Advances In Anatomic Pathology最新文献

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.

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.

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.

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.

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.

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.

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.

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.

Horseshoe kidney is a rare congenital anomaly with an unusually higher frequency of neuroendocrine tumors. Symptoms are rare, and, in most of the cases, are incidentally diagnosed. The clinical behavior of these tumors is heterogeneous and can be difficult to predict based on histology alone. Necrosis and percentage of Ki-67 may have a role in prognosis. Almost all tumors are carcinoids (well-differentiated neuroendocrine tumors) observed at an early age and with no sex dominance. It is not known the reason for the higher frequency of neuroendocrine tumors in horseshoe kidneys and the histogenesis is unknown. One of the hypotheses supports that renal carcinoid tumors may arise from neuroendocrine cells within foci of metaplastic or teratomatous epithelium within the kidney. With consonance with this hypothesis, there are reports of carcinoids in horseshoe kidneys associated with a cystic lesion lined by the intestinal epithelium, with mucinous differentiation and osseous metaplasia, arising in a mature teratoma of the kidney, arising within mature teratoma and clear cell renal cell carcinoma, with a mucinous cystadenoma element, and arising within mature cystic teratoma synchronous with primary adenocarcinoma. There is only one reported large cell neuroendocrine carcinoma of a horseshoe kidney in a 57-year-old Chinese woman. Herein, we report a patient that to the best of our knowledge is the first case of a combined well-differentiated neuroendocrine tumor and large-cell neuroendocrine carcinoma with rhabdoid features in horseshoe kidney. The histologic component of rhabdoid features expands the morphologic spectrum of neuroendocrine tumors in the horseshoe kidney. We provide a comprehensive review of the literature summarizing pertinent key clinical and pathologic aspects.