American Journal of Surgical Pathology最新文献

{"title":"Extensive Pathologic Invasion and Prognostic Implication of Gastric-Type Cervical Adenocarcinoma: A Comparative Analysis With Human Papillomavirus-Associated Adenocarcinoma.","authors":"Kyosuke Kamijo, Tsutomu Miyamoto, Shiori Oshima, Shiho Asaka, Manaka Shinagawa, Yoshinori Sato, Hirofumi Ando, Ryoichi Asaka, Marina Fujioka, Natsuki Uchiyama, Yusuke Yokokawa, Yasuhiro Tanaka, Yukiko Kusama, Uehara Takeshi, Yaeko Kobayashi, Tanri Shiozawa","doi":"10.1097/PAS.0000000000002369","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002369","url":null,"abstract":"<p><p>Gastric-type adenocarcinoma (GAS) is the most common subtype of human papillomavirus (HPV)-independent cervical adenocarcinomas and is associated with a poor prognosis. We used a gross morphologic classification system and imaging analysis to compare the clinicopathological features of GAS and HPV-associated adenocarcinoma (HPVA) and identify factors contributing to the poor prognosis of GAS. This retrospective 2-center study analyzed 33 patients with GAS and 70 with HPVA (stages IB-IVB) who underwent surgery between 1997 and 2023. GAS had a higher rate of positive surgical margins (21.2% vs. 0%, respectively, P<0.001) and unclear tumor boundaries on gross morphologic findings (47.8% vs. 8.8%, respectively, P<0.001). Discrepancies between clinical and pathologic T classifications were more common in GAS, leading to frequent upstaging (51.5% vs. 28.6%, respectively, P=0.029). Imaging analysis revealed that GAS was associated with a smaller median tumor cell area (19.8% vs. 55.7%, respectively, P<0.001), which was significantly correlated with unclear tumor boundaries. Perineural invasion (PNI) was significantly more frequent in GAS (69.7% vs. 10.0%, respectively, P<0.001). A Kaplan-Meier analysis showed that patients with PNI had significantly poorer overall survival (P<0.001). A Cox multivariate analysis identified an advanced pathologic stage, positive peritoneal cytology, and positive surgical margins as independent risk factors. The present results indicate that GAS has a unique \"stealth\" invasion pattern, possibly caused by low tumor density, leading to undetectable tumor boundaries and positive surgical margins. This suggests a greater risk of incomplete resection than HPVA, leading to a poorer prognosis.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the Clinical Prognosis of High-grade Appendiceal Mucinous Neoplasms.","authors":"Peggy Dartigues, Vahan Kepenekian, Claire Illac-Vauquelin, Véronique Verriele, Juliette Fontaine, Sylvie Isaac, Anne Chevallier, Séverine Valmary-Degano, Marie-Hélène Laverriere, Gerlinde Avérous, Frédéric Bibeau, Laurent Villeneuve, Olivier Glehen, Nazim Benzerdjeb","doi":"10.1097/PAS.0000000000002373","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002373","url":null,"abstract":"<p><p>High-grade appendiceal mucinous neoplasm (HAMN) is used to describe a rare epithelial neoplasm of the appendix characterized by pushing-type invasion and high-grade cytologic atypia. Its implications regarding lymph node spread and the necessity of right colectomy are currently debate. The objective of the present study was to assess the clinicopathologic characteristics, the risk of lymph node and peritoneal metastasis, and long-term outcomes of patients diagnosed as HAMN in comparison to low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma, treated by right hemicolectomy. A total of 443 patients diagnosed with LAMN (n=246), HAMN (n=34), or appendiceal adenocarcinoma (n=163) and who underwent right colectomy with lymph node dissection in all cases within 32 institutions of the French Network for Rare Peritoneal Malignancies (RENAPE) were included. The median age was 56.5 years (range: 21 to 91), and the majority were female (n=250, 56.4%) without difference between groups (P=0.604). Lymph node metastases were identified in 17.8% of appendiceal adenocarcinoma cases (29/163); none were found among LAMN or HAMN cases. A higher number of lymph nodes were analyzed in those treated for appendiceal adenocarcinoma than LAMN (P<0.001) and