Ectopic Parathyroid Hormone Secretion by A Penile Squamous Cell Carcinoma

ABSTRACT Objective: Ectopic paraneoplastic secretion of parathyroid hormone (PTH) is rare, with only 25 cases previously reported in the literature, including only 2 attributed to squamous cell carcinoma. The recent presentation of such a patient and subsequent review of the literature has alerted us to the need for clinicians to consider such an etiology in patients presenting with humeral hypercalcemia of malignancy. Methods: Significant hypercalcemia occurred in a 48-year-old male with metastatic squamous cell carcinoma of the penis. The patient had hypercalcemia, elevated PTH, and normal PTH-related protein (PTHrp), without evidence of tumoral skeletal involvement. Comorbid primary hyperparathyroidism was suspected, but ultrasound and sestamibi scans of the neck were negative, raising the possibility of ectopic PTH production. This was confirmed by computed tomography–guided needle biopsy of a thigh metastatic lesion showing positive histochemical staining for PTH-specific antibodies and markedly elevated PTH levels in the aspirated lesion fluid. Results: Paraneoplastic ectopic PTH production is well documented but rare. This is only the third such case to be reported due to squamous cell carcinoma and the first associated with a penile primary neoplasm. Diagnosis in our patient required exclusion of neoplastic lytic bone lesions, tumoral secretion of PTHrp, or comorbid primary hyperparathyroidism, as well as positive histochemical staining of tumor cells obtained at biopsy for PTH and very high levels of PTH from fluid aspirated from a metastasis. In spite of aggressive chemotherapy and management of hypercalcemia, the patient did not survive. Conclusion: Ectopic paraneoplastic PTH secretion is rare, but clinicians need to be alert to its possibility and aggressively seek out the diagnosis. Unfortunately, management is difficult, and even with aggressive treatment, survival is poor. Abbreviations: CT computed tomography; HHM humeral hypercalcemia of malignancy; PTH parathyroid hormone; PTHrp parathyroid hormone–related protein