Primary Diagnosis and REAL/WHO Classification of Non-Hodgkin’s Lymphoma by Fine-Needle Aspiration: Cytomorphologic and Immunophenotypic Approach W.A. Mourad, MD, FRCPC ,* A. Tulbah, MD, FRCPA , M. Shoukri, PhD, F. Al Dayel, MD, FRCPA , M. Akhtar, MD, FRCPA , M.A. Ali, MD, FRCPC , B. Hainau, MD, and J. Martin, MD, FRCPC The Revised European American lymphoma (REAL) and World Health Organization (WHO) classification of non-Hodgkin’s lym- phoma (NHL) relies on the constellation of cytologic, phenotypic, genotypic, and clinical characteristics of NHL. For the most part, the classification does not rely on architectural pattern for clas- sification of neoplasms. This classification makes it possible to diagnose and classify lymphomas by fine-needle aspiration (FNA). In this study, we attempted to evaluate the accuracy of FNA in diagnosing and classifying NHL within the context of the REAL/ WHO classifications. Cases included only those in which FNA was the primary diagnosis, followed by a surgical biopsy for confir- mation. Flow cytometry (FCM) for phenotyping was carried out whenever material was available. Two groups of pathologists were identified. Group A consisted of pathologists with background training in cytopathology and/or hematopathology (three pathol- ogists). Group B consisted of experienced surgical pathologists with no training in cytopathology and/or hematopathology (four pathologists). Seventy-four cases were included in the study. FCM phenotyping was performed in 53 cases (71%). Large cell lym- phoma constituted 63% of the cases. The remaining lymphomas included Burkitt’s, small lymphocytic, lymphoblastic, follicle cen- ter cell, Ki-1,mantle cell, marginal zone,and natural killer cell lymphoma. The diagnosis of lymphoma was rendered for all cases. The correct classification was seen in 63% of the cases. Classifi- cation was more accurate in immunophenotyped than in nonim- munophenotyped cases (84% vs 33%; P ⫽ 0.00004).Group A pathologists showed higher incidence of proper classification than group B (80% vs 56%; P ⫽ 0.046). The diagnosis and classifica- tion of NHL can be achieved in a large number of cases on FNA material. This accuracy can be increased if cytomorphologic cri- teria are established for different entities of NHL aided by FCM for phenotyping. Diagn.Cytopathol. 2003;28:191–195. © 2003 Wiley-Liss, Inc. Key Words: REAL/WHO classification; non-Hodgkin’s lympho- ma; FNAB The correct diagnosis and classification of malignant lym- phoma is an essential component in the management of the disease. Proper patient therapy cannot be achieved withou proper classification. Good clinicopathologic studies canno be obtained if the pathologic classification is discrepant wi the biologic and clinical behaviorof the lymphoma. An idealclassification of lymphoma should be simple, repro- ducible, and biologically relevant. Until a few years ago, no lymphoma classification could fulfill these basic criteria. In the past,classifications relied on pure histomorphologic characteristics, such as the Rappaport classification. 1 Some- times the classification relied on histomorphologic and in- complete immunophenotypic data, such as the Kiel classi- fication. 2 None of these and other classifications was able to fulfillthese basic criteria. More recently, the Revised Eu- ropean American Lymphoma (REAL) classification and its World Health Organization (WHO) modification promise to fulfillthese criteria. 3 The diagnosis and classification of non-Hodgkin’s lymphoma using the REAL/WHO classifi- cation have relied on the constellation of histomorphologic cytologic, and immunophenotypic characteristics that iden- tify each disease entity. 4,5 In previous classifications, the histologic pattern of growth of the lymphoma was an es- sential component of these classifications. Departments of Pathology and Biostatistics, King Faisal Specialist Hos- pital and Research Centre, Riyadh, Kingdom of Saudi Arabia *Correspondence to: Walid A. Mourad, M.D., Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354 (MBC-10), Riyadh,11211,Kingdom ofSaudi Arabia. E-mail: mourad@kfshrc.edu.sa Received 12 July 2002; Accepted 13 January 2003 DOI 10.1002/dc.10268 Published online in Wiley InterScience (www.interscience.wiley.com). ©2003 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 28, No 4 191