ERG Protein Expression in Prostatic Adenocarcinoma and Its Clinicopathological Features

Posted: April 1st, 2021, 2:00pm GMT

Condition: Prostate Adenocarcinoma
Intervention: Diagnostic Test: Immunohistochemistry of prostate biopsy
Sponsor: Assiut University
Not yet recruiting

Google - Acinic Cell Carcinoma

Types of Head and Neck Cancer - CU Anschutz Today

Posted: May 27th, 2021, 9:51pm GMT

Types of Head and Neck Cancer CU Anschutz Today
[Full text] Expression analysis of MIST1 and EMT markers - IJGM | IJGM - Dove Medical Press

Posted: April 13th, 2021, 7:17pm GMT

Expression analysis of MIST1 and EMT markers - IJGM | IJGM Dove Medical Press
A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience - The Oncologist

Posted: March 9th, 2021, 6:00am GMT

A Challenging Task: Identifying Patients with Cancer of Unknown Primary (CUP) According to ESMO Guidelines: The CUPISCO Trial Experience The Oncologist
Submandibular Gland: Anatomy, Function, and Treatment - Verywell Health

Posted: February 28th, 2021, 1:15am GMT

Submandibular Gland: Anatomy, Function, and Treatment Medically reviewed by Benjamin F. Asher, MD Verywell Health
Please Help Jim Lambert Fight Cancer - Sierra Wave: Eastern Sierra NewsSierra Wave: Eastern Sierra News - Sierra Wave

Posted: January 19th, 2021, 6:00am GMT

Please Help Jim Lambert Fight Cancer - Sierra Wave: Eastern Sierra NewsSierra Wave: Eastern Sierra News Sierra Wave
Westside football's Malik Stowers is still cancer-free and weighing college options - Independent Mail

Posted: December 21st, 2020, 6:00am GMT

Westside football's Malik Stowers is still cancer-free and weighing college options Independent Mail
Norris Burkes | Who’s your BFF? - Vacaville Reporter

Posted: October 3rd, 2020, 5:00am GMT

Norris Burkes | Who’s your BFF? Vacaville Reporter
Findings support adjuvant radiotherapy in cSCC with perineural invasion - Healio

Posted: August 12th, 2020, 5:00am GMT

Findings support adjuvant radiotherapy in cSCC with perineural invasion Healio
A Preliminary Study of CT Texture Analysis for Characterizing Epitheli | CMAR - Dove Medical Press

Posted: April 21st, 2020, 5:00am GMT

A Preliminary Study of CT Texture Analysis for Characterizing Epitheli | CMAR Dove Medical Press
The Role of Prognostic Factors in Salivary Gland Tumors Treated by Sur | CMAR - Dove Medical Press

Posted: February 11th, 2020, 6:00am GMT

The Role of Prognostic Factors in Salivary Gland Tumors Treated by Sur | CMAR Dove Medical Press
Microcystic adnexal carcinoma guidelines encourage high-quality care - Healio

Posted: July 24th, 2019, 5:00am GMT

Microcystic adnexal carcinoma guidelines encourage high-quality care Healio
Treating Acinic Cell Carcinoma - News-Medical.net

Posted: June 18th, 2019, 5:00am GMT

Treating Acinic Cell Carcinoma News-Medical.net
Hingham Middle School rides to support teacher with cancer - Wicked Local Hingham

Posted: June 12th, 2019, 5:00am GMT

Hingham Middle School rides to support teacher with cancer Wicked Local Hingham
Stage 4 pancreatic cancer survivor shares inspiring story - KTRK-TV

Posted: May 18th, 2019, 5:00am GMT

Stage 4 pancreatic cancer survivor shares inspiring story KTRK-TV
Mercedes-Benz Fashion Week: Robyn Lawley takes to runway after dad's death - Daily Telegraph

Posted: May 12th, 2019, 5:00am GMT

Mercedes-Benz Fashion Week: Robyn Lawley takes to runway after dad's death Daily Telegraph
Westside football player Malik Stowers remains positive in his battle against cancer - Anderson Independent Mail

Posted: May 1st, 2019, 5:00am GMT

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Community raises 20,000 for Hingham teacher with cancer - Wicked Local Hingham

Posted: March 5th, 2019, 6:00am GMT

Community raises 20,000 for Hingham teacher with cancer Wicked Local Hingham
Dunstable author hopes Sunny Days will inspire others - Dunstable Today

Posted: February 26th, 2019, 6:00am GMT

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Adjuvant radiation improves survival in advanced squamous cell carcinoma with certain features - Healio

Posted: February 11th, 2019, 6:00am GMT

Adjuvant radiation improves survival in advanced squamous cell carcinoma with certain features Healio
Award Acknowledges Licensing and Development Partnership Labmate Online - Labmate Online

Posted: January 26th, 2019, 6:00am GMT

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EP. 1: Understanding Tropomyosin Receptor Kinase Inhibitors - OncLive

Posted: June 25th, 2018, 5:00am GMT

EP. 1: Understanding Tropomyosin Receptor Kinase Inhibitors OncLive
Surgical margin should guide adjuvant radiation use for osteosarcomas of head and neck - Healio

Posted: November 10th, 2017, 6:00am GMT

Surgical margin should guide adjuvant radiation use for osteosarcomas of head and neck Healio
Minimally invasive endoscopic resection for the treatment of sinonasal | TCRM - Dove Medical Press

Posted: May 3rd, 2017, 5:00am GMT

Minimally invasive endoscopic resection for the treatment of sinonasal | TCRM Dove Medical Press
Thyroid tumor: It takes two to tango - Science Daily

Posted: August 8th, 2016, 5:00am GMT

Thyroid tumor: It takes two to tango Science Daily
Colorado Springs man looking to cross country, globe before he dies - Colorado Springs Gazette

Posted: June 14th, 2016, 5:00am GMT

Colorado Springs man looking to cross country, globe before he dies Colorado Springs Gazette
No nobility in cold-bloodedness – The Manila Times - The Manila Times

Posted: January 19th, 2016, 6:00am GMT

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Turning on the thyroid: Researchers determine mechanism that triggers normal and abnormal hormone production - Science Daily

Posted: January 8th, 2016, 6:00am GMT

Turning on the thyroid: Researchers determine mechanism that triggers normal and abnormal hormone production Science Daily
Treatment Strategies With NTRK Gene Rearrangements Emerge in Lung and Other Solid Tumors - Targeted Oncology

Posted: September 3rd, 2015, 5:00am GMT

Treatment Strategies With NTRK Gene Rearrangements Emerge in Lung and Other Solid Tumors Targeted Oncology
Parotid Tumors in Children | American Academy of Pediatrics - AAP Grand Rounds

Posted: February 1st, 2014, 6:00am GMT

Parotid Tumors in Children | American Academy of Pediatrics AAP Grand Rounds
First gene therapy study in human salivary gland shows promise - Science Daily

Posted: November 5th, 2012, 6:00am GMT

First gene therapy study in human salivary gland shows promise Science Daily
Cancer scare gives Bears' Podlesh whole new outlook - nwitimes.com

Posted: November 12th, 2011, 6:00am GMT

Cancer scare gives Bears' Podlesh whole new outlook nwitimes.com
Research and Markets: Salivary Gland Cytology: A Color Atlas - Business Wire

Posted: June 8th, 2011, 5:00am GMT

Research and Markets: Salivary Gland Cytology: A Color Atlas Business Wire
Obstacles and consistency written into Tim Sirk's legacy - KPCnews.com

Posted: March 26th, 2010, 5:00am GMT

Obstacles and consistency written into Tim Sirk's legacy KPCnews.com
Molecular Imaging Holds Promise For Early Intervention In Common Uterine Cancer - Science Daily (press release)

Posted: October 1st, 2009, 5:00am GMT

Molecular Imaging Holds Promise For Early Intervention In Common Uterine Cancer Science Daily (press release)

PubMed - Acinic Cell Carcinoma

NOR-1 immunostain is a good method to confirm the diagnosis of an oral acinic cell carcinoma

Fetched: June 19th, 2021, 5:00am GMT by Ying-Tai Jin

J Dent Sci. 2021 Jul;16(3):1030-1032. doi: 10.1016/j.jds.2020.11.012. Epub 2020 Dec 9.

NO ABSTRACT

PMID:34141123 | PMC:PMC8189867 | DOI:10.1016/j.jds.2020.11.012
Secretory carcinoma of salivary gland origin: A recently established masquerader

Fetched: June 9th, 2021, 5:00am GMT by Shilpi Budhiraja

Indian J Cancer. 2021 Apr-Jun;58(2):278-284. doi: 10.4103/ijc.IJC_274_20.

ABSTRACT

Secretory carcinoma (SC) of the salivary gland is considered to be a low-intermediate grade tumor with the potential of locally aggressive behavior. This tumor is similar both genetically (ETV6-NTRK3 fusion) and histologically to secretory carcinoma of the breast. We intent to share our experience of four cases of SC in terms of clinical behavior, pathological features, and treatment outcome. Medical records of four cases of SC were retrieved and analyzed for clinical presentation, surgical treatment, and outcome. Pathological data was reanalyzed along with immunohistochemistry. Out of the four identified SC cases, three were men. Two lesions originated from the parotid gland and two from minor salivary glands. Two of these cases exhibited features of locally aggressive pattern. SC of salivary gland origin has distinct histological and immunohistochemical features apart from the characteristic genetic translocation and fusion. Surgery with or without adjuvant radiotherapy is the treatment of choice. To establish the biological behavior of this tumor, larger case series with long-term follow-up is desirable.

PMID:34100414 | DOI:10.4103/ijc.IJC_274_20
Mucoacinar Carcinoma: A Rare Variant of Mucoepidermoid Carcinoma

Fetched: June 7th, 2021, 5:00am GMT by Manish Bundele

Am J Surg Pathol. 2021 Jun 7. doi: 10.1097/PAS.0000000000001752. Online ahead of print.

ABSTRACT

Mucoepidermoid carcinoma (MEC) is generally characterized by an admixture of mucous, epidermoid and intermediate type cells. Numerous variants morphologies are described and defined by stromal and/or cytoplasmic tinctorial characteristics. We now report 11 cases of MEC with serous acinar differentiation, reflecting a distal intercalated duct/acinar phenotype, which we designate as mucoacinar carcinomas. Seven patients were female while 4 were male with a mean age of 55 years (range: 21 to 72 y). Ten cases were from the parotid while 1 was from the submandibular gland. Mean size of the tumors was 1.8 cm (range: 0.7 to 4.5 cm). Three cases were low grade, 7 were intermediate grade, and 1 was high grade. Low to intermediate grade cases demonstrated prominent clear to vacuolated cells with focal serous acinar differentiation. The high-grade case showed a distinctive scattering of acinar cells interspersed between epidermoid cells. Periodic acid Schiff after diastase (9/9), SOX-10 (9/9), and DOG-1 (9/10) highlighted the acinar component. Six of 7 cases showed a focal acinar predominant NR4A3 expression. MAML2 fluorescence in situ hybridization was positive in all cases, in both acinar and mucoepidermoid components. Two cases tested by next generation sequencing showed standard CRTC1-MAML2 fusions. MSANTD3 and NR4A3 fluorescence in situ hybridization on the other hand were negative. Evidence thus suggests that mucoacinar carcinoma represents an acinar variant morphology in MEC, rather than a true MEC-acinic cell carcinoma hybrid, or collision tumor. The acinar differentiation, SOX-10, DOG-1, and even focal NR4A3 reactivity may thus be diagnostic pitfalls.

PMID:34091485 | DOI:10.1097/PAS.0000000000001752
Canine Gastric Carcinomas: A Histopathological and Immunohistochemical Study and Similarities with the Human Counterpart

Fetched: June 3rd, 2021, 5:00am GMT by Alexandros Hardas

Animals (Basel). 2021 May 14;11(5):1409. doi: 10.3390/ani11051409.

ABSTRACT

Canine gastric carcinoma (CGC) affects both sexes in relatively equal proportions, with a mean age of nine years, and the highest frequency in Staffordshire bull terriers. The most common histological subtype in 149 CGC cases was the undifferentiated carcinoma. CGCs were associated with increased chronic inflammation parameters and a greater chronic inflammatory score when Helicobacter spp. were present. Understanding the molecular pathways of gastric carcinoma is challenging. All markers showed variable expression for each subtype. Expression of the cell cycle regulator 14-3-3σ was positive in undifferentiated, tubular and papillary carcinomas. This demonstrates that 14-3-3σ could serve as an immunohistochemical marker in routine diagnosis and that mucinous, papillary and signet-ring cell (SRC) carcinomas follow a 14-3-3σ independent pathway. p16, another cell cycle regulator, showed increased expression in mucinous and SRC carcinomas. Expression of the adhesion molecules E-cadherin and CD44 appear context-dependent, with switching within tumor emboli potentially playing an important role in tumor cell survival, during invasion and metastasis. Within neoplastic emboli, acinar structures lacked expression of all markers, suggesting an independent molecular pathway that requires further investigation. These findings demonstrate similarities and differences between dogs and humans, albeit further clinicopathological data and molecular analysis are required.

PMID:34069167 | PMC:PMC8156491 | DOI:10.3390/ani11051409
PD-L1 expression and its clinicopathologic and genomic correlation in the non-small cell lung carcinoma patients: An Indian perspective

Fetched: June 1st, 2021, 5:00am GMT by Ekta Jain

Pathol Res Pract. 2021 May 24:153497. doi: 10.1016/j.prp.2021.153497. Online ahead of print.

ABSTRACT

BACKGROUND: Immunotherapy with checkpoint inhibitor programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies targeting the cellular immune checkpoints is the present area of interest showing promising results in patients with advanced non-small cell lung cancer (NSCLC). As there is paucity of PD-L1 expression data from the Indian perspective, we studied the correlation of clinicopathologic profile and oncogenic driver mutations in these patients.

