Histopathology最新文献

{"title":"Confirmation of monotypic immunofluorescence staining by mass spectrometry in a case of proliferative glomerulonephritis","authors":"Lyssa Van De Ginste, Annelore Vandendriessche, An S De Vriese, Jack Wetzels, Steven Van Laecke, Tri Q Nguyen, Michel Delforge, Rodrigo Gallardo, Joost Schymkowitz, Frédéric Rousseau, Francis Impens, Simon Devos, Amélie Dendooven","doi":"10.1111/his.70171","DOIUrl":"10.1111/his.70171","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"895-898"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147928958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant adenomyoepithelioma of the breast: seven cases illustrating morphological diversity and diagnostic challenges","authors":"Sompon Apornvirat,&nbsp;Edward Jaya Hadi,&nbsp;Mihir Gudi,&nbsp;Young Kyung Bae,&nbsp;Victor Ng,&nbsp;Yingjie Xiu,&nbsp;Chee Seng Tan,&nbsp;Chi Wei Mok,&nbsp;Ga Sze Hong,&nbsp;Georgette Chan,&nbsp;Peter Ang,&nbsp;Stephanie Cheng,&nbsp;Tse Hui Lim,&nbsp;Stephen B. Fox,&nbsp;Emad Rakha,&nbsp;Puay Hoon Tan","doi":"10.1111/his.70233","DOIUrl":"10.1111/his.70233","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Malignant adenomyoepithelioma (M-AME) is an extremely rare and morphologically diverse breast tumour, posing significant diagnostic and management challenges. We present seven cases of M-AME with different histological compositions to contribute additional data to the existing literature. Through these cases, we review and discuss potential pitfalls and classification challenges in diagnosing M-AME.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>We performed a retrospective clinicopathological review of seven cases of M-AME from women aged 45–74 years (median 53 years). Each case exhibited distinct architectural patterns and compositions of classic and malignant components: (1) Adenomyoepithelioma (AME) with metaplastic spindle and squamous cell carcinoma; (2) Invasive AME with an aberrant immunohistochemical profile; (3) Invasive AME with an adenomyoepithelial adenosis pattern; (4) Metaplastic spindle cell carcinoma arising from AME with suspicion of M-AME in situ; (5) Atypical AME with late lung metastasis harbouring HRAS p.G13R and in-frame PIK3R1 deletion; (6) and (7) M-AME in situ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>M-AME encompasses heterogeneous patterns that overlap with the infiltrative-like pattern of classic AME (adenomyoepithelial adenosis form of tubular AME) and metaplastic breast carcinoma. Recognition of the underlying AME architecture, coupled with immunohistochemical and molecular correlation, supports pragmatic classification into in situ or invasive M-AME or conventional breast carcinoma arising in the context of AME. Together with clinical, radiological, and molecular correlations, this approach can help guide appropriate management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"807-823"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myxoid neoplasms with MAP3K kinase fusion: a study of 39 cases","authors":"Nicolas Macagno,&nbsp;Diane Frankel,&nbsp;Alexandra Meurgey,&nbsp;Daniel Pissaloux,&nbsp;Adrien Buisson,&nbsp;Aline Baltrès,&nbsp;François Gouin,&nbsp;Gualter Vaz,&nbsp;Mehdi Brahmi,&nbsp;Armelle Dufresne,&nbsp;Anne-Valérie Decouvelaere,&nbsp;Aurélie Maran-Gonzales,&nbsp;Philippe Rochaix,&nbsp;Agnès Leroux,&nbsp;Nicolas Weinbreck,&nbsp;Arnaud de la Fouchardière,&nbsp;Jean-Yves Blay,&nbsp;Franck Tirode,&nbsp;Marie Karanian","doi":"10.1111/his.70230","DOIUrl":"10.1111/his.70230","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Myxomas are benign soft tissue neoplasms typically driven by activating <i>GNAS</i> mutations. However, a subset lacks this alteration and remains molecularly undefined. Recent reports have implicated <i>MAP3K</i> family gene fusions in rare myxoid neoplasms sharing features with myxoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>In this study, we characterise 39 <i>MAP3K</i>-rearranged myxoid tumours by integrating clinical, histopathological, immunohistochemical and molecular data. The cohort comprised predominantly middle-aged adults, with tumours distributed across a wide anatomic range (limbs, trunk, face), often in superficial locations. Histologically, the tumours were composed of bland spindle or histiocytoid cells embedded in an abundant myxoid stroma with features mimicking cellular myxoma, such as intermediate-to-high cellularity and broad fibrous septa. High-grade pleomorphism and necrosis were consistently absent. Immunohistochemistry revealed frequent CD34 and HMGA2 positivity, a low Ki-67 proliferation index, and preserved PRKAR1A expression. RNA sequencing identified diverse <i>MAP3K</i> gene