American Journal of Surgical Pathology最新文献

{"title":"Massive/Mass-forming Ductular Reaction Associated With Vascular Occlusion in Various Underlying Basic Liver Diseases.","authors":"Anne Kristin Fischer, Reinhard Büttner, Hans-Peter Fischer","doi":"10.1097/PAS.0000000000002449","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002449","url":null,"abstract":"<p><p>Massive/mass-forming ductular reaction of the liver (MDR) is occasionally in the differential diagnosis with true bile duct tumors. Our diagnostic histomorphological and immunohistochemical study of 14 cases from a consultant collective of 2970 cases follows the appearance of MDR with regard to various underlying liver diseases and the conditions of pathologic perfusion. We describe MDR measuring up to 7 cm in localized form or affecting up to 70% of the parenchyma in subacute liver necrosis. MDR developed in the context of severe inflammatory liver diseases and liver cirrhosis, as well as in colocalization with true malignant neoplasms such as hepatocellular carcinoma, epithelioid hemangioendothelioma, and hepatic angiosarcoma. In all cases, MDR was associated with intra- or directly perilesional thrombotic or tumorous obliteration of intrahepatic portal or hepatic veins or liver sinusoids. In end-stage liver cirrhosis, it was additionally associated with fibrotic occlusion of the portoseptal vascular bed. Further key diagnostic features of this hypoperfused, extensive parenchymal transformation included a monolayered network of small cytokeratin 7-, cytokeratin 19-, and CD56-positive ductules with fingertip-like endings, low proliferative activity (<3% Ki-67-positive cells), and embedded in a loose stroma. The pre-existing lobular architecture, including portal tracts or cirrhotic remodeling, was preserved. In conclusion, MDR of the liver is a rare, confluent pluriacinar and sometimes pseudo-tumorous transformation of the liver parenchyma that is associated with altered liver perfusion. Clinically and histomorphologically, it can mimic a true biliary neoplasm.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648348","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":"DNA Methylation Profiling Separates SDH-Deficient GISTs From KIT-PDGFRA-Driven GISTs and Identifies Predictive Biomarkers for Targeted Therapy.","authors":"Małgorzata Chłopek, Jerzy Lasota, Omkar Singh, Andrew M Blakely, John Glod, Kris Ylaya, Maciej Kaczorowski, Natálie Klubíčková, Anna Szumera-Ciećkiewicz, Piotr Rutkowski, Michal Michal, Zied Abdullaev, Kenneth D Aldape, Markku Miettinen","doi":"10.1097/PAS.0000000000002444","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002444","url":null,"abstract":"<p><p>Succinate dehydrogenase (SDH), a critical enzyme in the citric acid cycle and respiratory electron transport chain, consists of 4 subunits: SDHA, SDHB, SDHC, and SDHD. Deficiency of a single subunit leads to the loss of SDH activity which is implicated in the development of a subset of gastrointestinal stromal tumors (GISTs): SDH-deficient GISTs. These GISTs arise almost exclusively in the stomach, have a female predilection, and primarily affect children and young adults. Their characteristic morphologic features include multinodular architecture, lymphovascular invasion, and lymph node metastasis. At the molecular level, these tumors lack KIT, PDGFRA, BRAF, or NF1 mutations, which are alternative oncogenic drivers typically observed in GIST. Recently, a sarcoma DNA methylation classifier was developed and was shown to be a valuable diagnostic tool. This study evaluated the DNA methylation classifier results for 30 SDH-deficient GISTs and discovered that methylation profiles clustered in a unique region separate from GISTs and leiomyosarcomas. Moreover, MGMT promoter methylation, a predictive biomarker of tumor cell sensitivity to alkylating agent chemotherapy, was identified in 6 primary and 5 metastatic tumors. In addition, 3 primary and 4 metastatic tumors showed gain/low-level amplification of MDM4, which pathologically activates MDM4-p53 axis, a target of inhibitors. In summary, these findings expand the sarcoma DNA methylation classifier to include SDH-deficient GIST as a new sarcoma DNA methylation entity and identified 2 predictive biomarkers for targeted therapy: methylation of MGMT promoter and gain/low-level amplification of MDM4.