MATERIALS AND METHODS: Samples from 252 advanced NSCLCs patients were studied for PD-L1 expression through immunohistochemistry using rabbit anti-human PD-L1 monoclonal antibody (clone SP263) on Ventana BenchMark ULTRA autostainer. Simultaneously, genetic mutations were studied by next generation sequencing (for EGFR, ALK, ROS, MET, and BRAF). PD-L1 expression was analyzed for association with clinicopathologic features and various mutations.

RESULTS: PD-L1 positivity was seen in 134 patients (53.2 %). It was twice more prevalent in males than females. No significant correlation was observed between PD-L1 expression with age, gender, site of testing (primary vs. metastatic tumors), smoking status, tumor laterality, stage, or histologic type; however, there was significant difference among solid and acinar types of adenocarcinoma combined together vs. other adenocarcinoma subtypes (p = 0.013), and well and moderately differentiated vs. poorly differentiated tumors (p = 0.022). When types/extent of PD-L1 positivity (≥25 %) were compared with demographics, clinical, and pathologic variables, significant differences were observed across the tumor grades (high-grade vs. low-grade) (p = 0.009) and stages (p = 0.039). The PD-L1 expression failed to demonstrate any statistical significance with oncogenic drivers. High PD-L1 expression (TPS ≥ 50) was observed in 27.6 % patients, and it was more prevalent in female patients (32.4 %), aged ≥60 years (33.8 %), smokers (27.3 %), poorly differentiated (36.8 %) and stage IV tumors (28.2 %). Exon 19 deletion was more prevalent in PD-L1 negative tumors whereas exon 21 substitution (L858R) was seen more in PD-L1 positive tumors.

CONCLUSIONS: This is the largest Indian study demonstrating PD-L1 expression in NSCLC patients comparing with clinicopathologic and genomic parameters. PD-L1 expression was significantly associated with high-grade, solid, and acinar types of adenocarcinoma and advanced tumors. High PD-L1 expression was more prevalent in female patients, aged ≥60 years, smokers, and poorly differentiated and stage IV tumors (28.2 %). Exon 19 deletion was more in PD-L1 negative tumors whereas exon 21 substitution (L858R) was more in PD-L1 positive tumors. PD-L1 is a potential predictive marker stratifying patients who benefit from PD-1 pathway-targeted therapy.

PMID:34053784 | DOI:10.1016/j.prp.2021.153497
A case of a synchronous double cancer patient with pancreatic cancer, found during a full body examination and triggered by acinar cell carcinoma of the upper lip

Fetched: May 28th, 2021, 5:00am GMT by Mika Saito

Nihon Ronen Igakkai Zasshi. 2021;58(2):290-296. doi: 10.3143/geriatrics.58.290.

ABSTRACT

Acinar cell carcinoma is a tumor characterized by the proliferation of cells that resemble serous acinar cells. It accounts for 1% of all salivary gland tumors, with 90% or more of these tumors frequently occurring in the parotid gland and rarely occurring in the small salivary glands. This time, we experienced a patient suffering from synchronous double cancer, found during a full body examination and triggered by acinar cell carcinoma of the upper lip. The case involved a 76-year-old woman, with a chief complaint of swelling of her right upper lip. She became aware of the swelling of her right upper lip in May 2017, and due to a gradual increase in the size thereof, she visited our department in December. Eight days after her initial consultation, a total biopsy was performed under local anesthesia, upon which the patient was diagnosed with acinar cell carcinoma. In January 2018, we asked our otolaryngologist to conduct a close examination of the parotid gland. Although computed tomography indicated no problems with the parotid gland, pancreatic head cancer was suspected. She visited the Department of Gastroenterology at our hospital in February and was diagnosed with pancreatic cancer (stage IVb) by an endoscopic biopsy in March. Chemotherapy was initiated the same month, but she died in January 2020.

PMID:34039806 | DOI:10.3143/geriatrics.58.290
A Review Leveraging a Rare and Unusual Case of Basal Cell Carcinoma of the Prostate

Fetched: May 27th, 2021, 5:00am GMT by Lin He

Case Rep Pathol. 2021 May 4;2021:5520581. doi: 10.1155/2021/5520581. eCollection 2021.

ABSTRACT

Basal cell carcinoma (BCC) is a rare nonacinar variant of prostatic carcinoma. In spite of prostatic acinar adenocarcinoma being one of the most common carcinomas in prostate, <100 prostatic BCC cases have been reported to date. Adenoid cystic/cribriform histology has been described in varying proportions to occur in prostatic BCC and is reported to be associated with aggressive behavior and high risk of metastasis. Herein, we present a case of prostatic BCC with adenoid cystic morphology, comprehensively describe its immunohistochemical and MYB/MYBL1 gene rearrangement findings, discuss its differential diagnosis, and review the literature of this rare entity.

PMID:34035971 | PMC:PMC8116143 | DOI:10.1155/2021/5520581
Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes

Fetched: May 25th, 2021, 5:00am GMT by Vishwajith Sridharan

Pancreatology. 2021 May 15:S1424-3903(21)00162-9. doi: 10.1016/j.pan.2021.05.011. Online ahead of print.

ABSTRACT

BACKGROUND: Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series.

METHODS: This is a retrospective study conducted at a large healthcare system from 1996 to 2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test.

RESULTS: Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery was associated with improved survival in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy showed OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006).

CONCLUSION: Pancreatic ACC patients often present with advanced disease. Surgery was associated with survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.

PMID:34023183 | DOI:10.1016/j.pan.2021.05.011
High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance

Fetched: May 20th, 2021, 5:00am GMT by Alena Skalova

Adv Anat Pathol. 2021 Mar 17. doi: 10.1097/PAP.0000000000000298. Online ahead of print.

ABSTRACT

High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.

PMID:34009780 | DOI:10.1097/PAP.0000000000000298
NR4A3 (NOR-1) Immunostaining Shows Better Performance than DOG1 Immunostaining in Acinic Cell Carcinoma of Salivary Gland: a Preliminary Study

Fetched: May 8th, 2021, 5:00am GMT by Adepitan Owosho

J Oral Maxillofac Res. 2021 Mar 31;12(1):e4. doi: 10.5037/jomr.2021.12104. eCollection 2021 Jan-Mar.

ABSTRACT

OBJECTIVES: Acinic cell carcinoma of salivary gland harbours recurrent and specific chromosomal rearrangement [t(4;9)(q13;q31)], resulting in the translocation of secretory calcium-binding phosphoprotein gene cluster at 4q13 to nuclear receptor subfamily 4 group a member 3 at 9q31. This upregulates the transcription factor nuclear receptor subfamily 4 group A member 3, which can be detected by immunohistochemistry. The purpose of this pilot study is to evaluate the performance of nuclear receptor subfamily 4 group A member 3 immunostaining on whole-slide acinic cell carcinoma tissue, in comparison with discovered on GIST-1 immunostaining.

MATERIAL AND METHODS: We retrieved 6 cases of acinic cell carcinoma (AciCC), including 5 conventional low-grade and 1 dedifferentiated high-grade. Immunohistochemistry (IHC) for nuclear receptor subfamily 4 group A member 3 (NR4A3) and discovered on GIST-1 (DOG1) were performed at the University of Pittsburgh Medical Centre in Pittsburgh, Pennsylvania on all retrieved cases.

RESULTS: The result shows that NR4A3 IHC shows better performance than DOG1 IHC: 5 of the 6 (83.3%) AciCC cases (including the dedifferentiated high-grade) demonstrated strong diffuse nuclear staining for NR4A3, also five AciCC cases (including the dedifferentiated high-grade) demonstrated weak to moderate membranous staining with variable distribution for DOG1. Moreover, only 3 (50%) cases showed complete membranous staining with DOG1.

CONCLUSIONS: This pilot study showed that nuclear receptor subfamily 4 group A member 3 immunostaining is a sensitive marker for acinic cell carcinoma and of better utility than discovered on GIST-1 immunostaining in making a diagnosis of acinic cell carcinoma.

PMID:33959239 | PMC:PMC8085676 | DOI:10.5037/jomr.2021.12104
Identification and characterization of primary cilia-positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation

Fetched: May 2nd, 2021, 5:00am GMT by Kazuya Shinmura

J Pathol. 2021 Apr 30. doi: 10.1002/path.5688. Online ahead of print.

ABSTRACT

Primary cilia (PC) are non-motile, antenna-like structures on the cell surface. Many types of neoplasms exhibit PC loss, whereas in some neoplasms PC are retained and involved in tumourigenesis. To elucidate the PC status and characteristics of major salivary gland tumours (SGTs), we examined 100 major SGTs encompassing eight histopathological types by immunohistochemical analysis. PC were present in all (100%) of the pleomorphic adenomas (PAs), basal cell adenomas (BCAs), adenoid cystic carcinomas (AdCCs), and basal cell adenocarcinomas (BCAcs) examined, but absent in all (0%) of the Warthin tumours, salivary duct carcinomas, mucoepidermoid carcinomas, and acinic cell carcinomas examined. PC were also detected by electron-microscopic analysis using the NanoSuit method. It is worthy of note that the former category and latter category of tumours contained and did not contain a basaloid/myoepithelial differentiation component, respectively. The four types of PC-positive SGTs showed longer PC than normal and exhibited a characteristic distribution pattern of the PC in the ductal and basaloid/neoplastic myoepithelial components. Two PC-positive carcinomas (AdCC and BCAc) still possessed PC in their recurrent/metastatic sites. Interestingly, activation of the Hedgehog signalling pathway, shown by predominantly nuclear GLI1 expression, was significantly more frequently observed in PC-positive SGTs. Finally, we identified tau tubulin kinase 2 (TTBK2) as being possibly involved in the production of PC in SGTs. Taken together, our findings indicate that SGTs that exhibit basaloid/myoepithelial differentiation (PA, BCA, AdCC, and BCAc) are ciliated, and their PC exhibit tumour-specific characteristics, are involved in activation of the Hedgehog pathway, and are associated with TTBK2 upregulation, providing a significant and important link between SGT tumourigenesis and PC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID:33931860 | DOI:10.1002/path.5688
Hypoglycemia and seizures associated with canine primary hepatic neuroendocrine carcinoma

Fetched: April 27th, 2021, 5:00am GMT by Amanda R Dorn

J Vet Diagn Invest. 2021 Apr 26:10406387211012378. doi: 10.1177/10406387211012378. Online ahead of print.

ABSTRACT

A 10-y-old intact male Labrador Retriever dog had a history of ataxia, inability to stand, and grand mal seizures. Complete blood count and serum biochemistry profiles revealed profound hypoglycemia, mildly increased alanine aminotransferase (ALT) activity, mild hypernatremia, and lymphopenia. The seizures could not be controlled with intravenous dextrose, diazepam, or propofol. The dog was euthanized given poor quality of life, and an autopsy was performed. Primary autopsy findings included firm hepatic masses that ranged from dark-red to tan, with the largest ~1.5 cm diameter, and pulmonary edema. Histologic examination of the hepatic masses revealed redundant, several-cell-thick cords, and packeted or acinar arrangements of polygonal cells, supported on a fibrovascular stroma. The neoplastic cells were immunopositive for insulin, synaptophysin, and neuron-specific enolase immunohistochemistry; granules in the tumor cells had an affinity for Grimelius silver stain. The histologic features, as well as the immunohistochemical staining profile, identified the neoplasm as a primary multifocal hepatic neuroendocrine carcinoma. Neuroendocrine carcinomas are rare in dogs and usually occur in the gastrointestinal or respiratory tract.

PMID:33899610 | DOI:10.1177/10406387211012378
Comparative metabolomics studies of blood collected in streck and heparin tubes from lung cancer patients

Fetched: April 24th, 2021, 5:00am GMT by Erin Goldberg

PLoS One. 2021 Apr 23;16(4):e0249648. doi: 10.1371/journal.pone.0249648. eCollection 2021.

ABSTRACT

Metabolomics analysis of blood from patients (n = 42) undergoing surgery for suspected lung cancer was performed in this study. Venous and arterial blood was collected in both Streck and Heparin tubes. A total of 96 metabolites were detected, affected by sex (n = 56), collection tube (n = 33), and blood location (n = 8). These metabolites belonged to a wide array of compound classes including lipids, acids, pharmaceutical agents, signalling molecules, vitamins, among others. Phospholipids and carboxylic acids accounted for 28% of all detected compounds. Out of the 33 compounds significantly affected by collection tube, 18 compounds were higher in the Streck tubes, including allantoin and ketoleucine, and 15 were higher in the Heparin tubes, including LysoPC(P-16:0), PS 40:6, and chenodeoxycholic acid glycine conjugate. Based on our results, it is recommended that replicate blood samples from each patient should be collected in different types of blood collection tubes for a broader range of the metabolome. Several metabolites were found at higher concentrations in cancer patients such as lactic acid in Squamous Cell Carcinoma, and lysoPCs in Adenocarcinoma and Acinar Cell Carcinoma, which may be used to detect early onset and/or to monitor the progress of the cancer patients.

PMID:33891605 | PMC:PMC8064553 | DOI:10.1371/journal.pone.0249648
Utility of an immunocytochemical analysis for pan-Trk in the cytodiagnosis of secretory carcinoma of the salivary gland

Fetched: April 23rd, 2021, 5:00am GMT by Hiroko Ito

Diagn Cytopathol. 2021 Apr 22. doi: 10.1002/dc.24750. Online ahead of print.

