Hypercalcemia,Renal Failure,and Skull Lytic Lesions

Abstract

The findings of hypercalcemia, skull lytic lesions, and renal failure are usually characteristic for multiple myeloma. We herein describe an interesting case of B-cell follicular lymphoma that presented with many features mimicking multiple myeloma.

Case Description

A 69-year-old woman with a past history of coronary artery disease, hypertension, and dyslipidemia was admitted for rapidly progressive muscle weakness. She was previously asymptomatic until 8 weeks prior to admission when she started having predominantly proximal muscle weakness, mild back pain, poor appetite, and dysgeusia. She reported losing 30 to 40 pounds over the same time period. On admission, physical examination showed marked hepatosplenomegaly. Laboratory studies were significant for a severely elevated serum total calcium of 16.8 mg/dL and creatinine of 3.5 mg/dL indicative of acute renal injury. Her hemoglobin and platelets were mildly reduced at 10.4 g/dL and 117 × 10⁹/L, respectively. Subsequent testing revealed suppressed parathyroid hormone (PTH) levels, negative PTH-related peptide (PTHrP), mildly elevated lactate dehydrogenase, and almost 5 times the upper range of normal for serum angiotensin-converting enzyme (ACE) activity along with elevated levels of vitamin D metabolites.

Given strong suspicion for multiple myeloma, she underwent a skeletal survey, which revealed a 1.7-cm punched-out lytic lesion of the vertex of the skull (Figure 1). Interestingly, both serum and urine protein electrophoresis with immunofluorescence failed to demonstrate a monoclonal spike or clonal light chains. Serum free light chains demonstrated an elevated serum Kappa free light chain concentration at 32.1 mg/dL (reference range = 0.33-1.94 mg/dL) and a normal Lambda free light chain concentration at 1.35 mg/dL (reference range = 0.57-2.63 mg/dL) along with an imbalanced Kappa/Lambda free light chain ratio of 23.8. A bone marrow biopsy with flow cytometry studies were performed and surprisingly showed a low-grade B-cell lymphoma with a prominent histiocytic reaction (Figure 2). Subsequently, she underwent a lymph node biopsy, which revealed grade 3B follicular lymphoma (Figure 3). Further staging was performed with positron emission tomography, which showed diffuse patchy uptake within the proximal appendicular and axial skeleton in addition to increased uptake of the large lytic lesion of the skull. The patient was treated with aggressive hydration and Zoledronate with resolution of her hypercalcemia and acute renal injury. R-CHOP chemotherapy was later initiated with significant improvement of her other presenting symptoms.

Figure 1.

Skull radiographs.

Figure 2.

Bone marrow biopsy.

Figure 3.

Right inguinal lymph node biopsy.

Discussion

Hypercalcemia in the setting of B-cell lymphoma can result from various mechanisms. Malignancy-associated hypercalcemia is usually categorized into calcitriol-mediated hypercalcemia, PTHrP-induced hypercalcemia, and local osteolytic hypercalcemia.^1,2 In our patient, it seems that the main cause of hypercalcemia was mainly increased calcitriol production by the malignant lymphoma cells. However, the increased ACE serum activity and the finding of granuloma formation by epithelioid histiocytes may suggest that these activated lymphoma-neighboring histiocytes may also be contributing to our patient’s hypercalcemia.

B-cell lymphomas rarely present with hypercalcemia, renal failure, and lytic bone lesions, which are usually characteristic for multiple myeloma. ³ Negative serum and urine protein electrophoresis in the setting of hypercalcemia, lytic bone lesions, and renal failure should always prompt physicians to consider alternative diagnoses such as lymphoma. Differentiation between these 2 conditions cannot be made on the basis of imaging or general laboratory studies. Bone marrow biopsy and lymph node sampling is always necessary to make the final diagnosis.