Advances In Anatomic Pathology最新文献

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.

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.

Hemangioblastoma-like clear cell stromal tumor (HLCCST) of the lung is an exceptionally rare mesenchymal neoplasm that is generally considered benign. Current knowledge of this tumor remains limited. Histologically, HLCCST is defined by a hypervascular stroma with dilated blood vessels and is predominantly composed of epithelial-like cells arranged in solid sheets or nests with uniform morphology. Molecular genetic studies have identified YAP1::TFE3 gene fusions as a hallmark in most reported cases. To date, in addition to our case, a total of 19 HLCCST cases have been reported across 7 publications. Here, we present a comprehensive review of HLCCST, detailing its clinicopathologic features, key molecular alterations, and prognostic data of HLCCST. In addition, we emphasize the importance of accurate recognition and diagnosis of this rare tumor to ensure appropriate treatment and improved patient outcomes.

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.

The approach to eosinophilia and mast cell disorders in the bone marrow is diverse and depends on multiple factors including access to ancillary testing, resources to support testing, type of practice setting (eg, community, remote, tertiary care center or specialized referral center for these disorders) and whether there are options for clinical trial enrollment. That said, while there are some basic principles to the workup that we can all likely agree upon, individual practice habits will need to be tailored to suit an individual setting. As such, the approach presented in this manuscript is meant to serve as a practical guide and not as dogma per se. Importantly, an in-depth discussion of individual diseases and International Consensus Classification diagnostic criteria will not be covered, as the main focus of this article is the approach to these disorders. The reader is referred to a comprehensive discussion of these diseases and diagnostic criteria in several excellent articles. While there are clear areas of overlap between eosinophilia and mast cell conditions (eg, systemic mastocytosis associated with eosinophilia, myeloid neoplasm with eosinophilia, and tyrosine kinase rearrangements), it is the authors' opinion that it is perhaps easier to navigate these entities separately (eg, eosinophilia as one broad topic and mast cell conditions as another) and to recognize the settings in which overlap may exist and what testing might be considered. Eosinophilia and mast cell conditions will be discussed separately supplemented by generous use of figures and tables to highlight key points.

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.

Bone matrix-forming tumors are a group of neoplasms that exhibit differentiation toward any stage of osteoblast development. Their clinicopathologic features can resemble one another, yet their clinical management may vary significantly. Therefore, appropriate treatment requires accurate diagnosis, which can be challenging, especially with limited biopsy specimens. Recently, the driver genetic alterations underlying these neoplasms have been discovered, and their protein products can be targeted for diagnosis and therapy. Herein, we summarize the recent advances in our understanding of bone matrix-forming tumors and emphasize the integration of molecular genetics into their conventional clinicopathologic evaluation.

Cartilage-forming tumors are a broad and diverse group of neoplasms frequently affecting the skeleton. Distinguishing between the members of this group is important because of significant differences in treatment and prognosis. Accurate diagnosis can be challenging because of similarities in their clinical, radiographic, and pathologic features. Immunohistochemistry and molecular tools are helpful in select instances. Therefore, careful evaluation and correlation of these features are essential in arriving at the correct diagnosis and appropriate patient management. This review provides an overview of the current literature, emphasizing helpful features in diagnosis.

The accurate diagnosis of giant cell-rich tumors of bone is challenging, especially in limited tissue samples. This diverse group of neoplasms have similar and often ambiguous clinical presentations, radiologic features, and morphologic characteristics. During the last decade, the discovery of pathogenic recurrent genetic alterations has allowed the development of immunohistochemical surrogate markers and FISH assays that can help differentiate the entities of this broad group from one another. The correct diagnosis of these neoplasms is essential in the management of the affected patients.

Mesenchymal neoplasms of the gastrointestinal tract are rare compared with epithelial lesions. However, over the past few decades, the increasing volume of gastrointestinal endoscopy has expedited the recognition of several novel entities with varying clinical significance. Its spectrum extends from reactive changes and benign neoplasms to highly aggressive sarcomas. At the malignant end of the spectrum, the importance of correctly diagnosing these tumors is underscored by the specific therapeutic implications available for some tumor types (eg, tyrosine kinase inhibitors for gastrointestinal stromal tumors) that allow personalized treatments. Benign lesions frequently surface among routine polypectomy specimens, sometimes offering diagnostic challenges. However, precise classification is the only way to avoid prognostic uncertainty and overtreatment, and to recognize possible syndromic associations. Hereby, we offer a pragmatic review of the topic from the gastrointestinal pathologist's perspective, who, although more accustomed to epithelial neoplasms, can use an algorithmic approach to diagnose mesenchymal entities successfully.