Ewing Sarcoma of the Female Genital Tract: Clinicopathologic Analysis of 21 Cases With an Emphasis on the Differential Diagnosis of Gynecologic Round Cell, Spindle, and Epithelioid Neoplasms.

Ewing sarcoma is an uncommon neoplasm considered in the differential diagnosis of tumors with "small round cell" morphology, but its occurrence in the gynecologic tract has only been sporadically documented. Herein, we describe the largest cohort of Ewing sarcoma localized to the female genital tract to date, and emphasize their clinicopathologic resemblance to more common gynecologic neoplasms. Ewing sarcoma (n=21) was retrospectively identified from 5 institutions.

Genomic Catastrophe (Chromothripsis and Polyploidy) Correlates With Tumor Distribution in Extrauterine High-grade Serous Carcinoma.

Most extrauterine high-grade serous carcinomas (HGSCs) are thought to develop first in the distal fallopian tube. Most models of HGSC assume origin from relatively stable, noninvasive serous tubal intraepithelial carcinomas. However, widespread tumor involvement in the absence of a serous tubal intraepithelial carcinoma could occur after catastrophic genomic events (CGEs; such as chromothripsis or polyploidy).

Prevalence and genotype distribution of human papillomavirus in cervical adenocarcinoma (usual type and variants): A systematic review and meta-analysis.

Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in pathogenesis is still lacking. We first searched MEDLINE (PubMed), Embase, and Scopus databases (until October 2022), and systematically reviewed available literature. We then quantitatively estimated both pooled and genotype-specific prevalence of HPV DNA as well as the influence of various factors (e.

Inaugurating High-Throughput Profiling of Extracellular Vesicles for Earlier Ovarian Cancer Detection.

Detecting early cancer through liquid biopsy is challenging due to the lack of specific biomarkers for early lesions and potentially low levels of these markers. The current study systematically develops an extracellular-vesicle (EV)-based test for early detection, specifically focusing on high-grade serous ovarian carcinoma (HGSOC). The marker selection is based on emerging insights into HGSOC pathogenesis, notably that it arises from precursor lesions within the fallopian tube.

Dissection of Aberration for Cervical Adenocarcinoma Outcomes.

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in E542K, E545K, or H1047R were detected in 41.

Enhanced Efficacy of Aurora Kinase Inhibitors in G2/M Checkpoint Deficient Mutant Uterine Carcinomas Is Linked to the Summation of LKB1-AKT-p53 Interactions.

Uterine carcinoma (UC) is the most common gynecologic malignancy in the United States. mutant UCs cause a disproportionate number of deaths due to limited therapies for these tumors and the lack of mechanistic understanding of their fundamental vulnerabilities. Here we sought to understand the functional and therapeutic relevance of mutations in UC.

A Clinical and Pathologic Exploration of Suspected Peritoneal Endometriotic Lesions.

Endometriosis is generally histopathologically defined as the presence of at least 2 of the following: endometrial stroma, Müllerian epithelium, and/or hemosiderin-laden macrophages (HLM). Despite clinically evident endometriotic lesions, biopsies are frequently nondiagnostic. In this study, we conducted a large-scale review of biopsies of lesions clinically thought to represent endometriosis and correlate the histologic findings with clinical appearance to expand sensitivity of the pathologic definition of endometriosis, particularly in patients on hormonal therapy.

Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer.

Immune therapies have had limited efficacy in high-grade serous ovarian cancer (HGSC), as the cellular targets and mechanism(s) of action of these agents in HGSC are unknown. Here we performed immune functional and single-cell RNA sequencing transcriptional profiling on novel HGSC organoid/immune cell co-cultures treated with a unique bispecific anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody compared with monospecific anti-PD-1 or anti-PD-L1 controls. Comparing the functions of these agents across all immune cell types in real time identified key immune checkpoint blockade (ICB) targets that have eluded currently available monospecific therapies.

Mural nodules in mucinous ovarian tumors represent a morphologic spectrum of clonal neoplasms: a morphologic, immunohistochemical, and molecular analysis of 13 cases.

Mucinous ovarian tumors rarely harbor mural nodules, which have historically been classified as sarcoma-like, anaplastic carcinomatous, or sarcomatous on the basis of predominant morphologic features. The molecular relationship between mural nodules and associated mucinous ovarian tumors remains poorly characterized, as does the molecular pathogenesis of these mural nodules. Thus, we analyzed the morphological, immunohistochemical, and genetic features of 13 mucinous ovarian tumors and associated mural nodule(s).

Synovial Sarcoma of the Female Genital Tract: A Protean Mimic of Müllerian Neoplasia.

Synovial sarcoma most commonly occurs in the extremities but has rarely been described in the female genital tract. In this series, we describe the clinical, morphologic, immunohistochemical, and molecular features of 7 cases of vulvovaginal synovial sarcoma (vulva, n=6; vagina, n=1). We emphasize their wide morphologic spectrum, which can overlap significantly with other more common tumors at these sites, as highlighted by 2 cases initially diagnosed as other entities (endometrioid carcinoma and malignant peripheral nerve sheath tumor).

Molecular characterization of diffuse malignant peritoneal mesothelioma.

Malignant peritoneal mesothelioma is a rare aggressive tumor that arises from the peritoneal lining. While recurrent BAP1 mutations have been identified in a subset of mesotheliomas, molecular characteristics of peritoneal mesotheliomas, including those lacking BAP1 alterations, remain poorly understood. Using targeted next-generation sequencing, we examined the molecular features of 26 diffuse malignant peritoneal mesotheliomas.

Prostatic Metaplasia of the Vagina and Uterine Cervix: An Androgen-associated Glandular Lesion of Surface Squamous Epithelium.

Prostatic-type differentiation in the lower female genital tract is encountered rarely and its causes and clinical associations are not well established. Within the vagina, reports to date have invariably described ectopic prostatic-type differentiation as restricted to the lamina propria. We recently encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium.

Cloning of ground-state intestinal stem cells from endoscopic biopsy samples.

'Adult' or 'somatic' stem cells harbor an intrinsic ability to regenerate tissues. Heterogeneity of such stem cells along the gastrointestinal tract yields the known segmental specificity of this organ and may contribute to the pathology of certain enteric conditions. Here we detail technology for the generation of 'libraries' of clonogenic cells from 1-mm-diamter endoscopic biopsy samples from the human gastrointestinal tract.

Evidence for a Novel Endometrioid Carcinogenic Sequence in the Fallopian Tube With Unique Beta-Catenin Expression.

Epithelial proliferations in the fallopian tube have been characterized by some as stem cell outgrowths (SCOUTs) and divided into type I and type II. Type II SCOUTs exhibit diffuse cellular beta-catenin nuclear staining (β-catenin), implying a CTNNB1 mutation. SCOUTs are more common in perimenopausal and postmenopausal women and are associated with ovarian cancer but have not been linked directly to malignancy.

Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT): A Morphologic and Molecular Study of 26 Cases Confirms Recurrent NCOA1-3 Rearrangement.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain biological potential, that was recently reported to exhibit recurrent gene fusions involving NCOA2-3. The purpose of this study was to, using a larger sample size, better characterize the histopathologic and molecular diversity of UTROSCT. Twenty-six cases of UTROSCT from 5 institutions were selected for further study.