Hypercalcemia in a child with juvenile granulosa cell tumor of ovary: Report of an unusual paraneoplastic syndrome and review of the literature
A 15-year-old white girl was admitted with abdominal pain and vomiting for 2 days. Two days prior, she was seen by her primary physician for vomiting. She was prescribed intravenous metoclopramide without improvement. She was referred to the pediatric emergency unit for appendicitis suspicion. The girl was febrile with a body temperature of 38 °C. On physical examination, signs of puberty were appropriate for her age (she had menarche at age 14). A mass that was painful on palpation was located in the right lower quadrant. Headache was reported without alterations in level of consciousness, or other neurologic symptoms. Her vital signs were significant with respiratory rate of 24 breaths per minute, oxygen saturation of 96%, heart rate of 120 beats per min indicating tachycardia, and blood pressure of 136/85 mm Hg. Laboratory examination showed normal urea and creatinine, but corrected serum calcium was 14.9 mg/dl (3.70 mmol/l), phosphorus 0.50 mmol/l, LDH 348 U/l, and C-reactive protein level 259 mg/l. Serum parathyroid hormone-intact (PTH-i) level was 10 pg/ml (normal 10–65). Alpha fetoprotein and beta human chorionic gonadotropin were both normal at < 10 IU/ml. Serum CA-125 was 204 (normal, 0–35) U/ml, while serum CA-15-3 was normal. Serum inhibin was not ever checked. Electrocardiograph was normal. Abdominal ultrasonography demonstrated semisolid pelvic mass measuring 125 mm × 105 mm × 65 mm. An abdominal contrast-enhanced computed tomography scan revealed a right ovarian mass with pelvic ascites, without involvement of pelvic structures (). She was referred to intensive care unit for an antihypercalcemic treatment. Isotonic saline hydration was started together with intravenous infusion of pamidronate (1 mg/kg) and furosemide. An isotopic (99 mTc-HMDP-“Osteocis”) bone scanning did not detect bone metastasis.\nOn the six day after starting the management of hypercalcemia, she underwent a median infraumbilical laparotomy with right salpingo-oophorectomy, omentectomy and drainage of ascites. Her serum calcium remained normal.\nThe tumor measured 120 mm × 90 mm × 65 mm with soft consistency. Its external surface was smooth and intact. The cut surface was heterogeneous, showing bright yellow nodular areas alternating with hemorrhagic areas and small cystic structures (Fig. 2). The right fallopian tube and the omentum were normal.\nMicroscopic examination revealed a solid nodular proliferation of medium-sized cells with hypocellular edematous areas, tumor cell necrosis and some pseudofollicular structures. The tumor cells had moderate to large amounts of pale or eosinophilic cytoplasm with focal features of luteinization. The nuclei were round to oval without groove. The cells were mitotically active, averaging 7 mitoses per 10 high power fields (Fig. 3A). Immunohistochemical profile was the following: the tumor cells demonstrated positive reactivity for alpha-inhibin (B) which confirms the histological suspicion of a sex-cord stromal process. The tumor also expressed reactivity to calretinin, estrogen and progesterone receptors, CD56 and smooth muscle actin. The cells were focally positive for cytokeratin KL1. The tumor was negative for TTF1, synaptophysin and chromogranin, pS100, EMA, and CD99.\nThese morphological and immunohistochemical features were the ones of a juvenile granulosa cell tumor, excluding the hypotheses of a neuroendocrine carcinoma or a clear cell carcinoma of the ovary which are however the most common ovarian tumors associated with hypercalcemia.