Light microscopic, immunophenotypic, and molecular genetic study of autoimmune lymphoproliferative syndrome caused by fas mutation

This case provides a complete light microscopic, immunophenotypic, and mole cular 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 ch ild who was first clinically evaluated at the age of 16 months because of m arked generalized lymphadenopathy and hepatosplenomegaly. Histologic sectio ns of a cervical lymph node demonstrated a marked paracortical proliferatio n 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(-), T delta 1(-), [CD4(-), CD8(-)] double n egative profile on flow cytometric analysis. Southern blot analysis did not identify a clonal T or B cell population,:and sequencing of the ins gene i dentified a mutation that caused a single amino acid substitution in the in tracytoplasmic death domain of this protein. An enriched population of CD45 RO-negative naive T cells in the paracortex may explain the atypical histol ogic and immunophenotypic features of this case. Greater awareness of this heritable lymphoproliferative disorder will facilitate its recognition and minimize the possibility of misdiagnosis.