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590266","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":"Undifferentiated Melanoma: A Clinicopathologic and Gene Expression Analysis Study With Identification of HMGA2 as a Diagnostic Marker.","authors":"Grant M Fischer, Diogo Maia-Silva, Dora Dias-Santagata, Jason L Hornick, Eleanor Russell-Goldman","doi":"10.1097/PAS.0000000000002452","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002452","url":null,"abstract":"<p><p>Undifferentiated melanoma poses a unique diagnostic challenge as, by definition, it lacks expression of the melanocytic markers S100 protein, Sox10, Mart1, and HMB45. Despite this aberrant phenotype, undifferentiated melanoma is characterized by known melanoma driver alterations, including BRAF and NRAS mutations. Due to variable morphologic features and a lack of melanocytic differentiation, molecular diagnostics are often required for the identification of melanoma-compatible driver alterations to support the diagnosis. Here, we describe a cohort of 27 undifferentiated melanomas and employ gene expression profiling to compare undifferentiated melanoma to conventional melanoma in both matched cases arising in the same patients and unmatched cases. The histologic spectrum of undifferentiated melanoma was variable and included tumors composed of epithelioid, spindled, pleomorphic, rhabdoid and balloon cells, often with necrosis. Notably, a subset of undifferentiated melanomas demonstrated a prominent stroma, including myxoid and vascular components. We demonstrate that the histologic category is the main determinant of differential gene expression between conventional and undifferentiated melanoma. In addition, undifferentiated melanomas show several significantly upregulated gene expression pathways, including those associated with epithelial-mesenchymal transition. These data provide novel insights into the transcriptomic expression profile of undifferentiated melanoma and offer potential explanations for the unusual phenotype. Notably, HMGA2 was found to be the most significantly up-regulated gene in the undifferentiated melanoma cohort, with immunohistochemical studies demonstrating that HMGA2 is a sensitive and specific marker for the diagnosis of undifferentiated melanoma and for its distinction from mimics which show overlapping morphologic features and lack melanocytic differentiation.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599170","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":"Condylomatous Sinonasal Papilloma-A Distinct (Fourth) Subtype That is Commonly Associated With Low-risk Human Papillomavirus.","authors":"Ansa Mehreen, Mitra Mehrad, Kim A Ely, Jen-Fan Hang, Ying-Ju Kuo, Jaylou M Velez-Torres, Carla Penner, Rebecca D Chernock, Sara E Amin, Karan Saluja, James S Lewis","doi":"10.1097/PAS.0000000000002431","DOIUrl":"10.1097/PAS.0000000000002431","url":null,"abstract":"<p><p>Inverted papilloma (IP) is a benign neoplasm of the nasal cavity and paranasal sinuses, known for its variable risk of recurrence and potential for developing carcinoma. Emerging evidence has shown high rates of activating EGFR mutation, and a smaller subset is associated with low-risk human papillomavirus (lrHPV). While certain morphologic features, including an inverted growth pattern, are well-established, the presence of condylomatous features, such as large fungating lesions with thick undulating surface epithelium, hyperkeratosis, cytoplasmic clearing, raisinoid nuclei, and binucleation (koilocytic changes) in low-risk HPV-associated IP suggests that these tumors may be a distinct subtype of sinonasal papilloma (SP) with features similar to low-risk HPV-associated anogenital condylomas. This study presents a series of SP with condylomatous morphology and explores the association with lrHPV, the clinicopathologic features, and the rates of carcinoma development. In total, 17 cases of SP exhibiting condylomatous morphology were retrospectively identified. We performed lrHPV and high-risk HPV (hrHPV) RNA in situ hybridization and p16 immunohistochemistry and gathered detailed clinical and pathologic data along with treatment, disease follow-up, and outcomes. These condylomatous papillomas almost all developed in active smokers, were large, were primarily located in the nasal cavity (47%), and showed frequent transformation to invasive squamous cell carcinoma (29%). This malignant transformation rate is much higher than what has been reported for inverted, exophytic, and oncocytic papillomas. The tumors were almost uniformly associated with transcriptionally-active lrHPV (94%) and were consistently negative for p16 and hrHPV. This study shows that a subgroup of IPs with condylomatous morphology have a predilection for the nasal cavity, strong association with lrHPV, and high rates of carcinoma. These findings support the concept that these tumors are a distinct (fourth) type of SP with a higher risk of malignant transformation.