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.