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Malignant islet cell tumor associated with hypercalcemia.

Surgery 1995 January
BACKGROUND: Three cases of islet cell tumors of the pancreas with hypercalcemia were studied, and 16 similar cases have been found in a 25-year review of the English-language literature. The purpose of the study was to review the cause of the hypercalcemia and the clinical characteristics of the tumors.

METHODS: Tumor tissue retrieved from paraffin-embedded blocks was studied immunohistochemically for both parathyroid hormone (PTH) and PTH-related protein (PTHrP). PTH was measured in the serum in each patient and the serum PTHrP was measured by immunoassay in one patient.

RESULTS: One of our patients had a fatal serum calcium level of 26.4 mg/dl. PTHrP stains were positive in two of our tumors, and one patient had an elevated PTHrP serum level. Serum PTH levels were normal or low in each patient. All three tumors were malignant and extremely vascular. The total group of 19 patients have in common hypercalcemia associated with a normal or low serum PTH level. Although the cause of hypercalcemia has not been proved, the tumors apparently produce PTHrP, because seven of eight tumors stained positive for PTHrP and each of the four patients tested had an elevated PTHrP serum titer. The tumors are extremely vascular, are usually malignant (17 of 18), and become large, but they are compatible with a relatively long patient survival time.

CONCLUSIONS: These neuroendocrine tumors associated with hypercalcemia share several characteristics, but a claim that they represent another type of "functioning islet cell tumor" should await a clearer delineation of the cause of the hypercalcemia.

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