Advances In Anatomic Pathology最新文献

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.

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.

There are inherited germline variants that predispose patients to select mesenchymal tumors with associated tumor syndromes. While many of these tumors are clinically suspected or diagnosed early in life, pathologists can play a critical role in their initial recognition and reporting, prompting appropriate confirmatory testing and follow-up for the affected patient and screening for their family members. Hereditary conditions commonly encountered in association with bone and soft tissue pathology include Hereditary Multiple Osteochondromas, Familial Adenomatous Polyposis, Carney Complex, and Neurofibromatosis Type I. Additional syndromes include Rhabdoid Tumor Predisposition Syndrome, Familial Schwannomatosis, DICER1 syndrome, and others. Herein, we describe select bone and soft tissue tumors associated with familial syndromes, aiming to provide a guide for practicing surgical pathologists on how to recognize these lesions and when they should raise the possibility of an associated hereditary condition.

BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome is due to germline mutation of BAP1, a tumor suppressor gene. Patients with this syndrome has an increased susceptibility to the development of uveal melanomas, cutaneous melanomas, cutaneous atypical melanocytic lesions, mesotheliomas, clear cell renal cell carcinoma, and other tumors. These syndromic tumors exhibit an aggressive growth and earlier onset in comparison to sporadic tumors. In this review we outline the history, epidemiology, and genetics of this syndrome. The clinical presentation and histopathology of commonly developed tumors in syndromic patients, namely uveal melanomas, cutaneous atypical melanocytic lesions, mesotheliomas, and clear cell renal cell carcinoma are discussed.

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.

Histiocytic neoplasms are a diverse group of disorders arising from macrophages, dendritic cells, and monocytes of the mononuclear phagocyte system. These neoplasms encompass a clinical spectrum from indolent, self-limited, and localized conditions to highly aggressive malignancies. Since the publication of the Revised Fourth Edition of the World Health Organization (WHO) classification, advances in molecular diagnostics have improved our understanding of the pathogenesis and classification of these disorders. In contrast to the Revised Fourth Edition, the International Consensus Classification (ICC) now recognizes Rosai-Dorfman-Destombes disease as a neoplastic disorder and introduces ALK-positive histiocytosis as a distinct entity. This manuscript reviews the current concepts regarding histiocytic neoplasms, focusing on the diagnostic criteria recommended by the ICC based on histopathology, immunophenotype, molecular alterations, as well as clinical and imaging characteristics.

The International Consensus Classification (ICC) updated in 2022 the World Health Organization (WHO) classification of hematopoietic tumors (2016 revision of the 4th edition WHO classification). Although the major categories of myeloid neoplasms remained unchanged from the prior WHO classification, many disease entities including those in the myeloproliferative neoplasm (MPN) and myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) categories underwent updates. For all these disease subtypes, a careful integration of clinicopathologic findings and molecular data led to improved diagnostic definitions. Although the classification of MPNs received only minor changes, these included a simpler definition of accelerated phase of chronic myeloid leukemia. For the MDS/MPN group, in addition to the presence of one or more increased peripheral blood cell counts as evidence of myeloproliferative features, concomitant cytopenia as evidence of ineffective hematopoiesis is now an explicit diagnostic requirement for all the entities included in this category. The presence of specific mutations in the appropriate clinicopathologic context is now included in the diagnostic criteria for some of the MPN and MDS/MPN entities. This review aims to briefly discuss the diagnostic approach to MPNs and MDS/MPNs according to the ICC.

The International Consensus Classification (ICC) of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) expands on the work of prior classifications to refine the diagnostic criteria for MDS and AML and to identify specific genetic disease subtypes. This review summarizes the approach to the diagnosis of MDS and AML from the ICC perspective. For MDS, the significance of detecting mutations in SF3B1 , usually associated with ring sideroblasts, as well as the poor prognosis of mutations of TP53 are now included. For AML, new genetic categories are included, and the classification now incorporates additional clinically significant gene mutations by recognizing AML with TP53 mutation and AML with mutations in genes associated with prior therapy or MDS. Finally, the new category of MDS/AML is introduced for adult patients without recurrent de novo genetic abnormalities with 10% to 19% peripheral blood or bone marrow blasts that allow for more treatment flexibility based on clinical findings. While the increase in genetic categories and changes in blast cell requirements can be confusing, a stepwise approach is provided to allow easy use of the classification.