ABSTRACT

Secretory carcinoma (SC) of the salivary gland is a rare distinct clinicopathological entity characterized by the presence of the ETV6-NTRK3 fusion. Although the characteristic cytological features of SC have been recognized, its cytodiagnosis, especially differentiating SC from acinic cell carcinoma, is challenging. Recent studies have revealed that immunohistochemistry for pan-tyrosine receptor kinase (Trk) and nuclear receptor subfamily 4 group member 3 (NR4A3) are specific for SC and acinic cell carcinoma, respectively. However, the usefulness of immunocytochemical detection of these markers in the diagnosis of SC has not been addressed. Hence, the present study aimed to analyze the usefulness of immunocytochemical staining for pan-Trk and NR4A3 in the cytodiagnosis of SC. We enrolled eight patients with a histopathological diagnosis of SC who underwent preoperative fine-needle aspiration cytological examination. The cytological characteristics were reviewed and immunocytochemical staining for pan-Trk and NR4A3 was performed. The characteristic cytological features noted in the patient cohort included neoplastic cell clusters with a sheet-like and papillary cluster arrangement as well as single cells. Additionally, neoplastic cells with mild to moderately enlarged nuclei and small nucleoli, multi-vacuolated cytoplasm, and intracytoplasmic mucin were also observed. The immunocytochemical analyses clearly demonstrated that all eight specimens showed positive nuclear staining for pan-Trk, but were negative for NR4A3 expression. Although all cases of SC do not always show positive immunoreactivity for pan-Trk, immunocytochemical analysis for pan-Trk may be useful for the cytodiagnosis of SC along with assessment of the characteristic cytological features.

PMID:33885200 | DOI:10.1002/dc.24750
Pancreatic acinar cell carcinoma with extension into the main pancreatic duct: a case report

Fetched: April 14th, 2021, 5:00am GMT by Masato Kayahara

Surg Case Rep. 2021 Apr 13;7(1):90. doi: 10.1186/s40792-021-01172-0.

ABSTRACT

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare exocrine malignant tumor. Its widespread intraductal extension into the main pancreatic duct (MPD) is also rare.

CASE PRESENTATION: We report the case of a 71-year-old man with PACC with MPD extension. The patient was assessed with laboratory and radiographic investigations that facilitated a preoperative diagnosis. Endoscopic ultrasonography (EUS) and dynamic thin-slice multi-detector row computed tomography (MDCT) were useful for determining the resection line of the pancreas. EUS-guided fine needle aspiration (EUS-FNA) was also helpful in determining the tumor biology and treatment strategy. Distal pancreatectomy was performed. The MPD was occupied by the tumor 35 mm downstream and 5 mm upstream. Histopathologically, the pancreatic tail tumor extended continuously into the MPD. The tumor was solid with cells showing eosinophilic and granular cytoplasm, indicating the diagnosis of PACC. This is an interesting case of PACC with intraductal extension into the MPD. We discuss the possible mechanisms of tumor extension in this rare case together with a review of the literature.

CONCLUSIONS: We describe a rare pancreatic acinar cell carcinoma that could be adequately treated using preoperative precise imaging and histopathological evaluations. When an intraductal tumor extension in the MPD is encountered, the diagnosis of a rare pancreatic tumor should be considered, as in our case.

PMID:33847839 | PMC:PMC8044282 | DOI:10.1186/s40792-021-01172-0
Immunohistochemical Expression of Fatty Acid Synthase (FASN) is Correlated to Tumor Aggressiveness and Cellular Differentiation in Salivary Gland Carcinomas

Fetched: April 13th, 2021, 5:00am GMT by Camila Matsunaga de Angelis

Head Neck Pathol. 2021 Apr 11. doi: 10.1007/s12105-021-01319-3. Online ahead of print.

ABSTRACT

Fatty acid synthase (FASN) expression is closely related to cancer progression, in particular, tumor aggressiveness and poor prognosis. This study aimed to analyse the expression of FASN in carcinomas of the salivary glands and correlate it with Ki-67 expression. We analysed by immunohistochemistry the expression of FASN and Ki-67 on tissue sections from 7 cases of adenocarcinoma, not otherwise specified (AdNOS), 6 cases of polymorphous adenocarcinoma (PAC), 16 cases of acinic cell carcinoma (AcCC), 19 cases of adenoid cystic carcinoma (AdCC), 15 cases of epithelial-myoepithelial carcinoma (EMC); 10 cases of secretory carcinoma (SC), 13 cases of mucoepidermoid carcinoma (MEC), 10 cases of salivary duct carcinoma (SDC) and 7 cases of myoepithelial carcinoma (MC). These carcinomas were classified into aggressive and indolent regarding their biological behaviour. Additionally, MEC and AdCC were also classified according to the histological grade. High expression of FASN was found in SDC (100%), SC (100%), AcCC (68.7%) and AdNOS (57.2%). No association was found between FASN and Ki-67 expression. Aggressive carcinomas showed a higher rate of Ki-67 proliferation (p < 0.001) and greater expression of FASN when compared to indolent carcinomas (p < 0.05). With regards to carcinomas categorized as indolent, FASN expression was much higher in the lesions that presented cell differentiation (SC and AcCC). Also, FASN expression was significantly higher in high-grade AdCC and MEC when compared to low-grade tumors (p < 0.05). We concluded that FASN expression was correlated to tumor aggressiveness and cellular differentiation in salivary gland carcinomas.

PMID:33843033 | DOI:10.1007/s12105-021-01319-3
Metastatic Acinar Cell Carcinoma of the Pancreas: A Retrospective Cohort Study on Systemic Chemotherapy and Review of the Literature

Fetched: April 10th, 2021, 5:00am GMT by Elena Busch

Pancreas. 2021 Mar 1;50(3):300-305. doi: 10.1097/MPA.0000000000001765.

ABSTRACT

OBJECTIVES: Acinar cell carcinoma of the pancreas (pACC) forms a rare subgroup of pancreatic tumors. We report on our institutional experience with systemic first- and further-line therapy in patients with metastatic pACC and embed our findings in a review of the literature.

METHODS: Patients with stage IV pACC who started systemic treatment between 2008 and 2019 at our institution were identified via our institutional database. Clinical data were extracted from the patients' electronic data records. Survival times were calculated by the Kaplan-Meier method.

RESULTS: Six patients received a fluoropyrimidine- and oxaliplatin-containing first-line treatment, and 4 patients were started on gemcitabine-based protocols. Median progression-free survival was 4.8 months [95% confidence interval (CI), 3.3 to not available (n.a.)], and median overall survival was 15.3 months (95% CI, 10.1 to n.a.). Residual survival for second-line treatment was 2.1 months (95% CI, 1.3 to n.a.), although 1 patient experienced almost complete remission under targeted therapy.

CONCLUSIONS: The most encouraging and deep responses result from poly-chemotherapy with leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), which seems to be the appropriate choice in fit patients. Gemcitabine monotherapy seems without substantial activity in pACC. Whenever possible, patients with pACC should be screened for targetable mutations.

PMID:33835959 | DOI:10.1097/MPA.0000000000001765
Acinic Cell Carcinoma of the Breast: Report of a Case With Immunohistochemical and Next-Generation Sequencing Studies

Fetched: April 9th, 2021, 5:00am GMT by Kaitlin D Weaver

Int J Surg Pathol. 2021 Apr 7:10668969211008508. doi: 10.1177/10668969211008508. Online ahead of print.

ABSTRACT

Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation.

PMID:33827325 | DOI:10.1177/10668969211008508
High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance

Fetched: April 8th, 2021, 5:00am GMT by Alena Skalova

Adv Anat Pathol. 2021 May 1;28(3):107-118. doi: 10.1097/PAP.0000000000000298.

ABSTRACT

High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.

PMID:33825717 | DOI:10.1097/PAP.0000000000000298
Use of 68Ga-FAPI PET/CT for Evaluation of Peritoneal Carcinomatosis Before and After Cytoreductive Surgery

Fetched: March 31st, 2021, 5:00am GMT by Liang Zhao

Clin Nucl Med. 2021 Jun 1;46(6):491-493. doi: 10.1097/RLU.0000000000003611.

ABSTRACT

A 55-year-old woman underwent 18F-FDG and 68Ga-FAPI PET/CT for tumor detection and staging under the prospective study NCT04416165. Both scans showed a mass lesion with increased tracer uptake in the pancreas. Moreover, 68Ga-FAPI PET/CT showed a greater number of abnormal foci in the mesentery and omentum than that shown with 18F-FDG. These abnormal foci were suspected to be metastases from pancreatic cancer. The patient subsequently underwent a cytoreductive surgery, and postoperative histopathology confirmed the diagnosis of acinar cell carcinoma of pancreas. Follow-up 68Ga-FAPI PET/CT (3 months after surgery) showed an excellent response with decreasing 68Ga-FAPI activity in the whole abdomen.

PMID:33782310 | DOI:10.1097/RLU.0000000000003611
A gene-environment-induced epigenetic program initiates tumorigenesis

Fetched: March 27th, 2021, 5:00am GMT by Direna Alonso-Curbelo

Nature. 2021 Feb;590(7847):642-648. doi: 10.1038/s41586-020-03147-x. Epub 2021 Feb 3.

ABSTRACT

Tissue damage increases the risk of cancer through poorly understood mechanisms¹. In mouse models of pancreatic cancer, pancreatitis associated with tissue injury collaborates with activating mutations in the Kras oncogene to markedly accelerate the formation of early neoplastic lesions and, ultimately, adenocarcinoma^2,3. Here, by integrating genomics, single-cell chromatin assays and spatiotemporally controlled functional perturbations in autochthonous mouse models, we show that the combination of Kras mutation and tissue damage promotes a unique chromatin state in the pancreatic epithelium that distinguishes neoplastic transformation from normal regeneration and is selected for throughout malignant evolution. This cancer-associated epigenetic state emerges within 48 hours of pancreatic injury, and involves an 'acinar-to-neoplasia' chromatin switch that contributes to the early dysregulation of genes that define human pancreatic cancer. Among the factors that are most rapidly activated after tissue damage in the pre-malignant pancreatic epithelium is the alarmin cytokine interleukin 33, which recapitulates the effects of injury in cooperating with mutant Kras to unleash the epigenetic remodelling program of early neoplasia and neoplastic transformation. Collectively, our study demonstrates how gene-environment interactions can rapidly produce gene-regulatory programs that dictate early neoplastic commitment, and provides a molecular framework for understanding the interplay between genetic and environmental cues in the initiation of cancer.

PMID:33536616 | DOI:10.1038/s41586-020-03147-x
Pancreatic Acinar Cell Carcinoma with Concomitant Bullous Pemphigoid

Fetched: March 25th, 2021, 5:00am GMT by David Vavra

Clin Med Res. 2021 Mar;19(1):32-34. doi: 10.3121/cmr.2021.1595.

NO ABSTRACT

PMID:33757939 | PMC:PMC7987098 | DOI:10.3121/cmr.2021.1595
Acinar Cell Carcinoma with Morphological Change in One Month

Fetched: March 23rd, 2021, 5:00am GMT by Mio Ikeda

Intern Med. 2021 Mar 22. doi: 10.2169/internalmedicine.7121-21. Online ahead of print.

ABSTRACT

A 64-year-old man was admitted to our hospital to undergo examination of a pancreatic tumor accompanied by sudden epigastric pain. The tumor had a well-defined oval shape that was mostly less enhanced, with the exception of part of the tumor on the pancreatic head side, on contrast enhanced (CE)-CT. However, CE-CT performed one-month later revealed that the viable part of the tumor grew toward the pancreatic tail with the reduction of necrotic tissue. We performed distal pancreatectomy and the tumor was diagnosed as acinar cell carcinoma (ACC). One important characteristic of ACC is that it may develop morphological changes within a short period of time.

PMID:33746172 | DOI:10.2169/internalmedicine.7121-21
Concerted cell and in vivo screen for pancreatic ductal adenocarcinoma (PDA) chemotherapeutics

Fetched: March 18th, 2021, 5:00am GMT by Somayeh Layeghi-Ghalehsoukhteh

Sci Rep. 2020 Nov 26;10(1):20662. doi: 10.1038/s41598-020-77373-8.

ABSTRACT

PDA is a major cause of US cancer-related deaths. Oncogenic Kras presents in 90% of human PDAs. Kras mutations occur early in pre-neoplastic lesions but are insufficient to cause PDA. Other contributing factors early in disease progression include chronic pancreatitis, alterations in epigenetic regulators, and tumor suppressor gene mutation. GPCRs activate heterotrimeric G-proteins that stimulate intracellular calcium and oncogenic Kras signaling, thereby promoting pancreatitis and progression to PDA. By contrast, Rgs proteins inhibit Gi/q-coupled GPCRs to negatively regulate PDA progression. Rgs16::GFP is expressed in response to caerulein-induced acinar cell dedifferentiation, early neoplasia, and throughout PDA progression. In genetically engineered mouse models of PDA, Rgs16::GFP is useful for pre-clinical rapid in vivo validation of novel chemotherapeutics targeting early lesions in patients following successful resection or at high risk for progressing to PDA. Cultured primary PDA cells express Rgs16::GFP in response to cytotoxic drugs. A histone deacetylase inhibitor, TSA, stimulated Rgs16::GFP expression in PDA primary cells, potentiated gemcitabine and JQ1 cytotoxicity in cell culture, and Gem + TSA + JQ1 inhibited tumor initiation and progression in vivo. Here we establish the use of Rgs16::GFP expression for testing drug combinations in cell culture and validation of best candidates in our rapid in vivo screen.

PMID:33244070 | PMC:PMC7693321 | DOI:10.1038/s41598-020-77373-8
Ectopic ACTH Production Caused by Metastatic Parotid Gland Acinic Cell Carcinoma

Fetched: March 16th, 2021, 5:00am GMT by Jacob M Burch

AACE Clin Case Rep. 2021 Jan 8;7(1):32-35. doi: 10.1016/j.aace.2020.11.006. eCollection 2021 Jan-Feb.

ABSTRACT

OBJECTIVE: To present a case of adrenocorticotropic hormone (ACTH) hypersecretion caused by a metastatic acinic cell carcinoma (AcCC) of the parotid. Only 6 cases have been reported prior to October 2019. We believe that this condition is under-reported and hope that improved recognition will improve its reporting.

