X-linked lymphoproliferative disease: Pathology and diagnosis

X-linked lymphoproliferative disease (XLP) is a rare familial disorder resu lting in selective immunodeficiency to the Epstein-Barr virus (EBV), charac terized by uncontrolled proliferation of EBV-infected lymphocytes. Phenotyp es of this disease are variable and include fulminant infectious mononucleo sis, hypogammaglobulinemia, and malignant lymphoma. In this article, we des cribe a case of a previously healthy 4-year-old boy with serologic evidence of acute EBV infection who died of fulminant hepatic failure. Histopatholo gical examination of tissue obtained postmortem showed hemophagocytosis and prominent polymorphous infiltrates associated with necrosis in the liver, spleen, and lymph nodes. Semiquantitative polymerase chain reaction (PCR) u tilizing primers complementary to the EBV gene LMP2a performed on samples o f liver tissue demonstrated approximately 0.6 copies of the EBV gene per ce ll. Immunohistochemistry demonstrated Light chain restriction and PCR studi es of the immunoglobulin V-D-J region revealed two strong bands, consistent with a clonal B cell proliferation. Extended family history revealed that the boy's family was followed by the XLP Registry, which was established in 1978 to follow kindreds with XLP. The genetic abnormality associated with XLP has been localized to the Xq25, allowing RFLP analysis to identify fema le carriers and affected boys.