A plasma cell dyscrasia fable: AESOP and POEMS presenting concurrently
Sept. 7, 2016
There is a moral to every fable. In this commentary, it is that VEGF (vascular endothelial growth factor) may have multiple cutaneous manifestations, even in the same patient.
Rongioletti et al presented the case of a 70 year-old man with an IgA monoclonal gammopathy, paresthesias, and the simultaneous appearance of hyperpigmented plaques of the chest (interestingly in a Blaschkoid distribution) demonstrating sclerosis and vascular proliferation microscopically, an erythematous-violaceous plaque of the posterior neck/upper back which revealed “cutaneous mucinous angiomatosis” histologically, and hemangiomas with a “glomeruloid” pathology. His systemic work up demonstrated symmetrical demyelinization on EMG; CT scan with splenomegaly and two osteosclerotic lesions that corresponded to the two skin plaques; a lymph node biopsy revealing the plasmacytic variant of Castleman disease; and a bone marrow biopsy with < 10% plasma cell. The patient was lost to follow-up after receiving a recommendation for radiation to the osteosclerotic lesions (1).
VEGF belongs to a family of homodimeric proteins consisting of at least 6 members: VEGF-A (VEGF), VEGF-B, VEGF-C, VEGF-D, VEGF-E and Placental growth factor (PlGF). VEGF, the most abundant form, plays important roles in proliferation, migration and activation of endothelial cells as well as in promotion of permeability and fenestration of blood vessels. VEGF-C and -D are important for lymphangiogenesis; VEGF-B has a role in embryonic angiogenesis; and PlGF is a critical component of pathological angiogenesis. VEGF increases after injury and with inflammation. This results in a release of cytokines, such as tumor necrosis factor alpha (TNF-α), IL-1α, and IL-1β. This stimulates macrophages to release mediators, such as TGF-β1, which suppress the inflammatory response and initiate the repair process (2). The angiogenesis and fibrosis noted in the case report presented herein may certainly be explained by the presence of VEGF and its induction of the other cytokines.
The fact that this patient developed cutaneous lesions of POEMS (Polyneuropathy, Organomegaly, Endocrine, Monoclonal gammopathy, and Skin signs) and AESOP (Adenopathy and Extensive Skin patch Overlying a Plasmactyoma) is not surprising if viewed as a manifestation of an excess production of VEGF from the plasma cell dyscrasia.
Therapy is directed to the underlying plasmacytoma, as summarized in the abstract by Dispenzieri (3):
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.
1. Rongioletti F, et al. Skin manifestations of POEMS and AESOP in the same patient revealing plasma cell dyscrasia. J Cutan Pathol 2016 August 17 [Epub ahead of print].
2. Hu K, Olsen. BR. The roles of vascular endothelial growth factor in bone repair and regeneration. Bone 2016; 91: 30-8.
3. Dispenzieri A. POEMS syndrome: Update on diagnosis, risk-stratification, and management. Am J Hematol 2015; 90: 951-62.
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