Advances in Anatomic Pathology

In this review, we highlight and contextualize emerging morphologic prognostic and predictive factors in renal cell carcinoma. We focus on clear cell renal cell carcinoma (ccRCC), the most common histologic subtype. Our understanding of the molecular characterization of ccRCC has dramatically improved in the last decade. Herein, we highlight how these discoveries have laid the foundation for new approaches to prognosis and therapeutic decision-making for patients with ccRCC. We explore the clinical relevance of common mutations, established gene expression signatures, intratumoral heterogeneity, sarcomatoid/rhabdoid morphology and PD-L1 expression, and discuss their impact on predicting response to therapy...

The pathologic assessment of colorectal carcinoma specimens plays a crucial role in the therapeutic management of patients and disease prognostication. The TNM staging system is used globally and is a critical component of colorectal carcinoma pathology reporting. However, our experience informs us that there are significant variations in the assignment of the TNM stage, both between pathologists and between hospital centers. We identify several potential reasons for this, among them suboptimal gross and microscopic assessment of colorectal resection specimens and, later, nonuniformity in applying criteria set forth in pathologic TNM staging guidelines...

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...

The classification of thymoma continues to be a source of controversy in pathology. The difficulties in histologic classification are evident from the number of proposals that have been offered over the years, as well as for the continuous changes and modifications introduced by the World Health Organization to their classification system over the past 20 years. We analyze here some of the issues involved in the classification of these tumors and the difficulties encountered for practicing pathologists in deciphering the "letters and numbers" system devised by the World Health Organization...

Cervical cancer is the fourth most common cancer among women globally. Historically, human papillomavirus (HPV) infection was considered necessary for the development of both precursor and invasive epithelial tumors of the cervix; however, studies in the last decade have shown that a significant proportion of cervical carcinomas are HPV-independent (HPVI). The 2020 World Health Organization (WHO) Classification of Female Genital Tumors separates both squamous cell carcinomas (SCCs) and endocervical adenocarcinomas (ECAs) by HPV status into HPV-associated (HPVA) and HPVI 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...

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...

Testicular sex cord-stromal tumors (TSCSTs) are relatively rare, representing ~5% of testicular neoplasms overall. Historically, TSCSTs have been classified into 3 major entities: Leydig cell tumor, Sertoli cell tumor, and granulosa cell tumor. In recent years, immunophenotypic and molecular analyses have led to a more detailed understanding of the biological and genomic features of these neoplasms, resulting in the description of new entities, some of which have been included in the latest WHO classification...

#PathTwitter is a well-known virtual community that has historically been positive for pathologists, trainees, and medical students worldwide to communicate, collaborate, and connect for free. However, in 2023, the popular social media platform Twitter (parent company: X Corp.) transitioned to "X" and, with this, #PathTwitter evolved into #PathX. Although the overall user experience of X and Twitter has not changed significantly, this transition brought much anecdotal hesitancy from the online virtual pathology community early on...

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...

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...

Because of the unique anatomic structure of the nipple, a few specific breast lesions occur only at this site. Large lactiferous sinuses may be involved by inflammatory conditions such as squamous metaplasia of lactiferous ducts and ductal ectasia or be the site of uncommon superficial epithelial neoplasms such as nipple adenoma or syringomatous tumor of the nipple. Paget disease of the nipple may be secondary to intraepidermal extension of ductal carcinoma in situ in the underlying lactiferous ducts or develop from malignant transformation of Toker cells...

The standard of care for invasive cancers of the breast has been and continues to be to evaluate them for breast prognostic markers: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 by immunohistochemistry. Over 2 decades ago, a study was the first to report on the molecular subtypes of breast cancer. Four main subtypes were reported. Since then there have been some changes in the molecular subtype classification, but overall many studies have shown that this subtyping has clinical prognostic and predictive value...

Some histologic special types of breast carcinoma harbor specific recurrent genetic alterations that are not seen in other types of breast carcinoma (no special type), namely adenoid cystic carcinoma, secretory carcinoma, and tall cell carcinoma with reversed polarity. These tumors have unique morphologic features, are triple-negative, that is, do not express hormone receptors or HER2, and are generally associated with a favorable prognosis. Adenoid cystic carcinoma, like its counterpart in other organs, shows a MYB-NFIB fusion gene that is the result of a recurrent t(6;9)(q22-23;p23-24) translocation...

No abstract text is available yet for this article.

Pathology clinical practice has evolved by adopting technological advancements initially regarded as potentially disruptive, such as electron microscopy, immunohistochemistry, and genomic sequencing. Breast pathology has a critical role as a medical domain, where the patient's pathology diagnosis has significant implications for prognostication and treatment of diseases. The advent of digital and computational pathology has brought about significant advancements in the field, offering new possibilities for enhancing diagnostic accuracy and improving patient care...

This article reviewed the identification of breast cancer in the distant metastatic setting through traditional immunohistochemical markers, such as mammaglobin and GATA3, compared with the novel immunohistochemical stain, Trichorhinophalangeal syndrome-1 (TRPS1). We review previous studies evaluating TRPS1 staining, which were conducted using cytology specimens, as well as our recently conducted study evaluating this stain using surgical tissue samples, both from primary and distant metastatic invasive breast carcinoma...

In response to recent clinical trials that demonstrate the clinical benefit of antibody-drug conjugate drug therapy in breast cancer (BC) with human epidermal growth factor 2 (HER2) immunohistochemical scores of 1+ or 2+ and negative in situ hybridization results, a new concept of "HER2-low BC" has emerged to describe this newly relevant therapeutic category of BC. Clinical recognition of HER2-low BC has caused a paradigm shift in the therapeutic landscape and management of patients with BC and resulted in rapid changes in clinical practice guidelines...

Fibroepithelial lesions of the breast encompass a broad spectrum of lesions from fibroadenomas and their variants to phyllodes tumors, including their clinical range of benign, borderline, and malignant. Classification of this spectrum of neoplasms has historically and currently been based purely on morphology, although the nomenclature has shifted over the years largely due to the significant histologic overlap that exists primarily within the cellular fibroadenomas to borderline malignant phyllodes tumor categories...

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...