mean age at diagnosis was 43.8 years(range 6-78 years) and a male-to-female ratio of 2:1. On imaging, 92 % of cases had centrally located tumours and 37.3 % were early stage. The histopathological types included 70 cases (63 %) of mucoepidermoid carcinoma (MEC), 31 cases (27.7 %) of adenoid cystic carcinoma (ADCC), two cases of myoepithelial carcinoma, one case each of acinic cell carcinoma (ACC), clear cell carcinoma (CCC), epithelial myoepithelial carcinoma (EMC) and 5 others [including adenocarcinoma of minor salivary gland origin(n = 3), carcinoma with sebaceous differentiation(n = 1) and poorly differentiated carcinoma of salivary gland type(n = 1)]. The size of the tumours found in the resection specimens ranged from 1 cm to 13 cm, with an average size of 4.9 cm. High-risk attributes such as lymphovascular invasion (LVI), perineural invasion (PNI), pleural involvement, positive resection margins, and nodal metastasis were identified in 15.3 %, 15.3 %, 13.6 %,15.2 % and 6.7 % of cases, respectively. These attributes were found to be more frequent in ADCC than in MEC. Surgery was the main treatment modality [68/84 (80 %) cases]. ADCC cases had more recurrence and distant metastasis than MEC cases. The 3- year overall-survival (OS) and recurrence-free survival(RFS) were better in patients with age lesser than 60 years(p-value <0.0001), low pT stage (p-value 0.00038) and lower grade of MEC(p-value-0.0067).
CONCLUSION: It is crucial to have an acquaintance with the morphologic spectrum and immunophenotypic characteristics of PPSGT to recognize them in this unusual location. In tandem, it is crucial to differentiate them from conventional primary non-small cell lung carcinoma, as the management protocols and prognostic implications differ significantly.
PMID:38447254 | DOI:10.1016/j.anndiagpath.2024.152283