Uterine Tumor Resembling Ovarian Sex Cord Stromal Tumor (UTROSCT)

Abstract

ESR1 and GREB1 fusions have recently been described in uterine tumor resembling ovarian sex cord tumor (UTROSCT). Thus far, recurrences have been documented in a subset of those harboring GREB1 fusions, but not in those with ESR1 rearrangements. Here we describe the clinicopathologic features of 3 recurrent UTROSCTs with striking rhabdoid morphology (an unusual feature of these tumors overall) and ESR1-NCOA2 fusions. The patients were 32, 37, and 54 years at initial diagnosis and first recurrence occurred at 7, 9, and 32 years. The primary tumors (available in two cases) were centered in the myometrium and showed infiltrative borders. They predominantly grew in sheets and cords, but also had a pseudopapillary appearance. Cells were uniformly epithelioid with eccentric nuclei, prominent nucleoli, abundant eosinophilic globular/glassy (rhabdoid) cytoplasm, and infrequent mitoses (≤4/10 high-power fields [HPFs]). Recurrences were morphologically identical to the primary tumors, but demonstrated brisk mitotic activity (≥16/10 HPFs). The third tumor (with only recurrences available) had multiple patterns, including diffuse, corded, trabecular, and a focal retiform growth. Rhabdoid cells were conspicuous, but only comprised ~50% of the tumor, and mitoses numbered up to 2/10 HPFs. All tumors were strongly and diffusely positive for WT1, CAM5.2, ER, and PR, but negative for inhibin. Diffuse calretinin and desmin expression, as well as focal melan-A positivity, was noted in one tumor, but was negative in the others. In all 3 tumors, INI-1 and BRG-1 were retained, and ESR1-NCOA2 fusions were detected by targeted RNA sequencing. This study is the first to highlight an association between UTROSCTs with extensive rhabdoid differentiation, ESR1-NCOA2 fusions, and aggressive behavior. UTROSCTs are considered neoplasms of uncertain malignant potential, but have a benign course in most cases. Thus, it is important to be aware of these specific features and recommend long-term follow-up due to their propensity for late recurrences.

Recurrent uterine tumors resembling ovarian sex-cord tumors with the growth regulation by estrogen in breast cancer 1-nuclear receptor coactivator 2 fusion gene: a case report and literature review

“…Of these recurrent GREB1-rearranged cases, 3/4 harbored the GREB1-NCOA2 fusions and 1/4 the GREB1-CTNNB1 fusions. Interestingly, of the 4 UTROSCT cases harboring ESR1-NCOA2 with follow up information, three cases showed recurrence, as reported by Jennifer A. Bennett et al [1,20]. In contrast, no cases showed recurrence among the 10 cases of ESR1-NCOA3 positive UTROSCT with follow up information [1].…”

“…Neoplastic cells are small, round, ovoid to spindle with monotonous nuclei, inconspicuous or small to medium with distinct nucleoli, and occasionally have vascular invasion, heterologous elements, or necrosis. Recently, three cases of UTROSCTs with extensive rhabdoid differentiation and malignant behavior have been reported [20]. UTROSCTs exhibit a co-expression of epithelial, smooth muscle, sex-cord markers, and steroid receptors.…”

“…Except the four cases reported by Cheng-Han et al, seven patients with GREB1-NCOA2/NCOA1 fusion genes were diagnosed as having UTROSCT by authors (cases 5, 8, 9, 10,11, and 12), which suggested that at least a considerable proportion of these tumors with GREB1-rearrangement showed typical morphologic features of "UTROSCT". Recently, three cases of UTROSCT with extensive rhabdoid differentiation, malignant behavior, and ESR1-NCOA2 fusions have been reported [20]. Whether these tumors with specific gene rearrangement and aggressive clinical behavior should be regarded as poorly differentiated UTROSCT or as distinct uterine sarcomas need to be further investigated when additional cases have been reported.…”

Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior

“…6 Recurrent NCOA1-3 rearrangements in UTROSCT have been described in recent reports, with GREB1 and ESR1 as the 2 most frequent partner genes. [7][8][9] GREB1:: NCOA1, GREB1::NCOA2, ESR1::NCOA2, and ESR1:: NCOA3 fusions have all been reported in UTROSCT. In addition, CTNNB1 fused with GREB1 was reported in 1 UTROSCT.…”

“…8,11 In addition , Bennett et al reported a series of 3 cases of UTROSCTs harboring ESR1::NCOA2 fusions, which demonstrated rhabdoid morphology and aggressive behavior. 9 One more GTF2A1::NCOA2 UTROSCT was reported with similar morphology and aggressive behavior. 12 Interestingly, some uterine sarcomas with or without ovarian sex cord differentiation also harbor GREB1 rearrangements, including GREB1::NCOA1 and GREB1::NCOA2 fusions.…”