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

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 (<1.1 pmol/L) levels normalized rapidly. Histopathology confirmed verrucous carcinoma with dermal invasion; however, no lymph node metastasis occurred. <i>Pseudomonas aeruginosa</i> infection developed but resolved with topical treatment. Six-month follow-up magnetic resonance imaging showed no recurrence with sustained hypercalcemia resolution. This first documented case linking PTHrP-mediated hypercalcemia to verrucous carcinoma demonstrates that paraneoplastic hypercalcemia can occur in this typically indolent malignancy when dermal invasion occurs. Recognition of this rare syndrome is crucial for optimal management. Complete surgical excision achieved both oncological control and resolution of systemic complications, highlighting the importance of aggressive treatment when basement membrane invasion is present.