The American Journal of Surgical Pathology最新文献

{"title":"Prominent Pseudoacini in Focal Nodular Hyperplasia: A Potential Diagnostic Pitfall.","authors":"Donghai Wang,&nbsp;Iván A González,&nbsp;Pierre A Russo,&nbsp;Dhanpat Jain,&nbsp;Xuchen Zhang","doi":"10.1097/PAS.0000000000001931","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001931","url":null,"abstract":"<p><p>Pseudoacini are generally a morphologic feature of hepatocellular carcinoma (HCC), being absent or rare in benign hepatocytic tumors, such as hepatocellular adenoma. However, rarely these can be seen in focal nodular hyperplasia (FNH) and may pose diagnostic challenges, especially when prominent. The study was aimed to evaluate the occurrence of pseudoacini in FNH and their clinicopathologic correlations. A total of 95 FNH cases diagnosed from 2005 to 2020 were included in the study. A pseudoacinus was defined as a circular arrangement of hepatocytes around a central dilated lumen present within the lobular parenchyma of the lesion with or without inspissated bile. Among the 95 FNH cases, 28 (29.5%) showed pseudoacini, which were prominent in 12 (12.6%) cases. Of these 3 occurred in patients above 50 years old. The pseudoacini were numerous in 3 cases, leading to an initial consideration of HCC in the differential diagnosis, and 1 case was diagnosed as well-differentiated hepatocellular neoplasm on initial biopsy. All 12 cases showed map-like staining pattern for glutamine synthetase. The hepatocytes forming the pseudoacini were positive for CK7 and HepPar1, while the inner lumina were highlighted by CD10 and bile salt export pump immunostains similar to adjacent canaliculi. The presence of prominent pseudoacini was not significantly associated with any clinical or pathologic features. The findings suggest that pseudoacini are likely manifestation of hepatocyte biliary transdifferentiation associated with chronic cholestasis in the lesion. This feature may pose a potential diagnostic pitfall especially on needle biopsies and awareness is needed to avoid misdiagnosing this as HCC.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1380-1385"},"PeriodicalIF":5.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40396985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morules But Not Squamous Differentiation are a Reliable Indicator of CTNNB1 (β-catenin) Mutations in Endometrial Carcinoma and Precancers.","authors":"Shuang Niu,&nbsp;Elena Lucas,&nbsp;Kyle Molberg,&nbsp;Amanda Strickland,&nbsp;Yan Wang,&nbsp;Kelley Carrick,&nbsp;Glorimar Rivera-Colon,&nbsp;Katja Gwin,&nbsp;Jeffrey A SoRelle,&nbsp;Diego H Castrillon,&nbsp;Wenxin Zheng,&nbsp;Hao Chen","doi":"10.1097/PAS.0000000000001934","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001934","url":null,"abstract":"<p><p>Although collectively regarded as \"squamous differentiation (SD)\" in endometrial endometrioid carcinoma (EEC) and atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), morules (often referred to as \"squamous morules\") and true SD may represent two distinct phenomena. Here, we explored the distinction between morules versus SD and investigated the association of morules and SD with CTNNB1 mutations. A total of 270 cases of EEC and AH/EIN were studied, including EEC with (n=36) or without (n=36) morules and AH/EIN with (n=80) or without (n=118) morules. Cases were analyzed by immunohistochemistry and selected cases (n=20) by targeted next-generation sequencing panel. Near-perfect agreement was found between morules and glandular β-catenin nuclear staining in AH/EIN and EEC. A strong positive association was found between morules and glandular β-catenin nuclear staining ( P &lt;0.0001, Φ=0.59 in AH/EIN; P &lt;0.0001, Φ=0.85 in EEC). There was no association between (1) morules and glandular PAX2 or PTEN aberrant expression or (2) SD and aberrant expression of β-catenin, PAX2 or PTEN (Φ=0.09, β-catenin; Φ=0.16, PAX2; Φ=0.13, PTEN). CTNNB1 mutations were identified in all 20 selected morule-containing cases (100%). Next-generation sequencing was performed on 2 (preprogestin and postprogestin treatment) biopsies from 1 patient, revealing identical mutational profile in morules and glands. In conclusion, (1) SD and morules are distinct biological phenomena; (2) the presence of morules, but not SD, is a reliable indicator of CTNNB1 mutations in EEC and AH/EIN. Our findings demonstrate that SD and morules are distinct biological phenomena. Since morules but not SD are associated with β-catenin mutations, the distinction is clinically relevant and should be included in diagnostic reports.