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"873-881"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551756","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":"Genomics of T-Cell Lymphomas With CD30/CD15 Co-Expression: Comparison With Anaplastic Large-Cell Lymphoma, ALK-Negative.","authors":"Joao V Alves de Castro, Jung Kim, Manoj Tyagi, Liqiang Xi, Valerie Zgonc, Svetlana D Pack, Theresa Davies-Hill, Stefania Pittaluga, Mark Raffeld, Elaine S Jaffe","doi":"10.1097/PAS.0000000000002447","DOIUrl":"10.1097/PAS.0000000000002447","url":null,"abstract":"<p><p>The proper categorization of mature T-cell neoplasms with coexpression of CD30/CD15 is unresolved. Prior studies suggested an overlap with ALK-negative anaplastic large cell lymphoma (ALCL). We evaluated the morphologic, immunophenotypic, and molecular features of 28 T-cell lymphomas coexpressing CD30/CD15, and performed a comparison with 8 ALK/CD15-negative ALCL and published data. Clinical information was retrieved from the submitting physician. Immunohistochemistry, TRG and IG gene rearrangement, DNA and RNA targeted next-generation sequencing, and fluorescence in situ hybridization for DUSP22 rearrangement were performed. Cases were classified as conforming to 3 histologic variants: ALCL-like, Hodgkin-like, and PTCL-NOS-like. Median age was 62 years (range: 33 to 87). Male:female ratio was 3:1. Twenty-four cases presented with lymphadenopathy (24/28, 85.7%). Six cases had skin involvement (6/28, 21.4%), including 4 primary cutaneous cases (4/28, 14.3%). Ten cases were designated as ALCL-like, 12 as Hodgkin-like, and 2 as PTCL-NOS-like. There was frequent loss of T-cell markers, with expression of CD3 in 7/27 cases (25.9%), CD2 in 15/23 (65.2%), and expression of at least one cytotoxic marker in 13/24 (54.2%). DUSP22 was rearranged in 4 cases (4/16, 25%). The JAK-STAT pathway was frequently altered due to mutations in JAK1 (6/28, 21.4%), STAT3 (5/28, 17.8%), and JAK2 fusions (2/28, 7.1%). PI3K-AKT-mTOR pathway alterations due to PIK3R1 mutations (5/28, 17.8%) were also frequent and mutually exclusive with JAK-STAT pathway activation. In summary, most T-cell neoplasms with CD30/CD15 coexpression share clinical, morphologic, immunophenotypic, and molecular features with ALK -negative ALCL but do not segregate as a homogeneous entity as defined by histologic or genetic features.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551757","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":"Pseudopapillary Osteoblastic Tumor With Psammomatous/Dot-Like Calcification of the Jawbone: A Report of a Hitherto Undescribed Morphologic Variant of Osteoblastoma Supported by Molecular Analysis.","authors":"Maiko Tsuchiya, Yoshinao Kikuchi, Daisuke Komura, Naohiro Makise, Toru Motoi, Kimihide Kusafuka, Satoru Toyosawa, Ryosuke Hirata, Satoru Ogane, Mariko Yasui, Shiori Watabe, Hiroshi Uozaki, Tsuyoshi Ishida","doi":"10.1097/PAS.0000000000002445","DOIUrl":"10.1097/PAS.0000000000002445","url":null,"abstract":"<p><p>Osteoblastoma (OB) is a bone-forming tumor typically characterized by FOS rearrangements. When arising in the jawbone, the histologic features overlap with those of cementoblastoma (CB). We report the case of a 20-year-old man with a histologically uncategorized osteo-cementoblastic tumor in the jawbone. The tumor showed sheet-like or pseudopapillary structures with abundant calcifications, resembling psammoma body, cementum, or dot-like calcifications. Osteoid formation was minimal and the calcified materials displayed atypical features for OB, complicating definitive diagnosis. To elucidate the molecular basis of these unique features, we performed whole-genome sequencing and nanopore sequencing-based methylation analysis. These analyses confirmed the characteristic FOS rearrangement commonly observed in OB and revealed a novel fusion gene, FOS::FN1::FOS , which has not been reported previously. In addition, DNA methylation profiling confirmed clustering with OB, and genomic analysis demonstrated an almost flat copy-number profile, consistent with the typical features of OB. We hypothesize that this novel fusion gene, in combination with the unique anatomic site of the jawbone, may have contributed to the distinct histologic features. We propose this tumor as a hitherto undescribed morphologic variant of OB.