ABSTRACT
Bone involvement is a rare extranodal manifestation in patients with malignant lymphoproliferative diseases and has also been noted as a rare event in patients with Waldenstrom macroglobulinemia (WM). However, the actual prevalence has not been previously reported. We describe an unusual case of a patient with WM who presented with lower back pain and focal bone lesions at initial diagnosis. Magnetic resonance imaging (MRI) revealed multiple vertebral fractures. Positron emission tomography (PET) detected only nodal changes without pathological skeletal-related metabolic activity. Lymph node and bone marrow biopsies combined with an immunoglobulin M (IgM) M component revealed the diagnosis of WM. A next-generation sequencing (NGS) analysis using a targeted lymphoma panel of 59 recurrently mutated genes in lymphoid neoplasms showed mutations in the MYD88 and CD79B genes. After treatment with rituximab and bendamustine, the patient achieved a partial remission and pain relief. After 3 years of stable disease, a spontaneous subcapital fracture at the base of the femoral neck and new vertebral compression fractures occurred. Whole-body low-dose computed tomography (WB-LDCT) and bone density (dual energy X-ray absorptiometry (DEXA)) scan revealed marked osteopenia. After insertion of a hip prosthesis, examination of the removed hip showed infiltration of clonal lymphoplasmacytic cells. Our case confirms that one must be aware that bone involvement in patients with WM can occur as a rare manifestation. Interestingly, the MYD88/CD79B-mutated (MCD) genotype in diffuse large B-cell lymphoma is characterized by extranodal involvement and may also be involved in the pathogenesis of skeletal-related disease in the present case. As a follow-up to this unusual case, we have carried out an analysis based on the Danish Lymphoma Registry (LYFO) covering the entire national population in the period 2000 - 2020. The registry study included a cohort of 2,459 patients with WM and lymphoplasmacytic lymphoma. Our data revealed that primary bone involvement at diagnosis occurs in 1.75% of adults with WM. To the best of our knowledge, this is the first report of the prevalence of skeletal-related disease in a large nationwide cohort and defines bone involvement as an exceedingly rare event in WM.