POEMS syndrome: An elusive diagnosis
Authors: Jithma P. Abeykoon, Wilson I. Gonsalves, Jennifer Oliveira, Prashant Kapoor
Journal: American Journal of Hematology (2017)

A 61-year-old female, with lower-extremity paresthesias and weakness of 9-month duration, was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Initial evaluation revealed bilateral foot drop, areflexia, sensorimotor neuropathy with a demyelinating component, an elevated cerebrospinal fluid protein, leukocytosis, polycythemia and thrombocytosis, without JAK2 V617F mutation. CT scans identified sclerotic bone lesions (Figure 1A) and marrow biopsy demonstrated clusters of atypical megakaryocytes (Figure 1B). Karyotyping revealed translocation (9;22) in 1/50 cells, without additional structural abnormalities. Morphological features of chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia were absent. Serum immunofixation was not performed, but the other monoclonal protein studies were unremarkable. Although a diagnosis of CML was entertained, no CML-directed treatment was initiated. Despite 3 months of intravenous immunoglobulin for presumed CIDP, her symptoms progressed. Repeat monoclonal protein studies, 25 months later, showed IgA lambda only on serum immunofixation, with normal free light-chains. Characteristic bone marrow histopathologic and skeletal radiographic findings associated with POEMS syndrome. (A) Widespread sclerotic lesions throughout the spine and pelvis (arrow). (B) Megakaryocytic hyperplasia (arrows, [more than 6 megakaryocytes in HPF]), atypia with mild hyperchromia. (C) Lambda restricted plasma cells with partial rimming around lymphoid aggregates (arrows). [Color figure can be viewed at wileyonlinelibrary.com] Upon referral to our institution, POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes) syndrome was diagnosed as acrocyanosis, hypertrichosis and markedly elevated vascular endothelial growth factor (VEGF) levels (1177 pg/mL [normal: 31–86 pg/mL]) were evident. Mild hyperprolactinemia, subclinical hypothyroidism and hyperparathyroidism were also noted. Lymphoid aggregates rimmed by lambda light-chain restricted plasma cells (Figure 1C) were identified upon review of the previously performed marrow biopsy. CML was ruled out as rare Philadelphia chromosomal rearrangement with BCR-ABL fusion transcript in the absence of other chromosomal abnormalities, clinical symptoms and morphologic findings of CML, has been documented in healthy individuals.1 An echocardiogram showed left ventricular enlargement (ejection fraction 34%) with an apical thrombus and pulmonary function tests revealed a restrictive lung disease. Cyclophosphamide and warfarin were initiated. Poor cardiopulmonary function precluded autologous stem-cell transplantation. Within three months of diagnosis the patient died in the setting of worsening cardio-renal function. Peripheral neuropathy, lambda monoclonal gammopathy (mandatory major criteria) and skin changes as manifested by acrocyanosis (minor criterion)2 should have raised the suspicion of POEMS syndrome at initial presentation. Additionally, sclerotic bone lesions and elevated VEGF levels (both major criteria) aided in establishing the diagnosis.2 Thrombocytosis, erythrocytosis, endocrinopathy and restrictive lung disease provided corroborating evidence. The clinical course of an “atypical” CIDP, unresponsive to therapy, further heightened the suspicion of POEMS syndrome. Unique features, including megakaryocytic hyperplasia and lambda-restricted plasma cell rimming around lymphoid aggregates are frequently observed in POEMS syndrome.3 POEMS syndrome is a rare paraneoplastic plasma-cell disorder with myriad clinical manifestations which are often subtle and overlooked by clinicians in early stages.4 Misinterpretation of the diagnostic tests contributes to making the diagnosis more elusive. Delayed diagnosis can adversely impact both the quality of life and outcome of the patients as illustrated by our report.