POEMS Syndrome and Castleman Disease
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Direct answer
POEMS syndrome is a paraneoplastic plasma cell disorder with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes, driven largely by VEGF. Castleman disease is a lymphoproliferative disorder of lymph nodes with characteristic histology, classed as unicentric or multicentric. Lambda light-chain disease and sclerotic bone lesions point towards POEMS, whereas nodal histology and IL-6 activity point towards Castleman disease.
What you must remember
- POEMS mnemonic: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes, each assessed as part of the same clonal disorder.
- Diagnostic criteria: polyneuropathy and a clonal plasma cell disorder are mandatory, plus at least one major criterion (osteosclerotic lesion, Castleman disease or raised VEGF) and one minor criterion (such as organomegaly, endocrinopathy or skin changes).
- Light chain: lambda restriction is typical of POEMS, and the clonal protein is found on immunofixation even when it is faint.
- Bone lesions: POEMS shows osteosclerotic lesions, unlike the lytic lesions of classical multiple myeloma.
- Hyaline vascular Castleman: lollipop-like follicles with penetrating vessels and concentric onion-skin mantle layers; the commonest unicentric variant.
- Plasma cell Castleman: sheets of plasma cells in the nodes, more typical of multicentric disease with systemic symptoms.
- Multicentric Castleman: IL-6 driven, with fever, weight loss and anaemia; linked to HHV-8 and HIV, and treated with siltuximab (idiopathic disease) or rituximab (especially HHV-8 disease).
A stepwise approach to neuropathy with lymph nodes
The same patient may present with neuropathy, lymphadenopathy or both, so the workup is ordered around the clonal protein and the nodal histology. Each step separates the two conditions before the next test is chosen.
- Look for the neuropathy. A progressive, symmetrical polyneuropathy with enlarged lymph nodes or organs prompts a search for a plasma cell disorder.
- Confirm the clone. Serum and urine electrophoresis with immunofixation, plus serum free light chains, establish a monoclonal protein, with lambda restriction typical of POEMS.
- Image the bones. A skeletal survey with CT or MRI looks for sclerotic lesions, which favour POEMS over myeloma.
- Measure VEGF. Raised serum VEGF is a major diagnostic criterion for POEMS and also tracks disease activity.
- Biopsy the node. Excisional biopsy decides between hyaline vascular and plasma cell Castleman histology, and it rules out lymphoma.
- Test for HHV-8 and HIV. In multicentric disease, serology or PCR for HHV-8 and HIV status shapes the choice of therapy.
Where the exam tries to catch you
Exam questions pair these two diagnoses so that the discriminating clue has to be read correctly.
- Trap: Neuropathy with lymphadenopathy is labelled myeloma. Correct: sclerotic bone lesions, lambda restriction and the neuropathy define POEMS, whereas myeloma lesions are usually lytic.
- Trap: Multicentric Castleman disease is treated with excision, as in unicentric disease. Correct: multicentric disease is systemic and needs anti-IL-6 therapy or rituximab, because surgery cannot remove disease at several sites.
- Trap: Hyaline vascular histology is read as aggressive disease. Correct: it is the commonest unicentric variant, usually localised and cured by complete excision.
Frequently asked questions
What are the mandatory criteria for diagnosing POEMS syndrome?
Polyneuropathy and a clonal plasma cell disorder are the mandatory criteria for POEMS syndrome. At least one major criterion (osteosclerotic lesions, Castleman disease or raised VEGF) and at least one minor criterion (such as organomegaly, endocrinopathy or skin changes) are also required.
Which cytokine is raised in POEMS syndrome and why does it matter?
Vascular endothelial growth factor, VEGF, is raised in POEMS syndrome and contributes to fluid accumulation and skin changes. Raised serum VEGF is a major diagnostic criterion and a marker of disease activity in POEMS syndrome.
How does unicentric Castleman disease differ from multicentric Castleman disease?
Unicentric Castleman disease involves a single nodal region, is often asymptomatic and is usually cured by complete surgical excision. Multicentric Castleman disease involves several nodal regions with systemic symptoms and is treated with siltuximab or rituximab.
Which histological variant of Castleman disease is the commonest?
The hyaline vascular variant is the commonest form of unicentric Castleman disease. It shows follicles with penetrating vessels and concentric onion-skin mantle layers, whereas the plasma cell variant is more typical of multicentric disease.
Which virus is linked to multicentric Castleman disease?
Human herpesvirus 8 (HHV-8), also called Kaposi sarcoma-associated herpesvirus, is linked to a subset of multicentric Castleman disease, especially in people with HIV. Testing for HHV-8 and HIV status guides both diagnosis and therapy.