METHODS: Diagnosis in this case was done using surgical pathology of the primary tumor, involving lymph nodes, and a metastatic lesion. Following an initial misdiagnosis, a final diagnosis of AcCC was made using immunohistochemical staining. ACTH hypersecretion was diagnosed by testing for random ACTH, cortisol, and 24-hour urine aldosterone and cortisol levels.

RESULTS: A 57-year-old man presented with hypokalemia, lower-extremity edema, and left-side rib pain 7 months following excision of a 4-cm left-parotid tumor. Immunostaining positive for DOG-1, CK7, pan-cytokeratin (including CAM5.2), and SOX10 led to the diagnosis of AcCC. ACTH hypersecretion was diagnosed based on a random ACTH level of 307 pg/mL (normal morning value, 7.2-63 pg/mL), a cortisol level of 33 μg/dL (normal morning value, 4.3-19.8 μg/dL; normal PM value, 3.1-15.0 μg/dL), a 24-hour urine aldosterone level of <0.7 U (normal, 2.0-20 U), and a 24-hour urine cortisol level of 4564 U (normal, 3.5-45 U). The patient's ACTH hypersecretion and hypokalemia were treated with potassium replacement, amiloride, and ketoconazole. His metastatic recurrence was treated with radiotherapy, chemotherapy, and immunotherapy. The patient died after being diagnosed with sepsis secondary to multifocal postobstructive pneumonia 4 months after the diagnosis of his metastatic recurrence.

CONCLUSION: Ectopic ACTH production caused by metastatic AcCC is a rare phenomenon but has been increasingly described over the last 15 years. We believe that this condition likely has a greater prevalence than what is reported and that improved recognition will lead to improved outcomes.

PMID:33718604 | PMC:PMC7924161 | DOI:10.1016/j.aace.2020.11.006
Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival

Fetched: March 9th, 2021, 5:00am GMT by Ken Chow

Eur J Cancer. 2021 May;148:440-450. doi: 10.1016/j.ejca.2020.12.030. Epub 2021 Mar 5.

ABSTRACT

BACKGROUND: Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival.

METHODS: Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8).

RESULTS: A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH.

CONCLUSIONS: The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.

PMID:33678516 | DOI:10.1016/j.ejca.2020.12.030
Kirsten rat sarcoma virus protein overexpression in adenocarcinoma lung: Association with clinicopathological and histomorphological features

Fetched: March 9th, 2021, 5:00am GMT by Rahul Kumar Pandey

J Carcinog. 2020 Oct 8;19:9. doi: 10.4103/jcar.JCar_11_20. eCollection 2020.

ABSTRACT

CONTEXT: Lung cancer is the leading cause of cancer-related deaths worldwide. The constitutive activation of multiple signaling pathways is the major cause of carcinogenesis.

AIMS: The study evaluates the frequency of Kirsten rat sarcoma virus (KRAS) protein overexpression and correlates with clinicopathological and histomorphological features in non-small cell lung carcinoma (NSCLC)-adenocarcinoma.

SETTINGS AND DESIGN: Tertiary hospital-based retrospective and prospective case series included 100 cases of NSCLC-adenocarcinoma.

MATERIALS AND METHODS: The basic panel of Immunohistochemistry including Napsin-A, thyroid transcription factor-1 (TTF-1), and markers for squamous differentiation, p-40 was used in formalin-fixed paraffin-embedded tissue blocks. The KRAS monoclonal antibody (9.13, Thermo Fisher Scientific, USA) was used.

STATISTICAL ANALYSIS USED: The IBM-Statistical Package for the Social Sciences (SPSS) (SPSS, International Business Machines Corporation, New York, NY, USA) analysis software, version 16 was used for all statistical calculations.

RESULTS: KRAS protein expressed in 28.0% (28/100) cases. Cases were grouped as KRAS positive and negative. TTF-1 and Napsin-A were expressed in 89.25% (n = 25) and 92.86% (n = 26) cases, respectively. Stage IV clinical disease was identified in 55% of cases, and 36.84% of cases had a mean survival between 6 and 12 months. In KRAS positive group, the most common pattern of cellular arrangement was acinar/loose clusters pattern present in 64.29% (n = 21) and 75.0% (n = 18) cases followed by the solid pattern present in 42.86% of cases (n = 12), respectively. Necrosis was identified in 57.14% (n = 16) cases. Mucin pattern was present in 32.14% of cases (n = 9), which was significantly different when compared with the KRAS negative group (P = 0.036).

CONCLUSIONS: This finding may imply that KRAS mutations may not be entirely triggered by alterations induced by carcinogens in smoke. KRAS gene is frequently mutated in pulmonary tumors. It should be tested in NSCLC owing to its predictive and prognostic effects.

PMID:33679239 | PMC:PMC7921778 | DOI:10.4103/jcar.JCar_11_20
Tumour-Infiltrating Lymphocytes (TILs) and PD-L1 Expression Correlate with Lymph Node Metastasis, High-Grade Transformation and Shorter Metastasis-Free Survival in Patients with Acinic Cell Carcinoma (AciCC) of the Salivary Glands

Fetched: March 7th, 2021, 5:00am GMT by Selina Hiss

Cancers (Basel). 2021 Feb 25;13(5):965. doi: 10.3390/cancers13050965.

ABSTRACT

OBJECTIVES: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Acinic Cell Carcinoma (AciCC) of the salivary glands, to enable a correlation with clinico-pathological features and to analyse their prognostic impact.

METHODS: This single centre retrospective study represents a cohort of 36 primary AciCCs with long-term clinical follow-up. Immunohistochemically defined immune cell subtypes, i.e., those expressing T-cell markers (CD3, CD4 and CD8) or a B-cell marker (CD20) were characterized on tumour tissue sections. The number of TILs was quantitatively evaluated using software for digital bioimage analysis (QuPath). PD-L1 expression on the tumour cells and on immune cells was assessed immunohistochemically employing established scoring criteria: tumour proportion score (TPS), Ventana immune cell score (IC-Score) and combined positive score (CPS).

RESULTS: Higher numbers of tumour-infiltrating T- and B-lymphocytes were significantly associated with high-grade transformation. Furthermore, higher counts of T-lymphocytes correlated with node-positive disease. There was a significant correlation between higher levels of PD-L1 expression and lymph node metastases as well as the occurrence of high-grade transformation. Moreover, PD-L1 CPS was associated with poor prognosis regarding metastasis-free survival (p = 0.049).

CONCLUSIONS: The current study is the first to demonstrate an association between PD-L1 expression and lymph node metastases as well as grading in AciCCs. In conclusion, increased immune cell infiltration of T and B cells as well as higher levels of PD-L1 expression in AciCC in association with high-grade transformation, lymph node metastasis and unfavourable prognosis suggests a relevant interaction between tumour cells and immune cell infiltrates in a subset of AciCCs, and might represent a rationale for immune checkpoint inhibition.

PMID:33669038 | PMC:PMC7956490 | DOI:10.3390/cancers13050965
Prognostic impact of lung adenocarcinoma second predominant pattern from a large European database

Fetched: March 5th, 2021, 5:00am GMT by Pietro Bertoglio

J Surg Oncol. 2021 Feb;123(2):560-569. doi: 10.1002/jso.26292. Epub 2020 Nov 10.

ABSTRACT

BACKGROUND AND OBJECTIVES: Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS).

METHODS: We retrospectively collected data of surgically resected stage I and II adenocarcinoma.

SELECTION CRITERIA: anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas.

RESULTS: Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS.

CONCLUSIONS: The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.

PMID:33169397 | DOI:10.1002/jso.26292
Differential diagnosis between acinic cell carcinoma and pleomorphic adenoma using the quantitative parameters of contrast-enhanced ultrasound

Fetched: March 5th, 2021, 5:00am GMT by J-M Guo

Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1936-1943. doi: 10.26355/eurrev_202102_25093.

ABSTRACT

OBJECTIVE: To investigate the value of differential diagnosis between acinic cell carcinoma (ACC) and pleomorphic adenoma (PA) using the quantitative parameters of contrast-enhanced ultrasound (CEUS).

PATIENTS AND METHODS: Twenty-two ACC and 98 PA were retrospectively analyzed. These patients had been examined via routine pre-surgical two-dimensional ultrasound and CEUS. The examination results were confirmed by biopsy pathology. Qontrast 4.0 imaging analysis software was applied to obtain the maximum intensity (PEAK), time to peak (TTP), regional blood volume (RBV), regional blood flow (RBF), maximum signal intensity (SImax) and mean signal intensity (SImean) through quantitative analysis. The differences between ACC and PA were compared regarding the conventional ultrasound images and the quantitative parameters of CEUS. ROC curves were drawn to evaluate the diagnostic value of these parameters.

RESULTS: There were no statistically significant differences between salivary gland ACC and PA in the manifestations of conventional two-dimensional ultrasound examination regarding morphology, internal echo and the boundary (p > 0.05). However, there were significant differences in PEAK, RBV, RBF, SImax and SImean between ACC and PA (p < 0.05). Additionally, the five quantitative parameters of CEUS were all highly accurate diagnostic indicators. The maximum area under the curve of each parameter was 0.888, sensitivity 72.6%, specificity 90.9% and accuracy 81.8%.

CONCLUSIONS: The quantitative parameters of CEUS are helpful for differentially diagnosing salivary ACC and PA.

PMID:33660803 | DOI:10.26355/eurrev_202102_25093
Secretory Carcinoma of the Oral Cavity: A Retrospective Case Series with Review of Literature

Fetched: March 5th, 2021, 5:00am GMT by Shankar Venkat

Head Neck Pathol. 2021 Mar 3. doi: 10.1007/s12105-021-01310-y. Online ahead of print.

ABSTRACT

Secretory carcinoma (SC) is an uncommon salivary gland neoplasm of the oral cavity that microscopically may mimic acinic cell carcinoma (ACC) and mucoepidermoid carcinoma (MEC). This study describes a series of SC in minor glands with a literature review. We performed a retrospective search for oral SC, within the archives of the University of Florida, Oral Pathology and Surgical Pathology Biopsy services from 2010 to 2018. A total of 10 SCs were identified in the oral and maxillofacial region, four of which were in the minor salivary glands. The demographic, clinical, histological, and molecular findings were aggregated for all 4 cases. Patient age varied from 30 to 60 years, with an average of 45 years. Two cases each were in female and male patients. Two cases presented on the labial mucosa, and one each on the hard and soft palate. Immunohistochemical (IHC) staining showed mammaglobin positivity in all cases, GATA3 positivity in two cases, S100 positivity in three cases, and SOX10 positivity in only one case. Fluorescence in situ hybridization demonstrated positivity for ETV6-NTRK3 fusion in 4 cases. Although oral SC is rare, pathologists should be aware of the histologic overlap between the SC and other salivary gland neoplasms such as ACC and MEC. A judicious application of IHC staining would aid in diagnosis. SC should be considered in the differential diagnosis for intraoral salivary gland tumors.

PMID:33660147 | DOI:10.1007/s12105-021-01310-y
Intensity-modulated proton therapy (IMPT) versus intensity-modulated radiation therapy (IMRT) for the treatment of head and neck cancer: A dosimetric comparison

Fetched: March 3rd, 2021, 5:00am GMT by My-Lien Nguyen

Med Dosim. 2021 Feb 26:S0958-3947(21)00013-3. doi: 10.1016/j.meddos.2021.02.001. Online ahead of print.

ABSTRACT

It is the goal of this study to compare the dosimetric advantages of IMPT when compared to IMRT. From January 2019 to August 2020, 25 patients were treated with intensity modulated proton therapy (IMPT) at our institution for either recurrent, metastatic, benign, or primary tumors in the head and neck region. Twenty-one patients met criteria for dosimetric analysis. Histology of disease included squamous cell carcinoma, acinic cell carcinoma, sarcomatoid sinonasal carcinoma, paraganglioma, adenoid cystic carcinoma, salivary high grade carcinoma, and papillary thyroid carcinoma. For IMRT planning, gross tumor volume (GTV) and clinical target volume (CTV) were contoured with the expansion of 3-5 mm to create the planning target volume (PTV) and dose was prescribed to the PTV. For the IMPT planning, dose was prescribed to CTV and robust optimization was utilized which accounted for a 5 mm setup and range uncertainty. The minimum, mean and maximum target doses for IMRT and IMPT plans as well as mean and maximum normal tissue doses are reported for the 21 patients meeting criteria. Mean doses for IMRT and IMPT were 6278.2 cGy and 6449.8 cGyRBE respectively with p-value of 0.0001. Maximum doses for IMRT and IMPT were 6579.5 cGy and 6772.1 cGyRBE respectively with p-value of 0.0014. Minimum doses for IMRT and IMPT were 5440.6 cGy and 5617.9 cGyRBE respectively with p-value of 0.3576. IMPT had an overall advantage in OAR doses in the brain stem, spinal cord, optic structures, cochlea, larynx, contralateral parotid, and oral cavity with only a few exceptions. Our study thus demonstrates a dosimetric advantage for IMPT in treating head and neck tumors in mean and max dose delivered as well as dose to OARs. Given that our patient cohort were mainly unilateral head and neck cases, our study supports the treatment of this specific subset of patients regardless of histology with IMPT. This may aid in appropriate patient selection for IMPT treatment. Further studies will need to determine if this dosimetric advantage translates to a therapeutic advantage for patients.

PMID:33648823 | DOI:10.1016/j.meddos.2021.02.001
Clinical study of salivary gland malignant tumor with skull base metastasis

Fetched: March 2nd, 2021, 5:00am GMT by Lin Yao

Br J Neurosurg. 2021 Feb 27:1-7. doi: 10.1080/02688697.2021.1885616. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the clinical performance, pathological characteristics, treatment and prognosis of salivary gland malignant tumor (SGMT) with skull base metastasis.

