Advances In Anatomic Pathology最新文献

{"title":"Updates on the Molecular Classification of Endometrial Carcinoma.","authors":"Koen K Van de Vijver, C Blake Gilks, Tjalling Bosse","doi":"10.1097/PAP.0000000000000556","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000556","url":null,"abstract":"<p><p>The risk of recurrence and metastasis in patients with endometrial carcinoma varies widely, making evaluation of risk in individual patients critically important for planning effective adjuvant treatment. Tumor histotype and grade have been used, along with stage and lymphovascular space invasion (LVSI), but suboptimal reproducibility of histotype assignment (especially for high-grade tumors) and tumor grade have made risk assessment challenging. Similarly, single biomarkers such as L1CAM and beta-catenin have shown potential but none have emerged as well-validated and reproducible markers of risk in endometrial carcinoma. This changed with the finding of The Cancer Genome Atlas that there are 4 molecular subtypes of endometrial carcinoma, based on genomic architecture. Subsequently, a clinically applicable approach to endometrial carcinoma molecular subtype has emerged, based on sequencing of POLE to detect a limited number of pathogenic mutations, and immunostaining for mismatch repair (MMR) proteins and p53. This approach places each endometrial carcinoma into one of 4 molecular subtypes (POLEmut, MMRd, p53abn, and no specific molecular profile [NSMP]) that can be reproducibly diagnosed, show excellent concordance between the biopsy and hysterectomy specimen, are of prognostic significance, predict response to specific adjuvant therapies, and can be used to screen for underlying hereditary cancer susceptibility syndromes. Molecular subtype is now integrated into widely used endometrial carcinoma risk assessment guidelines and is a key component of the 2023 update to the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma. Recently, prognostic refinement of the 4 molecular groups introduces a possible fifth group showing absence of estrogen receptor (ER) expression and/or high histologic grade within the NSMP subtype. We will review the key features of endometrial carcinoma molecular subtypes, focusing on recent advances in molecular subtype diagnosis in practice.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219718","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":"Frontiers in Gynecologic Pathology: Molecular Insights, Emerging Neoplasms, and Diagnostic Challenges.","authors":"Gulisa Turashvili, Kyle M Devins, Esther Oliva","doi":"10.1097/PAP.0000000000000555","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000555","url":null,"abstract":"","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178775","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":"The Expanding Spectrum of DICER1-Associated Gynecologic Neoplasms.","authors":"Hyun-Soo Kim, Felix K F Kommoss, Gulisa Turashvili","doi":"10.1097/PAP.0000000000000553","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000553","url":null,"abstract":"<p><p>DICER1 tumor predisposition syndrome is a rare autosomal-dominant disorder resulting from heterozygous germline pathogenic variants in DICER1, a critical regulator of microRNA biogenesis and RNA interference. The syndrome predisposes individuals to a broad spectrum of benign and malignant neoplasms, primarily affecting pediatric and young adult populations. Gynecologic manifestations are notably heterogeneous and include the well-established associations with embryonal rhabdomyosarcoma and Sertoli-Leydig cell tumor. DICER1 alterations have also been identified in gynandroblastoma, a subset of adenosarcomas, and emerging entities such as DICER1-related Wilms-like uterine tumor and, less consistently, in rare examples of juvenile and adult granulosa cell tumor, Sertoli cell tumor, germ cell tumors, and carcinosarcoma. Despite their diverse anatomic sites, some of these neoplasms share recurrent morphologic hallmarks, including primitive mesenchyme, fetal-type epithelium and cartilage, rhabdomyosarcomatous and neuroectodermal differentiation, and anaplasia. Recent evidence has broadened the morphologic, molecular, and clinical understanding of DICER1-associated neoplasms. Recognition of these distinctive morphologic features is essential for prompting timely testing for DICER1 alterations and facilitating appropriate genetic counseling, surveillance, and early detection strategies for patients and their families. This review synthesizes current knowledge with emerging insights to enhance the diagnostic recognition of these rare yet clinically significant entities.