β‐Catenin and E‐cadherin expression in stage I adult‐type granulosa cell tumour of the ovary: correlation with tumour morphology and clinical outcome

Aims To expand the morphological spectrum of ovarian microcystic stromal tumour, a rare neoplasm considered to have a relatively constant morphology with microcysts, solid cellular regions and hyalinised fibrous stroma. Methods and results We report four ovarian neoplasms in patients aged 45, 56, 61 and 71 years with the characteristic immunophenotype of microcystic stromal tumour (diffuse nuclear positivity with beta‐catenin, cyclin D1 and WT1; diffuse cytoplasmic positivity with CD10; negative inhibin, calretinin, oestrogen receptor and progesterone receptor). The tumours had variant morphology (diffuse, nested and corded arrangements in three cases, including one with spindle cell elements; nested, corded and tubular in the other). A CTNNB1 point mutation in exon 3 (c.98C>G,p.S33C; c.100G>A,p.G34R; c.97T>G,p.S33A) was present in the three cases with material available for testing. Conclusions We feel that the cases we report are related to microcystic stromal tumour but with variant morphology; as such, the morphological spectrum of ovarian microcystic stromal tumour is broader than hitherto reported.

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“…Stewart et al . identified no nuclear staining with beta‐catenin in 62 ovarian adult granulosa cell tumours . Similarly, Ohishi et al .…”

Section: Discussionmentioning

confidence: 92%

Expanding the morphological spectrum of ovarian microcystic stromal tumour

et al. 2018

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“…In 2 recent studies, nuclear b-catenin staining was absent in a total of 94 granulosa cell tumors, although membranous and cytoplasmic immunoreactivity was detected in the majority of cases. 19,20 In the study by Maeda and colleagues, investigation and subsequent detection of aberrant nuclear b-catenin staining in 2 MSTs was prompted by the morphologic and immunohistochemical similarity between MST and solid pseudopapillary neoplasm (SPN) of the pancreas and ovary. 2,21,22 We acknowledge this important finding as an impetus to study b-catenin in the current largest available series of MST, but we are of the view that MST is a distinct entity from ovarian SPN.…”

Section: Discussionmentioning

confidence: 99%

Microcystic Stromal Tumor

Irving

Lee

Yip

et al. 2015

American Journal of Surgical Pathology

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Since our first description of the microcystic stromal tumor (MST) of the ovary, a rare and distinctive neoplasm with a definitional, usually striking microcystic pattern and a CD10+/vimentin+/inhibin-/calretinin- immunophenotype, 3 examples with β-catenin nuclear localization, and CTNNB1 mutation have been reported. We undertook a detailed immunohistochemical study and molecular analysis of CTNNB1 and FOXL2 of 15 cases of MST to further characterize this neoplasm and establish its histogenesis. Diffuse nuclear staining for FOXL2, WT-1, cyclin D1, and β-catenin was present in all tumors tested, and 12/15 were positive for steroidogenic factor-1 (SF-1). Heterozygous missense point mutations in exon 3 of CTNNB1 were detected in 8 of 14 cases, resulting in amino acid changes at codons 32, 34, 35, and 37. There was no correlation between CTNNB1 exon 3 mutation status and tumor immunophenotype. All 14 cases tested showed wild-type FOXL2. Our study establishes that MST of the ovary exhibits a characteristic FOXL2/SF-1/WT-1/cyclin D1/nuclear β-catenin-positive immunohistochemical profile, which may be useful in diagnosis and in the exclusion of histologic mimics. The presence of diffuse nuclear FOXL2 and WT-1 immunostaining in all cases and SF-1 in most supports the classification of MST within the sex cord-stromal category. Aberrant nuclear β-catenin expression, detected in all MSTs, appears to be the result of stabilizing CTNNB1 mutations in 57% of cases, providing further evidence that dysregulation of the Wnt/B-catenin pathway is involved in the tumorigenesis of MST and may involve activation of β-catenin with upregulation of cyclin D1.

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“…Sun and colleagues reported that the risk increased when tumours were larger than 13 cm [12]. Recently, reduced β-catenin expression has been associated with a worse disease free survival [19] and warrants further exploration.…”

Section: Prognostic Factorsmentioning

confidence: 97%