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1447-1455"},"PeriodicalIF":5.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40602952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clear Cell Carcinoma (CCC) of the Cervix is a Human Papillomavirus (HPV)-independent Tumor Associated With Poor Outcome: A Comprehensive Analysis of 58 Cases: Erratum.","authors":"","doi":"10.1097/PAS.0000000000001966","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001966","url":null,"abstract":"","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1317"},"PeriodicalIF":5.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40632067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Reply: Intraductal Carcinoma of the Prostate and Nuclear Size.","authors":"Hemamali Samaratunga,&nbsp;Brett Delahunt,&nbsp;John W Yaxley,&nbsp;Shulammite Johannsen,&nbsp;Lars Egevad","doi":"10.1097/PAS.0000000000001916","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001916","url":null,"abstract":"","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1315-1317"},"PeriodicalIF":5.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40577140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic Cysts: Reappraisal of the Classification, Terminology, Differential Diagnosis, and Clinicopathologic Characteristics in 258 Cases.","authors":"Ayse Armutlu,&nbsp;Brian Quigley,&nbsp;Hegyong Choi,&nbsp;Olca Basturk,&nbsp;Gizem Akkas,&nbsp;Burcin Pehlivanoglu,&nbsp;Bahar Memis,&nbsp;Kee-Taek Jang,&nbsp;Mert Erkan,&nbsp;Burcu Erkan,&nbsp;Serdar Balci,&nbsp;Burcu Saka,&nbsp;Pelin Bagci,&nbsp;Alton B Farris,&nbsp;David A Kooby,&nbsp;Diego Martin,&nbsp;Bobby Kalb,&nbsp;Shishir K Maithel,&nbsp;Juan Sarmiento,&nbsp;Michelle D Reid,&nbsp;N Volkan Adsay","doi":"10.1097/PAS.0000000000001930","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001930","url":null,"abstract":"<p><p>The literature on liver cysts is highly conflicting, mostly owing to definitional variations. Two hundred and fifty-eight ≥1 cm cysts evaluated pathologically using updated criteria were classifiable as: I. Ductal plate malformation related (63%); that is, cystic bile duct hamartoma or not otherwise specified-type benign biliary cyst (35 with polycystic liver disease). These were female predominant (F/M=2.4), large (10 cm), often multifocal with degenerative/inflammatory changes and frequently misclassified as \"hepatobiliary cystadenoma.\" II. Neoplastic (13%); 27 (10.5%) had ovarian-type stroma (OTS) and qualified as mucinous cystic neoplasm (MCN) per World Health Organization (WHO). These were female, solitary, mean age 52, mean size 11 cm, and 2 were associated with carcinoma (1 in situ and 1 microinvasive). There were 3 intraductal papillary neoplasms, 1 intraductal oncocytic papillary neoplasm, 1 cystic cholangiocarcinoma, and 2 cystic metastasis. III. Infectious/inflammatory (12%). These included 23 hydatid cysts (including 2 Echinococcus alveolaris both misdiagnosed preoperatively as cancer), nonspecific inflammatory cysts (abscesses, inflammatory cysts: 3.4%). IV. Congenital (7%). Mostly small (<3 cm); choledochal cyst (5%), foregut cyst (2%). V. Miscellaneous (4%). In conclusion, hepatic cysts occur predominantly in women (3/1), are mostly (90%) non-neoplastic, and seldom (<2%) malignant. Cystic bile duct hamartomas and their relative not otherwise specified-type benign biliary cysts are frequently multifocal and often misdiagnosed as \"cystadenoma/carcinoma.\" Defined by OTS, MCNs (the true \"hepatobiliary cystadenoma/carcinoma\") are solitary, constitute only 10.5% of hepatic cysts, and have a significantly different profile than the impression in the literature in that essentially all are perimenopausal females, and rarely associated with carcinoma (7%). Since MCNs can only be diagnosed by demonstration of OTS through complete microscopic examination, it is advisable to avoid the term \"cystadenoma/cystadenocarcinoma\" solely based on radiologic examination, and the following simplified terminology would be preferable in preoperative evaluation to avoid conflicts with the final pathologic diagnosis: (1) noncomplex (favor benign), (2) complex (in 3 subsets, as favor benign, cannot rule out malignancy, or favor malignancy), (3) malignant features.