Rare Lymphoma Revealed by a Lumbar Fracture in a 77-Year-Old Man

A 77-year-old man walked into a hospital in Suzhou, China, in January 2026 with a year of unexplained low back pain that had worsened over the previous month. Computed tomography revealed something alarming: the cortical bone of his L1 and L2 vertebrae had been disrupted, yet his bone mineral density did not meet the criteria for osteoporosis. There was no trauma to explain the damage. What followed was a diagnostic journey that ended in an exceptionally rare conclusion — Waldenström macroglobulinemia, a slow-growing B-cell lymphoma, presenting as an osteolytic pathological fracture of the lumbar spine.

Waldenström macroglobulinemia, or WM, is characterized by lymphoplasmacytic infiltration of the bone marrow and elevated serum monoclonal immunoglobulin M. It accounts for roughly 1% to 2% of all hematologic malignancies, with an annual incidence of about three per million people. Clinically overt osteolytic lesions and pathological fractures are uncommon in this disease, and their presence has traditionally been considered a hallmark of multiple myeloma instead. Cases in which a vertebral fracture is the very event that leads to the WM diagnosis remain rare, which is precisely why the medical team at the First Affiliated Hospital of Soochow University documented their patient in a case report published in Frontiers in Medicine.

The diagnostic work-up began with the knowledge that skeletal metastasis from solid tumors is the most frequent cause of osteolytic vertebral fracture in elderly patients. Serum tumor markers, including CEA, AFP and PSA, came back within reference ranges, making metastatic carcinoma less likely. Serum protein electrophoresis then showed a prominent M-spike in the gamma region, and immunofixation electrophoresis identified a single narrow band in the IgM lane with intense staining in the kappa lane. Quantitative testing revealed markedly elevated serum IgM at 23.10 grams per liter, against a reference range of 0.30 to 2.20 grams per liter. Serum free kappa light chain was 416.94 milligrams per liter, with a free kappa-to-lambda ratio of 11.659, pointing to a monoclonal IgM-kappa paraprotein. Notably, an IgM paraprotein rather than an IgG or IgA one is atypical for the pathological fractures associated with multiple myeloma.

Contrast-enhanced MRI of the lumbar spine added another clue: annular enhancement at the fracture margins, a slight departure from the typical diffuse vertebral infiltration seen in most multiple myeloma-related pathological fractures. The patient then underwent internal fixation surgery for the fracture, during which surgeons harvested a partial tissue biopsy from the fracture site under C-arm fluoroscopic guidance. Histopathological examination of that specimen revealed bone sequestra and marrow tissue containing lymphoid cells and plasma cells, with plasma cells accounting for roughly 6% of the cellularity and no sheets of atypical or immature plasma cells. Critically, no light-chain restriction was demonstrated on this decalcified specimen — the fracture-site biopsy proved non-diagnostic.

The definitive answer came after the patient was referred to hematology. A bone marrow aspirate was hypercellular, with lymphocytes accounting for 24% of nucleated cells, most showing irregular outlines with pseudopod-like cytoplasmic projections, alongside scattered plasma cells including binucleated forms. Combined with the monoclonal IgM-kappa paraprotein, a CD5-negative, CD10-negative clonal B-cell population and the absence of clonal plasma cells, the diagnosis was considered most consistent with WM, and IgM myeloma was excluded. Two important gaps remained: a trephine histology report describing the infiltration pattern was not available, and MYD88 L265P mutation testing was not performed. The patient was started on zanubrutinib, a next-generation Bruton’s tyrosine kinase inhibitor.

To place this case in context, the authors searched PubMed from inception to 1 July 2026 for reports of WM or lymphoplasmacytic lymphoma with osteolytic bone lesions or pathological fractures providing individual patient data. Of 105 records screened, twelve published cases met the criteria. These span nearly five decades, from a 1975 report of lytic osseous lesions treated with radiotherapy and melphalan plus prednisone, to a 2022 case in which a 72-year-old man’s L1 compression fracture was the first symptom of WM. Only one tabulated patient, reported in 2021, had non-IgM lymphoplasmacytic lymphoma with an IgA-lambda paraprotein. None of the tabulated patients received a BTK inhibitor.

