Clinical characteristics of high-grade lymphomas with immune genes in germline configuration

In a prospective study of 42 high-grade lymphomas which were categorized according to the Kiel classification, the clinical significance of immune genotyping was studied. Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements were investigated. In 33 cases the immune genotype confirmed the phenotype. In one case with equivocal phenotype a TCR beta-chain rearrangement proved the T-cell origin of the lymphoma. None of the cases showed a bigenotype. There were eight lymphomas with immunoglobulin and TCR beta-chain and gamma-chain genes in germline configuration, which were divided into a group of immature lymphomas and a group of lymphomas with a more mature phenotype. The immature lymphomas had widespread disease, rapid progression, and favorable prognosis after intensive chemotherapy. The group of T-cell and Ki-1 lymphomas with null-cell genotype was clinically heterogeneous. Three of four cases were secondary lymphomas after lymphomatoid papulosis, lymphomatoid granulomatosis, or Hodgkin's disease. All cases presented with extranodal involvement. Only one of these patients is in continuous remission. In conclusion, the lack of immunoglobulin and TCR beta-chain and gamma-chain gene rearrangements does not exclude the diagnosis of high-grade malignant lymphoma, especially in cases with unusual extranodal involvement. However, the DNA analysis identifies a null-cell genotype subset of high-grade lymphomas which may have clinical significance.