METHODS: Five SGMT patients with skull base metastasis were retrospectively studied. Major clinical symptoms included headache, facial paralysis, and ear hearing loss. Three patients had previous history of SGMT resection. All patients underwent preoperative computed tomography (CT) and magnetic resonance imaging (MRI). Craniotomy was performed in three patients, and all the five patients underwent radiotherapy and chemotherapy.

RESULTS: Two patients were confirmed as having adenocarcinoma, one patient was pathologically confirmed to have squamous cell carcinoma, one patient had ductal carcinoma, and one patient had acinar cell carcinoma. One patient died after 2 years of treatment, and the remaining 4 patients were followed up for 6 ∼ 24 months, suggesting that the tumor size was not enlarged or showed no local recurrence.

CONCLUSION: SGMT with skull base metastasis is extremely rare, and due to similar imaging characteristics, it can be easily misdiagnosed as meningioma or schwannoma. Early diagnosis, extent of invasion, surgery and combination of chemotherapy and radiotherapy are the prognostic factors of the disease.

PMID:33641541 | DOI:10.1080/02688697.2021.1885616
Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features

Fetched: March 1st, 2021, 5:00am GMT by Ziad M El-Zaatari

Ann Diagn Pathol. 2021 Jun;52:151719. doi: 10.1016/j.anndiagpath.2021.151719. Epub 2021 Feb 17.

ABSTRACT

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

PMID:33640702 | DOI:10.1016/j.anndiagpath.2021.151719
A correlation study of mismatch repair immunohistochemical protein expression of pancreatic solid tumors in cytology cell blocks and matching surgical specimens

Fetched: February 24th, 2021, 5:00am GMT by Andrei Teodosescu

Diagn Cytopathol. 2021 Jun;49(6):700-705. doi: 10.1002/dc.24724. Epub 2021 Feb 21.

ABSTRACT

INTRODUCTION: Only 15%-20% of newly diagnosed pancreatic ductal adenocarcinoma (PDAC) cases are surgically operable. Cytology samples may be the only source for guiding clinical management. Current research indicates that mismatch repair (MMR) status could be valuable for implementing novel treatment modalities. In this study, immunohistochemical (IHC) MMR protein expression on cytology cell blocks was compared with that of the correlating surgical resection specimens.

MATERIALS AND METHODS: A retrospective review of 120 pancreatic solid tumor needle biopsies from 2016 to 2019 was performed, and 15 experimental cases were selected comprising of cellular (>100 tumor cells and >100 benign positive control cells that include benign ductal cells and/or lymphocytes) alcohol-prefixed formalin-fixed cytology cell blocks (CB), and corresponding subsequent surgical resections (Surg). The cases include 13 PDACs (87%), 1 (6.5%) low grade neuroendocrine tumor (PNET), and 1 (6.5%) acinar cell carcinoma (ACC). A routine four-panel (MLH1, MSH2, MSH6, and PMS2) MMR IHC testing was performed. The percentage of protein expression was evaluated and compared between individual CB-Surg pairs.

RESULTS: About 8 of the 15 (53.3%) cytology cases showed matching protein expressivity with the surgical specimens for all four MMR markers (Table 1). The remaining 7 pairs (46.7%) appeared to have a partial concordance, including 6 values for which a surgical marker showed less expression, and 13 values for which a cytological marker showed less expression. [Table: see text] CONCLUSION: Cytology CB MMR protein panel testing could be a useful consideration for inoperable patients who would benefit from medical therapy such as immune checkpoint inhibition. However, the cellularity and overall quality of the CB is expected to be paramount in obtaining satisfactory IHC MMR results. The MMR results could be more confidently trusted when the staining is intact, but when not retained, they should be interpreted with caution in a low cellularity sample to avoid mistakenly identifying MMR-deficient tumors.

PMID:33615705 | DOI:10.1002/dc.24724
Clinical characteristics and treatment analysis of pancreatic acinar cell carcinoma: A single institutional comparison to pancreatic ductal adenocarcinoma

Fetched: February 24th, 2021, 5:00am GMT by Xing Huang

Surg Oncol. 2021 Feb 15;37:101528. doi: 10.1016/j.suronc.2021.101528. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare malignancy that accounts for less than 1% of primary pancreatic neoplasms. Currently, the lack of large-scale clinical studies limits our understanding of PACC. The aim of this study was to investigate the clinical characteristics and prognosis of PACC.

METHODS: In a retrospective analysis, 52 patients with PACC and 355 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent surgical interventions were evaluated. Clinical characteristics and treatment outcomes were compared between the two groups.

RESULTS: The mean age was lower for patients with PACC than for those with PDAC (mean: 50.8 ± 10.9 versus 59.4 ± 10.9 years; p < 0.001). Except for alpha-fetoprotein (AFP), tumour markers were also lower in the PACC group than the PDAC group. In regard to tumour characteristics, maximum diameters of the primary tumour [median (range): 5.0 cm (1.0-18.2 cm) versus 3.5 cm (0.6-15.0 cm); p < 0.001] and hepatic metastatic lesions [6.7 cm (1.5-12.6 cm) versus 1.2 cm (0.3-3.3 cm); p < 0.001] were larger in patients with PACC than patients with PDAC, but vascular invasion [23.1% (12/52) versus 35.5% (126/355); p = 0.044] and perineural invasion [7.7% (4/52) versus 56.1% (199/355); p < 0.001] were more common in patents with PDAC than in patients with PACC. For treatment, radical resection was performed in 57.7% of patients with PACC, which increased the 5-year survival rate to 31.8%. In regard to prognosis, the 5-year survival rate was 21.4% for PACC and 9.7% for PDAC (p < 0.0001).

CONCLUSIONS: PACC is more indolent than PDAC, which makes early diagnosis more difficult. Although the stage may be advanced at diagnosis, the overall survival (OS) of PACC is much better than that of PDAC, and the prognosis greatly improves after radical resection.

PMID:33611029 | DOI:10.1016/j.suronc.2021.101528
Bronchoalveolar Cancer

Fetched: February 24th, 2021, 5:00am GMT by Rebanta K. Chakraborty

2021 May 7. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.

ABSTRACT

Bronchioloalveolar 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.

Until the previous decade, strict pathologic criteria defined a bronchioloalveolar carcinoma 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. The subgroup has been renamed adenocarcinoma with lepidic growth and classified into subtypes based on the extent of invasive disease.

PMID:30020653 | Bookshelf:NBK513281
The contemporary trend in worsening prognosis of pancreatic acinar cell carcinoma: A population-based study

Fetched: February 24th, 2021, 5:00am GMT by Nie Duorui

PLoS One. 2020 Dec 17;15(12):e0243164. doi: 10.1371/journal.pone.0243164. eCollection 2020.

ABSTRACT

BACKGROUND: Primary acinar cell carcinoma (ACC) is a rare exocrine tumor of the pancreas with unclear clinical characteristics. Our goal was to determine the incidence and update the clinical characteristics and outcomes of ACC.

METHODS: Through the Surveillance, Epidemiology, and End Results (SEER) database, we identified 252 patients with the latest diagnosis of ACC (2004-2016). The age-adjusted incidence (AAI) was calculated using the SEER*Stat Software version 8.3.6. The Kaplan-Meier method was used to draw survival curves and differences among them were compared by the log-rank test. Cox proportional hazards models were used to evaluate factors that had independent predictive effects on the overall survival.

RESULTS: The AAI of pancreatic ACC was on the rise with the mean age at diagnosis of 63.79±14.79 years. Most patients (15.9%) had poorer differentiated tumors. The patients presented with distant stage were 54.4% compared with 53.1% between 1988 and 2003. The 1-, 2-, and 5-years survival rates for pancreatic ACC patients were 53.5%, 34.6%,17.5%, respectively (compared with 78.5%, 67.0%, and 42.8%, between 1988 and 2003). The multivariate COX analysis showed that the patient's age, surgery, chemotherapy, and summary stage, but not marital status were independent prognosis factors for ACC.

CONCLUSIONS: Pancreatic ACC is a highly malignant tumor with an increasing incidence in recent years. The rate of distant metastasis is increasing and the survival rate is worse than in the past, suggesting that it may require more aggressive treatment and follow-up. Surgery, radiotherapy, and chemotherapy are all effective treatments, but prospective studies are still needed to verify them.

PMID:33332471 | PMC:PMC7746196 | DOI:10.1371/journal.pone.0243164
Rare case of acinar cell carcinoma with multiple lesions in the pancreas

Fetched: February 24th, 2021, 5:00am GMT by Yuki Ikeda

JGH Open. 2020 Jun 29;4(6):1242-1243. doi: 10.1002/jgh3.12380. eCollection 2020 Dec.

ABSTRACT

We present the first case of pancreatic acinar cell carcinoma (PACC) with multiple lesions. A 55-year-old man with a pancretic tail mass on abdominal computed tomography (CT) was admitted to our hospital. Endoscopic ultrasound (EUS) showed a hypoechoic mass, and EUS-guided fine-needle aspiration (EUS-FNA) revealed the mass to be PACC. The patient underwent distal pancreatectomy, and two masses were identified in the pancreatic tail and body. Histologically, both masses had tumor cells similar to acinar cells and were positive for BCL-10. The patient was thus diagnosed with synchronous PACC. Ten months after the surgery, abdominal CT revealed a mass in the remnant pancreas. EUS showed a hypoechoic mass, and EUS-FNA determined it to be PACC. The patient underwent total remnant pancreatectomy. The histological imaging results were similar to those of the first resection. Finally, the patient was diagnosed with synchronous and metachronous PACC. The possibility of multiple occurrences in the pancreas should be considered with PACC.

PMID:33319067 | PMC:PMC7731799 | DOI:10.1002/jgh3.12380
Investigation of Sonographic Criteria for Reliable Identification of T1-T2 Low-Grade Malignant Tumors of the Parotid Gland

Fetched: February 24th, 2021, 5:00am GMT by Ferdinand Berner

Ultrasound Med Biol. 2021 Mar;47(3):471-477. doi: 10.1016/j.ultrasmedbio.2020.11.010. Epub 2020 Dec 10.

ABSTRACT

The aim of this study was to investigate sonographic findings of low-grade malignant tumors of the parotid gland. The sonographic findings of all patients treated for T1-T2 low-grade carcinomas of the parotid gland between 2003 and 2018 were retrospectively examined and compared with those of patients with pleomorphic adenomas for the following parameters: definition of tumor margins, echotexture, echogenicity, shape and vascularization. Statistical analysis was performed using the χ² test. A p value of <0.05 was considered statistically significant. A total of 310 patients (62 with T1-T2 low-grade malignant tumors, 248 with pleomorphic adenomas) were evaluated. Our analysis detected a statistically significant difference in the definition of margins, echotexture, echogenicity and shape. Furthermore, we could detect a specific pattern (anechoic islets in a small hypoechoic lesion with distal enhancement) appearing far more frequently in low-grade malignant lesions. It seems that there is still potential to reduce the incidence of the false working hypothesis "benign lesion" on imaging of low-grade malignant tumors.

PMID:33309444 | DOI:10.1016/j.ultrasmedbio.2020.11.010
Presentation and outcome of mixed neuroendocrine non-neuroendocrine neoplasms of the pancreas

Fetched: February 24th, 2021, 5:00am GMT by Anna Nießen

Pancreatology. 2021 Jan;21(1):224-235. doi: 10.1016/j.pan.2020.11.020. Epub 2020 Dec 3.

ABSTRACT

BACKGROUND/OBJECTIVES: Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) of the pancreas and periampullary region are extremely rare and heterogeneous malignancies. Literature is sparse, clinical management is not standardized and little is known about survival outcomes. The aim of this study was to identify pathological and radiological features of MiNEN and assess the outcome of surgical management.

METHODS: Patients undergoing surgery for pancreatic and periampullary MiNEN between 2001 and 2019 were retrospectively analysed based on a prospective database. Histological, radiological and clinical features were assessed. Survival was analysed in a nested case-control study and matched-pair analyses with pure neuroendocrine neoplasms (pNEN) and ductal adeno- or acinar cell carcinomas of the pancreas. A literature review with focus on survival after surgical resection was additionally performed.

RESULTS: Of 13 patients with MiNEN, 5 had acinar-MiNEN and 8 adeno-MiNEN. Two of 5 (40%) acinar-MiNEN and one adeno-MiNEN patients had liver metastases. All but one adeno-MiNEN (88%) showed preoperative radiological features of pancreatic adenocarcinoma, 3 of 5 (60%) acinar-MiNEN exhibited mainly neuroendocrine features. No surgical mortality was observed. The 5-year overall survival rate in all MiNEN was 40%. Five-year survival rate was 58% in adeno-MiNEN and comparable to that of matched ductal adenocarcinomas (36%) and pNEN (48%). Five-year overall survival rate was 20% in acinar-MiNEN, compared to 39% in acinar carcinoma patients and 59% in matched pNEN patients.

CONCLUSIONS: MiNEN are rare and difficult to distinguish from pure adenocarcinoma or neuroendocrine neoplasm preoperatively. Surgical resection would therefore be the treatment of choice in localized tumors.

PMID:33309225 | DOI:10.1016/j.pan.2020.11.020
The Decline of Salivary Adenocarcinoma Not Otherwise Specified as a Tumor Entity: Reclassification Using Contemporary Immunohistochemical Profiling and Diagnostic Criteria

Fetched: February 24th, 2021, 5:00am GMT by Lisa M Rooper

Am J Surg Pathol. 2021 Jun 1;45(6):753-764. doi: 10.1097/PAS.0000000000001636.

