Gamma heavy chain disease

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URI: http://hdl.handle.net/2042/68175  |   DOI : https://doi.org/10.4267/2042/68175
Title: Gamma heavy chain disease
Author: Bianchi, Giada; Anderson, Kenneth C
Abstract: Gamma heavy chain disease (HCD) is a 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) incapable of either reaching a quaternary conformation with the immunoglobulin light chain (IgL) and/or being degraded by the proteasome. The isotype of mutated IgH (α,γ or μ) determines the nomenclature of HCD subtypes. Less than 200 cases of gamma HCD have been published. Gamma HCD predominantly affects women in their 5th-6th decade of life, and a pre-existing autoimmune disease is present in about a quarter of patients. Rheumatoid arthritis (RA) is the most commonly associated autoimmune disorder, but association with systemic lupus erythematosus (SLE), Sjögren syndrome, myasthenia gravis, vasculitis and idiopathic thrombocytopenic purpura (ITP) has been reported. The vast majority of patients with gamma HCD have a localized or systemic lymphoplasmacytic lymphoma. Gamma HCD patients can present with disseminated lymphomatous involvement, localized (medullary or extramedullary) lymphomatous disease or with no apparent lymphomatous involvement. Disseminated lymphoma is the most common form, being diagnosed in 57-66% of patients with gamma HCD. These patients typically present with B symptoms such as fever, fatigue, and unintentional weight loss. Circa half of the patients have generalized lymphadenopathy, splenomegaly, and more rarely hepatomegaly. Twenty-five percent of patients with gamma HCD present with either localized medullary disease or localized extramedullary disease. Lymphomatous infiltration is present only in the bone marrow in the former, and in extranodal sites in the latter. The most common site of extranodal involvement is the skin, although involvement of thyroid and parotid, oropharynx, and gastrointestinal tract has been reported. Gamma HCD patients with no identifiable lymphoma at diagnosis (~9-17%) typically have a pre-existing autoimmune condition, with associated symptoms and signs. Definitive diagnosis is based on the identification of a gamma immunoglobulin heavy chain (IgH) without associated Ig light chain (IgL) assessed using serum or urine protein electrophoresis (SPEP or UPEP, respectively) and immunofixation (IF). Treatment ranges from expectant management for patients with no detectable lymphoma, to local surgical or radiation therapy for localized extramedullary disease, and combination therapies for systemic and localized medullary disease. Prognosis is very good in patients with no detectable lymphoma or completely treated, limited extramedullary lymphoma; patients with systemic disease can have a rapidly aggressive or more indolent course with highly variable median survival (1 month to over 20 years)
Subject: gamma heavy chain disease; B cell malignancy; Franklin disease; immunoglobulin heavy chain; Leukaemia Section; Adult; Aged; Female; *Heavy Chain Disease/complications/drug therapy; Humans; *Leukemia, Lymphoid/complications/drug therapy; Male; Adolescent; Antibodies, Monoclonal, Murine-Derived/administration & dosage; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use; Bendamustine Hydrochloride; Heavy Chain Disease/complications/*drug therapy/*pathology; Humans; Lymphoma, B-Cell, Marginal Zone/complications/*drug therapy/
Publisher: ARMGHM - Atlas Génétique des Cancers
Date: 2017

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