Adult granulosa cell tumours of the testis analogous to ovarian counterparts are exceptionally rare: analysis of a multicentric series and review of the literature

TL;DR

Testicular adult granulosa cell tumors differ from ovarian ones, especially in lacking a key mutation found in ovarian tumors.

Contribution

This study confirms the absence of FOXL2 p.Cys134Trp mutations in testicular AGCTs using NGS panels.

Findings

FOXL2 mutations were absent in 12 out of 20 testicular AGCTs analyzed.

CTNNB1 alterations were found in three tumors, with nuclear β-catenin expression in one.

Only 2 of 29 testicular AGCTs reported to date have shown FOXL2 p.Cys134Trp mutations.

Abstract

Testicular adult granulosa cell tumours (AGCTs) are rare and show several clinical–pathological differences with their ovarian counterparts. In a limited number of prior studies, FOXL2 p.Cys134Trp, the hallmark molecular alteration of ovarian AGCT, appeared to be infrequent in testicular AGCTs. However, the number of cases analysed to date is relatively small.

Twenty testicular AGCTs were analysed de novo using two different next‐generation sequencing (NGS) panels that cover sex cord‐stromal tumour (SCST)–relevant genes, including
FOXL2
,
CTNNB1
,
FH
and
DICER1
. Among 12 tumours (12/20; 60%) that were sequenced successfully, none harboured
FOXL2
mutations. Eight tumours (8/12, 66.7%) showed a wild‐type (WT) status for all genes assessed with the panels. Three tumours harboured pathogenic or likely pathogenic
CTNNB1
alterations. One of these exhibited predominant spindle cell morphology, while the other two showed focal tubular architecture. Immunohistochemistry performed in one of these tumours with available material showed β‐catenin expression in ~70% of tumor cell nuclei. The remaining AGCTs showed variants of uncertain significance (likely benign) in
KIT
and
MED12
. Considering the tumors asseseed in this study and those previously reported in the literature, only 2 of 29 neoplasms classified as testicular AGCTs have shown a
FOXL2
p.Cys134Trp mutation to date.

The present study confirms that SCSTs classified as AGCTs differ from their ovarian counterparts in that they largely lack FOXL2 mutations.

Assessment of twenty testicular AGCTs with two different next‐generation sequencing (NGS) panels reveals differences with ovarian AGCTs, including absence of hotspot FOXL2 variants.

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