Adult granulosa cell tumor, the most common malignant ovarian sex cord–stromal tumor,
harbors the characteristic mutation c.402C>G (p.C134W) in the FOXL2 gene in ~90% to
95% of cases. To date, no other variants of FOXL2 mutations have been identified in
these tumors. Here we report the first case of an adult granulosa cell tumor with
a novel FOXL2 point mutation c.398C>T (p.A133V) presenting in a 64-year-old postmenopausal
woman. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy
for atypical endometrial hyperplasia and gross examination revealed an incidental
3.2 cm right ovarian mass with a solid, bright yellow, homogeneous cut surface. Microscopically,
~30% of the tumor showed a nested growth pattern composed of uniform tumor cells with
oval nuclei and a moderate amount of pale cytoplasm, while the remaining areas consisted
of a bland storiform fibromatous stroma. Reticulin stain demonstrated loss of the
individual pericellular network within the nested areas, while the pericellular staining
pattern was retained in the background stromal component. FOXL2 sequencing analysis
was performed in both components and revealed a c.398C>T (p.A133V) mutation in the
nested component, whereas wild-type FOXL2 sequence was identified in the fibromatous
stroma. Sections from the uterus showed a low-grade endometrioid endometrial adenocarcinoma
with superficial myometrial invasion. The patient underwent adjuvant vaginal cuff
brachytherapy for the endometrial carcinoma and is alive and well at 8 months follow-up.
This case illustrates that new FOXL2 mutations may be detected in ovarian sex cord–stromal
tumors with increasing use of routine molecular testing, adding to the complexity
of the pathologic diagnosis. In the right morphologic and clinical context, a FOXL2
mutation—even if it is different from the dominant hotspot mutation c.402C>G (p.C134W)—can
support the diagnosis of adult granulosa cell tumor.
