Recurrent Hypercalcemia in Chronic Lymphocytic Leukemia Without Transformation: A Diagnostic Trap

Introduction: Hypercalcemia is an uncommon finding in chronic lymphocytic leukemia (CLL) and typically raises concern for Richter transformation or paraneoplastic processes. In patients with concurrent chronic kidney disease (CKD), calcium dysregulation may be multifactorial. We present a case of severe, recurrent hypercalcemia in relapsed CLL without transformation, ultimately attributed to metabolic bone disease. Case Description: A 65-year-old male with relapsed CLL, CKD stage IV, and prior acalabrutinib use presented with symptomatic hypercalcemia (Ca 14.7 mg/dL) and acute kidney injury. Labs showed suppressed PTH, negative PTHrP, and high-normal vitamin D. Treated with IV fluids, pamidronate, and intranasal calcitonin. PET scan revealed no transformation; bone scan showed diffuse skeletal uptake without focal lesions. Calcium normalized, but PTH later rose, consistent with secondary hyperparathyroidism. Discussion: Hypercalcemia in CLL is rare and typically prompts evaluation for transformation or paraneoplastic causes. Our patient had suppressed PTH, negative PTHrP, and unremarkable PET imaging, making malignancy-driven hypercalcemia unlikely. Bone scan revealed diffuse skeletal uptake, consistent with high-turnover bone disease. CKD, prior vitamin D use, and diuretic therapy likely contributed. Similar cases have emphasized the importance of excluding Richter transformation (Briones et al., 1997) and recognizing nonmalignant causes in advanced CLL (Shacham et al., 2021). In complex patients, hypercalcemia may reflect cumulative metabolic stress rather than active malignancy, reinforcing the value of a multidisciplinary approach.NM bone scan shows diffuse, symmetric radiotracer uptake in axial and appendicular skeleton, without focal lesions. Consistent with metabolic bone disease, not skeletal malignancy.