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The heavy-chain diseases (HCDs) are B-cell lymphoplasma cell proliferative disorders in which neoplastic cells produce monoclonal immunoglobulins (Ig) consisting of truncated heavy chains 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 Ig 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. The diagnosis is established from immunofixation of serum, urine, or secretory fluids in the case of α-HCD or from 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 non-Hodgkin 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 112–1 summarizes the features of the HCDs.

Table 112–1. Summary of Features of the Heavy-Chain Diseases

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: CH1 (2, 3, 4), constant region 1 (2, 3, 4); D, diversity; HC, heavy chain; HCD, heavy-chain disease; Ig, immunoglobulin; IPSID, immunoproliferative small intestinal disease; J, joining; V, variable.

Definition and History

γ-Heavy-chain disease (HCD) is not a specific pathologic process but is a biochemical expression of a mutant B-cell clone. The “disease” should be considered a serologically determined entity with a great variety of clinical and histopathologic features. It is defined by the recognition of monoclonal deleted γ chains devoid of light chains.

The first case of γ-HCD was described in 1964 by Franklin and colleagues,1 who observed a homogeneous band between γ and β globulin in an African American patient with generalized lymphadenopathy. Comparison of ...

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