fusions, most notably <i>MSI2</i>::<i>MAP3K3</i> and <i>MAP3K8</i>::<i>MAP3K3</i>, alongside several unique fusion partners. Transcriptomic clustering demonstrated a relationship between <i>MAP3K</i>-rearranged tumours, <i>GNAS</i>-mutant myxomas and a proximity with myxofibrosarcomas, while clearly distinguishing them from other myxoid sarcomas. Clinical follow-up indicated an indolent course with no evidence of metastasis and rare local recurrences; notably, one patient with positive surgical margins remained disease-free several years postoperatively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>MAP3K</i>-rearranged myxoid tumours represent a molecularly distinct subset of benign neoplasms that overlap histologically with cellular myxoma and must be distinguished from low-grade myxofibrosarcoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"796-806"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast core needle biopsy diagnosis and personalized treatment: navigating pitfalls and challenging lesions","authors":"Emad A. Rakha,&nbsp;Cecily Quinn,&nbsp;Puay Hoon Tan,&nbsp;Grace Callagy","doi":"10.1111/his.70186","DOIUrl":"10.1111/his.70186","url":null,"abstract":"<p>Most breast lesions can be diagnosed accurately on core needle biopsy (CNB); however, certain entities remain diagnostically challenging due to limited tissue sampling, morphological overlap with other lesions, unusual immunoprofiles or lack of reliable ancillary markers. These challenges are compounded by modern clinical requirements, particularly the increasing shift towards neoadjuvant therapy (NAT) where a definitive diagnosis is required before surgical excision. Misclassification may have clinically significant consequences, including inappropriate initiation of NAT or undertreatment of aggressive disease. This review provides a structured diagnostic approach to breast lesions that are particularly prone to misinterpretation on CNB. We discuss malignant lesions that should not trigger NAT, while highlighting the diagnostic and reporting pitfalls associated with microinvasive disease, where definitive confirmation of established invasion is often elusive on limited material. Key morphological clues, immunohistochemical strategies and the selective role of molecular testing in resolving differential diagnoses of overlapping and challenging lesions are emphasized. A transparent reporting style that acknowledges uncertainty, together with multidisciplinary collaboration and selective expert consultation, optimizes patient management. The review aims to provide practical guidance, avoid diagnostic pitfalls and promote safe decision-making when dealing with complex breast lesions on limited biopsy material.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"758-778"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological characterization of GLI1-altered mesenchymal neoplasms involving the dermis and subcutis: a series of eight cases","authors":"Joshua Del Papa,&nbsp;May Chan,&nbsp;Kyle Perry,&nbsp;Thomas Brenn,&nbsp;Katharina Wiedemeyer","doi":"10.1111/his.70247","DOIUrl":"10.1111/his.70247","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>GLI1-altered mesenchymal neoplasms are a recently described tumour group characterized by gene fusions or amplifications involving <i>GLI1</i>. They show a wide anatomical distribution and harbour potential to metastasize. This study aims to add to the data on GLI1-altered mesenchymal tumours involving the dermis and subcutis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Departmental files were searched for GLI1-altered mesenchymal neoplasms involving the dermis and/or subcutis. Clinicopathological features were reviewed, and cases were assessed by immunohistochemistry, <i>GLI1</i> in situ hybridization, and targeted next-generation sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight tumours were identified and located on the scalp (<i>n</i> = 3), gluteal region (<i>n</i> = 2), inguinal region (<i>n</i> = 1), supraclavicular area (<i>n</i> = 1), and the left index finger (<i>n</i> = 1). Seven men and one woman were affected (aged 24–78 years, median 53). Histopathologically, the tumours showed a multinodular growth pattern within the dermis and/or subcutaneous adipose tissue, were composed of ovoid cells with mild to moderate atypia, arranged in nests, sheets or strands. Most of them were associated with a rich capillary network. Mitotic activity was variable (0–22 per 10 high power fields). Necrosis was present in two cases. Gene fusion testing demonstrated a novel <i>TUBA1A</i>::<i>GLI1</i> fusion in one of three cases tested. This tumour showed strong SOX10 and S100 positivity by immunohistochemistry while the remaining tumours were negative or only focally positive for both markers. All patients were alive at last follow-up: seven disease-free without recurrences and one patient with advanced localized disease and metastasis to bone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Superficial GLI1-altered mesenchymal tumours show a spectrum of histopathological presentations, inconsistent immunophenotypes and variable biological behaviour.