HAMN (P=0.035). Regarding peritoneal metastasis, a higher proportion of cases were classified as high-grade with/without signet cells in patients treated for HAMN (P<0.001) and appendiceal adenocarcinoma (P<0.001) than those treated for LAMN. Among patients with perforation of the appendix, those treated for LAMN had longer overall survival (OS; P<0.001) and progression-free survival (PFS; P<0.0001) than those treated for appendiceal adenocarcinoma or those treated for HAMN; among patients without perforation, those treated for LAMN and HAMN had longer OS (P=0.042) and PFS (P=0.012) than those treated for appendiceal adenocarcinoma. No lymph node metastases were observed in patients treated for HAMN, and those without appendix perforation had a similar prognosis to LAMN. This study supports staging HAMN using the same system as LAMN and treating it with appendectomy alone in the absence of appendix perforation.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Histologic Features in Ameloblastoma With RASQ61R Mutation.","authors":"Ivan J Stojanov, Anna M Trzcinska, Mohammed Qaisi, Michel Kmeid, Elizabeth M Azzato, Akeesha A Shah","doi":"10.1097/PAS.0000000000002375","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002375","url":null,"abstract":"<p><p>Ameloblastoma is characterized histologically by evidence of ameloblastic differentiation and molecularly by MAPK pathway alterations, most frequently BRAFV600E mutation and RAS mutations, as well as by SMO mutations. This mutational profile is present across all histologic variants, including those occasionally lacking overt histologic evidence of ameloblastic differentiation, such as desmoplastic ameloblastoma and granular cell ameloblastoma. Recently, we have come across 4 cases of maxillary ameloblastoma demonstrating peculiar histologic features not accounted for by recognized histologic variants. Three intraosseous tumors were remarkably similar in histologic appearance and demonstrated a proliferation of spindled to basaloid cells in solid/sheet-like, cystic, and ribbon-like growth patterns within dense fibrous connective tissue. One case had numerous squamous morules and only 1 case, focally, demonstrated ameloblastic differentiation, yet all 3 cases harbored NRASQ61R mutation. A fourth case harbored HRASQ61R mutation and arose peripherally, in palatal (maxillary) gingiva, as a follicular-patterned neoplasm with bland squamoid morphology and scattered foci of ameloblastic differentiation. RAS Q61R immunohistochemistry was positive in both the tumor and overlying surface epithelium, in support of surface derivation. These 4 cases demonstrate that ameloblastoma may occasionally present with non-traditional histologic features, lacking categorization into known histologic variants and sometimes lacking any evidence of ameloblastic differentiation. In this setting, the differential diagnosis may be broad and include more indolent odontogenic neoplasms such as adenomatoid odontogenic tumor or squamous odontogenic tumor, odontogenic carcinomas, and non-odontogenic neoplasms. A high index of suspicion, followed by confirmatory molecular testing or mutation-specific immunohistochemistry, is necessary for accurate diagnosis.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRAF Gene Fusions in Melanoma: First Kinase Domain Duplication, New Fusion Partners, and Clinical Outcomes.","authors":"Igor Odintsov, Dale Davis, Daniel Pissaloux, Franck Tirode, Arnaud de la Fouchardiere, John Hanna","doi":"10.1097/PAS.0000000000002370","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002370","url":null,"abstract":"<p><p>BRAF gene fusions have been well-described in Spitzoid melanocytic lesions but can also occur uncommonly in conventional melanomas. Here we report a series of 17 melanomas harboring BRAF gene fusions as their putative primary genetic driver. All but one of these tumors occurred in adults (age range 13 to 96) with a relatively even sex distribution (41% female) and a broad distribution of anatomic sites. None of the tumors showed typical Spitzoid histomorphologic features. Molecular analysis identified the first