An update of molecular findings in uterine tumor resembling ovarian sex cord tumor and GREB1‐rearranged uterine sarcoma with variable sex‐cord differentiation

Abstract

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a uterine mesenchymal tumor defined histologically by showing sex cord‐like growth patterns, such as sheets, nests, trabeculae, cords, or tubules, with/without Sertoli‐like or Leydig‐like components, and immunohistochemically by exhibiting variable sex cord markers in addition to epithelial, myogenic, and sex hormone markers. Recent years have seen the emergence in UTROSCT of novel fusion genes that involve key genes in sex hormone pathways, including ESR1 and GREB1 as the 5′ partner, and (co)activator oncogenes, particularly NCOA1‐3, as the 3′ partner. While the identification of similar fusions in the majority of cases serves as a strong argument for UTROSCT to be a distinct entity, there is no denying significant clinicopathologic heterogeneity within the disease spectrum, which might to some extent correlate with the different fusion types. The current review gives a summary of the recently identified fusions in UTROSCT, along with their possible clinicopathologic relevance. Also discussed are unsolved issues including the relationship between UTROSCT and so‐called GREB1‐rearranged uterine sarcoma as well as other uterine mesenchymal tumors harboring similar fusions.

Uterine Tumor Resembling Ovarian Sex Cord Tumor With Aggressive Histologic Features Harboring a GREB1-NCOA2 Fusion: Case Report With a Brief Review

“…FISH analyses showed rearrangements of both the GREB1 and NCOA2 loci, further confirming the RNA sequencing results. We believe that our case of UTROSCT belongs to the emerging related group of uterine mesenchymal neoplasms that harbor GREB1 rearrangement and show variable degree of sex-cord differentiation 3,11.…”

“…The vast majority cases of UTROSCT behave in an indolent manner, but a small subset show adverse clinical courses (1)(2)(3). Due to its rarity and diversity of morphology, it is difficult to establish in UTROSCT which features, if any, are of prognostic significance.…”

“…While the identification of similar molecular abnormalities in the majority of cases provides strong support that UTROSCT is a distinct entity, there is significant clinicopathologic heterogeneity within this disease spectrum (1). Genotype and phenotype correlation has suggested that GREB1-rearranged UTROSCTs may have a higher tendency to behave aggressively (3,(10)(11)(12)(13). Herein, we report a UTROSCT with aggressive histologic features harboring a GREB1-NCOA2 fusion detected by RNA sequencing and validated by fluorescence in situ hybridization (FISH) analysis, with an emphasis on the diagnostic implications.…”

“…By definition, it displays predominantly or exclusively an epithelial appearance resembling ovarian sex cord tumors with architectural patterns including sheets, nests, trabeculae, cords, or tubules in varying proportions. Some cases may have retiform, glomeruloid, or morular structures (1)(2)(3). The neoplastic cells are usually small epithelioid with round to ovoid nuclei, slight nuclear pleomorphism, inconspicuous nucleoli, and scant eosinophilic cytoplasm.…”

Uterine tumor resembling an ovarian sex cord tumor: A case report and review of literature

“…To date, including this patient, approximately 90[ 3 - 48 ] cases have been reported in the literature. According to previous reports, the age of onset is 20 to 86 years; the average age is 50.6 years, the median age is 51 years, and the tumor size is 4 to 135 (average 47.6) mm.…”