This review underscores the diversity of the clinical manifestations and hematopathological features of gamma
heavy chain disease based on the detailed report of 16 patients evaluated in our chemical department, the analysis of 12 cases diagnosed in our laboratory, and the study of 81 cases previously reported. This condition is defined by the presence in the serum of
immunoglobulin molecules composed of deleted gamma heavy chains devoid of light chains. The production by the monoclonal B cells of these peculiar
proteins appears to result from multiple defects (deletions, insertions, and mutations) in both heavy and light chain genes leading to abnormal
mRNA splicing. Gamma
heavy chain disease is currently underdiagnosed. The diagnosis established by immunoelectrophoresis using specific
antisera combined, in some instances, with the immunoselection procedure, can easily be missed on serum electrophoretic patterns: a narrow abnormal band suggestive of a monoclonal component was found in only 10 of our 28 cases. The amount of
heavy chain disease protein in urine ranges from trace to 20 g/day and is usually moderate. Gamma
heavy chain disease most often presents as a
lymphoproliferative disorder featured by
lymphadenopathies,
splenomegaly, and constitutional symptoms. Extra-hematopoietic
tumor localizations, such as cutaneous or subcutaneous involvement or thyroid
tumor, may occur. Autoimmune disorders, notably
rheumatoid arthritis and
autoimmune hemolytic anemia or
thrombocytopenic purpura, are frequent (26% of cases). There is no specific histological pattern. The most frequent is a pleomorphic malignant lymphoplasmacytic proliferation mainly seen in bone marrow and lymph nodes. Some cases present with a predominantly plasmacytic proliferation or
chronic lymphocytic leukemia. Other patients are affected with
non-Hodgkin lymphoma of various morphologic types. Immunocytologic studies showed that a gamma
heavy chain disease protein may occur in the context of a double monoclonal lymphoproliferative process or in various B or T cell
malignancies that are not directly involved in the production of the abnormal
immunoglobulin. In some patients, the histologic appearance of the enlarged lymphoid organs showed only a moderate lymphoplasmacytic infiltration of uncertain
malignancy. More important, some patients showed no evidence of an underlying
lymphoproliferative disorder after several years of follow-up. The
clinical course of gamma
heavy chain disease varies from an
asymptomatic state to a rapidly progressive
malignancy. The choice of
therapy should entirely rely on the underlying clinicopathologic features, without taking into account the presence of the abnormal
protein.(ABSTRACT TRUNCATED AT 400 WORDS)