Pathological Case of the Month

Figure 1. A 15 × 12 × 12 cm (865 g) solid, tan-gray, hemorrhagic right ovarian mass with cystic degeneration removed from a 13-year-old girl with symptoms of hypercalcemia.

Figure 2. Small cell carcinoma of the ovary showing characteristic sheets of small round cells, frequent mitoses, and folliclelike structures.

Childhood hypercalcemia is usually chronic and asymptomatic. We described an adolescent girl with sudden onset of symptomatic hypercalcemia associated with ovarian small cell carcinoma.

The signs and symptoms of hypercalcemia^1,2 include nausea, vomiting, polyuria, polydipsia, dehydration, anorexia, and constipation. As calcium levels continue to rise, there may be altered consciousness, weakness, paresthesias, decreased QT interval, hypertension, and even paralysis. Most of the early signs and symptoms are nonspecific. Therefore, the diagnosis is easily confused with more common pediatric problems.

The differential diagnoses of hypercalcemia in children and adolescents^1-3 include primary hyperparathyroidism, hypervitaminosis D, familial hypocalciuric hypercalcemia, immobilization, neoplasia, and sarcoidosis. In addition, drugs (eg, thiazides, lithium carbonate, vitamin A analogues, alkalies), hyperthyroidism, or renal failure must be considered.

Although rare, the possibility of malignancy-related hypercalcemia in children^1,2 should also be considered. Tumors may increase serum calcium via osseous metastases, increased production of 1,25-dihydroxyvitamin D, or production of parathyroid hormone–related protein, which acts like parathyroid hormone to increase bone resorption and renal conservation of calcium.^1,2,4,5 Lymphomas or leukemia may be associated with hypercalcemia in children. Small cell carcinoma of the ovary is an extraordinarily rare tumor, typically occurring in the second to fourth decades of life and often presenting with hypercalcemia.^6,7

First described in 1982, small cell carcinoma of the ovary has been reported in females aged 7 to 43 years.⁶ In a review of 150 patients, 60% to 70% had preoperative hypercalcemia that was asymptomatic in all but 4 patients. One patient even underwent neck exploration with negative results before the ovarian tumor was discovered. Symptoms and signs on presentation included abdominal swelling, discomfort, menstrual irregularity, or an asymptomatic pelvic mass. The small cell carcinoma of the ovary was unilateral in 99% of patients, but half already had evidence of metastases. The tumors were large (average size, 15.3 cm), nodular, solid, tan-gray, and might have had areas of hemorrhage, necrosis, or cystic degeneration. Microscopically, tumor cells were usually small with round nuclei, scanty cytoplasm, and frequent mitoses. The cells typically grew in diffuse sheets that were frequently separated by folliclelike structures, and they often stained positive for parathyroid hormone–related protein.^6,8 The conventional treatment was surgery. Many combinations of chemotherapy and radiotherapy had been attempted with variable results.^6,7 In patients with stage IA disease (confined to 1 ovary, not through the capsule), one third remained disease free for 1 to 13 years after surgery, one half died within 2 years, and the remainder had recurrences. Almost all tumors above stage IA were fatal. Factors associated with a more favorable prognosis for stage IA tumors include an age of 30 years or older, normal preoperative calcium levels, tumor size less than 10 cm, and the absence of large cells.

In summary, small cell carcinomas of the ovary occur in young women and are associated with hypercalcemia and a high degree of malignancy. The pelvis should be investigated in every young woman with unexplained hypercalcemia to avoid overlooking an ovarian tumor.

Accepted for publication September 15, 1999.

We thank Edward C. Kohaut, MD, Nemours Children's Clinic, Pensacola, Fla, and Franklin Abbott, MD (Department of Radiology), William R. Bell, Jr, MD, and Everett Havard, MD (Department of Pathology), Sacred Heart Hospital, Pensacola, for their kind and expedient assistance.

Reprints: Helen Y. Hsiang, MD, 5153 N Ninth Ave, Pensacola, FL 32504 (e-mail: hhsiang@nemours.org).