Original ArticlesThe Spleen in the Wiskott-Aldrich Syndrome Histopathologic Abnormalities of the White Pulp Correlate with the Clinical Phenotype of the DiseaseVermi, William M.D.; Blanzuoli, Laura M.D.; Kraus, Madeleine D. M.D.; Grigolato, Piergiovanni M.D.; Donato, Francesco M.D.; Loffredo, Giuseppe M.D.; Marino, Carla E. M.D.; Alberti, Daniele M.D.; Notarangelo, Luigi D. M.D.; Facchetti, Fabio M.D., Ph.D.Author Information From the Departments of Pathology, Spedali Civili-University of Brescia, Brescia, Italy (W.V., L.B., P.G., F.F.); Washington University School of Medicine, St Louis, Missouri, U.S.A. (M.D.K.); Ospedale Gaslini, Genova, Italy (C.E.M.); Institute of Hygiene, University of Brescia, Italy (F.D.); Department of Pediatric Hematology, Ospedale Pausilipon, Napoli, Italy (G.L.); and Department of Pediatrics, Spedali Civili-University of Brescia, Brescia, Italy (D.A., L.D.N.). Address correspondence and reprint requests to Dr. Fabio Facchetti, Istituto di Anatomia Patologica, Università di Brescia, Spedali Civili di Brescia, I-25124 Brescia, Italy. The American Journal of Surgical Pathology: February 1999 - Volume 23 - Issue 2 - p 182-191 Buy Abstract The Wiskott-Aldrich syndrome (WAS) is a X-linked hematologic disorder characterized by thrombocytopenia, eczema, and immunodeficiency of variable severity. Reported here are the results of a morphologic, morphometric, and immunophenotypic analysis of splenic lymphoid tissue in 12 WAS patients with documented molecular defect and with different disease severity. Spleens from 29 age-matched patients with different diseases were used as controls. Paraffin-embedded tissue (from all cases) and fresh-frozen samples (from 5 WAS patients and 4 control subjects) were used to study the different white pulp compartments by classic morphologic, immunophenotyping, and image analysis techniques. Data were statistically analyzed by both parametric and nonparametric tests. Spleens from WAS patients showed a significant depletion of the total white pulp (p = 0.0008), T cell (p < 0.05), and B cell (p = 0.0002) areas and marginal zone (MZ) thickness (p < 0.0001). Among WAS patients, a negative correlation was found between the score of severity of the disease and all variables considered (Spearman's rank correlation coefficient, r = −0.79, r = −0.73, r = −0.68, and r = −0.56, respectively). In conclusion, this study shows that in WAS a general depletion of the splenic white pulp occurs, supporting the evidence that WAS is characterized by a combined immune defect. The significant reduction of the MZ may explain the inability of WAS patients to mount a response to T-independent antigens. © 1999 Lippincott Williams & Wilkins, Inc.