Advances In Anatomic Pathology最新文献

High-grade renal cell carcinoma (RCC), often diagnosed at advanced stages, significantly contributes to renal cancer-related mortality. This review explores the progress in understanding specific subtypes of high-grade RCC, namely fumarate hydratase (FH)-deficient RCC, anaplastic lymphoma kinase (ALK)-rearranged RCC, and SMARCB1-deficient renal medullary carcinoma, all of which are now recognized as molecularly defined entities in the WHO classification system (2022). While these entities each exhibit a morphologic spectrum that overlaps with other high-grade RCC, ancillary tools developed based on their distinctive molecular alterations can help establish a specific diagnosis, underscoring the importance of integrating molecular findings into diagnostic paradigms. It is important to exclude these specific tumor types in cases with similar morphologic spectrum before rendering a diagnosis of high-grade papillary RCC, collecting duct carcinoma, or RCC, NOS. Several gray areas exist within the spectrum of high-grade uncommon types of RCC, necessitating continued research to enhance diagnostic precision and therapeutic options.

Glandular lesions in the urinary tract or their associated pathologies can pose a diagnostic challenge. There is a variety of benign alterations and tumor types that need to be taken into account in differential diagnostic considerations. In recent times, efforts for better defining these alterations or lesions both on the histopathological and molecular levels have been undertaken. This article will provide an update on current diagnostic and molecular considerations of these lesions.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon malignancy involving the renal pelvis and ureter. Careful pathologic analysis plays a critical role in the diagnosis and clinical management of UTUC. In combination with clinical and radiologic evaluation, pathologic features can be used to stratify patients into low-risk and high-risk groups. This risk stratification can help clinicians select the optimal treatment for patients with UTUC, such as kidney-sparing (conservative) treatment, radical nephroureterectomy or ureterectomy, and perioperative systemic therapy. However, due to the technical difficulty of obtaining sufficient tissue from the upper urinary tract, it is often challenging for pathologists to accurately grade the tumor and assess tumor invasion in small biopsy specimens. Although the majority of UTUCs are pure urothelial carcinoma, a considerable subset of UTUCs show histologic subtypes or divergent differentiation. Recent studies have identified genetically distinct molecular subtypes of UTUC by examining DNA, RNA, and protein expression profiles. The prognosis of pT3 UTUC, particularly renal pelvic UC, remains controversial, and several studies have proposed subclassification of pT3 UTUC. Lynch syndrome is a significant risk factor for UTUC, and screening tests may be considered in young patients and those with familial histories of the disease. Despite significant progress in recent years, several issues remain to be addressed in the pathologic diagnosis, molecular classification, and treatment of UTUC.

Treatment-related neuroendocrine prostate cancer is a distinctive category of prostate cancer that arises after intensive suppression of the androgen receptor by next-generation therapeutic inhibition of androgen receptor signaling. The biological processes that set in motion the series of events resulting in transformation of adenocarcinoma to neuroendocrine carcinoma include genomic (loss of tumor suppressors TP53 and RB1, amplification of oncogenes N-MYC and Aurora Kinase A, dysregulation of transcription factors SOX2, achaete-scute-homolog 1, and others) as well as epigenomic (DNA methylation, EZH2 overexpression, and others). Pathologic diagnosis is key to effective therapy for this disease, and this is aided by localizing metastatic lesions for biopsy using radioligand imaging in the appropriate clinical context. As our understanding of biology evolves, there has been increased morphologic recognition and characterization of tumor phenotypes that are present in this advanced post-treatment setting. New and promising biomarkers (delta-like ligand 3 and others) have been discovered, which opens up novel therapeutic avenues including immunotherapy and antibody-drug conjugates for this lethal disease with currently limited treatment options.

Renal cell carcinoma (RCC) with tuberous sclerosis complex (TSC)/mammalian target of rapamycin (MTOR) pathway-related genomic alterations have been classically described in hereditary TSC syndrome setting involving germline mutations, whereby cells with a bi-allelic inactivation of genes originate tumors in a classic tumor-suppressor "two-hit" Knudson paradigm. Initial studies of TSC-associated RCC categorized tumors into 3 broad heterogeneous morphologic groups: RCC with smooth muscle stroma, chromophobe-like, and eosinophilic-macrocytic. Recently, a similar morphologic spectrum has been increasingly recognized in novel and emerging entities characterized by somatic mutations in the TSC1/2 and MTOR in patients who do not suffer from the TSC. Correct recognition of RCC with TSC / MTOR mutations is critical for accurate prognostication because such tumors with aggressive behavior have the potential to be tailored to mTOR inhibitors. Whether TSC/MTOR mutated renal epithelial neoplasms represent a distinct molecular class has been confounded by the fact that TSC1/2 , and the gene encoding the downstream protein MTOR, are mutated secondarily in ∼5% of the more common subtypes of RCC, including the commonest subtype of clear cell RCC. This review summarizes the expanding morphologic spectrum of renal tumors with TSC/mTOR pathway alterations, specifically for sporadically occurring tumors where these genomic alterations likely are primary pathologic events. Finally, a practical surgical pathology approach to handling these tumors, and a conceptual framework of renal epithelial tumors with TSC/MTOR mutations as a "family of tumors", is presented.

