X-Linked Lymphoproliferative Disease: Pathology and Diagnosis

X-linked lymphoproliferative disease (XLP) is a rare familial disorder resulting in selective immunodeficiency to the Epstein-Barr virus (EBV), characterized by uncontrolled proliferation of EBV-infected lymphocytes. Phenotypes of this disease are variable and include fulminant infectious mononucleosis, hypogammaglobulinemia, and malignant lymphoma. In this article, we describe a case of a previously healthy 4-year-old boy with serologic evidence of acute EBV infection who died of fulminant hepatic failure. Histopathological 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) utilizing primers complementary to the EBV gene LMP2a performed on samples of liver tissue demonstrated approximately 0.6 copies of the EBV gene per cell. Immunohistochemistry demonstrated light chain restriction and PCR studies 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 female carriers and affected boys.