Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Commonly Exhibits Positivity With Sex Cord Markers FOXL2 and SF-1 but Lacks FOXL2 and DICER1 Mutations

Abstract

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm which morphologically and immunohistochemically exhibits overlap with an ovarian sex cord tumor. Although many of these neoplasms are positive with markers of ovarian sex cord-stromal tumors, staining is often limited and the pathogenesis of UTROSCT is unknown. To further explore the sex cord lineage of UTROSCT, we studied 19 of these neoplasms and examined the expression of 2 recently described markers of ovarian sex cord-stromal tumors, FOXL2, and steroidogenic factor-1. We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors. Ten of 19 cases (53%) exhibited nuclear immunoreactivity with FOXL2 and 11 of 19 (58%) exhibited nuclear staining with steroidogenic factor-1. Neither FOXL2 nor DICER1 mutations were identified in any case where there was sufficient tumor tissue for analysis (18 and 9 cases, respectively). Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of UTROSCT.

Uterine Tumor Resembling Ovarian Sex Cord Tumors Type II with Vaginal Vault Recurrence

“…This neoplasm resembles an ovarian sex cord tumor. Even though several hypotheses have been raised to explain the histogenesis of UTROSCT-including its origin from sex cord cells, mesenchymal stem cells, and endometrial stromal tumors in which an excessive growth of sex cord cells occurs [7]-its pathogenesis is still unknown. In 1976, Clement and Scully [8] classified the neoplasm into two distinct subgroups based on clinical and histopathologic features.…”

Cytological features of uterine tumors resembling ovarian sex‐cord tumors in liquid‐based cervical cytology: a potential pitfall. Report of a unique and rare case

“…Most UTROSCTs exhibit benign behavior but occasionally recur or metastasize; hence, these tumors are considered neoplasms of uncertain malignant potential that rarely behave in an aggressive manner . Histogenesis remains uncertain, and postulated theories include derivation from ovarian sex cord cells that have been displaced during embryogenesis, derivation from uncommitted mesenchymal stem cells, and overgrowth of sex cord elements within an endometrial stromal neoplasm or an adenosarcoma . The last hypothesis appears unlikely because UTROSCTs lack JAZF1‐JJAZ1 gene fusion or PFH1 rearrangement, in contrast to endometrial stromal tumors with or without sex cord elements, suggesting an independent origin .…”

Practical Application of Lineage-Specific Immunohistochemistry Markers: Transcription Factors (Sometimes) Behaving Badly

“…148,149,153 However, uterine tumors resembling ovarian sex cord tumors, a rare mesenchymal tumor with architectural patterns resembling those of sex cord-stromal tumors, can sometimes be SF-1 þ . 154 SF-1 is also used in the most recent World Health Organization classification of pituitary adenomas (PAs) along with other TFs (eg, PIT-1 and T-PIT) to classify adenomas according to their pituitary lineage, rather than according to their hormone-producing profile. 155 In this classification, TFs are the basis for recognizing 3 deemed-relevant PA pathways: (1) PIT-1 þ prolactin-growth hormone and thyroid-stimulating hormone pathway; (2) SF-1 þ gonadotroph pathway; and (3) T-PIT þ corticotroph pathway.…”