The heavy-chain diseases (HCDs) are B-cell lymphoplasmacytic proliferative disorders in which neoplastic cells produce monoclonal immunoglobulins (Igs) consisting of truncated heavy chains (HCs) without attached light chains. The complex abnormalities of HCD proteins and the usual lack of normal light chains are a result of several distinct gene alterations, including somatic mutations, deletions, and insertions. HCDs involving the three main immunoglobulin classes have been described: α-HCD is the most common and has the most uniform presentation; γ- and μ-HCDs have variable clinical presentations and histopathologic features. (see Table 109–1) The diagnosis is established from immunofixation of serum, urine, or secretory fluids in the case of α-HCD or by immunohistologic analysis of the proliferating lymphoplasmacytic cells in nonsecretory disease. Treatment of α-HCD consists of antibiotics. If there is no response to antibiotics or if aggressive lymphoma is diagnosed, chemotherapy is indicated. Treatment of γ- and μ-HCDs depends on the underlying clinicopathologic features rather than on the presence of the abnormal protein. Table 109–1 summarizes the features of the HCDs.
Acronyms and Abbreviations
CH1 (2, 3, 4), constant region 1 (2, 3, 4); D, diversity; HC, heavy chain; HCD, heavy-chain disease; Ig, immunoglobulin; IPSID, immuno-proliferative small intestinal disease; J, joining; V, variable.
TABLE 109–1.Summary of Features of the Heavy-Chain Diseases ||Download (.pdf) TABLE 109–1. Summary of Features of the Heavy-Chain Diseases
| ||Types of Heavy-Chain Diseases |
|Features ||α ||γ ||μ |
|Year described ||1968 ||1964 ||1969 |
|Incidence ||Rare ||Very rare ||Very rare |
|Age at diagnosis ||Young adult (<30 years) ||Older adult (60–70 years) ||Older adult (50–60 years) |
|Demographics ||Mediterranean region ||Worldwide ||Worldwide |
|Structurally abnormal monoclonal protein ||IgA ||IgG ||IgM |
|MGUS phase ||No ||Rarely ||Rarely |
|Urine monoclonal light chain ||No ||No ||Yes |
|Urine abnormal heavy chain ||Small amounts ||Often present ||Infrequent |
|Sites involved ||Small intestine, mesenteric lymph nodes ||Lymph nodes, marrow, spleen ||Lymph nodes, marrow, liver, spleen |
|Pathology ||Extranodal marginal zone lymphoma (MALT or IPSID) ||Lymphoplasmacytoid lymphoma ||Small lymphocytic lymphoma, CLL |
|Associated diseases ||Infection, malabsorption ||Autoimmune diseases ||None |
|Therapy ||Antibiotics, chemotherapy ||Chemotherapy ||Chemotherapy |
γ-HEAVY-CHAIN DISEASE DEFINITION AND HISTORY
γ-Heavy-chain disease (HCD) is not a specific cytopathologic process; rather, it is a biochemical expression of a mutant B-cell clone. The disease should be considered a serologically determined entity with a variety of clinical and histopathologic features. It is defined by the recognition of monoclonal deleted gamma (γ) chains devoid of light chains.1 The first case of γ-HCD was described in 1964 by Franklin and colleagues,2 who observed a homogeneous band between γ- and β-globulin in an African-American patient with generalized lymphadenopathy. Comparison of the proteins in the urine with those ...