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The prevalence is unknown. There have only been about 120 cases reported in the worldwide literature but this condition is thought to be under-diagnosed.

Disease onset usually occurs between the ages of 40 and 90 years but the disease has also been seen in younger persons. Disseminated lymphoproliferative disease with lymphadenopathy, splenomegaly and hepatomegaly is the most common feature of gamma-HCD. Localized lymphoproliferative disease may be extramedullary (commonly cutaneous involvement) or may be located exclusively in the bone marrow. In other patients the disease can present with no apparent proliferative lymphoplasmacytic disease but instead an underlying autoimmune disorder such as rheumatoid arthritis, autoimmune hemolytic anemia or thrombocytopenic purpura (see these terms).

The cause of gamma-HCD is unknown.

The diagnosis of gamma-HCD is based on identification of free gamma-chains without associated light chains by immunofixation of serum and a concentrated urine specimen by using specific antisera. Patients presenting with a lymphoplasma-cell proliferative disorder should be evaluated for gamma-HCD. Immunofixation of serum and urine should be performed on patients with atypical lymphoplasma-cell proliferative disorders.

Because gamma-HCD is a heterogenous condition, the choice of therapy should rely on the underlying disorder. In an asymptomatic patient with minimal lymphoid proliferation no treatment is recommended. Any associated autoimmune disease should be managed with standard therapy without taking into account the existence of the abnormal monoclonal component. Melphalan and prednisone are used if proliferation is mainly plasmacytic. Chlorambucil, cyclophosphamide and vincristine may be beneficial if there is evidence of a progressive lymphoproliferative process. Radiation therapy and surgical removal of extramedullary plasmacytomas can be curative in some cases.

Gamma-HCD has a highly variable clinical course and ranges from an asymptomatic, benign, or transient process to a rapidly progressive neoplasm leading to a very poor prognosis.