POEMS Syndrome: An Elusive Diagnosis

Jithma P Abeykoon1 , Wilson I. Gonsalves1,2 , Jennifer Oliveira3 and Prashant Kapoor1,2

1
Department of Internal Medicine, 2Division of Hematology, 3Division of Hematopathology
Mayo Clinic, Rochester, MN, USA
E-mail: kapoor.prashant@mayo.edu

Corresponding author
Prashant Kapoor, MD, FACP
Assistant Professor of Medicine and Oncology, Mayo Clinic,
Division of Hematology
200 First Street SW, Rochester, MN 55905
Phone: 507-538-0591, Fax: 507-266-4972

Running head: POEMS Syndrome

Disclosure: Authors have nothing to disclose
Manuscript: 436 words, 1 image and 4 references

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
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‘Accepted Article’, doi: 10.1002/ajh.24845

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 American Journal of Hematology Page 2 of 6

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 (Image 1A) and marrow

biopsy demonstrated clusters of atypical megakaryocytes (Image 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.

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 (Image 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

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Page 3 of 6 American Journal of Hematology

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.

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 American Journal of Hematology Page 4 of 6

REFERENCE
1. Bose S, Deininger M, Gora-Tybor J, et al. The presence of typical and atypical BCR-ABL fusion genes in leukocytes of
normal individuals: biologic significance and implications for the assessment of minimal residual disease. Blood 1998;92:3362-
3367.
2. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the
diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538-548.
3. Dao LN, Hanson CA, Dispenzieri A, et al. Bone marrow histopathology in POEMS syndrome: a distinctive combination
of plasma cell, lymphoid, and myeloid findings in 87 patients. Blood 2011;117:6438-6444.
4. Warsame R, Yanamandra U, Kapoor P. POEMS Syndrome: an Enigma. Current hematologic malignancy reports
2017;12:85-95.

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Page 5 of 6 American Journal of Hematology

Image 1: 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).

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