Hypercalcemia in Upper Urinary Tract Urothelial Carcinoma: A Case Report and Literature Review

Abstract

Objective. We here report a patient with upper urinary tract urothelial carcinoma with hypercalcemia likely due to elevated 1,25-dihydroxyvitamin D. Methods. We present a clinical case and a summary of literature search. Results. A 57-year-old man, recently diagnosed with a left renal mass, for which a core biopsy showed renal cell carcinoma, was admitted for hypercalcemia of 11.0 mg/mL He also had five small right lung nodules with a negative bone scan. Both intact parathyroid hormone and parathyroid hormone-related peptide were appropriately low, and 1,25-dihydroxyvitamin D was elevated at 118 pg/dL. The patient's calcium was normalized after hydration, and he underwent radical nephrectomy. On the postoperative day 6, a repeat 1,25-dihydroxyvitamin D was 24 pg/mL with a calcium of 8.1 mg/dL. Pathology showed a 6 cm high-grade urothelial carcinoma with divergent differentiation. We identified a total of 27 previously reported cases with hypercalcemia and upper tract urothelial carcinoma in English. No cases have a documented elevated 1,25-dihydroxyvitamin D level. Conclusion. This clinical course suggests that hypercalcemia in this case is from the patient's tumor, which was likely producing 1,25-dihydroxyvitamin D. Considering the therapeutic implications, hypercalcemia in patients with upper urinary tract urothelial carcinoma should be evaluated with 1,25-dihydroxyvitamin D.

Relevance of concurrent hypercalcemia in ureteric sarcoidosis complicated with bladder urothelial carcinoma: a case report

“…Meanwhile, the clinical manifestation of hypercalcemia served as a clue to the differential diagnosis of ureteric sarcoidosis through the elevated levels of 1,25-(OH) 2 D 3 and sarcoidosis markers (ACE, lysozyme, and SIL-2R). However, it should be noted that urothelial carcinoma is rarely complicated by hypercalcemia as paraneoplastic syndrome [14][15][16]. In this case, no increase was observed in the PTHrP level, which has been most commonly associated with paraneoplastic hypercalcemia in various malignancies [15].…”

Humoral hypercalcemia of malignancy caused by renal pelvic urothelial carcinoma with broad squamous differentiation: An autopsy case

“…Asao et al reported a case of urothelial carcinoma and treatment-refractory hypercalcemia, possibly due to a serum elevation in 1,25 dihydroxy vitamin D produced by the tumor. 5 In this case, the serum levels of PTH and PTH-rP were within normal range, and bone metastasis was not detected in the patient's clinical course. 5 Further investigation is required to elucidate the pathogenesis of hypercalcemia in urothelial carcinoma.…”

“…5 In this case, the serum levels of PTH and PTH-rP were within normal range, and bone metastasis was not detected in the patient's clinical course. 5 Further investigation is required to elucidate the pathogenesis of hypercalcemia in urothelial carcinoma. In summary, we described an autopsy case of renal pelvic cancer causing HHM and metastatic calcification in multiple organs.…”

The authors respond to “Misconception about the cause of vitamin D toxicity”

“…9,10 Second, Charoenngam and colleagues cite a case report of a patient with a large upper urinary tract carcinoma, specifically metastatic clear cell renal carcinoma. 11 Our patient had a lower urinary tract urothelial noninvasive carcinoma of the bladder with no metastatic disease. Furthermore, nonmetastatic bladder cancer associated with humoral hypercalcemia is exceedingly rare, normally requiring excision of the carcinoma to treat elevated 1,25-dihydroxyvitamin D levels and hypercalcemia, as this condition is usually refractory to medical treatment.…”