Light Microscopic, Immunophenotypic, and Molecular Genetic Study of Autoimmune Lymphoproliferative Syndrome Caused by fas Mutation

This case provides a complete light microscopic, immunophenotypic, and molecular genetic analysis of autoimmune lymphoproliferative syndrome (ALPS), a rare benign cause of dramatic lymphadenopathy with atypical histology and phenotype that may be mistaken for malignancy. The patient is 3-year-old child who was first clinically evaluated at the age of 16 months because of marked generalized lymphadenopathy and hepatosplenomegaly. Histologic sections of a cervical lymph node demonstrated a marked paracortical proliferation of occasional small and intermediate-sized lymphocytes and numerous large immunoblasts, the majority of which displayed a CD3⁺, CD43⁺, CD45RO⁻ (OPD4, UCHL1) CD4⁻, CD8⁻ phenotype on paraffin sections, and which had a CD2⁺, CD3⁺, CD5⁺, CD56⁻, Tδ1⁻, [CD4⁻, CD8⁻] double negative profile on flow cytometric analysis. Southern blot analysis did not identify a clonal T or B cell population, and sequencing of the fas gene identified a mutation that caused a single amino acid substitution in the intracytoplasmic death domain of this protein. An enriched population of CD45RO-negative naive T cells in the paracortex may explain the atypical histologic and immunophenotypic features of this case. Greater awareness of this heritable lymphoproliferative disorder will facilitate its recognition and minimize the possibility of misdiagnosis. Received January 22, 1999; accepted April 7, 1999.