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

Abstract

Background Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are rare mesenchymal neoplasms predominantly arising in perimenopausal and postmenopausal women. UTROSCTs with growth regulation by estrogen in breast cancer 1 (GREB1)-rearrangement or GREB1-rearranged uterine tumors are exceptionally rare, with only 12 previously reported cases. Here, we report a case of UTROSCT with the GREB1-nuclear receptor coactivator 2 (NCOA2) fusion gene. Case presentation A 57-year-old woman presented with a 10.0 cm uterine mass. The tumor was composed of short spindle or epithelioid cells, arranged in diffused sheets, nested, and trabecular/cordlike. The tumor harbored the GREB1-NCOA2 fusion gene, as confirmed by RNA sequencing. The tumor recurred in the pelvis at 30 months after the initial diagnosis. We also compared the clinical and pathologic features of this case with those of the 12 previously published uterine GREB1-rearranged tumors. Of the combined 13 cases (present case and 12 previous cases), the mean age of patients was 64.8 years (range, 51–74 years). Of the nine reported cases of GREB1-rearranged tumor with follow up, four cases recurred or metastasized (44.4%). Microscopically, most tumors (10/12, 83.3%) showed infiltrative growth, and two were well demarcated. Mitotic figures ranged from 0 to 14 per 10 high-power fields (2 mm2; mean: 3.6). Lymphovascular invasion and necrosis were each present in two cases (2/12, 16.7% and 2/7, 28.6%, respectively). Conclusions This case provided further evidence that UTROSCTs with GREB1-rearrangement may have a high risk of recurrence/metastasis. Further studies are necessary to clarify the clinical features of this type of tumor, particularly the prognosis, potential treatment, and range of possible molecular events.

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

“…The NCOA1-3 genes encode nuclear receptor co-activators 1 to 3, belonging to the p160 family of steroid receptor co-activators, that when bound to nuclear receptors, stimulate transcription in a hormone-dependent manner. As uterine tissues typically show high ESR1 and GREB1 expression, the putative fusion oncoproteins retain the active promoter region of ESR1/GREB1 fused to the nuclear receptor coactivator domain of NCOA1-3, resulting in dysregulated expression of NCOA1-3, thus enhancing or interfering with the transactivation functionality (4,(10)(11)(12)(13). For GERB1-NCOA fused UTROSCTs, the breakpoints in GREB1 are reported to be located at exon 2 to intron 8, and in NCOA genes the breakpoints are usually located at exon 13 to 15 (3).…”

“…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.…”

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

“…The data for 23 UTROSCTs were collected from 2014 to 2021, including 4 diagnosed and treated with surgery at Fudan University Shanghai Cancer Center and 19 consultation patients with available slides and tissues. One of the cases was previously reported 15 . Another case was consulted in our department and reported by a local gynecologist, who sent the case for consultation 16 .…”

Uterine sarcomas: clinical practice guidelines for diagnosis, treatment, and follow-up, by Spanish group for research on sarcomas (GEIS)

“…Those more aggressive subtypes have been associated with extensive rhabdoid differentiation and GREB1 and ESR1-NCOA2 fusions. 114 – 117 …”