{"title":"MITF Pathway-Activated Cutaneous Neoplasms.","authors":"Michael Michal, Steven D Billings, Thomas Brenn","doi":"10.1097/PAP.0000000000000496","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000496","url":null,"abstract":"<p><p>Over the past few years, several fusion genes have been reported in dermal-based tumors, resulting in the activation of the microphthalmia (MITF) signalling pathway and a melanocytic phenotype by immunohistochemistry. The best-studied example of these tumors is clear cell sarcoma, which rarely may present as a primary dermal tumor. These tumors are characterized by EWSR1 gene rearrangements, typically with ATF1 and less commonly CREB1. More recently reported cutaneous tumors show gene fusions involving CRTC1::TRIM11, ACTIN::MITF, MITF::CREM, and MED15::ATF1. While the entities in this tumor group share many features, they show subtle distinguishing features, including clinical presentation, histopathologic features, immunophenotype, and outcome. The following overview provides a detailed discussion of these rare tumors with emphasis on differentiating features and differential diagnosis.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092325","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":"Updated Classification of Cutaneous Lymphoma.","authors":"John R Goodlad","doi":"10.1097/PAP.0000000000000487","DOIUrl":"10.1097/PAP.0000000000000487","url":null,"abstract":"<p><p>The International Consensus Classification (ICC) of myeloid and lymphoid neoplasms follows the precedent set in the Revised European-American lymphoma classification for modern lymphoma classifications by defining specific diseases on the basis of all the available morphologic, immunophenotypic, genetic, and clinical findings. Primary cutaneous lymphomas exhibit a broad range of clinical behavior ranging from lesions which spontaneously regress to those which run an aggressive, often fatal course. Accurate separation of entities is therefore essential for prognostication and to ensure appropriate treatment is administered. However, despite marked differences in clinical course, many subtypes of primary cutaneous lymphoma exhibit remarkably similar, often overlapping, and sometimes indistinguishable pathologic features. While molecular analysis has furthered our understanding of some of these disease entities, it does not yet facilitate robust distinction. Thus, clinical correlation retains a central role in both the diagnosis and classification of primary cutaneous lymphoma. This review aims to draw attention to problem areas in differential diagnosis and hopefully offer some practical suggestions for resolving difficult cases. It will also highlight recent advances in the field and discuss how they reinforce the current classification system and how they might impact of future classifications and treatment strategies.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"239-255"},"PeriodicalIF":5.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603361","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 Classification of Follicular Lymphoma and Related Entities.","authors":"Camille Laurent, James R Cook","doi":"10.1097/PAP.0000000000000481","DOIUrl":"10.1097/PAP.0000000000000481","url":null,"abstract":"<p><p>Follicular lymphoma (FL) is a mature B cell neoplasm classically characterized by B cells harboring the t(14;18) IGH::BCL2 leading to the overexpression of BCL2 in most cases. Conventional FL occurs in lymph nodes and typically shows a follicular B-cell proliferation expressing at least one germinal center marker. Two early lesions closely related to conventional FL are recognized as variants, namely in situ follicular neoplasia (ISFN), and duodenal-type follicular lymphoma (DTFL). FL lacking BCL2 rearrangement ( BCL2 -R negative) accounts for around 10% to 15% of FLs and constitutes a heterogeneous group of FLs. Most of these alternative forms of FL are considered as distinct entities separate from conventional FL in the 2022 International Consensus Classification. This review aims to summarize the key pathologic and diagnostic features of FL conventional and its alternative forms as well as further emphasize the increasing role of molecular studies in the diagnostic work-up.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"195-207"},"PeriodicalIF":5.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078210","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":"Advances in the Classification of Aggressive B-cell Lymphomas.","authors":"Leonie Frauenfeld, Elias Campo","doi":"10.1097/PAP.0000000000000484","DOIUrl":"10.1097/PAP.0000000000000484","url":null,"abstract":"<p><p>Aggressive B-cell lymphomas are a biologically and clinically very heterogeneous group of tumors that may be related to different stages of B-cell differentiation development. This review aims to summarize recent advances in the understanding of these tumors with a focus on the practical approach to the diagnosis of these entities. We analyze the defining characteristics of the different subtypes of aggressive B-cell lymphomas, including nodal and extranodal diffuse large B-cell lymphoma, virus-associated lymphomas, terminally differentiated B-cell lymphomas, high-grade B-cell lymphomas, and Burkitt lymphoma. This review particularly explores the integration of morphologic, immunophenotypic, and genetic data that refine diagnostic accuracy and prognostic stratification, underscoring the necessity for a standardized approach in clinical practice. By synthesizing current knowledge, this review aims to enhance the understanding of aggressive B-cell lymphomas within the context of the evolving classification system, paving the way for future research and clinical advancements.