Alterations in DNA damage response (DDR) and related genes are present in up to 25% of advanced prostate cancers (PCa). Most frequently altered genes are involved in the homologous recombination repair, the Fanconi anemia, and the mismatch repair pathways, and their deficiencies lead to a highly heterogeneous spectrum of DDR-deficient phenotypes. More than half of these alterations concern non- BRCA DDR genes. From a therapeutic perspective, poly-ADP-ribose polymerase inhibitors have demonstrated robust clinical efficacy in tumors with BRCA2 and BRCA1 alterations. Mismatch repair-deficient PCa, and a subset of CDK12-deficient PCa, are vulnerable to immune checkpoint inhibitors. Emerging data point to the efficacy of ATR inhibitors in PCa with ATM deficiencies. Still, therapeutic implications are insufficiently clarified for most of the non- BRCA DDR alterations, and no successful targeted treatment options have been established.

In this modern era of digital pathology, artificial intelligence (AI)-based diagnostics for prostate cancer has become a hot topic. Multiple retrospective studies have demonstrated the benefits of AI-based diagnostic solutions for prostate cancer that includes improved prostate cancer detection, quantification, grading, interobserver concordance, cost and time savings, and a potential to reduce pathologists' workload and enhance pathology laboratory workflow. One of the major milestones is the Food and Drug Administration approval of Paige prostate AI for a second review of prostate cancer diagnosed using core needle biopsies. However, implementation of these AI tools for routine prostate cancer diagnostics is still lacking. Some of the limiting factors include costly digital pathology workflow, lack of regulatory guidelines for deployment of AI, and lack of prospective studies demonstrating the actual benefits of AI algorithms. Apart from diagnosis, AI algorithms have the potential to uncover novel insights into understanding the biology of prostate cancer and enable better risk stratification, and prognostication. This article includes an in-depth review of the current state of AI for prostate cancer diagnosis and highlights the future prospects of AI in prostate pathology for improved patient care.

TFE3 -rearranged renal cell carcinoma (RCC) is a distinct, uncommon entity with more than 20 different fusion partners identified; however, histomorphology may be suggestive of specific fusion partners in select TFE3 -rearranged RCCs. For example, most MED15 :: TFE3 fusion associated RCCs exhibit multilocular cystic morphology, mimicking multilocular cystic renal neoplasm of low malignant potential. Here we present a case of MED15 :: TFE3 RCC in an older adult and review the literature with an emphasis on practical diagnostic approaches for predominantly cystic, low-grade, clear cell renal tumors.

Social media use in pathology has continued to grow and become more mainstream among pathologists, trainees, and medical students over the past decade. Twitter has historically been (and still seems to be) a positive platform for the social media pathology community to engage with each other virtually (ie, PathTwitter). However, as a new era of Twitter leadership began to unfold in October 2022, a young platform called "Mastodon" began to gain notice within this community as the hashtag #PathMastodon became prevalent. Founded in 2016 by Eugen Rochko, Mastodon is a decentralized, open-sourced, ads-free platform intended to promote public knowledge in a safe and public manner. When compared with Twitter, however, Mastodon is globally much smaller, and its medical professional server called "Med-Mastodon" is more cumbersome with certain features (eg, tracking analytics and username changes). Nevertheless, this new platform, which looks and feels much like Twitter, has great potential to provide continued medical education and virtual excellence among the social media pathology community. Thus, the purpose of this review is to provide a relevant synopsis of how Mastodon, Med-Mastodon, and #PathMastodon may benefit pathologists, trainees, and medical students who use social media. A qualitative analysis of pertinent peer-reviewed and non-peer-reviewed materials relative to the topic will be performed. In addition, we will provide a comparison of Mastodon and Twitter, provide example figures of #PathMastodon and related posts, and elaborate on the importance this discussion brings to the social media pathology community.