Introduction
Waldenström macroglobulinemia (WM) is a rare, indolent, lymphoproliferative disorder that represents 1% to 2% of all non-Hodgkin lymphomas (NHL) [1]. It is pathologically defined as lymphoplasmacytic lymphoma (LPL) by the World Health Organization and is characterized by bone marrow infiltration with clonal lymphoplasmacytic cells and IgM monoclonal gammopathy, although non-IgM secreting lymphoplasmacytic lymphomas have also been described [2, 3]. Lytic bone lesions are rare in WM/LPL and are often used a differentiating clinical feature between WM/LPL and multiple myeloma (MM), particularly IgM myeloma. In a large study series of 37 patients, Schuster et al. used strict defining criteria for IgM myeloma to make a clear distinction from WM/LPL since the approach to their treatment and prognosis varies significantly. The inclusion criteria considered were the presence of IgM monoclonal protein and ≥10% plasma cells in the bone marrow biopsy in addition to the characteristic lytic bone lesions with or without the most common cytogenetic abnormality of IgM myeloma i.e., translocation t(11;14). This study did not include patients based on non-specific clinical features of myeloma such as the presence of anemia, hypercalcemia, and renal failure or their immunophenotype [4-7]. However, lytic bone lesions in WM/LPL have been reported with little guidance on management. Rothschild et al documented in their clinical case study that WM/LPL has a combination of features of other hematologic malignancies such as myeloma and leukemia on both macroscopic and radiologic examination of osteolytic lesions. The lytic lesions of WM were either sharp spheroid lesions with effaced edges or abundant coalescing holes/pits with smooth edges and were identifiable from the numerous frontally resorptive non-spheroid leukemic lesions and the pit less although spheroid lesions of MM [8]. This is in contrast with MM, which tends to show four different forms of destructive bone changes on imaging studies- single expansile plasmacytoma, disseminated punched-out lytic lesions, diffuse skeletal osteopenia, or osteosclerosis [9, 10]. However, the biology of these differences in bone lesions between MM and WM/LPL are poorly understood. In a study by Papanikolaou et al, focal lytic bone disease was evident in 17 to 24% of WM cases when investigated retrospectively using either MRI (magnetic resonance imaging) or PET-CT (positron emission tomography-computed tomography) imaging, respectively [11]. Consequently, multiple studies have substantiated this rather unusual presentation in WM/LPL, while some even reported improvement of lytic lesions with treatment [12-16].
There is a paucity in the literature as to whether patients with WM/LPL and lytic bone lesions should be treated with chemoimmunotherapy or novel agents and whether bone strengthening agents should be used. A consensus panel from the 10th International Workshop on WM has updated both first line and salvage treatment recommendations. The preferred primary therapy options for symptomatic patients with WM include chemoimmunotherapeutic combination regimens of rituximab with alkylating agents (i.e., bendamustine, cyclophosphamide) and proteasome inhibitors (i.e., bortezomib) or with Bruton’s tyrosine kinase (BTK) inhibitors like ibrutinib. Treatment options need to be customized according to the individual patient’s clinical presentation and genomic features [17-20]. Studies for antiresorptive agents in WM/LPL are lacking, albeit many preclinical and randomized control studies of bisphosphonates and RANKL (receptor activator of nuclear factor-kappa B ligand) inhibitors in MM have demonstrated not only reduction of bone complications but potential anti-MM effects as well [21]. Herein we describe a case of LPL with lytic bone lesions who was treated with rituximab, cyclophosphamide, and dexamethasone and had achieved a CR with complete resolution of lytic bone lesions on PET-CT.