example of BRAF kinase domain duplication in melanoma, which raises interesting questions regarding the mechanism of fusion-induced BRAF activation. Although we did not identify histomorphologic features that could distinguish BRAF-fused melanomas from more conventional melanomas, we did observe a generally low tumor mutational burden and a lower rate of UV-associated mutational signatures (3/17; 18%), suggesting that BRAF-fused melanomas are molecularly and mechanistically distinct from conventional cutaneous melanomas. We report detailed treatment information and clinical outcomes for this series, with most patients having shown disease progression on systemic immunotherapy (8/12; 67%). Our results highlight the need for continued molecular subclassification to yield a comprehensive understanding of melanoma pathogenesis and have potential implications for therapeutic selection in BRAF-fused and perhaps other unconventional forms of melanoma.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Carcinomas Resembling Acinic Cell Carcinoma: Comprehensive Analysis of 14 Cases and Review of the Literature.","authors":"Fengxia Qin, Jiazhen Li, Yi Zheng, Chengying Jiang, Yumian Jia, Hui Sun, Huiqin Xue, Xiaozi Wang, Lu Wang, Xiaolong Qian, Yun Niu, Hannah Y Wen, Xiaojing Guo","doi":"10.1097/PAS.0000000000002363","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002363","url":null,"abstract":"<p><p>Acinic cell carcinoma (AciCC) of the breast is an exceptionally rare subtype of invasive breast carcinoma, often exhibiting a triple-negative phenotype and relatively indolent behavior. Since the first case reported by Roncaroli and colleagues in 1996, no more than 60 additional cases have been described in English medical journals, usually as case reports or small case series. In this study, we presented an in-depth analysis of 14 cases of AciCC of the breast, including 4 pure AciCCs and 10 AciCCs mixed with other histologic types. We reported the clinicopathologic characteristics, histologic components, treatment modalities including response to neoadjuvant treatment in 3 patients, and outcomes. In addition, we assessed the expression of nuclear transcription factor nuclear receptor subfamily 4 group A member 3 by immunohistochemistry and gene rearrangements by fluorescence in situ hybridization, which has been implicated in AciCC of the salivary gland. All 14 cases were negative for nuclear receptor subfamily 4 group A member 3 expression, and no gene rearrangements were detected. We also conducted a thorough review of the literature to highlight advancements in understanding this rare breast cancer subtype. This study aims to enhance clinical knowledge of AciCC of the breast and contributed to growing evidence that AciCC of the breast and AciCC of the salivary glands appear to be unrelated entities, despite sharing a similar histologic appearance.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic and Molecular Characterization of Gynecologic Carcinosarcomas With a Mesonephric-Like Carcinomatous Component.","authors":"Rachelle P Mendoza, Melisa Y Tjota, Donghyuk N Choi, David B Chapel, David L Kolin, Elizabeth D Euscher, Julieta E Barroeta, Tricia A Numan, Deyin Xing, Michelle Afkhami, Rania Bakkar, Ricardo R Lastra","doi":"10.1097/PAS.0000000000002368","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002368","url":null,"abstract":"<p><p>Carcinosarcoma with a mesonephric-like carcinomatous component (MLCS) is a rare subtype of gynecologic malignancy recently described in the literature. This study aims to expand the genomic characterization of MLCS by performing independent molecular analysis of the carcinomatous and sarcomatous components in a series of MLCS. Eight cases of gynecologic MLCS (endometrial, lower uterine segment, and ovarian) were identified and underwent clinicopathologic evaluation. Genomic DNA extraction and next-generation sequencing (NGS) were performed separately from the carcinomatous and sarcomatous components of 4 tumors, while 2 tumors underwent NGS of combined carcinomatous and sarcomatous components. The average age at diagnosis was 65.6 years (range 