Perineal Verrucous Carcinoma Associated With Hypercalcemia: First Clinical Report of Parathyroid Hormone–Related Protein-producing Tumor

Summary: Cancer-related hypercalcemia typically indicates poor prognosis and occurs most commonly in squamous cell carcinoma cases. However, its occurrence in patients with verrucous carcinoma, a clinically indolent subtype, has never been reported. We present the first documented case of verrucous carcinoma–related hypercalcemia caused by parathyroid hormone–related protein (PTHrP) production. A 49-year-old man presented with weight loss, fatigue, and severe hypercalcemia. He had a 3-year history of a scrotal mass that was diagnosed as perineal verrucous carcinoma based on histopathologic examination. Laboratory results revealed markedly elevated calcium (13.0 mg/dL) and PTHrP (6.6 pmol/L) levels, confirming tumor-associated hypercalcemia. The cauliflower-like tumor measuring 17 × 15 cm involved the penis and scrotum. Complete surgical resection with bilateral inguinal lymph node dissection was performed. Split-thickness skin grafts provided wound coverage over the large perineal defect. Immunohistochemical staining confirmed PTHrP production by tumor cells that had invaded beyond the basement membrane. Postoperative calcium (9.8 mg/dL) and PTHrP (