SAT-LB63 A Case of PTHrP-Negative Hypercalcemia of Malignancy

Case Presentation: A 55-year-old male who had recently arrived from Haiti presented to the Emergency Department with chief complaint of a progressively enlarging neck mass. He first noticed the mass in 2000. From 2000-2017, he underwent resection of the mass three times in Haiti, with recurrence after each surgery. On presentation, he reported unintentional 10 kg weight loss over several months and night sweats. Endocrine was consulted for evaluation of hypercalcemia. On examination and imaging, 8.7 x 14.0 x 14.0 cm fungating tumor on the nape of his neck extending to the occipital area and cervical lymphadenopathy were noted. Labs were notable for WBC of 21.7 K/uL, hemoglobin of 6.0 g/dL, calcium of 12.0 mg/dL, albumin of 3.1 g/dL, free calcium of 6.4 mg/dL, corrected calcium of 12.6 mg/dL, phosphorus of 2.6 mg/dL, and intact PTH of < 4 pg/mL. The PTH-related peptide (PTHrP) level was found to be normal at 19 pg/mL (reference range 14–27 pg/mL). SPEP was normal. Neck mass and cervical lymph nodes were biopsied. Histopathological examination of neck mass showed an ulcerated, moderately-differentiated squamous cell carcinoma with multifocal areas of necrosis. There was no evidence of malignancy in the cervical lymph nodes. CT scan showed 3 mm lung nodules, thought to be granulomas, and no clear evidence of metastatic disease. Hypercalcemia was treated with IV hydration and one dose of bisphosphonate and patient underwent resection of neck mass. Immediately after surgery, his calcium level precipitously decreased and has remained normal in the months since surgery. Discussion: Hypercalcemia of malignancy is a common finding affecting up to 44.1% of patients with malignancy (1,2). The major mechanism, accounting for approximately 80% of malignancy-related hypercalcemia, is mediated via PTHrP, which can cause hypercalcemia by increasing bone resorption and renal tubule calcium reabsorption (2). Squamous cell carcinoma (SCC), especially of the lungs, breast, or GI tract, is more frequently associated with hypercalcemia. There are also several case reports of primary cutaneous SCC associated with hypercalcemia. In these cases, tumors were large and hypercalcemia was thought to be due to elevated PTHrP (3,4,5). The skin has been shown to express PTHrP and PTHrP receptors (10). PTHrP has also been detected in 100% of cutaneous SCCs even in the absence of hypercalcemia. (6,7). Furthermore, PTHrP mRNA has been localized in 100% of squamous tumors with hypercalcemia and PTHrP peptide were detected in 91% of cases in a study of 11 patients (9). The patient presented in this case did not have an elevated level of PTHrP. However, resolution of hypercalcemia with resection of the mass supports a diagnosis of hypercalcemia of malignancy. This case illustrates that hypercalcemia due to primary cutaneous SCC typically, but not always, results in an elevated serum PTHrP level.