A Rare Case of POEMS-Associated Multicentric Castleman Disease with an Atypical Osteolytic Presentation

To the editor, Castleman disease (CD) is a rare heterogeneous lymphoproliferative disorder characterized by distinctive lymph node histopathology and clinical manifestations ranging from localized lymphadenopathy to severe systemic inflammatory disease.It is classified into unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD).UCD involves a single lymph node region, whereas MCD usually presents with generalized lymphadenopathy and multiorgan involvement.MCD is further categorized into human herpesvirus-8associated MCD and idiopathic MCD (iMCD) [1].POEMS syndrome is a paraneoplastic multisystem disorder caused by plasma cell dyscrasia and characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes.Additional manifestations may include extravascular volume overload, papilledema, thrombocytosis, and sclerotic bone lesions [2].A rare but clinically significant variant is POEMS-associated multicentric CD (POEMS-MCD).Diagnostic criteria require polyradiculoneuropathy and monoclonal gammopathy with at least one major feature such as elevated vascular endothelial growth factor (VEGF), osteosclerotic bone lesions, or lymph node histopathology consistent with CD.Recognizing this entity is crucial because management generally requires plasma cell-directed therapy rather than cytokine-targeted therapy used for idiopathic MCD [3].CD is identified in approximately 11%-30% of patients with POEMS syndrome, most commonly as the multicentric plasma cell variant [2,3].The pathogenesis of this association is not completely understood but is thought to involve dysregulated cytokine signalling, particularly overproduction of interleukin-6 and VEGF, leading to systemic inflammation, angiogenesis, lymphoid proliferation, and increased vascular permeability.These overlapping inflammatory and plasma cell-driven mechanisms contribute to the shared clinicopathological features observed in POEMS-MCD [1,2].However, atypical presentations with unusual skeletal lesions or incomplete features may occur, causing diagnostic difficulty and misdiagnosis as plasma cell disorders.A 43-year-old man presented with progressive shortness of breath, abdominal fullness, tingling sensation in both lower limbs and swelling in both sides of the neck that had gradually enlarged over one year.Examination revealed cervical lymphadenopathy with hepatosplenomegaly and ascites; neurological evaluation showed distal muscle wasting with reduced power, absent lower limb reflexes along with reduced vibration and proprioception below the knees.Laboratory evaluation showed hemoglobin 11.2 g/dL, leukocyte count 8 × 10⁹/L, and thrombocytosis (5.5 × 10⁵/µL).Serum protein electrophoresis demonstrated a monoclonal band (1.3 g/dL), and immunofixation confirmed IgG lambda monoclonal gammopathy with elevated lambda free light chains (228 mg/L).Serum β2-microglobulin (11.01 mg/L) and VEGF (500 pg/mL) were elevated.Nerve conduction studies revealed demyelinating sensorimotor polyneuropathy involving both lower extremities.Positron emission tomography revealed fluorodeoxyglucose-avid cervical lymphadenopathy, hepatosplenomegaly, bilateral pleural effusion, ascites, and multiple FDG-avid vertebral lytic lesions involving C3, D8, D11, and L4 with partial collapse of D11 (Figure 1A,1B).Excisional lymph node biopsy showed features of CD with atretic germinal centres, onion-skin mantle zones, and marked plasmacytosis (Figure 1C,1D).Immunohistochemistry showed CD20-positive follicles and CD38/CD138-positive plasma cells with lambda light chain restriction; HHV-8 staining was negative.Bone marrow examination revealed normocellular marrow with 6% plasma cells.The constellation of monoclonal gammopathy, polyneuropathy, CD histology, organomegaly, lymphadenopathy, and extravascular fluid overload suggested POEMS-MCD.The patient was treated with bortezomib, cyclophosphamide, and dexamethasone (VCD), with significant clinical and laboratory improvement after four cycles. u n c o r r e c t e d p r o o fPolyclonal hypergammaglobulinemia is typical of iMCD; however, small monoclonal spikes (<3 g/dL) may occasionally occur, creating diagnostic overlap with plasma cell disorders, particularly POEMS syndrome [1].Patients with POEMS syndrome frequently exhibit systemic manifestations such as progressive demyelinating neuropathy, organomegaly, thrombocytosis, volume overload, and elevated VEGF levels, while bone marrow plasma cell infiltration is often limited compared with overt multiple myeloma [2,3].Skeletal involvement in POEMS syndrome is usually osteosclerotic; however, uncommon osteolytic variants have also been reported and may radiologically resemble multiple myeloma, metastatic malignancy, or lymphoma-associated lytic lesions [4,5].This case highlights diagnostic challenges of osteolytic lesions in POEMS syndrome-associated MCD mimicking multiple myeloma; early recognition enables effective plasma cell-directed therapy.