PSAT208 A Case of Hypercalcemia From PTHrP-Producing Fibromyxoid Sarcoma Responsive to Glucocorticoid Therapy

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is a major cause of humoral hypercalcemia of malignancy. PTHrP-induced hypercalcemia can also occur in benign disorders including pneumonia, SLE, HIV, sarcoidosis, and mammary hyperplasia. Treatment for PTHrP-induced hypercalcemia includes treating the underlying disorder and general management of hypercalcemia. CLINICAL CASE: A 70-year-old male with a chronic left thigh mass following trauma 12 years prior diagnosed as myositis ossificans, presented with worsening pain and swelling over the mass. Evaluation revealed serum calcium 18.6 mg/dl, PTH 10 ng/L (18-90), 25(OH)D 7 ng/ml (20-50), 1,25(OH)(2)D 15 pg/ml (20-79), PTHrP 9.3 pmol/L (≤ 4.2), negative SPEP, UPEP, serum light chains and immunofixation, and no bony lesions. MRI showed a large heterogenous mass centered in the left adductor muscle compatible with chronic hematoma with myositis ossificans. FDG PET/CT scan showed FDG avidity and calcification of the left thigh without any other site of uptake. Combination of IV hydration, denosumab and zoledronic acid lowered his calcium to 9.5 mg/dl, but levels increased again within 10 days. Repeated treatments with zoledronic acid initially led to modest lowering of calcium to 10.5 mg/dl, but he became refractory to treatment after 6 weeks, with calcium increasing to 12.3 mg/dl.Two biopsies of the mass were performed, including an open biopsy. The pathology showed nonpolarizable crystalline material with foreign giant cell reaction, without evidence for malignancy. It was concluded therefore that the patient's PTHrP-induced hypercalcemia was secondary to an inflammatory granulomatous condition. Since it had been reported that PTHrP-induced hypercalcemia in SLE and sarcoidosis responded to glucocorticoids, we initiated treatment with methylprednisolone 24 mg daily. After 7 days, the calcium declined from 12.3 to 10.5 mg/dl and PTHrP declined to 2.5 pmol/L. When the methylprednisolone dose was reduced to 12 mg daily, calcium increased to 11.4 mg/dl and PTHrP to 5 pmol/L. Increasing the methylprednisolone briefly back to 24 mg daily, and then 20 mg daily, lowered calcium to 9.0 mg/dl, increased PTH to 74 ng/L, and normalized PTHrP to 1.3 pmol/L. As long-term management with high-dose steroids was not a tenable option, a decision was made to resect the mass. The pathological diagnosis of the surgical mass was low-grade fibromyxoid sarcoma (LGFMS). Immunohistochemical studies identified PTHrP in surrounding vasculature, suggesting possible tumor-vessel interaction. CONCLUSION: PTHrP-mediated hypercalcemia is rarely seen in sarcomas and treatments include coadministration of bisphosphonates, chemotherapy and surgery. We report here the first case of PTHrP-induced hypercalcemia from LGFMS with sustained lowering of calcium and PTHrP levels with glucocorticoid treatment. Further studies are needed to elucidate the mechanism of glucocorticoids in the treatment of PTHrP-induced hypercalcemia and could include lowering levels of inflammatory cytokines that stimulate PTHrP production from tumor cells, or by directly suppressing PTHrP gene expression. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.