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"970-976"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551758","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":"The Clinicopathologic Features of Inflammatory Breast Carcinoma (IBC) With Lobular Features.","authors":"S Emily Bachert, Allison M Onken, Allison S Cleary, Faina Nakhlis, Jennifer R Bellon, Beth A Overmoyer, Filipa Lynce, Beth T Harrison","doi":"10.1097/PAS.0000000000002446","DOIUrl":"10.1097/PAS.0000000000002446","url":null,"abstract":"<p><p>Inflammatory breast carcinoma (IBC) is an aggressive form of breast cancer. Prior studies have reported the presence of lobular histology in a small percentage of tumors from patients with IBC. However, the significance of these lobular features in IBC has yet to be fully characterized. We performed a comprehensive retrospective review of patients with IBC with lobular features (IBC-LF) to evaluate their clinicopathologic features. Our IBC program registry included 524 patients over a 20-year interval, 74 (14%) of whom had lobular features. Pathology material was available for review for 28 patients, and these patients were the focus of this study. On the basis of study criteria, 12 were classified as pure invasive lobular carcinoma (ILC) and 16 as invasive carcinoma with ductal and lobular features (IDLC). All were histologic grade 2-3. Receptor profiles included ER+/HER2- in 14/28 (50%), ER-/HER2- in 7/28 (25%), and ER(+/-)/HER2- in 7/28 (25%). In the 12 cases of pure ILC, 11 showed variant morphologic features, including 6 (50%) with pleomorphic apocrine features, 3 (25%) with a solid growth pattern, 1 with signet ring-cell, and 1 with histiocytoid features. All ILC cases showed negative or aberrant staining for E-cadherin, p120, and beta-catenin on immunohistochemical studies. Dermal lymphovascular invasion was seen in 13 (46.4%) cases, while direct dermal invasion was seen in 14 (50%) cases. Our study confirms that IBC may arise from pure ILC, with negative E-cadherin expression, and usually with variant morphology. This is the first study to detail the morphologic and immunophenotypic characteristics of IBC-LF.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"882-889"},"PeriodicalIF":4.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551698","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 Characteristics of Immune Checkpoint Inhibitor-related Pancreatitis.","authors":"Feidi Chen, Monika Vyas, Matthew Gosse, Vikram Deshpande, Matthew W Rosenbaum","doi":"10.1097/PAS.0000000000002398","DOIUrl":"10.1097/PAS.0000000000002398","url":null,"abstract":"<p><p>The advent of immune checkpoint inhibitors (ICIs), although associated with adverse events, has heralded a new era in cancer therapy. ICI-related pancreatitis is a rare adverse effect of ICIs. The nonspecific clinical manifestations have posed diagnostic challenges, and the detailed histologic features remain largely unknown. This study aims to characterize the clinical and histopathologic features of ICI-related pancreatitis to increase awareness and improve diagnostic accuracy. We retrospectively identified 5 specimens from 4 patients from our database and consultation practice. We reviewed demographic, clinical, serological, and radiologic data and examined each specimen's histologic features. Patients (2 female, 2 male) were all prescribed anti-PD-1 monoclonal antibodies (1 on Nivolumab and 3 on Pembrolizumab) for metastatic melanoma, unresectable colon cancer, metastatic pancreatic adenocarcinoma, and urothelial carcinoma. The onset of ICI-related pancreatitis ranged from 28 to 473 days after ICI initiation. All 4 patients showed elevated amylase and/or lipase. Two patients presented with the chief complaint of abdominal pain. The other 2 initially asymptomatic patients showed hypointense mass lesions on imaging resembling malignant processes. The most common histologic findings were acinar-centric mixed inflammatory infiltrate (5/5 specimens) followed by atrophy (4/5 specimens) and fibrosis (4/5 specimens). Storiform fibrosis was identified in one patient who was biopsied twice. Other findings included edema (3/5 specimens) and acinar-to-ductal metaplasia (3/5 specimens). Granulocytic epithelial lesion was identified in 2 specimens. No obliterative phlebitis or granulomas were identified. By immunohistochemistry, the inflammatory infiltrates were predominately composed of CD3+ T cells with a variable CD4 to CD8 ratio. Neutrophils and eosinophils were readily identifiable with rare plasma cells. Management included stopping the ICI and starting steroids. Whereas 1 patient lacked follow-up information, 2 patients showed marked improvement. One patient succumbed to severe ICI-related myocarditis. In conclusion, ICI-related pancreatitis shows overlapping clinical-radiologic features with malignancy and autoimmune pancreatitis with the potential for chronic injury. Although ICI-related pancreatitis lacks the classic histologic features of autoimmune pancreatitis, there is considerable histologic overlap, particularly on small biopsies. Therefore, correlation with the patient's medications is critical when evaluating pancreatic specimens with nonspecific chronic pancreatitis histologic patterns.