Atypical Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, and Skin Changes (POEMS) Syndrome

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare paraneoplastic syndrome that occurs mostly in the context of lambda-restricted plasma cell disorders. Diagnosis is made when patients have certain disease-defining criteria. Atypical presentations of POEMS are suspected when patients do not meet those predefined diagnostic criteria.  An 82-year-old female patient was referred to the hematology clinic for persistent thrombocytosis. The patient had a history of stroke and was asymptomatic, and the clinical exam was noncontributory except for the presence of small axillary lymph nodes. Workup demonstrated a picture of an IgG kappa monoclonal gammopathy (MG), with an elevated serum free kappa light chain, a normal free lambda light chain, and an increased kappa/lambda ratio, prompting further evaluation for an underlying plasma cell disorder. Bone marrow biopsy showed plasma cell neoplasm at 20% to 30%. Both the karyotype and the plasma cell fluorescence in situ hybridization (FISH) prognosis panel were normal. Lymph node (LN) core needle biopsy showed follicular hyperplasia. Smoldering multiple myeloma (SMM) was considered. Due to the patient's clinical history, a diagnosis of atypical POEMS was entertained. Vascular endothelial growth factor (VEGF) was elevated. Electromyography (EMG) testing for sensory and motor conduction for lower limbs revealed abnormal findings aligning with subclinical polyneuropathy. This strongly favored the diagnosis of atypical POEMS. Initially, our patient was evaluated for an underlying plasma cell disorder, since the presence of monoclonal protein, monoclonal gammopathy of undetermined significance (MGUS), was the highest on the differential. When the bone marrow biopsy showed a 20% to 30% plasma cell infiltration, SMM was diagnosed. However, the presence of certain characteristic features for POEMS, including nodal enlargement and thrombocytosis, led to entertaining the differential diagnosis of POEMS. Markedly elevated serum VEGF levels further reinforced the diagnosis. Clinically absent neuropathy raised the concern for an atypical POEMS, but subsequently, EMG testing showed that the patient has subclinical polyneuropathy, which provided additional support for the diagnosis of atypical POEMS.  To meet the diagnosis of POEMS syndrome, challenging criteria should be fulfilled. Polyneuropathy and lambda-restricted are major criteria for the diagnosis of typical POEMS syndrome. In our case, the patient had a kappa-restricted variant and subclinical polyneuropathy, compounding this atypical POEMS presentation. This case report highlights the importance of a broad differential, including atypical presentations, while at the same time, highlighting the importance of early detection to ensure proper management for better outcomes.