50 to 83 years). MLCS patients were diagnosed at FIGO stage I (n=3), stage II (n=2), stage III (n=2), and stage IV (n=1). The carcinomatous and sarcomatous components were observed to harbor the same single nucleotide variations. All cases had less than 10 mutations/Mb and were microsatellites stable. All cases (6/6, 100%) harbored KRAS point mutations in codon 12, including the following variants: p.G12D (n=2), p.G12A (n=2), and p.G12V (n=2). Five cases showed additional alterations in ARID1A (case 1), PTEN (case 2), PIK3CA (case 4), SPOP (case 6), TET1 (case 6), BUB1 (case 7), LYN (case 7) and PTPRD (case 7). The presence of both KRAS and PTEN/PIK3CA alterations suggests a combined endometrioid and mesonephric differentiation in MLCS.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEK :: AFF2 Fusion Sinonasal and Skull Base Nonkeratinizing Squamous Cell Carcinoma : A Clinical Outcome Study Compared With Conventional Sinonasal Squamous Cell Carcinoma.","authors":"Stephanie A Hart, Jen-Fan Hang, Rebecca D Chernock, Michael W Mikula, Lisa Rooper, Sara E Amin, Karan Saluja, Justin A Bishop, Yu Hsiu Chen, Nicole A Cipriani, Stephanie N David, William D Dupont, W Dale Plummer, Karen T Ferrer, Ariana Geromes, Min-Shu Hsieh, Juan C Hernandez-Prera, Ying-Ju Kuo, Eiichi Sasaki, Qiuying Shi, Tra Truong, Jaylou M Velez Torres, James S Lewis","doi":"10.1097/PAS.0000000000002335","DOIUrl":"10.1097/PAS.0000000000002335","url":null,"abstract":"<p><p>DEK :: AFF2 fusion nonkeratinizing squamous cell carcinoma (NKSCC) is an emerging entity in the sinonasal tract, temporal bone, and skull base. However, the clinical behavior of these tumors has not been well studied. Here, we report the largest cohort of DEK :: AFF2 carcinomas to determine if morphology, mitotic rate, and/or Ki-67 IHC are associated with patient outcomes, including a comparison with high-risk human papillomavirus (HPV)-associated and independent patients. We solicited cases of molecularly or AFF2 immunohistochemistry (IHC) proven DEK :: AFF2 SCC from surgical pathologists to collect patient demographic, clinical, and outcome data. Using representative H&E slides, we characterized the morphology and counted mitoses. Ki-67 immunohistochemistry was performed. We also compared the DEK :: AFF2 survival rates to those in a cohort of AFF2 IHC-negative HPV-associated and HPV-independent SCC. DEK :: AFF2 carcinomas most commonly arose in the nasal cavity (13/30, 43%), and the average number of recurrences was 1.8 (range: 0 to 10). At the last follow-up, most patients were disease free (19/30, 63%) or were alive with disease (9/30, 30%). There was an average mitotic rate of 2 per 2 mm 2 (range: 0 to 9) and Ki-67 proliferation rate of 26% (range: 3% to 60%). Local recurrence was common, but morphology, mitotic activity, and Ki-67 index were not associated with recurrence or survival. On Kaplan-Meier survival analysis, DEK :: AFF2 patients had lower disease-free survival but otherwise had similar outcomes to conventional SCC patients. Our multi-institutional study shows that local recurrence is common in DEK :: AFF2 fusion nonkeratinizing SCC patients, but patients have survival rates similar to conventional SCC. Despite showing a range of different features and proliferation rates, traditional grading by morphology, mitotic rate, and/or Ki-67 activity does not seem to be predictive of outcome.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"130-137"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time Marches On.","authors":"Stacey E Mills","doi":"10.1097/PAS.0000000000002348","DOIUrl":"10.1097/PAS.0000000000002348","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"97"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma : Identification of an MCD-like Subtype.","authors":"Fangli Peng, Takuro Igawa, Tomohiro Urata, Hiroki Kobayashi, Tetsuya Isoda, Sawako Ono, Takehiro Tanaka, Daisuke Ennisshi, Yoshinobu Maeda, Hidetaka Yamamoto","doi":"10.1097/PAS.0000000000002329","DOIUrl":"10.1097/PAS.0000000000002329","url":null,"abstract":"<p><p>Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare aggressive lymphoma. Recently, genetic