ABSTRACT

The classification of salivary gland carcinomas has become increasingly specific over the last decade with the definition of new tumor types, documentation of novel molecular and immunohistochemical findings, and development of more refined diagnostic criteria. In this setting, it is unclear how many salivary tumors still cannot be easily categorized-and whether such tumors represent undifferentiated malignancies or include additional definable entities. Relying largely on current classification schemes and contemporary immunohistochemical panels, we reassessed salivary tumors previously diagnosed as adenocarcinoma, not otherwise specified (ACA NOS) from 2 large academic medical centers. Fifty-seven ACA NOS (72%) could be reclassified as more specific entities including 31 salivary duct carcinomas (39%), 7 polymorphous adenocarcinomas (9%), 5 epithelial-myoepithelial carcinomas (6%), 4 myoepithelial carcinomas (5%), 4 secretory carcinomas (5%), 1 acinic cell carcinoma (1%), 1 basal cell adenocarcinoma (1%), 1 intraductal carcinoma (1%), and 1 clear cell carcinoma (1%) as well as 2 metastatic squamous cell carcinomas (3%). Of reclassified cases, 21 (37%) represented variant histologies within these categories. ACA NOS comprised 11% of salivary malignancies before reclassification, but only 4% after reclassification. The remaining 22 ACA NOS demonstrated heterogeneous features, with an association between histologic grade and clinical outcome. In effect, ACA NOS is becoming a bygone entity as modern classification schemes and ancillary techniques now permit more specific typing of a majority of these tumors, potentially facilitating more specific prognostication and treatment. Additional distinctive entities such as mucinous adenocarcinoma may still be definable within the ACA NOS category.

PMID:33284193 | DOI:10.1097/PAS.0000000000001636
The expression of trefoil factor 3 is related to histologic subtypes and invasiveness in lung adenocarcinoma

Fetched: February 24th, 2021, 5:00am GMT by Wenjuan Luo

Oncol Lett. 2021 Jan;21(1):63. doi: 10.3892/ol.2020.12325. Epub 2020 Nov 19.

ABSTRACT

Adenocarcinoma is the most common histological type of lung cancer and has various histologic subtypes, including lepidic, papillary, acinar and invasive mucinous adenocarcinoma. Histologic subtypes are associated with tumor invasiveness. For example, the lepidic subtype is less invasive than the papillary/acinar subtype. Trefoil factor 3 (TFF3) is a small secreting protein that is a member of the trefoil factor family, which is involved in mucosal stabilization and repair through its mitogenic and antiapoptotic activities. TFF3 overexpression is associated with various types of cancer. In lung cancer, TFF3 is expressed significantly in adenocarcinoma. However, the relationship between TFF3 expression and histologic subtypes in lung adenocarcinoma is unclear. The current study immunohistochemically revealed that, beside invasive mucinous carcinoma, the expression of TFF3 in papillary and acinar adenocarcinoma was significantly higher than that in lepidic adenocarcinoma. To further confirm these results, the expression of TFF3 in cases with both lepidic and papillary/acinar areas were examined. The expression of TFF3 in papillary/acinar areas was significantly higher when compared with lepidic areas in a single sample. Furthermore, using the lung adenocarcinoma cell line A549, TFF3-knockdown cells were generated. The results revealed that knockdown of TFF3 attenuated invasion. In vitro and immunohistochemical assays using clinical samples demonstrated that TFF3 expression was associated with lung adenocarcinoma invasiveness. To the best of our knowledge, the current study is the first to report that TFF3 expression was associated with the histologic subtypes of lung adenocarcinoma.

PMID:33281974 | PMC:PMC7709562 | DOI:10.3892/ol.2020.12325
Pancreatic panniculitis and elevated serum lipase in metastasized acinar cell carcinoma of the pancreas: A case report and review of literature

Fetched: February 24th, 2021, 5:00am GMT by Rainer Christoph Miksch

World J Clin Cases. 2020 Nov 6;8(21):5304-5312. doi: 10.12998/wjcc.v8.i21.5304.

ABSTRACT

BACKGROUND: Pancreatic panniculitis is an extremely rare condition associated with different underlying pancreatic disorders and characterized by subcutaneous fat necrosis induced by elevated serum lipase levels. These lesions usually affect the lower extremities and may precede abdominal symptoms of pancreatic disease. Acinar cell carcinoma (ACC) of the pancreas is a rare pancreatic neoplasm, accounting for only 1%-2% of pancreatic tumors in adults.

CASE SUMMARY: We present the case of a 72-year-old man with ACC of the pancreatic head and synchronous liver metastases. Both the primary tumor and liver metastases were resected. Serum lipase was elevated before surgery and decreased to normal postoperatively. Rising serum lipase levels at follow-up led to the diagnosis of hepatic recurrence. This disease progression was then accompanied by pancreatic panniculitis, with subcutaneous fat necrosis and acute arthritis. To the best of our knowledge, only 4 cases have been reported in the literature and each showed a similar association of serum lipase levels with pancreatic panniculitis and progression of ACC.

CONCLUSION: Clinical symptoms and progression of ACC may correlate with serum lipase levels, suggesting potential usefulness as a follow-up biomarker.

PMID:33269263 | PMC:PMC7674712 | DOI:10.12998/wjcc.v8.i21.5304
FGF21 in obesity and cancer: New insights

Fetched: February 24th, 2021, 5:00am GMT by Weiqin Lu

Cancer Lett. 2021 Feb 28;499:5-13. doi: 10.1016/j.canlet.2020.11.026. Epub 2020 Nov 29.

ABSTRACT

The endocrine FGF21 was discovered as a novel metabolic regulator in 2005 with new functions bifurcating from the canonic heparin-binding FGFs that directly promote cell proliferation and growth independent of a co-receptor. Early studies have demonstrated that FGF21 is a stress sensor in the liver and possibly, several other endocrine and metabolic tissues. Hepatic FGF21 signals via endocrine routes to quench episodes of metabolic derangements, promoting metabolic homeostasis. The convergence of mouse and human studies shows that FGF21 promotes lipid catabolism, including lipolysis, fatty acid oxidation, mitochondrial oxidative activity, and thermogenic energy dissipation, rather than directly regulating insulin and appetite. The white and brown adipose tissues and, to some extent, the hypothalamus, all of which host a transmembrane receptor binary complex of FGFR1 and co-receptor KLB, are considered the essential tissue and molecular targets of hepatic or pharmacological FGF21. On the other hand, a growing body of work has revealed that pancreatic acinar cells form a constitutive high-production site for FGF21, which then acts in an autocrine or paracrine mode. Beyond regulation of macronutrient metabolism and physiological energy expenditure, FGF21 appears to function in forestalling the development of fatty pancreas, steato-pancreatitis, fatty liver, and steato-hepatitis, thereby preventing the development of advanced pathologies such as pancreatic ductal adenocarcinoma or hepatocellular carcinoma. This review is intended to provide updates on these new discoveries that illuminate the protective roles of FGF21-FGFR1-KLB signal pathway in metabolic anomalies-associated severe tissue damage and malignancy, and to inform potential new preventive or therapeutic strategies for obesity-inflicted cancer patients via reducing metabolic risks and inflammation.

PMID:33264641 | PMC:PMC7779663 | DOI:10.1016/j.canlet.2020.11.026
Notch3 Knockout Suppresses Mouse Mammary Gland Development and Inhibits the Proliferation of 4T1 Murine Mammary Carcinoma Cells via CCL2/CCR4 Axis

Fetched: February 24th, 2021, 5:00am GMT by Wei Xiong

Front Cell Dev Biol. 2020 Nov 17;8:594372. doi: 10.3389/fcell.2020.594372. eCollection 2020.

ABSTRACT

Our previous study found that Notch3 knockout mice exhibit defects in mammary gland development. To elucidate the underlying mechanism, tissue samples were subjected to RNA-seq, GO, and KEGG enrichment analyses and qRT-PCR validation. Of enriched pathways, chemokine signaling pathway and cytokine-cytokine receptor interaction were noticed in both Notch3^wt/wt/Notch3^wt/- and Notch3^wt/wt/Notch3^-/- mice, in which the expression of chemokine ligand 2 (CCL2) was sharply reduced in Notch3^wt/- and Notch3^-/- mammary gland tissues. The Mouse ENCODE transcriptome data reveal that the mammary gland fat pad exhibits a high CCL2, CCR2, and CCR4 expression, indicating that these molecules play important roles during mammary gland development. Specifically, defective mammary glands in Notch3 knockout mice could be partially rescued by CCL2 overexpression lentivirus through intraductal injection. An in vitro study showed that CCL2 overexpression promoted the proliferation, migration, and cancerous acinar formation of 4T1 cells, which could rescue the defective migration of 4T1 cells caused by Notch3 knockdown. We also found that Notch3 transcriptionally regulated the expression of CCL2 in a classical pattern. Our findings illustrated that Notch3-regulating CCL2/CCR4 axis should be an important signaling pathway for mammary gland development and should be a candidate target for breast cancer therapy.

PMID:33244467 | PMC:PMC7685216 | DOI:10.3389/fcell.2020.594372
Correlation between magnetic resonance imaging and extemporaneous and definitive histological examination of parotid gland tumors: a case series

Fetched: February 24th, 2021, 5:00am GMT by Najib Zouhair

Pan Afr Med J. 2020 Sep 22;37:80. doi: 10.11604/pamj.2020.37.80.21192. eCollection 2020.

ABSTRACT

Parotid gland tumor is complex and poses diagnostic and therapeutic problems. The purpose of this study was to assess the role of extemporaneous examination in the management of patients with parotid gland tumors. We report a pro and retrospective analytical study of a series of cases of salivary gland tumors, whose data were collected in the ENT and in the department of cervical-facial Surgery at the University Hospital in Casablanca, between January 2012 and December 2015. Seventy two cases of parotid tumors were recorded. The sex-ratio (H/F) was 0.94, 0.76 for patients with benign tumors and 1.62 for patients with malignant tumors. The average age was 47 years (15- 75 years). The median of consultation time was 40 months. Clinical symptoms were dominated by parotid swelling (100%), pain in 25% of patients, facial palsy in 6%, and cervical adenopathies in 10%. Ultrasound was recommended in 80% of patients. MRI was performed in 26% of cases. All patients underwent surgery, 76% of patients underwent exofacial parotidectomies and 24% total conservative parotidectomies. This treatment was associated with ganglion resection in 24% of cases and radiotherapy in 24% of cases. Extemporaneous examination was performed in 71% of patients, its susceptibility was 89% and its specificity 88%. Definitive histological diagnosis was confirmed by anatomopathological examination in all cases. We confirmed benign and malignant tumors in 71% and 29% of cases respectively. Benign tumors were dominated by pleomorphic adenoma (59%), while malignant lesions were dominated by mucoepidermoid carcinoma (38%). The postoperative course was marked by: discrete haematoma in 4% of cases, transient facial palsy in 15%, superinfection of the wound in 3% and post-parotidectomy Frey´s syndrome in 3% of patients. One patient had labial recurrence of acinar cell carcinoma. No cases of death were noted. Parotid gland tumors are characterized by a great histological variability. Differentiation between malignant tumor and benign tumor is often difficult. Currently, MRI is the imaging test of choice. Extemporaneous examinationis is very useful intraoperatively when it is necessary to communicate with the pathologist. Multidisciplinary approach is adopted including ENT, oncological, radiotherapeutic, pathological and radiological approaches. Prognosis depends on the histological type, the stage of progression and treatment.

PMID:33244343 | PMC:PMC7680246 | DOI:10.11604/pamj.2020.37.80.21192
Histo- and clinico-pathological analysis of a large series of triple-negative breast cancer in a single center in China: Evidences on necessity of histological subtyping and grading

Fetched: February 24th, 2021, 5:00am GMT by Shuang Zhang

Chin J Cancer Res. 2020 Oct 31;32(5):580-595. doi: 10.21147/j.issn.1000-9604.2020.05.03.

ABSTRACT

OBJECTIVE: To investigate histo-pathological distribution and clinico-pathological significance in a large Chinese triple-negative breast cancer (TNBC) patients serials based on the latest understanding of its clinico-pathological diversity, and to provide more information to clinicians to improve precision of individualized treatment of TNBC.

METHODS: A retrospective analysis was performed on patients with TNBC at Breast Disease Center, Peking University First Hospital between January 2010 and December 2019. Histo- and clinico-pathological characteristics were analyzed by Chi-square test and Student's t-test, and prognoses were calculated using Kaplan-Meier method and a Cox proportionate hazards model. Bonferroni correction was used to correct for multiple comparison.

RESULTS: Conventional type of TNBC (cTNBC) were identified in 73.7% of 582 TNBC, while special type of TNBC (sTNBC) were 26.3%, including 71 apocrine carcinoma, 20 medullary carcinoma, 31 metaplastic carcinoma, 18 invasive lobular carcinoma, 7 invasive micropapillary carcinoma, 5 adenoid cystic carcinoma and 1 acinic cell carcinoma. Compared to sTNBC, cTNBC was associated with high histologic grade (P<0.001) and lower androgen receptor (AR) expression (P<0.001). TNM stage of low-grade cTNBC was significantly lower than that of high-grade cTNBC (P=0.002). Although no significant difference, there was a trend that the rate of 5-year disease-free survival (DFS) and 5-year overall survival (OS) were longer in high-grade cTNBC than in high-grade sTNBC (P=0.091 and 0.518), and were longer in low-grade sTNBC than in high-grade sTNBC (P=0.051 and 0.350). Metaplastic carcinomas showed larger tumor size (P=0.008) and higher proliferative Ki67 index (P=0.004) than cTNBCs.

CONCLUSIONS: Results from our cohort imply that sub-categorization or subtyping and histological grading could be meaningful in pathological evaluation of TNBC, and need to be clarified in more large collections of TNBC.

PMID:33223753 | PMC:PMC7666778 | DOI:10.21147/j.issn.1000-9604.2020.05.03
Fine needle aspiration of salivary gland carcinomas with high-grade transformation: A multi-institutional study of 22 cases and review of the literature

Fetched: February 24th, 2021, 5:00am GMT by Masato Nakaguro

Cancer Cytopathol. 2020 Nov 19. doi: 10.1002/cncy.22388. Online ahead of print.