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1219-1233"},"PeriodicalIF":5.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40577137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic Spectrum of Secondary Solid Tumors of the Prostate of Nonurothelial Origin: Multi-institutional Evaluation of 85 Cases.","authors":"Andres M Acosta,&nbsp;Jennifer B Gordetsky,&nbsp;Katrina Collins,&nbsp;Adeboye O Osunkoya,&nbsp;Ankur R Sangoi,&nbsp;Hiroshi Miyamoto,&nbsp;Chia-Sui Kao,&nbsp;Kiril Trpkov,&nbsp;Geert J L H Van Leenders,&nbsp;Sara E Wobker,&nbsp;Fiona Maclean,&nbsp;Priti Lal,&nbsp;Reba E Daniel,&nbsp;Fadi Brimo,&nbsp;Matthew Wasco,&nbsp;Michelle S Hirsch,&nbsp;Nicholas Baniak,&nbsp;Julio A Diaz-Perez,&nbsp;Kristine M Cornejo,&nbsp;Bonnie Choy,&nbsp;Rohit Mehra,&nbsp;Sean R Williamson,&nbsp;Jonathan I Epstein,&nbsp;Andres Matoso","doi":"10.1097/PAS.0000000000001907","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001907","url":null,"abstract":"<p><p>Secondary involvement of the prostate by urothelial or hematolymphoid neoplasms is relatively common and well-described. In contrast, less is known about the clinicopathologic spectrum of secondary solid tumors of the prostate of nonurothelial origin. This study evaluated a series of secondary nonurothelial solid tumors of the prostate diagnosed at 21 institutions. Eighty-five patients with a median age at diagnosis of 64 years were included. Sixty-two patients had clinically manifest disease (62/85, 73%), 10 were diagnosed incidentally (10/85, 12%), and 13 (13/85, 15%) had no detailed clinical data available about symptomatology at presentation. Among patients with clinically manifest disease, the most common symptoms and signs were lower urinary tract symptoms (either obstructive of irritative; 36/62, 58%), abdominal or pelvic pain or discomfort (16/62, 26%), and hematuria (12/62, 19%). Metastasis and direct invasion occurred at roughly similar frequencies (47% vs. 42%) in this series, and in 11% of the cases, the mechanism of spread to the prostate was unclear/uncertain. Overall, among tumors with confirmed sites of origin, the most common primary sites were gastrointestinal tract (53/85, 62%), lung (9/85, 11%), skin (6/85, 7%), and testis (4/85, 5%). Among metastases, the most common tumor types were lung carcinomas (9/40, 23%), colorectal adenocarcinomas (7/40, 18%), melanoma (6/40, 15%), and germ cell tumors (6/40, 15%). This study demonstrated that secondary involvement of the prostate by solid tumors of nonurothelial origin is commonly symptomatic and that the most frequent sites of origin are the gastrointestinal tract, lung, skin, and testis. These findings are worth considering when lesions with unusual cytomorphology and/or architecture are encountered in prostate specimens.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1269-1276"},"PeriodicalIF":5.6,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40639057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"9p24.1 Genetic Alteration and PD-L1 Expression Are Characteristic of De Novo and Methotrexate-associated Epstein-Barr Virus-positive Hodgkin Lymphoma, But Not Methotrexate-associated Hodgkin-like Lesions.","authors":"Sawako Shiraiwa,&nbsp;Yara Yukie Kikuti,&nbsp;Joaquim Carreras,&nbsp;Yusuke Kondo,&nbsp;Ken Ohmachi,&nbsp;Yoshiaki Ogawa,&nbsp;Hiroshi Kawada,&nbsp;Shinji Sato,&nbsp;Yuka Gion,&nbsp;Yasuharu Sato,&nbsp;Naoya Nakamura,&nbsp;Kiyoshi Ando","doi":"10.1097/PAS.0000000000001899","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001899","url":null,"abstract":"<p><p>Although the alteration of the 9p24.1 chromosome locus and PD-L1 overexpression is found in nodular sclerosis classic Hodgkin lymphoma, whether these aberrations occur in CHL and Hodgkin-like lesion (HLL) of methotrexate-associated lymphoproliferative disorder (MTX-CHL and MTX-HLL) is unknown. We compared the clinicopathologic features, the genomic status of the 9p24.1 locus and PD-L1 expression in a series of 34 patients including 17 with Epstein-Barr virus-positive de novo CHL, 7 with MTX-CHL, 10 with MTX-HLL using an immunofluorescence in situ hybridization method and