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102634","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":"Mesonephric and Mesonephric-Like Proliferations of the Gynecologic Tract.","authors":"Lawrence Hsu Lin, Jelena Mirkovic, Elizabeth D Euscher","doi":"10.1097/PAP.0000000000000554","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000554","url":null,"abstract":"<p><p>Mesonephric remnants are vestiges of Wolffian ducts located adjacent to the Müllerian ducts. Proliferations arising from these remnants are uncommon and classified as benign, including mesonephric hyperplasia, Gartner and rete cysts, papillary cystadenoma, rete adenoma, and female adnexal tumor of probable wolffian origin (only rare cases of the latter exhibited malignant behavior), or malignant, including mesonephric adenocarcinoma and carcinosarcoma. Morphologic evaluation aided by immunohistochemistry, especially in carcinomas, is the cornerstone to establish the correct diagnosis. In contrast to mesonephric adenocarcinoma, which arises predominantly in the cervix and is frequently associated with mesonephric hyperplasia, mesonephric-like adenocarcinoma is currently considered to be a neoplasm of Müllerian derivation that undergoes transdifferentiation into a Wolffian phenotype. There is significant morphologic, immunohistochemical, genetic and epigenetic overlap between mesonephric carcinoma and mesonephric-like carcinoma. However, distinctive features are seen in each of these entities, including primary site (cervix vs. corpus/extrauterine locations), associated precursors (mesonephric remnants/hyperplasia vs. atypical endometrial hyperplasia/endometriosis/other Müllerian neoplasm), and some differences in the immunohistochemical (more frequent ER and TTF1 positivity in mesonephric-like carcinoma) and molecular profiles (mesonephric-like adenocarcinoma more frequently harbors genetic alterations reported in other Müllerian tumors, such as PIK3CA, PTEN, and CTNNB1). In this review, we provide a detailed overview of the clinicopathologic and molecular features of benign mesonephric proliferations, mesonephric-derived tumors, and mesonephric-like adenocarcinoma, as well as their differential diagnoses.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102689","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":"The Role of the Surgical Pathologist in the Recognition of Hereditary Neuroendocrine Tumors.","authors":"Silvia Uccella, Claudio Luchini, Atsuko Kasajima, Günter Klöppel, Stefano La Rosa","doi":"10.1097/PAP.0000000000000551","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000551","url":null,"abstract":"<p><p>About 10% of neuroendocrine tumors (NETs) can occur in the context of several different hereditary tumor syndromes, and, in a not negligible number of cases, their diagnosis precedes the clinical identification of the hereditary syndrome. In this context, the role of a pathologist can be crucial in identifying these sentinel cases. Indeed, early recognition of inherited NETs has significant clinical value, both for guiding therapeutic strategies and for managing at-risk family members. Modern pathologists play a central role not only in the accurate diagnosis and subtyping of NETs but also in recognizing specific morphologic features that may point to a germline etiology. When morphology does not show peculiar features suggestive of a hereditary context, integrating morphology with clinical context may, however, help identify appropriate genetic testing. In the present paper, we provide an organ-based overview of the most important morphologic and immunohistochemical features, along with their molecular correlates, of pituitary, parathyroid, thoracic, and digestive NETs arising in the context of hereditary tumor syndromes.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918024","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":"MicroRNAs as Biomarkers of Germ Cell Tumors-Focus on Impact and Limitations in Current Clinical Practice Paradigms.","authors":"Agnese Orsatti, Nuno Tiago Tavares, Bruno Oliveira-Lopes, Costantino Ricci, Carmen Jerónimo, Rui Henrique, João Lobo","doi":"10.1097/PAP.0000000000000552","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000552","url":null,"abstract":"<p><p>Testicular germ cell tumors (TGCTs) are the most common malignancies in young-adult males and represent a biologically heterogeneous group of neoplasms. Despite excellent overall prognosis, conventional serum tumor markers lack sufficient sensitivity and specificity in several key clinical settings, including early metastatic disease, postchemotherapy residual masses, and surveillance. Over the past decade, microRNAs of the miR-371~373 cluster have emerged as highly accurate biomarkers in this setting. Among them, circulating miR-371a-3p has demonstrated sensitivity and specificity exceeding 90% for viable, nonteratomatous TGCTs across multiple cohorts, consistently outperforming traditional markers. miR-371a-3p levels closely reflect tumor burden, showing rapid decline after orchiectomy and during effective chemotherapy, and rising at relapse, enabling near real-time disease monitoring. Importantly, miR-371~373 is differentiation-dependent (which can be used as readout for studies on the pathobiology of TGCT phenotypes). It is present in nonteratomatous germ cell components, uniformly absent in teratoma and absent/low in somatic-type malignancies, a feature that both underpins its clinical utility and defines one of its main limitations. This review summarizes the biological rationale underlying miR-371~373 expression in TGCTs and examines current clinical applications of miR-371a-3p across diagnosis, staging, surveillance, and postchemotherapy assessment. Moreover, we discuss analytical considerations, health-economic implications, and emerging data in the biologically related ovarian and extragonadal germ cell tumors. Remaining challenges and future directions for standardized clinical implementation are also addressed.