classification using Next Generation Sequencing (NGS) demonstrated that PSDLBCL largely consists of the MCD genotype, which has a poor prognosis mainly driven by MYD88 L265P and CD79B gene abnormalities. This study investigated the prevalence and clinicopathological significance of MYD88 L265P and CD79B Y196 mutations using droplet digital PCR in 55 patients with PSDLBCL, as well as the translocation of BCL2 / BCL6 / c-Myc with FISH. We found mutations in MYD88 L265P (29/55, 52.7%) and CD79B Y196 (20/55, 36.4%). The MCD-like subtype, defined by the mutation of MYD88 and/or CD79B , was found in 32 out of 55 cases (58.2%). This subtype largely consists of non-GCB type (31/32, 96.9%; P <0.01) and double-expressor cases (20/32, 62.5%; P =0.01) compared with the MYD88 / CD79B co-wild type, with BCL6 translocation in a small subset (2/32, 6.3%) and no translocations of BCL2 (0/32) or c-Myc (0/32). The MCD-like subtype tended to relapse in specific sites such as the central nervous system, testis, and/or skin compared with the co-wild type ( P =0.03), showing poorer outcomes in overall survival ( P =0.02) and progression-free survival ( P =0.01). In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"159-168"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFE3 -rearranged Head and Neck Neoplasms : Twenty-two Cases Spanning the Morphologic Continuum Between Alveolar Soft Part Sarcoma and PEComa and Highlighting Genotypic Diversity.","authors":"Abbas Agaimy, Michael Michal, Ali Abdelsatir, Azza A Abdelsatir, Sawsan Abdulrahim, Jan Laco, Stephan Ihrler, Lars Tögel, Robert Stoehr, Justin A Bishop, Nasir Ud Din, Michal Michal","doi":"10.1097/PAS.0000000000002334","DOIUrl":"10.1097/PAS.0000000000002334","url":null,"abstract":"<p><p>TFE3 rearrangements characterize histogenetically, topographically, and biologically diverse neoplasms. Besides being a universal defining feature in alveolar soft part sarcoma (ASPS) and clear cell stromal tumor of the lung, TFE3 fusions have been reported in subsets of renal cell carcinoma, perivascular epithelioid cell tumor (PEComa), epithelioid hemangioendothelioma and ossifying fibromyxoid tumors. TFE3 -related neoplasms are rare in the head and neck and may pose diagnostic challenges. We herein describe 22 TFE3 fusion neoplasms affecting 11 males and 11 females aged 4 to 79 years (median, 25) and involving different head and neck sites: sinonasal cavities (n = 8), tongue (n = 4), oral cavity/oropharynx (n = 3), salivary glands (n = 2), orbit (n = 2), and soft tissue or unspecified sites (n = 3). Based on morphology and myomelanocytic immunophenotype, 10 tumors qualified as ASPS, 7 as PEComas (3 melanotic; all sinonasal), and 5 showed intermediate (indeterminate) histology overlapping with ASPS and PEComa. Immunohistochemistry for TFE3 was homogeneously strongly positive in all cases. Targeted RNA sequencing/FISH testing confirmed TFE3 fusions in 14 of 16 successfully tested cases (88%). ASPSCR1 was the most frequent fusion partner in ASPS (4 of 5 cases); one ASPS had a rare VCP::TFE3 fusion. The 6 successfully tested PEComas had known fusion partners as reported in renal cell carcinoma and PEComas ( NONO, PRCC, SFPQ , and PSPC1 ). The indeterminate tumors harbored ASPSCR1::TFE3 (n = 2) and U2AF2::TFE3 (n = 1) fusions, respectively. This large series devoted to TFE3-positive head and neck tumors illustrates the recently proposed morphologic overlap in the spectrum of TFE3 -associated mesenchymal neoplasms. While all PEComas were sinonasal, ASPS was never sinonasal and occurred in diverse head and neck sites with a predilection for the tongue. The indeterminate (PEComa-like) category is molecularly more akin to ASPS but shows different age, sex, and anatomic distribution compared with classic ASPS. We report VCP as a novel fusion partner in ASPS and PSPC1 as a novel TFE3 fusion partner in PEComa (detected in one PEComa). Future studies should shed light on the most appropriate terminological subtyping of these highly overlapping tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"104-112"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}