The epidemiology of skeletal involvement in WM depends heavily on how patients are imaged. In a Danish nationwide population-based cohort of 2,459 patients with WM or lymphoplasmacytic lymphoma, primary bone involvement at diagnosis was recorded in only 1.75%. By contrast, a single-centre series from the University of Arkansas for Medical Sciences, in which patients were systematically imaged, reported focal bone disease in approximately 17% to 24% on MRI and PET-CT, respectively. More recently, osseous involvement at diagnosis was found in 18% of 112 patients with lymphoplasmacytic lymphoma or WM, including pathological fractures in four patients, and it did not significantly affect response or survival. Clinically overt pathological fractures remain uncommon, but subclinical skeletal involvement is probably under-recognized when advanced imaging is not performed routinely.

The closest comparison to the present case is the 2022 report by Lin and colleagues. That patient also presented with an L1 compression fracture as the first symptom of WM, with an IgM-lambda paraprotein of 6.17 grams per liter, CD5-negative CD10-negative clonal B cells, and a detected MYD88 L265P mutation, making his diagnosis better supported by molecular data. The new case differs in several respects. Lin’s patient had lumbar osteoporosis with a T-score of minus 2.7, which may have contributed to the fracture, whereas the Suzhou patient’s bone mineral density was only in the osteopenic range. The new lesion involved two contiguous vertebrae with disc involvement and spinal instability, requiring open posterior screw fixation rather than vertebroplasty or kyphoplasty. The paraprotein burden was also substantially higher, and unlike Lin’s patient, who declined systemic therapy, this patient received first-line zanubrutinib.

The authors openly grappled with an uncomfortable possibility: because the fracture-site specimen showed no clonal infiltrate, could the fracture be coincidental rather than caused by WM? Several findings argue for WM involvement. The osteolytic destruction with cortical disruption of two vertebrae is not a feature of osteoporotic fractures, and there was no history of trauma. Metastatic carcinoma and myeloma were excluded as far as possible, leaving WM as the only neoplasm identified. WM infiltrates the bone marrow diffusely or interstitially in about 90% of cases, and spinal MRI detects vertebral marrow involvement in more than 90% of patients, making lumbar involvement highly probable given iliac marrow involvement. The fracture-site specimen also showed a higher plasma-cell fraction than the iliac aspirate, with a kappa-predominant pattern concordant with the serum paraprotein. Still, the specimen was taken from the fracture line, where necrosis, hemorrhage and repair predominate, and only a plasma-cell and carcinoma panel was applied. Direct involvement therefore remains probable rather than proven.

Postoperative CT confirmed stable instrumentation, and follow-up at one and three months showed no new fractures or tumor infiltration, with the patient remaining in stable condition on zanubrutinib. Longer follow-up is needed to determine whether the drug confers skeletal benefit in WM, though BTK inhibition suppresses osteoclast differentiation in preclinical models and remineralization of lytic lesions has been reported with ibrutinib in small lymphocytic lymphoma. The practical lesson for clinicians is concrete: when WM or another lymphoproliferative disorder is suspected before surgery, a lesion-directed biopsy away from the fracture line, with B-cell immunohistochemistry, light-chain studies and, where possible, MYD88 L265P testing, should be planned — because fracture-site biopsies may come back empty-handed exactly when the answer matters most.

Subject of Research: A rare case of Waldenström macroglobulinemia presenting as an osteolytic lumbar vertebral fracture, with a literature review of similar reported cases.

Article Title: Waldenström macroglobulinemia presenting with lumbar vertebral fracture as the initial symptom: a rare case report and literature review

Article References: Xu, L., Shen, C., Mi, J., Hu, Z., Sheng, Q., Zhu, P., Song, Z., & Zhou, F. (2026). Waldenström macroglobulinemia presenting with lumbar vertebral fracture as the initial symptom: a rare case report and literature review. Frontiers in Medicine, 13, Article 1947916. https://doi.org/10.3389/fmed.2026.1947916

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1947916

Keywords: Waldenström macroglobulinemia, lymphoplasmacytic lymphoma, pathological fracture, lumbar vertebrae, monoclonal IgM, multiple myeloma, bone marrow biopsy, zanubrutinib, BTK inhibitor, osteolytic lesions, case report, differential diagnosis