ABSTRACT

BACKGROUND: High-grade transformation (HGT) is a rare process whereby conventional low- to intermediate-grade salivary gland carcinomas (SGC) transform into high-grade, poorly or undifferentiated malignancies with focal or complete loss of their conventional histomorphologic features. Because tumors with HGT are associated with a worse prognosis than their conventional counterparts, preoperative recognition of HGT may be of benefit for optimal patient management. Using a multi-institutional approach, we describe the largest fine needle aspiration (FNA) cohort of salivary gland carcinomas with HGT.

METHODS: The archives of 9 large academic medical centers were searched, and 22 cases of SGC with HGT were identified by surgical excision accompanied by preoperative FNA. Clinical and cytomorphologic features were retrospectively reviewed.

RESULTS: The male-to-female ratio was 14:8, and the mean patient age was 60.2 years. The average tumor size was 3.6 cm, and 19 cases were from the parotid gland. Acinic cell carcinoma with HGT was the most common tumor subtype, comprising 12 cases with HGT, followed by adenoid cystic carcinoma, secretory carcinoma, and other subtypes. Eighteen cases were classified as malignant; however, a specific diagnosis of HGT was not made. Sixteen cases contained a high-grade cytologic component, and 7 cases had a mixture of both conventional and high-grade components retrospectively.

CONCLUSIONS: SGC with HGT should be considered in the differential diagnosis of a salivary gland aspirate exhibiting high-grade cytomorphologic features. The presence of distinct tumor populations, conventional and high-grade, should prompt consideration of HGT, especially when the conventional component is acinic cell carcinoma or adenoid cystic carcinoma.

PMID:33211402 | DOI:10.1002/cncy.22388
The surgical management of metastatic pancreatic acinar cell carcinoma and associated pancreatic panniculitis-A case report and literature review

Fetched: February 24th, 2021, 5:00am GMT by Edward M Clarke

Int J Surg Case Rep. 2020;76:539-544. doi: 10.1016/j.ijscr.2020.10.062. Epub 2020 Oct 19.

ABSTRACT

INTRODUCTION: Pancreatic panniculitis is a rare manifestation of benign and malignant pancreatic disease. The presentation of pancreatic panniculitis is non-specific and thus diagnosis is often delayed. When associated with malignancy, pancreatic panniculitis confers a poor prognosis. This case demonstrates the successful surgical management of this paraneoplastic phenomenon following resection of the underlying pancreatic acinar cell carcinoma and associated liver metastasis.

PRESENTATION OF CASE: A 71-year-old female with debilitating subcutaneous lower limb lesions had a delayed diagnosis of pancreatic panniculitis. A formal diagnosis of pancreatic acinar cell carcinoma with liver metastasis was established and the disease was determined to be resectable. Pre-operatively, serum lipase measured 10,825 U/L. The patient proceeded to an open left hemihepatectomy and radical distal pancreatectomy with complete resection of malignant disease. Six days post-operatively the serum lipase levels normalised, and the panniculitis began to settle. The patient proceeded to adjuvant FOLFORINOX chemotherapy. Twenty months post-surgery, the patient remains disease-free and without any evidence of panniculitis.

DISCUSSION: Due to the rarity of pancreatic acinar cell carcinoma, guidelines based on prospective data do not exist. Most management is based on retrospective analyses. A survival benefit may be achieved with more aggressive surgical management compared to other pancreatic cancer types. Pancreatic acinar cell carcinoma may show a slower rate of disease progression, an increased likelihood of resectability of disease at presentation and is more likely to undergo potentially curative resection.

CONCLUSION: Aggressive surgical management of resectable metastatic pancreatic acinar cell carcinoma can treat pancreatic panniculitis and provide sustained disease-free survival from pancreatic cancer.

PMID:33207427 | PMC:PMC7599369 | DOI:10.1016/j.ijscr.2020.10.062
Acinic cell carcinoma of the salivary gland in the adult and paediatric population: a survival analysis

Fetched: February 24th, 2021, 5:00am GMT by Anders Sideris

ANZ J Surg. 2020 Nov 17. doi: 10.1111/ans.16421. Online ahead of print.

ABSTRACT

BACKGROUND: Acinic cell carcinoma (AcCC) is a rare malignant neoplasm of the salivary glands and generally considered to be a low-grade tumour. Surgical treatment is often curative, but a more aggressive high-grade variant has been associated with poorer survival and propensity for distant metastasis. No standard treatment guidelines exist and the approach to treatment is varied in the published series. The aim of this study is to present the experience of three major hospitals in Sydney, Australia, in treating AcCC of the salivary gland, with a focus on clinico-pathological features of disease and their associations with survival outcomes.

METHODS: Adult and paediatric cases of AcCC of the salivary gland during the time period 1979-2018 were retrospectively included. Demographic, clinico-pathological, treatment and survival outcome data were extracted. Survival analysis was undertaken to assess the effect of clinical and pathological variables on overall and disease-free survival.

RESULTS: Thirty-two cases were reviewed (29 adult and three paediatric). Thirty tumours (93.8%) were parotid gland primary tumours. Mean overall and disease-free survival was 17.0 ± 0.7 and 16.0 ± 0.9 years, respectively. Features associated with poorer survival were cT staging >1, presence of preoperative clinical facial nerve deficit and local recurrence. Positive margins were associated with recurrence.

CONCLUSION: These data suggest that disease-free and overall survival in AcCC of the salivary gland is excellent with surgery as the first-line treatment. Poor survival outcomes are uncommon and may be associated with locally advanced disease in the presence of other well-established high-risk features.

PMID:33205582 | DOI:10.1111/ans.16421
Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

Fetched: February 24th, 2021, 5:00am GMT by Larissa Di Villeneuve

Front Oncol. 2020 Oct 22;10:580141. doi: 10.3389/fonc.2020.580141. eCollection 2020.

ABSTRACT

Salivary gland carcinomas (SGCs) account for <5% of head and neck malignant neoplasms, further subcategorized in over 20 histological subtypes. For the most part, treatment for advanced disease is guided by morphology. SGCs in general respond poorly to a wide array of standard chemotherapy, with short durability, and significant toxicity. More recently, next-generation sequencing provided significant input on the molecular characterization of each SGC subtype, not only improving diagnostic differentiation between morphologically similar tumor types but also identifying novel driver pathways that determine tumor biology and may be amenable to targeted therapy. Among the most common histological subtype is adenoid cystic carcinoma, which often harbors a chromosome translocation resulting in an MYB-NFIB oncogene, with various degrees of Myb surface expression. In a smaller subset, NOTCH1 mutations occur, conferring a more aggressive pattern and potential sensitivity to Notch inhibitors. Salivary duct carcinomas may overexpress Her-2 and androgen receptors, with promising clinical outcomes after exposure to targeted therapies approved for other indications. Secretory carcinoma, previously known as mammary analog secretory carcinoma, is distinguished by an ETV6-NTRK3 fusion that can both help differentiate it from its morphologically similar acinar cell carcinoma and make it susceptible to Trk inhibitors. In the present article, we discuss the molecular abnormalities, their impact on tumor biology, and therapeutic opportunities for the most common SGC subtypes and review published and ongoing clinical trials and future perspectives for this rare disease.

PMID:33194707 | PMC:PMC7649804 | DOI:10.3389/fonc.2020.580141
Malignant epithelial/exocrine tumors of the pancreas

Fetched: February 24th, 2021, 5:00am GMT by Claudio Luchini

Pathologica. 2020 Sep;112(3):210-226. doi: 10.32074/1591-951X-167.

ABSTRACT

Pancreatic malignant exocrine tumors represent the most important cause of cancer-related death for pancreatic neoplasms. The most common tumor type in this category is represented by pancreatic ductal adenocarcinoma (PDAC), an ill defined, stroma-rich, scirrhous neoplasm with glandular differentiation. Here we present the relevant characteristics of the most important PDAC variants, namely adenosquamous carcinoma, colloid carcinoma, undifferentiated carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, signet ring carcinoma, medullary carcinoma and hepatoid carcinoma. The other categories of malignant exocrine tumors, characterized by fleshy, stroma-poor, circumscribed neoplasms, include acinar cell carcinoma (pure and mixed), pancreatoblastoma, and solid pseudopapillary neoplasms. The most important macroscopic, histologic, immunohistochemical and molecular hallmarks of all these tumors, highlighting their key diagnostic/pathological features are presented. Lastly, standardized indications regarding gross sampling and how to compile a formal pathology report for pancreatic malignant exocrine tumors will be provided.

PMID:33179623 | DOI:10.32074/1591-951X-167
Heterotopic acinic cell carcinoma: A literature review and clinical implications

Fetched: February 24th, 2021, 5:00am GMT by Ivo Starek

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2021 Mar;165(1):13-18. doi: 10.5507/bp.2020.047. Epub 2020 Nov 12.

ABSTRACT

This is a review of the clinical and histopathological published data on very rare heterotopic acinic cell carcinomas (AcCCs) with suggested optimal management. Extrasalivary AcCCs originate primarily in parotid lymph nodes. They present at low clinical stage, show mostly low-grade histopathology and are circumscribed with a complete nodal capsule. Extracapsular dissection was advocated as adequate therapy. In rare cases with positive surgical margins, a completion parotidectomy or adjuvant radiotherapy should follow. Heterotopic high-grade AcCCs are rare, necessitating radical surgery including neck dissection and adjuvant radiotherapy. The short term prognosis is excellent, long term outcomes are not known. Longer term follow-up is essential.

PMID:33177745 | DOI:10.5507/bp.2020.047
Pulmonary Adenocarcinomas of Low Malignant Potential: Proposed Criteria to Expand the Spectrum Beyond Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma

Fetched: February 24th, 2021, 5:00am GMT by Ilyas Yambayev

Am J Surg Pathol. 2021 Apr 1;45(4):567-576. doi: 10.1097/PAS.0000000000001618.

ABSTRACT

Lung cancer screening has improved mortality among high-risk smokers but has coincidentally detected a fraction of nonprogressive adenocarcinoma historically classified as bronchoalveolar carcinoma (BAC). In the National Lung Screening Trial (NLST) the majority of BAC-comprising 29% of computed tomography-detected stage I lung adenocarcinoma-were considered overdiagnosis after extended follow-up comparison with the control arm. In the current classification, adenocarcinoma in situ and minimally invasive adenocarcinoma have replaced BAC but together comprise only ∼5% of stage I lung adenocarcinoma. Lepidic and subsets of papillary and acinar adenocarcinoma also infrequently recur. We, therefore, propose criteria for low malignant potential (LMP) adenocarcinoma among nonmucinous adenocarcinoma measuring ≤3 cm in total, exhibiting ≥15% lepidic growth, and lacking nonpredominant high-grade patterns (≥10% cribriform, ≥5% micropapillary, ≥5% solid), >1 mitosis per 2 mm2, angiolymphatic or visceral pleural invasion, spread through air spaces or necrosis. We tested these criteria in a multi-institutional cohort of 328 invasive stage I (eighth edition) and in situ adenocarcinomas and observed 16% LMP and 7% adenocarcinoma in situ/minimally invasive adenocarcinoma which together (23%) approximated the frequency of overdiagnosed stage I BAC in the NLST. The LMP group had 100% disease-specific survival. The proposed LMP criteria, incorporating multiple histologic parameters, may be a clinically useful "low-grade" prognostic group. Validation of these criteria in additional retrospective cohorts and prospective screen-detected cohorts should be considered.

PMID:33177339 | DOI:10.1097/PAS.0000000000001618
Volume and Mass Doubling Time of Lung Adenocarcinoma according to WHO Histologic Classification

Fetched: February 24th, 2021, 5:00am GMT by Jung Hee Hong

Korean J Radiol. 2021 Mar;22(3):464-475. doi: 10.3348/kjr.2020.0592. Epub 2020 Oct 30.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification.

MATERIALS AND METHODS: Among the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed.

RESULTS: The median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma.

CONCLUSION: The tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification.

PMID:33169551 | PMC:PMC7909861 | DOI:10.3348/kjr.2020.0592
Therapeutic implications of immune-profiling and EGFR expression in salivary gland carcinoma

Fetched: February 24th, 2021, 5:00am GMT by Emily Guazzo

Head Neck. 2021 Mar;43(3):768-777. doi: 10.1002/hed.26529. Epub 2020 Nov 9.

ABSTRACT

BACKGROUND: Data relating to the efficacy of immune checkpoint inhibitors (ICI) for salivary gland carcinomas (SGC) is gradually evolving with responses varying among different histotypes. To address these disparities, this retrospective analysis examined the prevalence of recognized biomarkers of response to ICI; namely programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), combined positive score (CPS), epidermal growth factor receptor (EGFR), and microsatellite instability (MSI) in patients with SGC with an aim to determine any prognostic or survival benefits and stratify the use of ICI in this disease.

PATIENTS AND METHODS: Of 52 patients with primary SGC eligible for this study, the most common histological types were adenoid cystic carcinoma (n = 17, 33%), salivary duct carcinoma (n = 14, 27%), mucoepidermoid carcinoma (n = 11, 21%), and acinic cell carcinoma (n = 6, 11%). Immunohistochemistry (IHC) was performed using the Ventana Discovery Ultra auto-staining platform for EGFR, PD-1, PD-L1, and mismatch repair (MMR) proteins. CPS ≥1 defined PD-L1 positive cases and log-rank testing was performed to examine the relationship between PD-L1 expression status and disease-free survival (DFS) and overall survival (OS).

RESULTS: CPS positivity was seen in 9 (17.3%) patients, none of which were adenoid cystic carcinoma. All 52 (100%) cases expressed retained MMR proteins inferring microsatellite stability (MSS) and EGFR expression was identified in 45 of 52 (86.5%) patients. CPS positivity (score ≥1) was significantly associated with advanced pathological T status (P = .021), advanced pathological N status (P = .006), high histological tumor grade (P = .045), and positive histological margin (P = .023). Patients with PD-L1 positivity in tumor cells did not have an inferior 3-year OS (P = .93).

