RESUMO
Molecular profiling was performed in 50 problematic ovarian sex cord-stromal tumours (SCSTs) most of which were seen in consultation. Following analysis, 17 were classified as adult granulosa cell tumour (AGCT), 16 of which showed a FOXL2 sequence variant (mutation); the initial favoured diagnosis in five of the cases was benign thecoma/fibrothecoma. Thirteen tumours ultimately classified as cellular fibroma or thecoma were FOXL2 sequence variant negative which was helpful in excluding AGCT. All six Sertoli-Leydig cell tumours (SLCTs) demonstrated DICER1 'hot spot' sequence variants, and one case each of AGCT and SLCT showed high grade histological transformation associated with a concurrent TP53 sequence variant. All eight unclassified SCSTs were negative for FOXL2 mutations and the six tested cases were DICER1 wild type; however, three tumours demonstrated MET, CTNNB1 or TP53 sequence variants. Four cases were classified as juvenile granulosa cell tumour, and one of these harboured a GNAS sequence variant. The single gynandroblastoma and microcystic stromal tumours in the series demonstrated FOXL2 and CTNNB1 alterations, respectively. In summary, molecular analysis aids in accurate classification of challenging ovarian SCSTs and sometimes leads to revision of the favoured provisional diagnosis. TP53 sequence variants may be associated with dedifferentiation in both SLCTs and AGCTs.
Assuntos
Neoplasias Ovarianas/classificação , Tumores do Estroma Gonadal e dos Cordões Sexuais/classificação , Tumor da Célula Tecal/classificação , Proteína Supressora de Tumor p53/genética , beta Catenina/genética , Desdiferenciação Celular , RNA Helicases DEAD-box/genética , Feminino , Proteína Forkhead Box L2/genética , Humanos , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/patologia , Ribonuclease III/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumor da Célula Tecal/genética , Tumor da Célula Tecal/patologiaRESUMO
Papillary proliferations of the endometrium (PPEs) are uncommon lesions that are often associated with endometrial polyps. PPEs occasionally precede or co-exist with atypical endometrial hyperplasia or adenocarcinoma, but their pathogenesis and relationship to endometrial neoplasia is uncertain. In the present study 11 PPEs, including eight benign papillary proliferations (BPPs) and three complex papillary hyperplasias (CPHs) were examined immunohistochemically for expression of PAX2, BAF250a, p16, ß-catenin and DNA mismatch repair (MMR) proteins. Molecular analysis was also performed on the CPHs using targeted next generation sequencing (NGS). All PPEs demonstrated at least one immunohistochemical abnormality with altered expression of p16 and PAX2 in nine and seven cases, respectively, and ß-catenin in one case. However, none of the cases showed loss of BAF250a or MMR protein staining. All CPHs showed KRAS mutations with additional mutations in AKT1 and FBXW7 in one case each, and both PIK3CA and CTNNB1 in the remaining case. Therefore, PPEs demonstrate immunophenotypical and molecular overlap with endometrial endometrioid neoplasia, although loss of BAF250a and MMR protein function do not appear to contribute significantly to these lesions. KRAS mutations may be important drivers in CPHs but this finding needs to be confirmed in larger studies.