Diffuse Large B-cell Lymphoma Presenting with Hypercalcemia and Multiple Osteolysis

Abstract

Osteolysis and hypercalcemia are observed in 5-15%, and 10%, respectively, of malignant lymphoma patients during their clinical course. However, both osteolysis and hypercalcemia are uncommon at onset of the disease. We encountered a 24-year-old male non-Hodgkin's lymphoma patient who had multiple osteolytic lesion from the onset of the disease and repeated episodes of hypercalcemia during the clinical course. The patient died with refractory disease. We studied the expression of chemokines which might affect bone resorption using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Increased expressions of MIP-1alpha, MIP-1beta and RANKL, which are osteoclast-activating factors, were observed in the RNA derived from the patient's lymphoma cells. The secretion of osteoclast-activating factors such as MIP-1alpha by the tumor cells (and/or bone marrow stromal cells) might be involved in the etiology of osteolysis and hypercalcemia in some malignant lymphoma cases.

Proinflammatory chemokine gene expression influences survival of patients with non-Hodgkin’s lymphoma

“…This chemokine is involved in antigen-dependent B-cell activation [36]. In our study, we did not notice differences in CCL4 expression between lymphoma and reactive lymph nodes.…”

“…The role of CCL3 in nHL has not been described yet. Matsuhashi et al presented a case report of a patient with diffuse B-cell lymphoma, who demonstrated strong osteolytic changes in bones at the diagnosis of lymphoma [36]. Additionally increased CCL3 expression was present, which could explain massive osteolysis.…”

Refractory hypercalcemia: Unusual presentation for diffuse large B cell lymphoma

“…Laboratory tests revealed white cell count of 5,800/mm 3 Figure 1). On further investigation, parathyroid hormone (PTH) level was suppressed at 4 pg/ml, PTH-related peptide (PTHrP) was normal with value of 1.9 pmol/L.…”

“…[9] Hypercalcemia can occur occasionally in DLBCL and few cases of DLBCL have been reported to be associated with refractory hypercalcemia [10,11] but hypercalcemia at initial presentation is unusual. [3] There have been few reported cases of hypercalcemia in DLBCL as a result of increased PTHrP which activates osteoclastic bone resorption and release of calcium and phosphate from bone. It occurs via increased osteoblast receptor activator of nuclear factor κB ligand (RANKL) expression and activation of the receptor activator of nuclear factor κB (RANK) located on osteoclast precursors.…”

“…[2] Patients with DLBCL can occasionally develop hypercalcemia due to various factors but hypercalcemia at onset of disease is uncommon. [3] We present a case of elderly female who presented with refractory hypercalcemia, workup of which led to the diagnosis of DLBCL.…”