Microcystic Stromal Tumor of the Ovary With Mutation in Exon 3 of β-catenin

Abstract

Microcystic stromal tumor of the ovary is a very rare ovarian tumor with distinctive microcystic histologic features and a characteristic immunophenotype of stromal tumor. However, its origin, tumor pathogenesis, and prognosis have not been well established until now. We report a very unusual case of a microcystic stromal tumor of the ovary with a mutation in exon 3 of the β-catenin (CTNNB1) gene. Macroscopically, the fragmented ovarian tumor showed a diffuse solid mass. Microscopically, the tumor had a pathognomonic histologic pattern of solid and cellular areas with microcysts and fibrous hyalinized stroma. Immunohistochemical staining with CD10, vimentin, CD99, and β-catenin showed positive expression. However, α-inhibin and E-cadherin showed negativity. Mutational analysis revealed a point mutation in exon 3 of the β-catenin (CTNNB1) gene.

Microcystic Stromal Tumor

“…These findings further establish that the tumorigenesis of MST involves dysregulation of the Wnt/b-catenin pathway. [2][3][4]28 b-catenin has a key role in cell-cell adhesion and binds to the cytoplasmic region of E-cadherin and acatenin at adherens junctions. 28 b-catenin also plays a critical role in the transduction of Wnt signals; in the absence of Wnt signaling, b-catenin joins a destruction complex, where it undergoes CK1a and GSK-3b phosphorylation and is subsequently degraded.…”

“…Interestingly, the S33C and S33P mutations found in 3 previous MSTs were not detected in any of our cases. 2,3 Of note, S37, as well as S33, are critical N-terminal GSK-3b phosphorylation sites. 28 Furthermore, the presence of diffuse cyclin D1 staining in all 15 MSTs provides indirect evidence that activation of b-catenin with upregulation of cyclin D1 may play a role in the tumorigenesis of MST.…”

“…1 As demonstrated in our original study, and in 4 subsequently reported cases, MSTs are uniformly positive for CD10 and vimentin. [1][2][3][4] Inhibin, calretinin, and epithelial membrane antigen are typically negative, and focal cytokeratin positivity may occasionally be observed. In 2011, Maeda et al 2 reported 2 MSTs with aberrant b-catenin nuclear accumulation and identical mutations in exon 3 of CTNNB1, implicating dysregulation of the Wnt/b-catenin pathway in the pathogenesis of this neoplasm.…”

“…Two additional MSTs with nuclear b-catenin, including 1 with CTNNB1 mutation, have also been very recently reported. 3,4 In a follow-up to our original study, and in light of these recent data, we sought to expand the immunohistochemical and molecular genetic profile of MST, with emphasis on markers having high sensitivity and specificity for sex cord-stromal tumors. We also hoped that further data generated from study of the largest available series of MST would reinforce the most appropriate categorization, serve as a practical aid in distinction from tumors that may enter the differential diagnosis, and inform the pathogenesis of this rare ovarian neoplasm.…”

Expanding the morphological spectrum of ovarian microcystic stromal tumour

“…For example, in a recent study of 10 microcystic stromal tumours, we identified CTNNB1 and APC mutations in eight and two cases, respectively . Mutations in CTNNB1 and APC genes are mutually exclusive in microcystic stromal tumour and they result directly in nuclear immunoreactivity with beta‐catenin and cyclin D1 through activation of the Wnt signalling pathway . Herein, we report four ovarian neoplasms with a different morphology but an identical immunophenotype and molecular events to microcystic stromal tumour.…”