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"208-219"},"PeriodicalIF":5.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982421","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 Classification of Hematopoietic Neoplasms: The Why, How, and Who? (Part l).","authors":"Daniel A Arber, James R Cook","doi":"10.1097/PAP.0000000000000489","DOIUrl":"10.1097/PAP.0000000000000489","url":null,"abstract":"","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"193-194"},"PeriodicalIF":5.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456466","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":"Modern Approach to Nodal T-Cell Lymphomas.","authors":"Sarah L Ondrejka, Laurence de Leval","doi":"10.1097/PAP.0000000000000492","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000492","url":null,"abstract":"<p><p>In recent decades, there have been many meaningful contributions to the pathology literature with respect to T-cell lymphoma pathogenesis and biology and improved diagnostics. We know more about disease classification, clinical characteristics, immunophenotype, and genetics than ever before, and yet diagnosis of nodal T-cell lymphomas continues to be a challenging exercise. Complicating interpretation are the many non-neoplastic mimickers of peripheral T-cell lymphoma including drug effects, viruses, autoimmune, and idiopathic conditions, that must be considered when faced with an abnormal lymph node biopsy. The number of immunohistochemical stains required to make a diagnosis of T-cell lymphoma is not standardized and may be exhaustive, requiring judicious use of tissue sections. Clonality studies may contribute to the diagnosis, though questions remain about test modality, when to exercise interpretive caution, and what to do if a clone cannot be demonstrated. Use of next generation sequencing in the diagnosis of nodal T-cell lymphomas is increasing, but how the data can be practically applied to diagnosis is still under examination. The goal of this paper is to consider nodal T-cell lymphoma diagnosis and classification in a modern context, using a question-and-answer format to capture the interest of the reader and address common pathology consultation queries.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":"32 3","pages":"220-238"},"PeriodicalIF":5.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952054","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":"Multimodal Generative AI for Anatomic Pathology-A Review of Current Applications to Envisage the Future Direction.","authors":"Ehsan Ullah, Mirza Mansoor Baig, Asim Waqas, Ghulam Rasool, Rajendra Singh, Ashwinikumar Shandilya, Hamid GholamHossieni, Anil V Parwani","doi":"10.1097/PAP.0000000000000498","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000498","url":null,"abstract":"<p><p>This review focuses on the purported applications of multimodal Gen-AI models for anatomic pathology image analysis and interpretation to predict future directions. A scoping review was conducted to explore the applications of multimodal Gen-AI models in advancing histopathology image analysis. A comprehensive search was conducted using electronic databases for relevant articles published within the past year (July 1, 2023 to June 30, 2024). The selected articles were critically analyzed to identify and summarize the applications of multimodal Gen-AI in anatomic pathology image analysis. Multimodal Gen AI models reported in the literature claim moderate to high accuracy on tasks including image classification, segmentation, and text-to-image retrieval. This review demonstrates the potential of multimodal Gen AI models for useful applications in pathology, including assisting with diagnoses, generating data for education and research, and detection of molecular features from anatomic pathology images. These models use data from a few academic institutions thus they require validation on diverse real-world data. There is an urgent need to build consensus models for optimal model performance through multicenter collaboration using a federated learning approach and the use of carefully curated synthetic anatomic pathology data. These models also need to achieve reliability, generalizability and meet the standards required for clinical use. Despite the rigorous need for evaluation and the need to address genuine concerns, multimodal GenAI models present a promising perspective for the advancement and scalability of anatomic pathology.