Advances In Anatomic Pathology最新文献

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.

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.

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.

Preneoplastic and neoplastic biliary disease comprises biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasms, mucinous cystic neoplasms (MCNs), and cholangiocarcinoma and their variants. Correct recognition of these entities can be challenging, especially on small/needle biopsies, but is required to plan therapy and guide transplant in the setting of cirrhosis. Salient histologic features of these entities, along with ancillary use of immunostains and key molecular findings aiding in diagnosis, are discussed. Type 2 intraductal papillary neoplasm of the bile ducts is typically associated with an invasive malignancy and lack unique molecular features associated with the Type 1 intraductal papillary neoplasm, thus they are called "papillary cholangiocarcinoma" by some authors. Some of the cholangiocarcinoma variants, like enteroblastic and mucoepidermoid, are under-recognized and can pose diagnostic challenges. The tubulocystic and cholangioblastic variants are relatively recently described but are being increasingly recognized. The cholangioblastic variant has a novel NIBPL-NACC1 fusion described in the more recent larger series reported, making it a somewhat unique variant of cholangiocarcinoma. Nomenclature of the cholangioblastic variant is in evolution as is the link between adenofibroma and the tubulocystic variant. Correct recognition of these variant subtypes would aid in long-term studies to better determine the prognosis in these subtypes.