Uterine Mesenchymal Tumors: Updates on Pathology, Molecular Landscape, and Therapeutics

Abstract

Background: Mesenchymal uterine tumors are a diverse group of neoplasms with varying biological potential. Many of these neoplasms can have overlapping morphologic similarities, which, in some instances, render their diagnosis and categorization thorough histomorphologic examination inconclusive. In the last decade, an exponential amount of molecular data aiming to more accurately characterize and, consequently, treat these tumors have accumulated. Objective: The goal of this narrative review is to provide a pathologic review, a genetic update, and to know the new therapeutic avenues of primary uterine mesenchymal neoplasms.

Keywords: gynecology; mesenchymal tumor; molecular update; pathology.

Figure 1

The World Health Organization’s 2020 classification of mesenchymal uterine tumors (adapted from WHO [1]).

Figure 2

(A) Spindle-cell (conventional) tumors consist of fusocellular cells with eosinophilic cytoplasm arranged in long, interlacing fascicles with readily visible nuclear pleomorphism [H&E, 10×]. (B,C) Tumor cell necrosis characterized by a geographical distribution and sudden shift from viable to non-viable tumor cells [H&E, 20× and 10×]. (D) Myxoid stroma in myxoid leiomyosarcomas [H&E, 10×].

Figure 3

A low-grade endometrial stromal sarcoma. (A) The infiltrative tumor [T] growth pattern with irregular tongue-like extension [*] into the myometrium [H&E, 4×]. (B) Monotonous round to spindle cell proliferation in vague whirling pattern around spiral-like arterioles [H&E, 4×]. (C) Tumor cells are diffusely positive for endometrial stromal marker CD10 [4×]. (D) Tumor nuclei are strongly positive for estrogen receptor [ER, 10×].

Figure 4

Perivascular epithelioid cell tumor (PEComa). (A) Epithelioid and/or spindled cells arranged in discohesive nests with delicate thin-walled vessels [H&E, 4×]; (B) Radial/perivascular distribution of tumor cells with clear-to-eosinophilic granular cytoplasm and stromal hyalinization are characteristic features and variably present [H&E, 20×]; (C) Tumor cells are positive for smooth muscle marker desmin [20×]; (D) Tumor cells show scattered positivity for melanocytic marker HMB45 [20×].

Figure 5

Uterine tumors resembling ovarian sex cord tumor (UTROSCT). (A,B) Epithelial-like cells arranged into sheet and retiform-like formations resembling sex cord-stromal tumors of the ovary. The nuclei are ovoid with minimum cytological atypia [H&E, 10× and 20×]. (C–F) Polyphenotypic immunohistochemical profile with varied positivity for sex cord markers (calretinin, inhibin), epithelial markers, and estrogen receptors [10× and 20×].