Diagnostics · Published 2026-08-05 · DOI 10.3390/diagnostics16152464
Sarah Bouri, Philomène Lavis, Jean-Christophe Noël
<b>Background and Clinical Significance:</b> Steroid cell tumours of the ovary, not otherwise specified (SCT-NOSs), are rare sex cord–stromal neoplasms with a poorly characterised molecular landscape, in which only exceptional <i>CTNNB1</i> mutations have so far been reported and no recurrent driver alteration is firmly established. A better characterisation of their molecular spectrum has clinical significance for accurate diagnostic categorisation of ovarian sex cord–stromal tumours and for the identification of potentially targetable pathway alterations in this rare entity. <b>Case Presentation:</b> We report two consecutive SCT-NOSs of the right ovary, retrieved from the archives of the Department of Pathology of the Hôpital Universitaire de Bruxelles and of Curepath. Both underwent comprehensive sex cord–stromal and differential immunohistochemistry and targeted next-generation sequencing on a 168-gene panel with a mean coverage of 2690× (Case 1) and a 17-gene panel (Case 2) (MGI DNBSEQ-T7 for Case 1; Ion GeneStudio S5 for Case 2). A 56-year-old post-menopausal woman (Case 1) and a 50-year-old immunosuppressed woman with a history of renal transplantation and lymphoma (Case 2) both presented with rapidly progressive virilisation. The two right ovarian tumours (20 to 25 mm, no Reinke crystals) displayed an unambiguous sex cord–stromal immunophenotype (α-inhibin, calretinin, SF-1 and Melan-A positive; CD10, WT1, EMA, AE1/AE3 and PAX8 negative), with aberrant nuclear and cytoplasmic β-catenin staining. Sequencing identified a pathogenic <i>CTNNB1</i> c.133T>C p.(Ser45Pro) variant in Case 1 and a pathogenic <i>CTNNB1</i> c.95A>T p.(Asp32Val) variant in Case 2, with wild-type <i>FOXL2</i> in both. <b>Conclusions:</b> Three of the four molecularly characterised <i>CTNNB1</i>-mutated SCT-NOSs converge on the two principal GSK-3β phosphorylation residues of β-catenin, identifying Wnt/β-catenin-pathway dysregulation as a potentially recurrent event and providing additional evidence for the involvement of the Wnt/β-catenin pathway in an emerging molecular subset of SCT-NOS. In a tumour with the canonical sex cord–stromal immunophenotype, an exon 3 <i>CTNNB1</i> hotspot mutation should not be regarded as evidence against the diagnosis of SCT-NOS and may help define a distinct molecular subset.
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Bouri, S., Lavis, P., Noël, J. (2026). Two Cases of Steroid Cell Tumour, Not Otherwise Specified, of the Ovary with Distinct Exon 3 CTNNB1 Hotspot Mutations (p.D32V and p.S45P): Further Evidence of Wnt/β-Catenin-Pathway Involvement. Diagnostics. https://doi.org/10.3390/diagnostics16152464