Monoclonal B cell proliferation in lymphoproliferative disease associated with herpes virus type 6 infection

Clonal gene rearrangements and aneuploidy are commonly recognized as characteristics of malignancy. We challenge this by an observation of a 3 1/2 year old boy with chronic benign lymphadenopathy, connatal splenomegaly and peripheral lymphocytosis. His brother and mother suffered from similar disease without progression. Cervical lymph node biopsy from our patient revealed a benign histology corresponding to the clinical course; however, clonal rearrangements of the JH and TCR gamma gene were demonstrated in lymph node cells and DNA aneuploidy in 11% of bone marrow cells. Immunohistology showed an inverse T-helper/T-suppressor cell ratio with polyclonal B cell increase and extensive lymphocyte activation. In situ hybridization demonstrated foci of lymphoid cells in the paracortical zone with expression of herpes virus type 6 genome. In addition, the patient, his brother and his mother showed serological evidence of active infection with the human herpes virus-6 (HHV-6). The association of HHV-6 infection, monoclonality and benign lymphoproliferation is discussed.