Mu heavy chain disease

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URI: http://hdl.handle.net/2042/68177  |   DOI : https://doi.org/10.4267/2042/68177
Title: Mu heavy chain disease
Author: Bianchi, Giada; Anderson, Kenneth C
Abstract: Mu heavy chain disease (HCD) is the most rare variant of HCD, a family of syndromes associated with or representing a B cell malignancy variant. The hallmark characteristic and the pathogenic mechanism of HCD is the synthesis of a mutant, misfolded immunoglobulin heavy chain (IgH) which cannot form a quaternary conformation with the immunoglobulin light chain (IgL) and/or be degraded by the proteasome. The isotype of mutated IgH (α,γ or μ) determines the nomenclature of HCD subtypes. Less than 50 cases of mu HCD have been reported. The first two cases of mu HCD were described in the 1970s. The disease was diagnosed in men in their late fifties complaining of unremitting joint pain/stiffness. Mu HCD affects predominantly Caucasian men in their 5th-6th decades. Similar to the other HCD, the etiopathogenesis of mu HCD is unknown, but most patients have a concurrent lymphoproliferative disorder resembling chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). There are single case reports of mu HCD in association with myelodysplastic syndrome (MDS), systemic amyloidosis, and diffuse large B cell lymphoma (DLBCL).(Witzens et al., 1998; Kinoshita et al., 2004) Association of mu HCD with recurrent pulmonary infections, portal hypertension, systemic lupus erythematosus, and pancytopenia has also been described.(Wahner-Roedler and Kyle, 2005) Presenting symptoms/signs of mu HCD are secondary to the associated lymphoproliferative disorder: the majority of patients have splenomegaly: 75% patients present with hepatomegaly; and 40% patients have superficial lymphadenopathy. In the first case reports of mu HCD and in 20% cases overall, patients presented with lytic bone lesions associated with lymphocytic infiltration of the bone marrow space. A hypoproliferative anemia is the most common laboratory finding in mu HCD, followed by thrombocytopenia. Lymphocytosis can be present. While serum protein electrophoresis (SPEP) is typically normal, immunofixation (IF) detects monoclonal mu IgH in polymers of different sizes without an associated light chain. Biclonal gammopathy with the presence of a second, intact IgM has been reported. Cytologic examination of bone marrow aspirate smears typically shows plasma cells with prominent cytoplasmic vacuoles and small, round lymphocytes. Upon immunophenotypic analysis, pathologic cells are typically positive for CD19, CD20, CD38, and cytoplasmic IgM, but lack light chain expression. However, dim expression of CD5 and kappa light chain has been rarely reported. Given the paucity of cases, there is no standard treatment for mu HCD. Patients with a laboratory diagnosis of mu HCD who are otherwise asymptomatic can be managed expectantly without any active therapy. If a lymphoproliferative disorder is detected, treatment regimens have included: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone); CVP (cyclophosphamide, vincristine and prednisone); as well as single agent cyclophosphamide or fludarabine. Prognosis is variable, with disease ranging from highly aggressive to more indolent. The reported median overall survival is 2 years (less than one month to over 10 years); importantly, delay in the diagnosis of mu HCD is common due to technical difficulties in detecting the pathologic IgH, thus leading to underestimation of overall survival. A spontaneous remission of mu HCD has been reported.
Subject: mu heavy chain disease; B cell malignancy; immunoglobulin heavy chain; Leukaemia Section; Heavy Chain Disease/diagnosis/immunology/*pathology/therapy; Humans; Immunophenotyping; Prognosis; Arthritis, Rheumatoid/*complications; Blood Protein Electrophoresis; Bone Marrow/*pathology; Diagnosis, Differential; Heavy Chain Disease/complications/*diagnosis
Publisher: ARMGHM - Atlas Génétique des Cancers
Date: 2017

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