When Foot Drop Tells a Bigger Story: POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Plasma Cell Disorder, and Skin Changes) Syndrome Revealed by Femoral Plasmacytoma

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome is a rare multisystem disorder caused by a monoclonal plasma cell dyscrasia, often presenting with a constellation of neuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. Its initial manifestations frequently overlap with more common causes of chronic progressive neuropathy, such as chronic inflammatory demyelinating polyneuropathy (CIDP) and diabetic or paraproteinemic neuropathies, which can obscure the diagnosis and delay definitive treatment. We report a 45-year-old male with progressive bilateral lower-limb distal-predominant weakness and numbness over three months, in whom the clinical picture and cerebrospinal fluid findings initially supported a working diagnosis of CIDP, despite coexisting thrombocytosis, skin hyperpigmentation, and newly diagnosed diabetes mellitus. Electroneuromyography showed severe sensorimotor mixed axonal and demyelinating neuropathy, and cerebrospinal fluid analysis demonstrated albuminocytologic dissociation, further reinforcing the initial impression of CIDP and illustrating the diagnostic conflict. However, serum studies identified an IgA lambda monoclonal protein, and fluorodeoxyglucose positron emission tomography revealed a solitary, metabolically active lesion in the right femur, raising suspicion for an underlying plasma cell dyscrasia rather than isolated inflammatory neuropathy. Histopathological examination of the femoral lesion confirmed a lambda-restricted plasmacytoma with minimal bone marrow plasma cell infiltration, fulfilling the diagnostic criteria for POEMS syndrome in conjunction with polyneuropathy, monoclonal plasma cell disorder, plasmacytoma, thrombocytosis, and skin changes. This case highlights the importance of considering POEMS syndrome in patients with atypical or treatment-refractory CIDP-like presentations and systemic features, and it underscores how a stepwise, multidisciplinary diagnostic approach incorporating electrophysiology, advanced imaging, and targeted histopathology can resolve overlapping differentials and guide timely, targeted therapy.