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Special Feature |

Pathological Case of the Month FREE

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Section Editor: Enid Gilbert-barness, MD

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Arch Pediatr Adolesc Med. 2002;156(1):84. doi:.
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Published online

DENOUEMENT AND DISCUSSION: ACUTE SYMPTOMATIC HYPERCALCEMIA ASSOCIATED WITH OVARIAN SMALL CELL CARCINOMA

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 hypercalcemia1,2 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 adolescents13 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 children1,2 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).

Rudolph  AMHoffman  JIERudolph  CD Hypercalcemia. Rudolph's Pediatrics 20th ed Stamford, Conn Appleton & Lange1996;1884- 1847
Aurbach  GDMarx  SJSpiegel  AMWilson  JDedFoster  DWed Hypercalcemia. William's Textbook of Endocrinology 8th ed Philadelphia, Pa WB Saunders Co1992;1445- 1456
DiGeorge  AMBehrman  REedKliegman  RMedArvin  AMed Hyperparathyroidism. Nelson Textbook of Pediatrics 15th ed Philadelphia, Pa WB Saunders Co1996;1609- 1611
Grill  VRankin  WMartin  TJ Parathyroid hormone–related protein (PTHrP) and hypercalcemia. Eur J Cancer. 1998;34222- 229
Link to Article
Matias-Guiu  XPrat  JYoung  R  et al.  Human parathyroid hormone–related protein in ovarian small-cell carcinoma: an immunohistochemical study. Cancer. 1994;731878- 1881
Link to Article
Young  RHOliva  EScully  RE Small-cell carcinoma of the ovary, hypercalcemic type: a clinicopathological analysis of 150 cases. Am J Surg Pathol. 1994;181102- 1116
Link to Article
Scully  RE Small-cell carcinoma of hypercalcemic type. Int J Gynecol Pathol. 1993;12148- 152
Link to Article
Scully  REedYoung  RHedClement  PBed General features of ovarian tumors; miscellaneous primary tumors. Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament Washington, DC Armed Forces Institute of Pathology1998;Atlas of Tumor Pathology 3rd ser (pt 23) 27- 50316- 320

Tables

References

Rudolph  AMHoffman  JIERudolph  CD Hypercalcemia. Rudolph's Pediatrics 20th ed Stamford, Conn Appleton & Lange1996;1884- 1847
Aurbach  GDMarx  SJSpiegel  AMWilson  JDedFoster  DWed Hypercalcemia. William's Textbook of Endocrinology 8th ed Philadelphia, Pa WB Saunders Co1992;1445- 1456
DiGeorge  AMBehrman  REedKliegman  RMedArvin  AMed Hyperparathyroidism. Nelson Textbook of Pediatrics 15th ed Philadelphia, Pa WB Saunders Co1996;1609- 1611
Grill  VRankin  WMartin  TJ Parathyroid hormone–related protein (PTHrP) and hypercalcemia. Eur J Cancer. 1998;34222- 229
Link to Article
Matias-Guiu  XPrat  JYoung  R  et al.  Human parathyroid hormone–related protein in ovarian small-cell carcinoma: an immunohistochemical study. Cancer. 1994;731878- 1881
Link to Article
Young  RHOliva  EScully  RE Small-cell carcinoma of the ovary, hypercalcemic type: a clinicopathological analysis of 150 cases. Am J Surg Pathol. 1994;181102- 1116
Link to Article
Scully  RE Small-cell carcinoma of hypercalcemic type. Int J Gynecol Pathol. 1993;12148- 152
Link to Article
Scully  REedYoung  RHedClement  PBed General features of ovarian tumors; miscellaneous primary tumors. Tumors of the Ovary, Maldeveloped Gonads, Fallopian Tube, and Broad Ligament Washington, DC Armed Forces Institute of Pathology1998;Atlas of Tumor Pathology 3rd ser (pt 23) 27- 50316- 320

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