SAT-120 Humoral Hypercalcemia of Malignancy Caused by Squamous Cell Carcinoma of the Penis

Abstract

Background. Humoral hypercalcemia of malignancy (HHM) accounts for approximately 80% of hypercalcemia associated with cancer. We present an unusual case of HHM caused by recurrent squamous cell carcinoma of the penis. Case. A 45 year old male was brought to the emergency department (ED) due to worsening confusion over 48 hours. History was notable for squamous cell carcinoma of the penis initially diagnosed 12 years ago and managed by partial penectomy and ilioinguinal lymphadenectomy. Recurrence had been diagnosed approximately 30 days before presentation to the ED. The patient was somnolent, disoriented, and unable to follow commands. Admission laboratories were remarkable for new occurrence of hypercalcemia (serum calcium corrected for low albumin 17.0 mg/dL, 8.6–10.3) and acute renal failure (Cr 1.7 mg/dL, 0.6–1.3; BUN 44 mg/dL, 7–25). No masses or hemorrhages were observed on head imaging, though computed tomography of the chest, abdomen, and pelvis revealed multiple lung and liver masses and lytic bone lesions. Biopsy of a rib mass confirmed metastatic squamous cell carcinoma. Intact PTH level was suppressed at 1 pg/mL (12–88), but parathyroid hormone related protein (PTHrP) was significantly elevated at 120 pM (0.0–2.3). HHM due to PTHrP was diagnosed. Corrected calcium level reached a nadir of 9.5 mg/dL on hospital day seven after saline hydration, calcitonin, and zoledronic acid, but high dose denosumab (120 mg weekly) was started hospital day 10 after corrected calcium level increased to 11.7 mg/dL. Despite corrected calcium levels consistently in the range of 10.5–11.5 mg/dL for the remainder of hospitalization, the patient’s mental status failed to improve. He expired on hospital day 24. Conclusions. Squamous cell carcinoma of the penis is rare in the United States, with only about 2,000 cases diagnosed annually. Though squamous cell carcinomas are collectively the most common cause of PTHrP-related hypercalcemia, there are only a few cases of PTHrP-related hypercalcemia due to squamous cell carcinoma of the penis documented in the peer reviewed literature. As in our patient’s case, other penile carcinoma patients with PTHrP-related hypercalcemia have had regionally advanced or metastatic disease and limited therapeutic response to bisphosphonates. Our patient’s survival after occurrence of hypercalcemia was also similar to other published cases of penile carcinoma complicated by PTHrP-related hypercalcemia. This case confirms the potential for penile carcinoma to cause HHM through hypersecretion of PTHrP like squamous cell carcinomas of the lung, head, and neck. Denosumab may be a more effective treatment option than a bisphosphonate based on the therapeutic experience in this case and others. PTHrP-related hypercalcemia appears to be a strong indicator of limited life expectancy for penile carcinoma as for other malignancies.