American Journal of Surgical Pathology最新文献

{"title":"Odontogenic Myxoma Harbors Widespread Loss of Heterozygosity and Not Trisomies.","authors":"Igor Odintsov, Tony G Kleijn, Scott T Ryall, Baptiste Ameline, Fei Dong, Karoly Szuhai, Daniel Baumhoer, Paola Dal Cin, Arjen H G Cleven, David J Papke","doi":"10.1097/PAS.0000000000002379","DOIUrl":"10.1097/PAS.0000000000002379","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"523-525"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603598","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":"Atypical Intraductal Proliferation in Prostate Needle Core Biopsy: Validation as a Marker of Unsampled Adverse Pathology in a Clinicopathologic Series of 142 New Patients.","authors":"Roshan Bhattarai, Jesse K McKenney, Reza Alaghehbandan, Xuefeng Liu, Roni M Cox, Jonathan L Myles, Christopher G Przybycin, Sean R Williamson, Christopher J Weight, Zeyad Schwen, Jane K Nguyen","doi":"10.1097/PAS.0000000000002376","DOIUrl":"10.1097/PAS.0000000000002376","url":null,"abstract":"<p><p>Atypical intraductal proliferation (AIP) of the prostate is characterized by morphologic features exceeding that of high-grade prostatic intraepithelial neoplasia but not meeting strict diagnostic criteria for intraductal carcinoma. We examined the clinical significance of AIP in biopsy specimens. Patients with AIP diagnosed on biopsy were identified from surgical pathology archives. Initial biopsies, any repeat biopsies, and any radical prostatectomy (RP) slides were rereviewed. We also identified a control group of 50 consecutive patients with available prostate biopsies showing invasive prostatic adenocarcinoma but no AIP and having paired RP for comparison. Medical records were searched for nonsurgical treatment and clinical outcome status. Patients with initial biopsies showing invasive adenocarcinoma with either grade group (GG) ≥3 and/or unfavorable histology (as recently defined) were excluded from both the study and control groups. Correlation with subsequent adverse pathology at rebiopsy or RP, as defined by separate criteria: unfavorable histology, large cribriform/intraductal carcinoma, GG ≥3, pN1, and/or pM1, was assessed for both groups. Phosphate and tensin (PTEN) homolog and ETS-related gene (ERG) immunohistochemistry were performed on biopsies with available paired RP, using standard protocols. One hundred forty-two patients with AIP met inclusion criteria. At initial biopsy, 16 patients (11.3%) had AIP without concomitant invasive carcinoma, whereas 126 (88.7%) also had invasive adenocarcinoma. Of the 126 invasive tumors with AIP meeting study criteria, 19 (15.1%) were GG 1 and 107 (84.9%) GG 2. One hundred thirty-nine of 142 patients with AIP (97.9%) had available clinical follow-up (mean: 36.9 mo). Fifty-two (36.3%) patients with AIP underwent RP, 36 (25.4%) had brachytherapy, 28 (19.7%) had radiotherapy, 17 (12%) remained on active surveillance, 2 (1.4%) had cryoablation, 2 (1.4%) received androgen deprivation therapy, and 1 (0.7%) had high-intensity focused ultrasound. Forty-seven of 52 patients undergoing prostatectomy (90.3%) had glass slides available for review: 30 (63.8%) were GG2, 13 (27.7%) GG3, 1 (2.1%) GG4, and 3 (6.4%) GG5. Seventeen (36.2%) patients were staged as pT2, 25 (53.2%) pT3a, and 5 (10.6%) pT3b. Forty-two of 47 (89.4%) patients had associated unfavorable histology on prostatectomy, including 41 (87.2%) with large cribriform/intraductal carcinoma, 17 (36.2%) GG≥3, and 5 (10.6%) with metastatic disease. In the 36 AIP lesions examined for PTEN and ERG immunoreactivity, 14 (38.9%) had concomitant PTEN loss and ERG over-expression, 6 (16.7%) showed PTEN loss only, and 6 (16.7%) had ERG overexpression only. AIP morphology was more predictive of risk for unfavorable histology at RP than PTEN/ERG immunophenotype. Seventeen patients not undergoing RP had rebiopsy, of which 5 (29.4%) had at least one adverse feature identified on repeat biopsy. Nineteen of 50 patients (38%) in the non-AIP control group had ","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"515-522"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490392","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":"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":"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":"471-480"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","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":"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":"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":"439-447"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","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":"SALL4 as a Useful Marker for the Distinction of Various Gestational Trophoblastic Disease Subtypes: Choriocarcinoma From Other Trophoblastic Lesions and Early Complete Hydatidiform Mole From Partial Mole and NonMolar Villi.","authors":"Alexis Trecourt, Marie Donzel, Lucie Gaillot-Durand, Pierre A Bolze, François Golfier, Pierre Descargues, Touria Hajri, Claire Mauduit, Mojgan Devouassoux-Shisheboran, Fabienne Allias","doi":"10.1097/PAS.0000000000002358","DOIUrl":"10.1097/PAS.0000000000002358","url":null,"abstract":"<p><p>The distinction between choriocarcinoma and residual trophoblastic cell proliferation from a complete hydatidiform mole/invasive mole (CHM/IM) without villi is challenging on curettage materials. We investigated whether SALL4 immunostaining could help differentiate various gestational trophoblastic diseases. Placental site nodules (PSN; n=10), atypical PSN (APSN; n=8), placental site trophoblastic tumors (PSTT; n=9), epithelioid trophoblastic tumors (ETT; n=5), gestational choriocarcinomas (n=31), partial hydatidiform moles (PHM; n=13), CHM/IM (n=47), and nonmolar products of conception (POC) (n=26) were included. SALL4 immunostaining was quantified (0 [1% to 10%], [11% to 100%]) and characterized (scattered single-cell or clustered nuclear positivity) in 2 locations: cytotrophoblast/intermediate trophoblast and villous stromal fibroblasts. A diffuse (11% to 100%) and clustered pattern of SALL4 immunostaining in cytotrophoblast/intermediate trophoblast was statistically associated with choriocarcinomas (74.2%, 23/31) as compared with PSN (0/10; P <0.0001), APSN (0/8; P =0.0002), PSTT (0/9; P <0.0001), ETT (0/5; P =0.0034), PHM (0/13; P <0.0001), CHM/IM (0/47; P <0.0001), and nonmolar POC (0/26; P <0.0001). Most nonchoriocarcinoma samples showed no SALL4 expression; when present, it was of low level (1% to 10%) and with a scattered single-cell staining in 3/9 PSTT (33%), 1/13 PHM (7.7%), 19/47 CHM/IM (40%), and 1/26 nonmolar POC (1.7%). These results were confirmed using a validation cohort. In addition, 66% (31/47) of CHM/IM villous stromal fibroblasts showed SALL4 expression (11% to 100%) (all before 14 gestational weeks), whereas this level of expression was never observed in PHM (0/13), nor in nonmolar POC (0/26; P <0.0001). Finally, a clustered and >10% SALL4 immunostaining in cytotrophoblast/intermediate trophoblast favors choriocarcinoma diagnosis. SALL4 expression in >10% villous stromal fibroblasts before 14 gestational weeks favors CHM/IM rather than PHM and nonmolar POC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"417-428"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Grade Papillary Thyroid Carcinoma, Diffuse Sclerosing Subtype: A Series of 18 Cases Detailing the Pathologic Features, Potential for Misdiagnosis, and Aggressive Clinical Behavior.","authors":"Ronald A Ghossein, Daniel W Scholfield, Howard Qin, Ashok R Shaha, Ian Ganly, Bin Xu","doi":"10.1097/PAS.0000000000002371","DOIUrl":"10.1097/PAS.0000000000002371","url":null,"abstract":"<p><p>High-grade differentiated thyroid carcinoma is a novel classification defined by elevated mitotic count (MC) of ≥5/2 mm 2 and/or tumor necrosis. It may assume a phenotype of papillary thyroid carcinoma, diffuse sclerosing subtype (PTC-DS), and can be termed HGPTC-DS. A detailed clinicopathologic review was conducted on a large series of 18 cases of HGPTC-DS. A control group of 41 PTC-DSs with genomic data was also included. Histologically, HGPTC-DS showed typical features of PTC-DS and HG areas, often exhibiting solid architecture of uniform squamoid cells admixed with tumor necrosis, frequently the comedo type. All HGDTC-DSs had tumor necrosis. The MC was often low (median 1/2 mm 2 ). PTC nuclear features were retained and no nuclear pleomorphism was seen. HGPTC-DS was often subjected to misdiagnosis. Among the 7 external cases, the initial diagnosis was anaplastic carcinoma in 1 and PTC in 5. Compared with PTC-DS, HGPTC-DS was associated with positive resection margin, AJCC