Immune-mediated multisystem injury associated with monoclonal gammopathy of clinical significance: a case report.

Monoclonal gammopathy of clinical significance (MGCS) refers to disorders in which small B-cell or plasma-cell clones produce pathogenic monoclonal immunoglobulins that cause organ injury independent of tumor burden. Because the clinical spectrum is heterogeneous and diagnostic criteria remain evolving, MGCS is frequently underrecognized, particularly when organ manifestations precede detectable paraproteinemia. We report a 52-year-old man with multisystem manifestations including cutaneous xanthomatosis, inflammatory myopathy, cryoglobulinemia, and possible cardiac involvement. The patient initially presented with progressive polymyalgia, leukopenia, and yellow-brown cutaneous plaques. Immune abnormalities had been documented several years before detection of monoclonal protein. Laboratory evaluation revealed IgG-λ monoclonal gammopathy with type I cryoglobulinemia, complement consumption, and autoantibody positivity, indicating systemic immune activation. Bone marrow examination demonstrated only 1.4% λ-restricted clonal plasma cells. Skin biopsy confirmed xanthomatous infiltration, while muscle biopsy showed myopathic changes without amyloid deposition. Cardiac imaging demonstrated asymmetric septal hypertrophy with patchy late gadolinium enhancement. Treatment with bortezomib-cyclophosphamide-dexamethasone led to marked clinical improvement, including resolution of myalgia, regression of skin lesions, normalization of leukopenia, and disappearance of cryoglobulins, although low-level paraprotein persisted. This case highlights that immune-mediated organ injury may precede measurable clonal expansion in MGCS and supports the concept that pathogenic monoclonal immunoglobulins can act as immune effectors driving systemic inflammation.