POEMSsyndrome: 2017 Update on diagnosis, risk stratification, and management

Abstract

Disease Overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome.Diagnosis: The diagnosis of POEMS syndrome is made with 3 of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria.Risk Stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy Risk-Adapted Therapy: For those patients with a dominant sclerotic plasmacytoma, first-line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3-6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low-dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. The benefit of anti-VEGF antibodies is conflicting. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.

POEMS neuropathy: optimising diagnosis and management

“…Patients with bone marrow involvement on bone marrow biopsy, or three or more plasmacytomas, are considered to have systemic disease; two or fewer plasmacytomas is considered as focal disease. Figure 4 provides a treatment algorithm that depends on the extent of disease 27…”

51-year old man with tingling, burning and progressive limb weakness

“…Bardwick coined the acronym POEMS in 1980 21. Two-thirds of patients with POEMS syndrome have clonal plasma cells on an iliac crest biopsy 22. Such patients have distinctive bone marrow histopathology findings, including the constellation of lambda-restricted monoclonal gammopathy, plasma cell rimming around lymphoid aggregates and megakaryocytic hyperplasia 23.…”

“…Such patients have distinctive bone marrow histopathology findings, including the constellation of lambda-restricted monoclonal gammopathy, plasma cell rimming around lymphoid aggregates and megakaryocytic hyperplasia 23. The remainder present with solitary or multiple plasmacytomas with a normal bone marrow 22. The monoclonal protein is usually IgG or IgA lambda light-chain type.…”

“…Table 3 gives the diagnostic criteria for POEMS syndrome 22. This patient fulfilled both the mandatory major criteria, one of the other major criteria (sclerotic bone lesion), three of the minor criteria (organomegaly, extravascular volume overload and skin changes) and supportive criteria (weight loss and clubbing) for the syndrome.…”

“…11%–30% of patients with POEMS who have a documented clonal plasma cell disorder, also have Castleman’s disease 22. This is a rare lymphoproliferative disorder characterised by lymphoid hyperplasia and capillary proliferation.…”