eighth edition pT3b and pT4a/4b disease, gross extrathyroidal extension (ETE), a higher number of regional lymph nodes metastasis, a larger size of nodal metastasis, decreased recurrence-free survival (RFS) and regional recurrence-free survival ( P <0.05). Among the 9 HGPTC-DSs sequenced, 5 harbored RET fusions, 2 had STRN::ALK fusion, and 1 had BRAF p.V600E mutation. In conclusion, HGPTC-DS is a rare high-grade carcinoma characterized by uniform squamoid area with comedo-type tumor necrosis, high pT stage, gross ETE, large volume nodal metastasis, poor RFS, and RRFS. Given its rarity, it may be subjected to misdiagnosis as PTC and anaplastic carcinoma.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"481-489"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717920","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":"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":"508-514"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","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":"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":"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":"499-507"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984543/pdf/","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":"OA","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":"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":"429-438"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","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":"Clinicopathologic Features and Viral Status of Low-risk HPV6 and HPV11-Associated Squamous Cell Carcinoma of the Uterine Cervix and Vulva.","authors":"Guy A Williams, Annie A Wu, Henrietta C Eugene, Ya-Chea Tsai, Margaret Wong, Hiro Nonogaki, Richard B S Roden, Chien-Fu Hung, Tzyy-Choou Wu, Russell Vang, Deyin Xing","doi":"10.1097/PAS.0000000000002367","DOIUrl":"10.1097/PAS.0000000000002367","url":null,"abstract":"<p><p>Despite being designated as \"noncarcinogenic\" human papillomavirus (HPV) types, mono-infection with HPV6 or HPV11 has been found in squamous cell carcinomas (SCCs) at specific sites, including the larynx, penis, anus, and rarely, the lower female genital tract. The association between clinicopathologic features, viral status, and the carcinogenic mechanisms related to these low-risk HPVs remains unclear. The current study characterizes a series of low-risk HPV6 and HPV11-associated SCCs of the uterine cervix (6 cases) and vulva (2 cases). The diagnosis of SCC was made through the identification of stromal invasion in 6 cases. In case 2, the diagnosis of cancer was made after metastases to the sigmoid colon and liver. The patient in case 6 was diagnosed with intramucosal papillary SCC given multiple recurrences. While all tumors displayed a similar verruco-papillary architecture, the cytologic features, and immunostaining patterns suggest 2 groups of lesions: one with high-grade cytology and a high Ki-67 proliferation index (>60% of lesional cells), and the other with low-grade cytology and a low Ki-67 (20% to 30% of lesional cells). The detection of HPV6 in 7 of 8 cases underscores its critical role in carcinogenesis at these anatomic sites. Case 8 represented the only patient who was infected with HPV11 and who had a well-controlled human immunodeficiency virus infection. Correlating with viral status, all cases, except case 7, demonstrated a negative or focal p16 staining pattern. In case 7, despite a block pattern of p16 staining often seen in predicting high-risk HPV, we employed several methods to confirm HPV6 as the sole HPV infection. Although this descriptive study does not establish an etiological mechanism for how HPV6/11 leads to malignant transformation, our results exclude the possibility of viral integration through a quantitative polymerase chain reaction-based analysis of the E2/E6 ratio. Our study highlights and expands upon the clinicopathologic features of a distinct group of low-risk HPV6/11-associated SCCs in the cervix and vulva. Although rare, recognizing this group of lesions is important for pathologists and oncologists, as it provides a basis for guiding appropriate prevention strategies and treatment modalities based on the viral type.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"458-470"},"PeriodicalIF":4.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}