FOXL2 Mutation Status in Sex Cord-stromal Tumors Cannot be Predicted by Morphology.

Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The histopathologic diagnosis of these tumors can be challenging. A recurrent somatic mutation of the forkhead box L2 (FOXL2) gene has been identified in adult GCT. In this retrospective single-center study of 44 SCST, a morphologic review together with analysis of FOXL2 C134W was evaluated in relation to tumor morphology. In addition, TERT promoter mutation testing was performed. Twelve of 36 cases got an altered diagnosis based on morphology alone. The overarching architectural growth pattern in 32/44 (72.7%) tumors was diffuse/solid with several tumors showing markedly heterogeneous architecture. In correlation to FOXL2 C134W mutation status, cytoplasmic color, and nuclear shape, differed between the FOXL2 C134W positive and FOXL2 C134 W negative groups, but these differences were not significant when comparing them separately. Nineteen of 44 cases underwent TERT promoter sequencing with a positive result in 3 cases; 2 adult GCTs and 1 cellular fibroma. Three patients developed a recurrence of which 2 were FOXL2 C134W positive adult GCTs and the third was an unclassified SCST. In conclusion, the morphologic and immunohistochemical diagnosis of different SCSTs is challenging and one cannot reliably identify FOXL2 mutation-positive tumors solely by morphologic features. Therefore, broad use of molecular analysis of the FOXL2 C134W mutation is suggested for SCSTs, and further studies are needed to evaluate the clinical outcome of these tumors as well as the diagnostic and prognostic implications of TERT promoter mutations.

Wessman S ，Fuentes BB ，Severin-Karlsson J ，Westbom-Fremer S ，Nistér M ，Kokaraki G ，Petta TB ，Haglund F ，Carlson JW ... -  《-》

Detection of FOXL2 C134W Mutation Status by a Novel BaseScope In Situ Hybridization Assay is Highly Sensitive and Specific for Adult Granulosa Cell Tumors.

Hammer PM ，Wang A ，Beard C ，Zdravkovic S ，Tenney T ，Liang B ，Das I ，Bremer R ，Wang LC ，McCluggage WG ，Stewart CJR ，Howitt BE ... -  《-》

FOXL2 Mutation Analysis of Ovarian Sex Cord-Stromal Tumors: Genotype-Phenotype Correlation With Diagnostic Considerations.

Buza N ，Wong S ，Hui P 《-》

DICER1 and FOXL2 mutations in ovarian sex cord-stromal tumours: a GINECO Group study.

FOXL2 mutation has been consistently identified in adult granulosa cell tumours (A-GCTs). DICER1 mutations have been described predominantly in Sertoli-Leydig cell tumours (SLCTs). The prognostic implication of these mutations remains uncertain, as moderately sized studies have yielded variable outcomes. Our aim was to determine the implications of DICER1 and FOXL2 mutations in 156 ovarian sex cord-stromal tumours (SCSTs). FOXL2 mutations were found in 94% of pathologically confirmed A-GCTs (95/101), in one of eight juvenile granulosa cell tumours (J-GCTs), and in two of 19 SLCTs. DICER1 mutations in the RNase IIIb domain were found in six of 19 SLCTs, two of eight J-GCTs, and one of 12 undifferentiated SCSTs (Und-SCSTs). Comparison of DICER1-mutated SLCTs with DICER1-non-mutated SLCTs showed that patient age at diagnosis was lower and oestrogen receptor expression was more frequent in DICER1-mutated tumours. With a median follow-up of 22 months, two of five DICER1-mutated SLCTs relapsed, in contrast to none of eight DICER1-non-mutated tumours. Our results suggest that, in contrast to FOXL2 mutations in A-GCT, DICER1 mutations in SLCT might be more useful for prognosis than for diagnosis. However, study of a larger cohort of patients is necessary to establish this. Identification of genetic alterations in SCST offers promising therapeutic options.

Goulvent T ，Ray-Coquard I ，Borel S ，Haddad V ，Devouassoux-Shisheboran M ，Vacher-Lavenu MC ，Pujade-Laurraine E ，Savina A ，Maillet D ，Gillet G ，Treilleux I ，Rimokh R ... -  《-》

Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Commonly Exhibits Positivity With Sex Cord Markers FOXL2 and SF-1 but Lacks FOXL2 and DICER1 Mutations.

Croce S ，de Kock L ，Boshari T ，Hostein I ，Velasco V ，Foulkes WD ，McCluggage WG ... -  《-》