{"title":"Steatotic Liver Disease: Navigating Pathologic Features, Diagnostic Challenges, and Emerging Insights.","authors":"Jingjing Jiao, Xuchen Zhang","doi":"10.1097/PAP.0000000000000483","DOIUrl":"10.1097/PAP.0000000000000483","url":null,"abstract":"<p><p>Steatotic liver disease (SLD) is now used as an overarching category encompassing five subcategories: metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic and alcohol related/associated liver disease (MetALD), alcohol-related/associated liver disease (ALD), SLD with specific etiology, and cryptogenic SLD. This review summarizes foundational and recent advances in the histologic evaluation of SLD, including common pathologic features across all subcategories, distinctions associated with different etiologies, scoring and grading systems, and the evolution of digital pathology techniques for SLD assessment.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"387-401"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078213","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":"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":"414-426"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","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":"Rare Liver Diseases With Near-Normal Histology: A Review Focusing on Metabolic, Storage, and Inclusion Disorders.","authors":"Xiaotang Du, Hanlin L Wang","doi":"10.1097/PAP.0000000000000488","DOIUrl":"10.1097/PAP.0000000000000488","url":null,"abstract":"<p><p>Despite the growing availability of noninvasive and faster diagnostic modalities, biopsy remains an important tool in the diagnosis and management of liver diseases. However, it is not uncommon that liver biopsies reveal normal or near normal histologic findings in patients with abnormal liver biochemistries, elevated autoantibodies, clinical findings suggestive of portal hypertension, systemic autoimmune or inflammatory diseases, hepatomegaly, cirrhosis by imaging, or other indications. These scenarios present significant diagnostic challenges and are rarely discussed in detail in the literature or textbooks. This article aims to provide a comprehensive review of a group of selected rare liver diseases, with a focus on metabolic, storage and inclusion disorders, that may exhibit a near-normal histology on biopsy. By recognizing subtle histologic features and correlating with clinical history, laboratory results and imaging findings, it is often possible to narrow down the differential diagnosis. In many cases, this integrative approach can yield a definitive diagnosis, allowing for tailored treatment and better patient outcomes.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"363-374"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456464","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":"Molecular Advances in Cholestatic Liver Diseases.","authors":"Raima Memon, Romil Saxena","doi":"10.1097/PAP.0000000000000502","DOIUrl":"10.1097/PAP.0000000000000502","url":null,"abstract":"<p><p>The list of genetically defined causes of cholestatic liver diseases continues to expand; it currently includes mutations affecting bile acid synthesis, basolateral and apical membrane transporters, bile duct development, canalicular tight junctions, and bile acid conjugation, among others. The most frequently identified mutations in large multi-institutional studies of cholestasis occur in JAG1, ATP8B1, ABCB11, ABCB4, SERPINA1 , and CFTR . Mutations in JAG1 , SERPINA1 , and CFTR cause Alagille syndrome, alpha-1 antitrypsin deficiency, and cystic fibrosis, respectively. Mutations in ATP8B1 , ABCB11 , and ABCB4 cause a spectrum of diseases that range from the episodic, nonprogressive benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy to the severe and rapidly progressive familial intrahepatic cholestasis. These cholestatic disorders present a wide range of symptoms and overlapping clinical features. However, in contemporary practice, diagnosis is often easily and rapidly established by clinically available comprehensive gene panels. In addition to diagnosis, these panels also aid in the discovery of novel genes or variants as potential causes of cholestasis. Genetic mutations may also be responsible for drug-induced cholestasis, as the liver plays a vital role in metabolism of drugs and xenobiotics. Uptake into hepatocytes and elimination into the bloodstream or bile of drugs and xenobiotics involve transporters across the basolateral and apical hepatocellular membranes, respectively. Therefore, mutations in any of the transporters lead to impaired metabolism and/or elimination of these substances. Furthermore, a large number of drugs and xenobiotics have a transcriptional or functional inhibitory effect on transporters such as BSEP and MDR3, setting the stage for the all-too-common drug-induced cholestasis.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"375-386"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315753","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":"Drug-induced Liver Injury: Pathology Patterns and Common Culprits.","authors":"Paige H Parrack, Lei Zhao","doi":"10.1097/PAP.0000000000000506","DOIUrl":"10.1097/PAP.0000000000000506","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) has an incredible range of morphologic presentations, from acute extensive necrosis to resolving injury with ceroid-laden macrophages. The diversity in presentation on biopsy is diagnostically challenging, but DILI is becoming more widely recognized, especially with the aid of resources like LiverTox. Some medications, such as acetaminophen, have well-established patterns of injury. However, newer medications, such as immune checkpoint inhibitors, are continually being developed, and our understanding of their effects on the liver are evolving. In this chapter, we will focus on the DILI patterns and frequently encountered DILI culprits. Ultimately, DILI is a diagnosis of exclusion, and close clinical correlation is essential when navigating the differential.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"402-413"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774492","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}
Luisa Santoro, Federica Grillo, Maria D'Armiento, Anna Maria Buccoliero, Michele Rocco, Jacopo Ferro, Alessandro Vanoli, Barbara Cafferata, Maria Cristina Macciomei, Claudia Mescoli, Mara Cananzi, Rita Alaggio, Matteo Fassan, Luca Mastracci, Paola Francalanci, Paola Parente
