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

Abstract

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.

Practical roles for molecular diagnostic testing in ovarian adult granulosa cell tumour, Sertoli–Leydig cell tumour, microcystic stromal tumour and their mimics

“…Among ovarian sex cord–stromal tumours, no FOXL2 C134W mutations have been identified in cellular fibromas, sclerosing stromal tumours, MCSTs, steroid cell tumours, Sertoli cell tumours, sex cord tumours with annular tubules (SCTATs), or gynandroblastomas . The C134W FOXL2 mutation has been identified in 1.6% (1/62) of conventional fibromas, 20% (7/35) of thecomas, 3% (2/59) of juvenile granulosa cell tumours (JGCTs), 13% (12/90) of SLCTs, 50% (6/12) of granulosa theca cell tumours, and 8% (2/24) of gynandroblastomas . These observations raise a nosological dilemma regarding the gold standard for tumour classification: morphology, immunophenotype, molecular phenotype, or some combination thereof.…”

“…FOXL2 mutation testing is valuable in this setting. Among eight studies reporting on 59 cases of JGCT, all but two cases lacked a mutation . Neither the morphology nor the outcome of these two cases was described.…”

“…Immunohistochemical stains are not of value, because these tumours share the same immunophenotype. Initial studies reported that up to 9% of SLCTs contain a FOXL2 mutation . Two recent studies reported conflicting findings.…”

“…This descriptive category has been used for a variety of diagnostic scenarios, mostly tumours with features suspicious for granulosa cell tumour (AGCT and JGCT) and/or Sertoli–stromal cell tumour (SLCT and Sertoli cell tumour), and thus carrying a risk for malignant behaviour. One study of 12 such cases reported that none contained FOXL2 mutation, whereas one study reported that one of four such cases did contain a mutation . Neither the morphological features nor clinical outcomes were described.…”

“…The discovery of this association led to a landmark sequencing study in 2012 that identified somatic missense mutations in the RNase IIIB domain of DICER1 in a majority of ovarian SLCTs . Subsequent studies have confirmed that somatic or germline mutations of DICER1 constitute a common signature of ovarian SLCTs . The practical implications for pathologists include the diagnostic role for DICER1 mutation testing in tumours with a differential diagnosis that includes SLCT, and the screening role of molecular testing to triage patients with SLCT for genetic counselling and formal risk assessment for DICER1 syndrome.…”