Microcystic Stromal Tumor Is a Distinct Ovarian Neoplasm Characterized by β-Catenin Alteration
Daichi Maeda, Junji Shibahara, Takahiko Sakuma, Kazunori Sueyoshi, Akiko Sakata, Masayuki Noguchi, Masashi Fukayama. The University of Tokyo, Tokyo, Japan; Osaka Rosai Hospital, Sakai, Japan; Kagoshima Municipal Hospital, Kagoshima, Japan; The University of Tsukuba, Tsukuba, Japan
Background: Microcystic stromal tumor (MCST) is a recently described subtype of ovarian tumor characterized by a prominent microcystic histological pattern and diffuse immunoreactivity for CD10 and vimentin. Descriptions regarding the histological features of MCST are limited, and the pathobiology remains unclear. Here, we report four cases of ovarian MCST in which we have performed extensive histological, immunohistochemical, and genetic investigations to determine its distinctiveness among ovarian neoplasms.
Design: In addition to the morphological characterization of ovarian MCSTs, we performed immunohistochemical comparisons between ovarian MCSTs and a variety of sex cord-stromal tumors. Markers examined in this study include vimentin, CD10, β-catenin, WT-1, α-inhibin, calretinin, ER, PgR, EMA, and cytokeratin AE1/3. Further, two of the MCSTs were analyzed using direct sequencing for a mutation in exon 3 of the β-catenin gene.
Results: The patients' ages ranged from 32 to 41 years. One patient had a past history of familial adenomatous polyposis (FAP). Microscopically, all four tumors showed similar histological features: generally bland tumor cells with round to ovoid nuclei growing in microcystic, macrocystic, and solid patterns. Intervening thick fibrous stroma were observed. Immunohistochemically, tumor cells were diffusely and strongly positive for CD10, vimentin, and WT-1, but negative for α-inhibin, calretinin, ER, PgR, and EMA. Cytokeratin expression was variable. Importantly, we detected aberrant nuclear expression of β-catenin protein in all four cases. In contrast, none of the sex cord-stromal tumors examined showed nuclear expression of β-catenin. Mutation analyses performed in two of the non-FAP patient cases revealed the presence of the c.98C>G mutation in exon 3 of β-catenin.
Conclusions: Our immunohistochemical analyses showed that MCST is a distinct ovarian neoplasm characterized by aberrant nuclear expression of β-catenin. The results of our immunohistochemical and mutation analyses, along with the presence of MCST in an FAP patient, strongly suggest that dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the pathogenesis of ovarian MCST. Finally, by comparing the immunophenotype of MCST with other ovarian sex cord-stromal tumors, we were able to identify unique features of MCST and a panel of markers useful for differential diagnosis
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 198, Tuesday Morning