{"title":"Clinicopathologic Features of Primary Immunodeficiency Monogenic Disease-related Very Early Onset Inflammatory Bowel Disease: Focus on Gastrointestinal Histologic Features in IFIH1 Mutations.","authors":"Luisa Santoro, Federica Grillo, Maria D'Armiento, Anna Maria Buccoliero, Michele Rocco, Jacopo Ferro, Alessandro Vanoli, Barbara Cafferata, Maria Cristina Macciomei, Claudia Mescoli, Mara Cananzi, Rita Alaggio, Matteo Fassan, Luca Mastracci, Paola Francalanci, Paola Parente","doi":"10.1097/PAP.0000000000000457","DOIUrl":"10.1097/PAP.0000000000000457","url":null,"abstract":"<p><p>Very early onset inflammatory bowel disease (VEO-IBD) is a clinical term referring to IBD-like symptomatology arising in children younger than 6 years. VEO-IBD may be due to polygenic etiology in \"pure\" IBD (Crohn disease-CD and ulcerative colitis-UC), or it may be caused by primary immunodeficiency underlined by monogenic disease. Primary immunodeficiency monogenic diseases have a Mendelian inheritance and affect the immune system with multiorgan morbidity and possible effects on the gastrointestinal system. Primary Immunodeficiency monogenic diseases differ from \"pure\" IBD as the latter primarily affect the gastrointestinal tract with mitigated extraintestinal symptomatology. Since their first description, primary immunodeficiency monogenic diseases, although rare, have been the subject of increasing interest due to their dramatic phenotype, difficulty in reaching a timely diagnosis, and specific therapeutic approach. In this paper, we present a brief review of primary immunodeficiency monogenic diseases, focusing on to their clinicopathologic features as well as delving, in greater detail, into monogenic diseases caused by IFIH1 mutations. The clinicopathologic features of 4 patients with IFIH1 , a gene involved in interferon pathway deficiency, will be described using a histologic pattern of damage approach confirming the need to avoid the histologic diagnosis of VEO-IBD in children younger than 6 years.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"427-435"},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974802","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":"Alveolar Soft Part Sarcoma: An Updated Review.","authors":"Pedram Argani, Cristina R Antonescu","doi":"10.1097/PAP.0000000000000513","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000513","url":null,"abstract":"<p><p>In 1952, Christopherson and colleagues described the distinctive clinical and pathologic features of alveolar soft part sarcoma (ASPS). For nearly half a century, controversy raged regarding the putative cell of origin of this peculiar neoplasm. Following the identification of the characteristic der(17)t(X;17)(p11;q25) translocation and discovery of the resulting ASPSCR1::TFE3 gene fusion in 2001, the current consensus is that alveolar soft part sarcomas represent one of several gene fusion-driven sarcomas which lack a normal cellular counterpart. This updated review highlights the clinical and pathologic features of this intriguing neoplasm.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298008","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":"Perivascular Cell Tumors (PEComas) of the Genitourinary Tract: A Summary.","authors":"Susan K Potterveld, Pedram Argani, Ankur R Sangoi","doi":"10.1097/PAP.0000000000000512","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000512","url":null,"abstract":"<p><p>Perivascular cell tumors (PEComas) in the genitourinary tract have an overwhelming propensity to occur in the kidney, where they are synonymously referred to as angiomyolipomas (AMLs). Although less common, PEComas may occur throughout the urinary tract (particularly involving the bladder) and may rarely appear in the prostate/seminal vesicle and testis. Herein, we describe the wide clinicopathologic characteristics of genitorurinary PEComas both of renal and extrarenal origin.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129853","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":"A Primer on Bluesky (and PathSky) for Pathologists, Trainees, and Medical Students.","authors":"Casey P Schukow, Lavisha S Punjabi, Emma Khan","doi":"10.1097/PAP.0000000000000491","DOIUrl":"10.1097/PAP.0000000000000491","url":null,"abstract":"<p><p>Social media (SoMe) has become an integral tool in modern pathology, facilitating education, research, mentorship, and professional networking. However, the evolving landscape of SoMe platforms presents both opportunities and challenges for pathologists. Bluesky, a decentralized platform launched publically in 2024 has gained significant traction among pathologists as an alternative to \"traditional,\" or more widely-used, platforms like Twitter/X. This narrative review explores the role of SoMe in pathology, introduces Bluesky and its pathology-focused community PathSky, and compares it with other platforms. In addition, practical guidance on joining Bluesky and engaging with PathSky is provided. By embracing innovative platforms like Bluesky, pathologists can enhance collaboration, education, and professional growth in the digital age.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"356-360"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699361","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":"Hepatoblastoma: Comprehensive Review With Recent Updates.","authors":"Jingjing Jiao, Romil Saxena, Raffaella Morotti","doi":"10.1097/PAP.0000000000000495","DOIUrl":"10.1097/PAP.0000000000000495","url":null,"abstract":"<p><p>Hepatoblastoma (HB), the most common primary malignant liver tumor of childhood, demonstrates remarkable histologic heterogeneity and can be classified into epithelial or mixed epithelial-mesenchymal subtypes. This review summarizes updates in histologic classification, molecular signatures, staging, and risk stratification of HB. The Children's Hepatic tumors International Collaboration represents an international effort to standardize the study of rare pediatric liver tumors; emphasis continues to remain on improving risk stratification by a combination of clinical, histologic, and molecular features to tailor treatment in a bid to reduce toxicity while maintaining or improving efficacy. Pure fetal HB is cured by complete resection without the need for adjuvant chemotherapy. Malignant rhabdoid tumors have been parsed out from small cell undifferentiated HBs by negative INI-1 staining on immunohistochemistry; these tumors require a distinct and more aggressive chemotherapeutic regimen. The significance of recently characterized \"blastema\" component in HB remains to be elucidated. Hepatocellular neoplasm, not otherwise specified, is a provisional diagnostic category for tumors exhibiting either intermediate or a combination of both HB and hepatocellular carcinoma histologic features. The Children's Hepatic tumors International Collaboration risk stratification algorithm includes age as an important discriminator of risk, in addition to AFP, metastasis, and PreTreatment EXTent of disease stage and its annotations.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":" ","pages":"309-316"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771191","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}