Paraneoplastic Hypercalcemia Associated with Juvenile Granulosa Cell Tumor

Background

Juvenile granulosa cell tumor (JGCT) is a rare subtype of ovarian sex cord-stromal tumors. Its reported incidence is between 0.58–1.6/100 000/year, with 90% of the JGCT occurring in young females less than 30 years of age, and only up to 5% diagnosed in prepubertal age. JGCT is included in a European network for very rare tumors in childhood (European Cooperative Study Group for Pediatric Rare Tumors: EXPeRT) which has been founded in 2008 to improve knowledge, diagnosis and treatment of rare pediatric cancers (Bisogno G et al., Klin Padiatr 2012; 224: 416–420).

Only 2 documented cases of JGCT have been associated with paraneoplastic hypercalcemia, one in an adult woman (Piura B, Wiznitzer A, Shaco-Lecy R, Arch Gynecol Obstet 2008; 277: 257–262) and the second in a child (Daubenton JD, Sinclair-Smith C, Med Pediatr Oncol 2000; 34: 301–303). In patients suspected of having JGCT with paraneoplastic hypercalcemia, it is crucial to rule out ovarian small cell carcinoma (OSCC), of which 66% are associated with paraneoplastic hypercalcemia (OSCCHT). OSCC have a similar tumor morphology to JGCT, but do not express inhibins. Young patients diagnosed with OSCC have a particulary poor prognosis, and require radical ­surgery and adjuvant chemotherapy even for stage I tumors. In contrast, patients with stage I JGCT have an excellent ­prognosis.