Abstract
Background: Heavy chain disease (HCD) is a rare lymphoproliferative disorder characterized by a monoclonal heavy chain (HC) unattached to a light chain (LC). IgGHCD or γHCD typically presents as a lymphoproliferative disorder with lymphadenopathy and hepatosplenomegaly. Myeloma has been described associated with γHCD but only with a second intact Ig paraprotein. This report describes a unique presentation of multiple myeloma with monoclonal free γ3HC and kappa free light chains.
Case: A 34 year old gentleman presented with mild persistent neutropenia following two episodes of pneumonia, 18 months previously. He admitted to persistent night sweats but no other significant history. Baseline investigations revealed a mild anaemia, neutropenia and a large IgG paraprotein with no associated light chain. Bone marrow aspirate and trephine confirmed myeloma. The patient was treated with cyclophosphamide, thalidomide and dexamethasone and has had a very good partial remission. He is awaiting a sibling allogeneic peripheral blood stem cell transplant.
Investigations and results: Serum Electrophoresis confirmed a large IgG paraprotein (23g/l) with no associated light chain in the serum and identified as γ3 subclass by radial immunodiffusion. Western blot showed the γ3HC was truncated with a large deletion. Markedly elevated free kappa (κ) LC (503.58 mg/l [3.30–19.4]) were found in the serum with gross skewing of the kappa/lambda ratio. Urine electrophoresis revealed separate γHC and κ LC paraproteins. Western blot of the fractionated urine protein demonstrated different sized κLC aggregates. Flow cytometry of the marrow aspirate revealed an unusual staining pattern; CD5,19,38,45+ve and CD20,22,23,34,56,138 –ve plasma cells. Cytoplasmic staining revealed 2 distinct populations of plasma cells, the first producing γ3HC and the second only free κLC. Cytogenetics and FISH analysis for 14q, p53 and c-myc abnormalities were normal.
Discussion: This is the first description of a Biclonal Myeloma with separate plasma cell populations producing γ3HC and κLC paraproteins. The biclonality confirms the free HC occurs as a result of abnormal synthesis not cleavage. The clinical and immunological findings are clearly different to typical findings in both γ3HCD and Myeloma. HCD has an appalling prognosis and this case is likely to have been ‘smouldering’ for 18 months, evidenced by the 2 pneumonias and persistent night sweats. There is no lymphadenopathy or organomegaly associated with γ3HCD. The immunophenotype of the malignant plasma cells is unique. Other atypical features include frank proteinuria, with a HC in the urine, but normal renal function and no radiological or biochemical evidence of bone involvement. We propose that this unique biclonal myeloma has distinct immunological and clinical features.
Author notes
Disclosure: Research Funding: Author S Harding manages the R&D department at the Binding site Ltd and performed the investigative experiments free of charge.
