Category: Calcium/Bone Disorders
Hypercalcemia is a common finding in patients with systemic malignancies and could be related to overexpression of parathyroid hormone-related protein (PTHrP). Chronic decubitus ulcers could undergo malignant transformation to squamous cell carcinoma (SCC). We present a rare case of keratinizing SCC in decubitus ulcer producing PTHrP to cause humoral hypercalcemia of malignancy (HHM).
A 46-year-old AA man with a history of T7 paraplegia due to a gunshot wound (GSW), chronic sacral decubitus ulcers, colostomy, and the suprapubic catheter was admitted for sepsis. The sepsis was attributed to extensive decubitus ulcers with underlying osteomyelitis. The calcium was 14.9 mg/dL (8.4-10.4). The corrected calcium for albumin was 16 mg/dL. The biochemical evaluation revealed PTH 2.2 pg/ml (12-88), vitamin D 7 ng/ml (20-100), 1,25-OH vitamin D < 8 pg/ml (18-72) and PTHrp 3.9 pMol/L (< 2.0). The CT abdomen revealed extensive enhancement of the pelvic soft tissues, bony destruction and pelvic adenopathy which is suspicious for carcinoma. The biopsy of the ulcer was consistent with invasive keratinizing SCC. The SCC was unresectable due to the extensive disease. He was not considered a candidate for chemotherapy or radiation therapy. Hypercalcemia was treated with IV fluids, calcitonin, cinacalcet, and bisphosphonates. He received zoledronic acid 4 mg IVBP and subsequently on day 13 and day 23. There was a temporary improvement in hypercalcemia for a few days after zoledronic acid followed by relapse. Two weeks later, he received denosumab 120 mg for refractory hypercalcemia. The corrected calcium continued to be elevated at 13.4 mg/dL and therefore received denosumab seven days later. He developed hypocalcemia two weeks after the denosumab requiring calcium supplementation for a few weeks. The refractory hypercalcemia responded to denosumab despite no reduction in PTHrP producing tumor burden. He succumbed to complications of SCC.
Hypercalcemia is a potentially fatal paraneoplastic complication of malignancy. HHM due to paraneoplastic secretion of PTHrP associated with SCC arising from cutaneous ulcer is extremely rare. Despite conventional treatments including fluid resuscitation, a bisphosphonate, and calcimimetics; patient required denosumab which has been reported to be effective in refractory hypercalcemia.
Malignant transformation of non-healing decubitus ulcer should be followed very closely, and denosumab could be a treatment option in bisphosphonate refractory HHM.
University of Alabama at Birmingham
I was born and raised in Turkey. After medical school graduation, moved to New Haven to do post-doctoral education at Yale University then continued on my studies at University of Illinois at Chicago. In 2015, I started my residency in internal Medicine at Mercy Catholic Medical Center in Pennsylvania. Past year I was accepted to Endocrinology, Diabetes and Metabolism fellowship at University of Alabama at Birmingham, and currently continuing on my training as a fellow there.