immunohistochemistry. The proportions of cells with 9p24.1 genetic alteration in CD30-positive Hodgkin/Reed-Sternberg cells of de novo CHL, MTX-CHL and MTX-HLL were 55%, 68%, and 24%, respectively. The positive rates of PD-L1 measured by immunohistochemical H-scores of de novo CHL, MTX-CHL and MTX-HLL were 142±38, 157±75, and 70±42, respectively. Alteration of the 9p24.1 gene and expression of PD-L1 protein were correlated with all 3 diseases (correlation coefficient, 0.731). Both alteration of the 9p24.1 gene and overexpression of PD-L1 protein were observed in Epstein-Barr virus-positive de novo CHL and MTX-CHL but not in MTX-HLL. In conclusion, MTX-CHL has similar pathogenesis-like de novo CHL, but MTX-HLL seems to be a different disease from de novo CHL and MTX-CHL.</p>","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":" ","pages":"1017-1024"},"PeriodicalIF":5.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40532955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localized Malignant Peritoneal Mesothelioma (LMPeM) in Women: A Clinicopathologic Study of 18 Cases","authors":"A. Malpica, E. Euscher, Mario L. Marques-Piubelli, R. Miranda, K. Raghav, K. Fournier, P. Ramalingam","doi":"10.1097/PAS.0000000000001924","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001924","url":null,"abstract":"Localized malignant peritoneal mesothelioma is a rare tumor with limited information in the literature. In this study, we present our experience with 18 cases seen in our hospital over a period of 43 years (1978 to 2021). Patients’ median age was 55 years (y) (range: 33 to 79 y) and most of them were Caucasians. Patients presented with abdominal pain (11), ascites and right leg swelling (1), abdominal mass (1), and as incidental finding (1). Thirty percent of patients reported asbestos exposure, and all patients with available information had family history of tumors; a third had personal history of tumors. Seventy-seven percent had some form of abdominopelvic surgery and/or inflammatory process. Most cases had microscopic features typically seen in malignant mesothelioma; however, some cases had confounding features such as signet-ring cells, spindle cells, clear cell changes, and adenomatoid tumor-like appearance. BAP-1 by immunohistochemistry was lost in 1/3 cases. Only 1 patient underwent genetic testing and had an MSH2 germline mutation. Homozygous deletion of CDKN2A by FISH was not found in 1 tested case, although next-generation sequencing identified a CDKN2A pathogenic mutation. 16/18 (88%) had surgical treatment, and some also received adjuvant chemotherapy. The mean overall survival (OS) of our patients was 80.4 months (95% confidence interval: 54.3-106.52); the 3-year OS was 79%, while the 5-year OS was 52.6%. Fifty-three percent of patients had recurrences and 20% had tumor progression. Although the limited sample precludes definitive conclusions, small tumor size, low-grade cytology, and low mitotic index appeared to be associated with an indolent behavior.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124242303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superficial CD34-Positive Fibroblastic Tumor","authors":"W. J. Anderson, F. Mertens, A. Mariño-Enríquez, J. Hornick, C. Fletcher","doi":"10.1097/PAS.0000000000001927","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001927","url":null,"abstract":"Superficial CD34-positive fibroblastic tumor (SCD34FT) is a rare soft tissue neoplasm that shows overlapping features with PRDM10-rearranged soft tissue tumor (PRDM10-STT). This study characterizes the clinicopathologic, immunohistochemical, and molecular features of SCD34FT in a series of 59 cases. Fluorescence in situ hybridization to assess for PRDM10 rearrangement was performed in 12 tumors. Immunohistochemistry for CADM3 and WT1 was performed; CADM3 was also assessed in histologic mimics. Our cohort of 33 male and 26 female had a median age of 42 (range: 14 to 85) years. Tumors were most commonly located in the lower limb (73%), upper limb (8%), back (7%), and supraclavicular region (3%). The median tumor size was 3.0 cm (range: 1.0 to 9.0 cm). Clinical follow-up in 32 patients (median duration: 26 mo) revealed 2 local recurrences (6%). One patient developed regional lymph node metastases which were completely excised. Microscopically, SCD34FT