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"875-885"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological characteristics of sonic hedgehog hepatocellular adenomas with special focus on small lesions","authors":"Paulette Bioulac-Sage,&nbsp;Christine Sempoux,&nbsp;Brigitte Le Bail,&nbsp;Skander Korbi,&nbsp;Claire Castain,&nbsp;Bettina Bisig,&nbsp;Arnaud Ducatel,&nbsp;Nora Frulio,&nbsp;Laurence Chiche,&nbsp;Charles Balabaud","doi":"10.1111/his.70234","DOIUrl":"10.1111/his.70234","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Sonic hedgehog hepatocellular adenomas (sh-HCA) are prone to bleed. Focusing on small sh-HCA (1–4 cm), we documented and compared their clinicohistopathological characteristics, with those observed in large sh-HCA nodules (5–9.5 cm), including the cause of surgery and association with symptomatic bleeding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Macroscopic and microscopic features of resected sh-HCA were reviewed in 17 patients divided in three groups: group 1a corresponding to seven patients with sh-HCA nodules of 5 cm and larger; group 1b: the same patients of group 1a whose resected specimens contain nodules smaller than 5 cm, and group 2: 10 patients with sh-HCA smaller than 5 cm, resected for variable indications. The diagnosis of sh-HCA was confirmed by immunohistological overexpression of arginosuccinate synthase-1 with molecular demonstration of activation of the sonic hedgehog pathway in 9/17 cases and robust exclusion of other HCA subtypes. Clinical data were available with focus on bleeding signs in all patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All 17 patients showed similar clinical characteristics. Macroscopic haemorrhage and microscopic features of vascular damage such as sinusoidal dilatation, congestion, ischaemic changes, microhaemorrhage and fluid-filled cavities were found in both larger and smaller nodules, independent of their sizes and mode of discovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results showed that small sh-HCA, whatever their mode of discovery, are histologically similar to the larger ones. These similarities in the vascular-circulatory histopathological features, regardless of the size of the adenomas, emphasized the bleeding tendency of sh-HCA. Necrotico-haemorrhagic areas may gradually reduce the size of the tumour, in which case a conservative approach may be considered.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"824-834"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal immunoglobulin-associated kidney lesions with coexistent pathological patterns: clinicopathological features and outcomes","authors":"Yujie Wang,&nbsp;Yao Lin,&nbsp;Jiao Li,&nbsp;Hanzhi Chen,&nbsp;Zhen Zhang,&nbsp;Gen Wang,&nbsp;Shaoshan Liang,&nbsp;Fan Yang,&nbsp;Feng Xu,&nbsp;Xiaodong Zhu,&nbsp;Liang Wang,&nbsp;Caihong Zeng","doi":"10.1111/his.70242","DOIUrl":"10.1111/his.70242","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Monoclonal gammopathy-associated kidney lesions typically present with a single pathological pattern, but the coexistence of multiple patterns in the same patient is rare and poorly characterized. This study aimed to delineate the clinicopathological spectrum and outcomes of these complex cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Twenty-three patients with coexistent pathological patterns were identified from native kidney biopsies. The most frequent combinations were light chain cast nephropathy (LCCN) with light chain deposition disease (LCDD) (34.8%), followed by LCCN with light chain amyloidosis (AL) (21.7%) and LCCN with light chain proximal tubulopathy (LCPT) (21.7%). Multiple myeloma was the predominant underlying haematological disorder (87.0%). Compared with isolated AL, the LCCN+AL group showed more severe acute tubular injury and chronic tubulointerstitial damage (both <i>P</i> &lt; 0.05). The LCCN+LCDD group exhibited more severe acute injury but milder chronic fibrosis than isolated LCDD (<i>P</i> &lt; 0.05). The LCCN+LCPT group had the most favourable prognosis, whereas the LCCN+AL group had the worst, with a median survival of only 32 months and significantly higher mortality than isolated LCCN, isolated AL and LCCN+LCPT groups (all <i>P</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Monoclonal gammopathy-associated kidney lesions with coexistent pathological patterns represent a highly heterogeneous entity with distinct features and varied prognoses. The combination of LCCN with AL identifies a particularly high-risk group. Kidney biopsy is crucial for precise classification and prognosis assessment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"863-874"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant struma ovarii: advances in molecular pathogenesis, classification, diagnosis and treatment","authors":"Yu Miyama,&nbsp;Tomonori Kawasaki,&nbsp;Daisuke Shintani,&nbsp;Morihiro Higashi,&nbsp;Masanori Yasuda,&nbsp;Taku Homma","doi":"10.1111/his.70238","DOIUrl":"10.1111/his.70238","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"901-905"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocervical gastric-type AIS: a rare histologic finding that further supports the hypothesis of a pyloric-type metaplastic origin","authors":"Michele Paudice,&nbsp;Veronica Parrella,&nbsp;Giulia Scaglione","doi":"10.1111/his.70150","DOIUrl":"10.1111/his.70150","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gastric-type adenocarcinoma in situ (gAIS) is a rare, HPV-independent precursor of cervical adenocarcinoma with incompletely defined histogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To report a case of gAIS and its association with pyloric-type gastric metaplasia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A case of gAIS in a 70-year-old woman with atypical glandular cells (Pap test) and negative HPV molecular testing was evaluated histologically and immunohistochemically.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Conization revealed atypical glandular epithelium. The lesion was CK7/CDX2 positive, with mutant-type p53 expression, and negative for CK20, PAX8 and p16. Adjacent pyloric-type gastric metaplasia was identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The association with pyloric-type metaplasia supports a possible metaplastic origin and highlights diagnostic challenges in limited samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case supports a possible link between gAIS and pyloric-type gastric metaplasia, underscoring the importance of accurate recognition in HPV-independent cervical lesions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"892-894"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147592007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippo pathway disruption and YAP1 activation in anogenital papillary squamous intraepithelial lesion","authors":"Gloria Zhang,&nbsp;Karen L. Talia,&nbsp;W. Glenn McCluggage,&nbsp;Robert A. Soslow,&nbsp;Bin Yang","doi":"10.1111/his.70239","DOIUrl":"10.1111/his.70239","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Papillary squamous intraepithelial lesion (PSIL), also known as papillary immature metaplasia, is a rare anogenital lesion associated with low-risk human papillomavirus (HPV) infection. The molecular pathogenesis of PSIL remains unclear. This study aims to investigate the activation of YAP1, a Hippo pathway co-activator, in PSIL and compare it to condyloma and papillary HSIL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>YAP1 activation was evaluated by immunohistochemistry using an antibody specific for activated/unphosphorylated YAP1 (act-YAP1) in 36 PSIL cases, 20 condyloma and 2 papillary HSIL cases. HPV genotyping and chromogenic in situ hybridization (CISH) were performed to determine HPV status. Low-risk HPV, predominantly HPV6, was detected in 78.6% of PSILs. CISH revealed a diffuse fine punctate distribution of low-risk HPV E6/E7 transcripts in PSIL, distinct from the large focal clusters seen in condyloma, but similar to high-risk HPV in HSIL. All PSILs showed non-block p16 expression. Act-YAP1 immunostaining demonstrated YAP1 activation in 86.1% of PSILs (72.2% diffuse, 13.9% focal), resembling the pattern in papillary HSIL but differing from condyloma, which exhibited nuclear act-YAP1 only in basal and granular layers. No significant associations were found between YAP1 activation and HPV status or immunoprofiles of p16, p53, Rb1 and CK7.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PSILs demonstrate prominent YAP1 activation, implicating Hippo pathway disruption as a potential driver of PSIL pathogenesis. These findings support a distinct molecular profile of PSIL and provide insight into the biological mechanisms underlying this rare lesion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":"89 5","pages":"849-862"},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.70239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}