Aggressive Seropositive Rheumatoid Arthritis With Diffuse Osteolytic Bone Lesions, Hypercalcemia, and Lymphadenopathy Masquerading as Hematologic Malignancy: A Case Report.

Aggressive seropositive rheumatoid arthritis (RA) typically manifests with marginal joint erosions and periarticular osteopenia but rarely presents with diffuse osteolytic lesions mimicking malignancy. A 65-year-old woman presented with subacute back pain and incidentally discovered hypercalcemia (calcium 12.7 mg/dL). Imaging revealed multifocal lytic lesions of the axial and appendicular skeleton highly suggestive of multiple myeloma or metastatic disease, along with supraclavicular lymphadenopathy. Extensive evaluation including bone marrow biopsy demonstrated polyclonal plasmacytosis without evidence of hematologic malignancy. Lymph node excision revealed reactive follicular hyperplasia. Subsequent rheumatologic assessment identified symmetric inflammatory polyarthritis, rheumatoid nodules, rheumatoid factor 191 IU/mL, and anti-cyclic citrullinated peptide (anti-CCP) antibodies 2630 U/mL, establishing the diagnosis of aggressive seropositive RA. Bursectomy of a right elbow mass confirmed necrobiotic granulomatous inflammation consistent with a rheumatoid nodule. Treatment with methotrexate, leflunomide, and rituximab led to resolution of hypercalcemia, substantial improvement in joint symptoms, and radiographic stabilization of lytic lesions. This case highlights how RANKL-mediated osteoclast activation and anti-CCP antibody-driven bone resorption can, in rare instances, produce malignancy-mimicking diffuse osteolysis and hypercalcemia, and underscores the importance of considering RA in the differential diagnosis of diffuse lytic bone lesions. The diagnosis was supported by fulfillment of 2010 ACR/EULAR classification criteria, histologic confirmation of rheumatoid nodules, and dramatic response to disease-modifying antirheumatic therapy.