CONCLUSION: The data from this retrospective study highlighting the uniform microsatellite stability alongside the low prevalence of CPS positivity suggests that only a minority of SGC patients may benefit from ICI therapy alone. The high rates of EGFR expression in SGC may be a target to augment immune checkpoint therapy response.

PMID:33169486 | DOI:10.1002/hed.26529
A Very Rare Complication of Vocal Fold Augmentation With Calcium Hydroxylapatite: Neck Abscess

Fetched: February 24th, 2021, 5:00am GMT by Ory Madgar

J Voice. 2020 Nov 2:S0892-1997(20)30409-4. doi: 10.1016/j.jvoice.2020.10.018. Online ahead of print.

ABSTRACT

INTRODUCTION: Vocal fold injection augmentation is performed routinely for the treatment of glottic insufficiency especially due to unilateral vocal fold paralysis. There are numerous materials that are used for injection laryngoplasty, calcium hydroxylapatite being one of them.

CASE REPORT: We present an interesting case of a 64-year-old male patient with metastatic acinic cell carcinoma of the right parotid gland, who underwent right vocal cord injection laryngoplasty with calcium hydroxylapatite for right vocal cord paralysis with glottal insufficiency and developed a neck abscess.

DISCUSSION: This is the first report in the literature of neck abscess following vocal fold injection laryngoplasty using calcium hydroxylapatite. It seems that over injection of the vocal fold gave rise to extravasation of the injected material outside the laryngeal framework which later became a nidus for infection.

CONCLUSIONS: We present the first case in the literature of neck abscess following vocal fold injection laryngoplasty using calcium hydroxylapatite. Clinicians should be aware of this rare but dangerous complication.

PMID:33153855 | DOI:10.1016/j.jvoice.2020.10.018
Expression of NR4A3/NOR-1 in acinic cell carcinoma of the salivary gland

Fetched: February 24th, 2021, 5:00am GMT by K Cheng

Zhonghua Bing Li Xue Za Zhi. 2020 Nov 8;49(11):1142-1146. doi: 10.3760/cma.j.cn112151-20200224-00127.

ABSTRACT

Objective: To investigate the diagnostic role of NR4A3/NOR-1 immunohistochemistry in acinic cell carcinoma (AciCC) of the salivary gland. Methods: A total of 142 tumors were collected from 2004 to 2020 at Nanjing Jinling Hospital, including 24 cases of AciCCs, 12 salivary gland secretory carcinomas,14 salivary duct carcinomas,16 adenoid cystic carcinomas,3 basal cell carcinomas,13 mucoepidermoid carcinomas,7 myoepithelial carcinomas,15 pleomorphic adenomas,15 warthin tumor, 8 myoepithelioma,8 basal cell adenomas, and 7 oncocytomas; 28 normal salivary gland tissues and 2 pancreatic AciCC were also included. Results: NR4A3/NOR-1,a nuclear marker,was positive in 91.7% (22/24) of AciCC of the salivary gland,while DOG1,a membranous and cytoplasmic marker, demonstrated a sensitivity of 95.8% (23/24);there was no significant difference in the overall positive rates(P=0.551), but the stain pattern was different. NR4A3/NOR-1 was negative in normal salivary gland tissues and any other types of tumors in the salivary gland; however,DOG1 showed apical staining in the acinar cells in the salivary gland,as well as salivary gland secretory carcinomas,adenoid cystic carcinomas,basal cell carcinomas,mucoepidermoid carcinomas,myoepithelial carcinomas and basal cell adenomas(P<0.001). NR4A3/NOR-1 showed a high sensitivity(91.7%) and specificity(100%) to identify AciCC of the salivary gland,and in combination with DOG1, the sensitivity increased to 100%. Furthermore, NR4A3/NOR-1 were only positive for AciCC arising from salivary glands but not pancreas(0/2)(P=0.018). Conclusion: NR4A3/NOR-1 is a special and sensitive biomarker for AciCC of salivary glands; combined NR4A3/NOR-1 and DOG1 can be an ideal diagnostic immunohistochemical panel for AciCC.

PMID:33152819 | DOI:10.3760/cma.j.cn112151-20200224-00127
The cytologic and immunohistochemical findings of pancreatic mixed acinar-endocrine carcinoma

Fetched: February 24th, 2021, 5:00am GMT by Rachel Whitehair

Diagn Cytopathol. 2021 Feb;49(2):287-294. doi: 10.1002/dc.24641. Epub 2020 Oct 31.

ABSTRACT

BACKGROUND: The classification of epithelioid pancreatic neoplasms based on fine-needle aspiration (FNA) is important for proper management, as distinction of pancreatic neuroendocrine neoplasms from other similar appearing lesions can result in significantly different treatment. Mixed acinar-endocrine carcinomas (MAEC) are genetically related to acinar carcinomas and are treated as such. We reviewed cases of MAEC to better characterize their cytologic and immunohistochemical features.

METHODS: Eight FNAs of MAECs were identified and reviewed. A chart review for each case was conducted.

RESULTS: All patients were male, 42-68 years of age, and presented with either Stage 3 or 4 disease. Smear backgrounds of all cases showed naked nuclei without significant necrosis. The smears were cellular with cells arranged in either three-dimensional (3D) clusters with intervening capillaries or singly dispersed. Acinar formation was a prominent feature. Cells were round to oval with small to moderate amounts of delicate cytoplasm. The nuclei were round to oval with mild to moderate anisonucleosis with granular chromatin and small nucleoli. Apoptotic bodies and mitoses were noted in most cases, with Ki67 indices of 10%-48%. All tumors, by definition, demonstrated expression of trypsin and synaptophysin with variable chromogranin expression (50%).

CONCLUSION: The cytology of acinar cell carcinoma shares features with aspirates of other nonductal adenocarcinoma neoplasms of the pancreas. A clue to the diagnosis is that tumors show high Ki67 indices and a diagnosis of MAEC should be excluded anytime a diagnosis of Grade 2 or 3 well-differentiated neuroendocrine tumor or high-grade neuroendocrine carcinoma is in the differential.

PMID:33128511 | DOI:10.1002/dc.24641
Clinical Analysis of Acinar Cell Carcinoma of the Pancreas: A Single-Center Experience of 45 Consecutive Cases

Fetched: February 24th, 2021, 5:00am GMT by Wentao Zhou

Cancer Control. 2020 Jan-Dec;27(1):1073274820969447. doi: 10.1177/1073274820969447.

ABSTRACT

BACKGROUNDS: Acinar cell carcinoma of the pancreas is a rare malignancy, and its features remain unclear. We aimed to analyze the clinical characteristics, treatment and prognosis of acinar cell carcinoma with our institutional case series.

METHODS: Patients diagnosed with acinar cell carcinoma in our hospital between 2005 and 2019 were reviewed. Investigations on clinicopathological features, treatment details and long-term survival were performed.

RESULTS: A total of 45 pathologically confirmed acinar cell carcinomas were identified. The median age at diagnosis was 58 years with a male-to-female ratio of 3.1:1. There were 24 (53.3%) localized, 5 (11.1%) locally advanced and 16 (35.6%) metastatic cases, with a pancreatic head-to-body/tail ratio of 1:1.4 for all the primary lesions. In the localized group, there were 10 pancreatoduodenectomy, 12 distal pancreatectomy, 1 total pancreatectomy, and 1 distal pancreatectomy combined with proximal gastrectomy. Among the locally advanced and metastatic cases, 13 patients received chemotherapy, 1 received concurrent radiochemotherapy, 1 underwent synchronous resection of primary tumor and liver metastasis, 1 underwent palliative operation, 1 underwent exploratory laparotomy, and 4 required no treatment. The median overall survival of this series was 18.9 months with a 5-year survival rate of 19.6%. Moreover, the resected acinar cell carcinoma patients were associated with prolonged survival compared with the unresected cases (36.6 vs. 8.5 months, P < 0.001).

CONCLUSIONS: Surgical resection could improve the long-term survival of acinar cell carcinoma patients, which might also improve the prognosis of selected metastatic cases. Large-scale studies are needed to further clarify the biological behavior and clinical features, and to seek the optimal treatments.

PMID:33121259 | DOI:10.1177/1073274820969447
Unusual cerebrospinal fluid finding of intracytoplasmic granules in metaplastic carcinoma of the breast with acinar differentiation

Fetched: February 24th, 2021, 5:00am GMT by Ruhani Sardana

Diagn Cytopathol. 2020 Oct 28. doi: 10.1002/dc.24648. Online ahead of print.

ABSTRACT

Cerebrospinal fluid (CSF) evaluation for total and differential cell count is a common practice in pathology for evaluation of various disease conditions. Although rare, these CSF samples yield interesting and unusual morphological findings, which are not only of academic interest, but also may play key roles in diagnosis. For diagnosing metastatic carcinoma in brain and meninges, CSF examination is one of the important tools along with imaging studies. Metaplastic breast carcinoma (MBC) encompasses a rare (<1% of all breast cancers), aggressive and highly heterogeneous group of tumors. MBC is almost always estrogen receptor, progesterone receptor and Her2 negative (triple negative) and shows frequent early distant metastases as well as sub-optimal response to systemic therapies. The involvement of leptomeninges is most commonly associated with these triple- negative subtypes. In this report, we present an unusual case of malignant cells with prominent intracytoplasmic granules in CSF smears of a 46-year-old female with metastatic MBC with acinar differentiation. An extensive review of literature in English language did not return any other reports of a similar finding.

PMID:33118313 | DOI:10.1002/dc.24648
Clinicopathologic Features and Survival Trends for Acinic Cell Carcinoma of the Major Salivary Glands: A Surveillance, Epidemiology, and End Results Population Analysis

Fetched: February 24th, 2021, 5:00am GMT by Erin A Kaya

World J Oncol. 2020 Oct;11(5):188-196. doi: 10.14740/wjon1312. Epub 2020 Oct 15.

ABSTRACT

BACKGROUND: We analyzed a population-based national registry to identify the most influential patient pretreatment and treatment factors affecting overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with acinic cell carcinoma (ACC) of the major salivary glands.

METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) related to survival, a total of 1,254 patients with diagnosed ACC of the major salivary glands from 1975 to 2016 met inclusion criteria. Factors significant for OS and CSS were determined using univariate and multivariate analysis with the Cox proportional hazards model.

RESULTS: Univariate OS analysis demonstrated that surgery favorably influenced longer survival compared to no surgery (hazard ratio (HR) 2.35, P < 0.05). Patient age was found to be highly predictive of superior OS (divided into 10-year age bands, P < 0.0001, younger age better). In multivariate OS analysis, there were statistically significant worse outcomes for men (HR 1.54, P < 0.05), grades III/IV (HR 2.5, P < 0.05), and distant disease (HR 3.55, P < 0.05) or regional disease (HR 1.22, P < 0.05). Patients diagnosed during years 1996 - 2016 had better OS when compared to earlier decades 1975 - 1995 (HR 1.38, P < 0.05). In univariate analysis, the mean CSS for grades I, II, and III/IV were 429 months (95% confidence interval (CI), ± 38.39), 426 months (95% CI, ± 25.73) and 198 months (95% CI, ± 66.38). Multivariate analysis of CSS further demonstrated that there were statistically significant worse outcomes for men (HR 1.68, P < 0.05), grade III/IV (HR 3.2, P < 0.05), tumor size greater than 40 mm (P < 0.001), and distant disease (HR 4.48, P < 0.05) or regional disease (HR 1.84, P < 0.05).

CONCLUSIONS: To our knowledge, this is the largest population-based study of OS and CSS of major salivary gland ACC. We found that the patient pretreatment and treatment factors including younger age at diagnosis, female sex, early stage, lower grade, surgical excision, and recent year of diagnosis are associated with improved survival in patients diagnosed with ACC of the major salivary glands. We hope that this information will aid in construction of further research projects that better refine optimal treatment protocol of individualized patient care.

PMID:33117462 | PMC:PMC7575277 | DOI:10.14740/wjon1312
Cytological Diagnosis of Acinic Cell Carcinoma. A Study of Four Cases with Emphasis on Differential Diagnosis and DOG1 Expression

Fetched: February 24th, 2021, 5:00am GMT by Sheefa Haq

J Cytol. 2020 Jul-Sep;37(3):155-156. doi: 10.4103/JOC.JOC_175_18. Epub 2020 Jul 13.

NO ABSTRACT

PMID:33088038 | PMC:PMC7542039 | DOI:10.4103/JOC.JOC_175_18
Malignant Tumors of the Palate

Fetched: February 24th, 2021, 5:00am GMT by Allen Young

2020 Oct 22. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–.

ABSTRACT

Malignancies of the hard and soft palate have a wide variety of characteristics. The hard palate, a subsite of the oral cavity, comprises the palatine bone's horizontal plate and the palatine process of the maxillary bone. Its boundaries include the alveolar ridge anteriorly, the soft palate posteriorly, the nasal cavity superiorly, and the oral cavity inferiorly. The hard palate is rich in minor salivary glands with close interaction between its mucosa and the underlying periosteum. This unique composition creates a different array of malignancies compared with other oral subsites.

The soft palate, on the other hand, is a subsite of the oropharynx. It is bordered by the hard palate anteriorly, palatoglossal and palatopharyngeal muscles laterally, and the uvula posteriorly. The most common malignant tumor histologies of the hard and soft palate include squamous cell carcinoma (SCC), mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), polymorphous low-grade adenocarcinoma (PLGA), low-grade papillary adenocarcinoma (LGPA), acinic cell carcinoma (ACC), mucosal melanoma (MM), Kaposi sarcoma (KS), and non-Hodgkin lymphoma (NHL).

PMID:33232096 | Bookshelf:NBK564515

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