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885954","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":"Diagnosis and Reporting of Intraductal Carcinoma of the Prostate: A Guide for Practising Pathologists With Excerpts From the Genitourinary Pathology Society and the International Society of Urological Pathology Joint Expert Consultation.","authors":"Rajal B Shah, Murali Varma, Ming Zhou, Gladell P Paner, Glen Kristiansen","doi":"10.1097/PAP.0000000000000547","DOIUrl":"10.1097/PAP.0000000000000547","url":null,"abstract":"<p><p>Atypical intraductal proliferations of the prostate span a spectrum from high-grade prostatic intraepithelial neoplasm (HGPIN) to intraductal carcinoma of the prostate (IDCP), with progressively more atypical architectural and cytologic features and at least partial retention of basal cells. IDCP is strongly associated with coexisting high-grade, advanced invasive prostate cancer (PCa). In contrast, unifocal HGPIN is not associated with a significantly increased risk of PCa on subsequent biopsies. Atypical intraductal proliferation (AIP), the term recommended by WHO for proliferations with morphologic features borderline between HGPIN and IDCP, shares molecular and clinicopathological traits with IDCP and serves as a marker of unsampled adverse pathology. Despite progress in understanding IDCP and AIP, their accurate diagnosis and reporting remain challenging. This review provides recommendations on the diagnosis and reporting of IDCP and AIP, stemming from a recent joint expert consultation of the Genitourinary Pathology Society and the International Society of Urological Pathology, to help surgical pathologists optimally diagnose and report atypical intraductal proliferations. The diagnosis of IDCP in biopsies and resections should follow the updated Guo and Epstein criteria, with basal cell immunohistochemistry as needed. Rarely, marked (pleomorphic/bizarre) intraductal cytologic atypia alone may suffice for an IDCP diagnosis. The term AIP should be used only when proliferations are equivocal yet favor IDCP; such cases should be reported as \"AIP, suspicious for IDCP.\" The diagnosis of cribriform HGPIN should not be made on biopsy; instead, such atypical lumen-spanning proliferations with loose cribriform architecture should be reported as \"AIP, suspicious for IDCP.\" When available, ERG and PTEN immunohistochemistry can help differentiate from HGPIN. Adopting these recommendations would reduce interobserver variability, promote consistent communication with clinicians, and enhance patient management.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"331-341"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366690","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":"Advancing Digital Pathology With Large Language Models.","authors":"Partha P Ray","doi":"10.1097/PAP.0000000000000505","DOIUrl":"10.1097/PAP.0000000000000505","url":null,"abstract":"","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"385-386"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726363","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":"Authors' Reply: Advancing Digital Pathology With Large Language Models.","authors":"Ehsan Ullah, Casey P Schukow, Mahul B Amin, Anil V Parwani","doi":"10.1097/PAP.0000000000000518","DOIUrl":"10.1097/PAP.0000000000000518","url":null,"abstract":"","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"386-387"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508627","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":"Demystifying Idiopathic Adulthood Ductopenia: Diagnosis and Differential Diagnosis.","authors":"Haiyan Jing, Xiaotang Du, Hanlin L Wang","doi":"10.1097/PAP.0000000000000531","DOIUrl":"10.1097/PAP.0000000000000531","url":null,"abstract":"<p><p>Idiopathic adulthood ductopenia (IAD) is a rare chronic cholestatic liver disorder characterized by progressive loss of interlobular bile ducts in the absence of an identifiable etiology. Its histologic hallmark, ductopenia, is nonspecific and occurs across many cholestatic disorders, which complicates its recognition. IAD is therefore a diagnosis of exclusion, requiring thorough evaluation to rule out immune-mediated cholangiopathies, infections, genetic or metabolic diseases, drug-induced injury, and neoplasia. Advances in molecular diagnostics have increasingly uncovered monogenic cholangiopathies in adults previously classified as IAD, thereby narrowing the truly idiopathic category. In this article, we provide a comprehensive review of the disease, with emphasis on its clinical presentation, histopathologic characteristics, differential diagnoses, and emerging concepts.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"371-384"},"PeriodicalIF":2.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571821","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}