Bhatti Khazra, Nazir Aqsa, Ostergaard Simon, Schejbel Lone, Norgaard Peter, Gjerdrum Lise M R, Moghaddas Mahnaz, Nielsen Torsten H, Munksgaard Lars, Pedersen Lars M
Institute of Science and Environment, Roskilde University, Roskilde, Denmark.
Department of Pathology, Zealand University Hospital, Roskilde, Denmark.
J Hematol. 2022 Dec;11(6):233-239. doi: 10.14740/jh1073. Epub 2022 Dec 30.
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 and 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 -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.
骨受累是恶性淋巴增殖性疾病患者罕见的结外表现，在华氏巨球蛋白血症（WM）患者中也被视为罕见事件。然而，此前尚未报道过其实际患病率。我们描述了一例不寻常的WM患者，初诊时出现下背部疼痛和局灶性骨病变。磁共振成像（MRI）显示多处椎体骨折。正电子发射断层扫描（PET）仅检测到淋巴结变化，无病理性骨骼相关代谢活性。淋巴结和骨髓活检结合免疫球蛋白M（IgM）M成分确诊为WM。使用针对淋巴瘤的包含59个在淋巴肿瘤中反复突变基因的靶向panel进行的下一代测序（NGS）分析显示 和 基因发生突变。在接受利妥昔单抗和苯达莫司汀治疗后，患者达到部分缓解且疼痛缓解。疾病稳定3年后，股骨颈基底部出现自发性头下型骨折和新的椎体压缩性骨折。全身低剂量计算机断层扫描（WB-LDCT）和骨密度（双能X线吸收法（DEXA））扫描显示明显的骨质减少。植入髋关节假体后，对取出的髋关节检查显示有克隆性淋巴浆细胞浸润。我们的病例证实必须意识到WM患者的骨受累可作为一种罕见表现出现。有趣的是，弥漫性大B细胞淋巴瘤中的 -突变（MCD）基因型以结外受累为特征，在本病例中可能也参与了骨骼相关疾病的发病机制。作为对这一不寻常病例的后续研究，我们基于丹麦淋巴瘤登记处（LYFO）对2000 - 2020年期间的全国人口进行了分析。该登记处研究纳入了2459例WM和淋巴浆细胞淋巴瘤患者队列。我们的数据显示，1.75%的成年WM患者在诊断时出现原发性骨受累。据我们所知，这是首次在大型全国性队列中报告骨骼相关疾病的患病率，并将骨受累定义为WM中极为罕见的事件。
