Differentials
Monoclonal gammopathy of undetermined significance
SIGNS / SYMPTOMS
Asymptomatic condition. No end-organ damage (bone lesions, anaemia, hypercalcaemia, renal dysfunction).[39]
Solitary plasmacytoma
SIGNS / SYMPTOMS
Localised bone pain or soft-tissue swelling.
INVESTIGATIONS
Presence of monoclonal plasmacytosis on biopsy of the solitary lesion (bone or soft tissue), without evidence of plasma cells on bone marrow biopsy. No other osteolytic lesions on bone imaging, except the diagnostic lesion. No end-organ damage that can be attributed to lymphoplasma cell proliferative disorder.
Waldenström's macroglobulinaemia
SIGNS / SYMPTOMS
No bone pain. Frequently presents with symptoms of hyperviscosity, such as mucosal bleeding and neurological, ocular, and cardiovascular abnormalities. Also presents with organomegaly and lymphadenopathy.
INVESTIGATIONS
Serum electrophoresis shows IgM >30,000 mg/L (30 g/L). Presence of lymphocytes or plasmacytoid lymphocytes on bone marrow biopsy. Bone imaging is negative for osteolytic lesions. Patients may have evidence of increased serum viscosity.
Amyloidosis
SIGNS / SYMPTOMS
Fatigue and weight loss are common symptoms. Hepatomegaly and macroglossia occur in approximately 10% of patients. Renal insufficiency occurs in 50% of patients. Nephrotic syndrome, congestive heart failure, orthostatic hypotension, carpal tunnel syndrome, and peripheral neuropathy may be presenting features.
INVESTIGATIONS
Positive apple-green birefringence when biopsy specimen (e.g., bone marrow) is stained with Congo red.
Bone marrow biopsy shows fewer than 5% monoclonal plasma cells.
Heavy chain disease
SIGNS / SYMPTOMS
Most common presenting symptoms are weakness, fatigue, and fever, associated with lymphadenopathy and hepatosplenomegaly.
INVESTIGATIONS
Characterised by the presence of a portion of the immunoglobulin heavy chain in the serum or urine or both. Also associated with the presence of lymphoplasmacytic marrow infiltrate.
Non-Hodgkin's lymphoma
SIGNS / SYMPTOMS
Presenting symptoms may include fever, night sweats, and weight loss. Presenting signs are spleen and lymph node enlargement.
INVESTIGATIONS
Lymph node biopsy is diagnostic. Lymphocytic infiltrate may occur in the bone marrow. Peripheral blood flow cytometry may be suggestive of clonal lymphocytosis.
Plasma cell leukaemia
SIGNS / SYMPTOMS
Presenting symptoms include acute onset of weakness, fatigue, bone pain, confusion, altered mental status, and peripheral neuropathy.
INVESTIGATIONS
Peripheral blood smear shows ≥5% circulating plasma cells.[75]
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes)
SIGNS / SYMPTOMS
Presenting symptoms may include polyneuropathy, hepatosplenomegaly, lymphadenopathy, oedema, pleural effusion, ascites, hyperpigmentation, hypertrichosis, acrocyanosis, plethora, and haemangioma.
INVESTIGATIONS
Bone marrow clonal plasma cells <10%; elevated lambda free light chains; elevated vascular endothelial growth factor (VEGF); elevated interleukin 6 (IL-6); endocrine abnormalities (e.g., thyroid function tests); positive for Castleman disease.[76]
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