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"730-739"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794449","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":"Comparison of HER2 Scoring Systems in Endometrial Cancer: Toward Optimization of HER2-Directed Therapies.","authors":"Ekaterina Menshikova, Kristin Deeb, Elizabeth M Genega, Krisztina Hanley, Gulisa Turashvili","doi":"10.1097/PAS.0000000000002392","DOIUrl":"10.1097/PAS.0000000000002392","url":null,"abstract":"<p><p>Endometrial carcinomas (EC) show variable HER2 protein expression or gene amplification and may be eligible for HER2-directed therapy (trastuzumab or antibody-drug conjugates (ADCs) such as trastuzumab-deruxtecan). HER2 testing is currently recommended in advanced-stage/recurrent serous carcinomas and carcinosarcomas. However, no universally adopted reporting guidelines exist, and institutional practices vary. We aimed to analyze our experience with HER2 testing and compare gynecologic (GyC), gastric (GaC), and breast (BrC) criteria. We identified ECs with available HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) results where applicable. HER2 IHC was reassessed using GyC, GaC, and BrC. The overall HER2-positivity rates were 31% by GyC and BrC, and 35.7% by GaC. The scoring systems significantly differed, with 69.8% concordance between GaC and GyC ( P <0.001) and 99.2% concordance between BrC and GyC. Our results emphasize the importance of using the appropriate HER2 scoring criteria depending on the type of intended HER2-directed therapy as well as comprehensive yet perspicuous reporting of HER2 status to ensure optimal clinical outcomes in EC patients.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"674-685"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707969","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":"CK17 Immunohistochemistry Is a Useful Adjunct in the Diagnosis of HPV-independent, TP53-wild-type Verruciform/Acanthotic Vulvar Intraepithelial Neoplasia (vaVIN).","authors":"Emily M Hartsough, Rosalynn M Nazarian, Jaclyn C Watkins","doi":"10.1097/PAS.0000000000002383","DOIUrl":"10.1097/PAS.0000000000002383","url":null,"abstract":"<p><p>Verruciform/acanthotic vulvar intraepithelial neoplasia (vaVIN) is a rare, recently defined HPV-independent, TP53- wild type lesion of the vulva that predisposes to vulvar squamous cell carcinoma (VSCC). VaVIN encompasses a variety of histomorphologic subtypes, including verruciform lichen simplex chronicus (vLSC), differentiated exophytic vulvar intraepithelial lesion (DEVIL), and vulvar acanthosis with altered differentiation (VAAD). Given the rarity of the lesion, subtle histopathologic features, and overlap with other preneoplastic entities and benign dermatoses, vaVIN is a diagnostic challenge. Therefore, immunohistochemistry (IHC) may be a helpful diagnostic adjunct in differentiating vaVIN from mimickers. Cytokeratin 17 (CK17) immunohistochemistry has been previously described as a useful diagnostic tool in diagnosing differentiated vulvar intraepithelial neoplasia (dVIN) and VSCC and has only recently been applied to vaVIN. In this study, we identified a total of ten cases of vaVIN, including four classified as vLSC, five classified as DEVIL, and one classified as VAAD. CK17 was expressed by all vaVIN lesions, with superficial to suprabasal expression in the vLSC subtype and uniform suprabasal expression in the DEVIL and VAAD subtypes. The pattern of CK17 expression may be helpful in differentiating vaVIN subtypes, notably demonstrating only superficial expression in some cases of the least aggressive phenotype, vLSC. Suprabasal expression corresponds to the more aggressive phenotypes of DEVIL and VAAD. However, additional confirmatory studies in a larger cohort are needed to validate these findings.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"658-662"},"PeriodicalIF":4.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584341","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}