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958072","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":"Advances in Hepatocellular Carcinoma: Molecular Insights, Histologic Subtypes, and Differential Diagnosis.","authors":"Wei Zheng, Yulin Haw, Hanlin L Wang","doi":"10.1097/PAP.0000000000000501","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000501","url":null,"abstract":"<p><p>Significant advancements over the past 2 decades have reshaped our understanding and diagnostic capabilities for hepatocellular carcinoma (HCC). These advancements span molecular insights into key driver gene mutations and chromosomal aberrations, refined recognition of distinct histologic subtypes, improved differentiation from precursor and benign hepatic lesions, and enhanced strategies for interpreting challenging biopsy samples. The discovery of driver mutations such as TERT promoter, CTNNB1, and TP53, along with chromosomal alterations, has provided essential tools for identifying malignancy and understanding tumor behavior. Concurrently, the recognition of distinct morphomolecular HCC subtypes has underscored the importance of integrating histologic and molecular findings for accurate diagnosis and prognostic assessment. In addition, differentiating HCC from dysplastic nodule and hepatocellular adenoma remains a diagnostic challenge, often requiring a combination of morphologic, immunohistochemical, and molecular approaches. Moreover, the interpretation of biopsy samples from borderline hepatocellular neoplasms highlights the limitations of conventional pathology alone and the need for comprehensive diagnostic strategies. This review aims to provide an updated overview of these interconnected aspects, emphasizing their collective role in advancing the precision diagnosis of HCC.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962361","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}
Despoina Myoteri, Stratigoula Sakellariou, Dina G Tiniakos
{"title":"Histopathology of Autoimmune Hepatitis: An Update.","authors":"Despoina Myoteri, Stratigoula Sakellariou, Dina G Tiniakos","doi":"10.1097/PAP.0000000000000500","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000500","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is a rare immune-mediated chronic liver disease that is diagnosed based on a combination of biochemical, immunologic, and histologic features and the exclusion of other causes of liver disease. According to the new consensus criteria of the International Autoimmune Hepatitis Pathology Group (IAIHPG), the likely histologic features include a chronic hepatitis pattern of injury with a lymphoplasmacytic portal infiltrate, interface activity, and portal-based fibrosis. More than mild lobular hepatitis with any of the above features can also be diagnosed as likely AIH in the absence of features of another liver disease. Centrilobular injury with prominent hepatocellular necrosis and mononuclear inflammation may represent an acute-onset disease and indicate possible AIH in the absence of concurrent liver disease. Kupffer cell hyaline bodies and portal lymphocyte apoptosis are significantly associated with AIH, whereas emperipolesis and hepatocellular rosette formation are nonspecific features indicative of disease severity. Liver histology is an integral part of the clinical diagnostic scoring system and is required to confirm or support AIH diagnosis. Substitution of the histologic component of the simplified AIH scoring system with the consensus IAIHPG criteria has been proposed to optimize clinical diagnosis. This review explores the significant role of histopathology in AIH by analyzing its main features and current histologic diagnostic criteria, different AIH presentations, differential diagnosis, assessment of concurrent liver disease, and identification of AIH variants with primary cholangiopathy.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958606","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":"Other Primary Epithelial Neoplasms of the Liver.","authors":"Wai Szeto, Rifat Mannan","doi":"10.1097/PAP.0000000000000494","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000494","url":null,"abstract":"<p><p>Primary liver carcinoma (PLC) is the sixth most common malignancy worldwide and the third leading cause of cancer-related mortalities. Hepatocellular carcinoma (HCC) is the most prevalent form of PLC, followed by intrahepatic cholangiocarcinoma (iCCA). In addition, there is a group of rarer PLCs that do not fit neatly into the HCC or iCCA categories. This review explores this heterogeneous group, including combined hepatocellular-cholangiocarcinoma (cHCC-CCA), intermediate cell carcinoma (ICC), mixed hepatocellular-neuroendocrine carcinoma, and undifferentiated primary liver carcinoma. cHCC-CCA is a rare subtype of PLC, characterized by both hepatocytic and cholangiocytic differentiation within the same tumor. The latest WHO classification (2019, fifth edition) redefined cHCC-CCA by eliminating the \"stem cell subtypes\" and emphasized that diagnosis should primarily rely on morphologic features, supported by immunohistochemical staining to better define subtypes. Intermediate cell carcinoma is a subtype of cHCC-CCA and is comprised of monomorphic tumor cells that exhibit characteristics intermediate between hepatocytes and cholangiocytes, with immunohistochemical expression of hepatocytic and cholangiocytic markers within the same cell. Another rare entity, combined HCC and neuroendocrine carcinoma (NEC), contains an admixture of HCC and NEC components within the same tumor. Undifferentiated primary liver carcinoma, on the other hand, lacks definitive lineage differentiation beyond an epithelial phenotype. These heterogeneous PLCs pose diagnostic challenges owing to their mixed/unusual histologic features and overlapping immunohistochemical markers. They tend to have poor prognoses, highlighting the critical importance of accurate and timely diagnosis.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810274","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}