Abstract Background Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder characterized by the presence of a monoclonal protein (M-protein) without features of multiple myeloma or end-organ damage. Sarcoidosis, a multisystem granulomatous disease of unclear etiology, may rarely coexist with MGUS. Fewer than 30 cases have been reported in the literature, raising questions about a possible immunologic link between the two entities. Both conditions involve immune dysregulation—sarcoidosis with chronic antigenic stimulation and MGUS with clonal plasma cell proliferation—which may share overlapping pathogenic pathways. Case Presentation A 79-year-old man with a history of coronary artery disease and pericardial window placement presented with progressive bilateral lower extremity numbness and paresthesia over one year. He denied diabetes, alcohol use, or toxin exposure. Initial laboratory evaluation revealed normal vitamin levels and HbA1c. Electromyography demonstrated a length-dependent axonal sensorimotor polyneuropathy. Serum protein electrophoresis identified an IgG kappa monoclonal spike, and immunofixation confirmed monoclonal gammopathy. Bone marrow biopsy showed 3% plasma cells with hyperdiploidy and gains in chromosomes 9, 11, and 15—findings consistent with MGUS rather than multiple myeloma. Subsequent PET/CT imaging revealed bilateral hilar and mediastinal lymphadenopathy. Endobronchial ultrasound-guided (EBUS) biopsy demonstrated non-caseating granulomas without evidence of malignancy, confirming pulmonary sarcoidosis. Rheumatologic and infectious workups were negative. The patient was started on a corticosteroid taper (prednisone 40 mg daily, gradually reduced) and trimethoprim-sulfamethoxazole prophylaxis. Over the following months, his respiratory symptoms and neuropathy improved, with radiographic resolution of lymphadenopathy. His MGUS remained stable on serial monitoring, with no increase in M-protein or plasma cell burden. Discussion and Conclusion While the coexistence of sarcoidosis and MGUS may be coincidental, several reports suggest that chronic antigenic stimulation in sarcoidosis could trigger monoclonal plasma cell proliferation. Conversely, MGUS-related immune dysregulation may promote granulomatous inflammation. Systemic manifestations such as hypercalcemia, neuropathy, and cytopenias may overlap in both disorders. This case underscores the importance of comprehensive evaluation in patients with concurrent granulomatous and monoclonal findings and highlights the need for continued surveillance given the lifelong risk of MGUS progression. This abstract is funded by: None
Sidhu et al. (Fri,) studied this question.