Diagnostic challenges in multiple myeloma: A case series of atypical neurological, renal, and skeletal presentations

Abstract

Multiple myeloma (MM) is a clinically heterogeneous plasma-cell malignancy in which reliance on conventional 
diagnostic markers, including CRAB features and serum protein electrophoresis, may contribute to delayed or missed diagnosis. This case series describes four patients presenting with atypical, organ-predominant manifestations that obscured early recognition of MM. Presentations included non-compressive conus medullaris syndrome due to diffuse vertebral marrow infiltration, nephrotic syndrome secondary to Amyloid Light chain (AL) amyloidosis, delayed diagnosis of kappa light-chain myeloma with progressive osteolytic disease despite initially non-diagnostic monoclonal studies, and true non-secretory myeloma identified during evaluation for acute infection. In two cases, initial serum monoclonal protein studies were negative, contributing to diagnostic delay. Contemporary evidence emphasizes the need for early integration of serum-free light-chain assays, advanced imaging, and bone marrow evaluation in patients with high clinical suspicion, even when classical features are absent.