comprised spindled and pleomorphic cells with glassy cytoplasm and occasional granular cell change. Fluorescence in situ hybridization confirmed PRDM10 rearrangement in 3/8 cases (38%). SCD34FT frequently expressed CADM3 (95%) and WT1 (75%). CADM3 was less diffusely positive in pleomorphic hyalinizing angiectatic tumor (40%), pleomorphic liposarcoma (20%), and undifferentiated pleomorphic sarcoma (10%). We corroborate that SCD34FT is indolent but may rarely metastasize to lymph nodes without adverse outcomes. CADM3 and WT1 may be useful in the distinction from histologic mimics. Since cases of SCD34FT with and without demonstrable PRDM10 rearrangement were clinicopathologically indistinguishable, our study further supports that SCD34FT and PRDM10-STT likely constitute a single entity.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"114 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117329390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastroesophageal Glomus Tumors","authors":"D. Papke, L. Sholl, L. Doyle, C. Fletcher, J. Hornick","doi":"10.1097/PAS.0000000000001925","DOIUrl":"https://doi.org/10.1097/PAS.0000000000001925","url":null,"abstract":"Although criteria for malignancy have been established for glomus tumors of soft tissue, there are no accepted criteria for gastroesophageal glomus tumors, the behavior of which is considered to be unpredictable. Recently, both benign and aggressive gastroesophageal glomus tumors have been shown to harbor CARMN::NOTCH2 fusions, but, as yet, there are no described genetic features that predict clinical behavior. Here, we evaluated 26 gastroesophageal glomus tumors to investigate histologic and genetic features that might predict malignant behavior. Seventeen patients (65%) were male. The median age at presentation was 54.5 years (range: 16 to 81 y). Primary sites were stomach (25 tumors) and distal esophagus (1). The median tumor size was 4.05 cm (range: 0.8 to 19.5 cm). Tumors were composed of lobules of rounded cells with sharp borders, palely eosinophilic to clear cytoplasm, and round nuclei. All tumors involved the muscularis propria, and 12 also involved the serosal surface. Mitoses ranged from <1 to 53/10 HPF (median: 5/10 HPF). Sixteen tumors, including all 15 with mitoses ≥2/10 HPF, showed atypia (3 mild, 10 moderate, 3 severe), defined as spindle cell morphology, nuclear irregularity, nuclear size variability, enlarged nuclei, or coarse chromatin. Considering these histologic features and clinical behavior, tumors were classified as malignant (15 tumors) if they measured ≥5 cm or showed both atypia and mitoses ≥2/10 HPF, or benign (11 tumors) if these criteria were not met. Follow-up was available for 19 patients (73%; range: 1 to 15 y; median: 5.8 y), including 7 with benign tumors and 12 with malignant tumors. Two patients with malignant tumors had metastases at presentation, and 7 developed metastases subsequently. Follow-up was available for 8 of 9 patients with metastatic disease. Two were alive with disease at most recent follow-up. One underwent resection of a liver metastasis, with no subsequent metastases in 3 years of follow-up. Five patients died of metastatic disease. By immunohistochemistry, smooth muscle actin was diffusely positive in all evaluated tumors, and caldesmon and synaptophysin were positive in 94% and 73%, respectively. Sequencing identified NOTCH2 alterations in 4 benign tumors (80%) and 8 malignant tumors (80%), including CARMN::NOTCH2 fusions in 2 benign and 5 malignant tumors. All 5 sequenced benign tumors lacked complex copy number alterations (CNAs), whereas all 10 sequenced malignant tumors showed complex CNAs, including recurrent loss of 9p21.3 (4/10, variably including CDKN2A/B and MTAP) and ATRX inactivation (4/10). Complex CNAs were identified in all sequenced tumors that were ≥5 cm, exhibited both cytologic atypia and ≥2 mitoses/10 HPF, involved the serosa or metastasized. We propose that gastroesophageal glomus tumors ≥5 cm or with both atypia and mitoses ≥2/10 HPF should be considered malignant. Copy number analysis might be helpful in borderline cases.","PeriodicalId":275221,"journal":{"name":"The American Journal of Surgical Pathology","volume":"142 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132086428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}