Arch Pathol Lab Med—Vol 127, October 2003 EBV in Pediatric vs Adult Hodgkin Lymphoma—De Matteo et al 1325 Comparison of Epstein-Barr Virus Presence in Hodgkin Lymphoma in PediatricVersus Adult Argentine Patients Elena De Matteo, MD; Anahı ´ Vijnovich Baro ´n, MD; Paola Chabay; Jose ´ Porta, MD; Marta Dragosky, MD; Marı ´a Victoria Preciado, PhD ● Context.—In developed countries and high socioeco- nomic groups, Hodgkin lymphoma has an initial peak in young adulthood, whereas in undeveloped countries and low socioeconomic groups, it shows an early childhood peak. In developing countries, 90% of children are infect- ed with the Epstein-Barr virus (EBV) by the age of 6 years, but in developed countries, only 30% to 40% are sero- positive by that age. Early childhood EBV infection in 75% of Argentine patients was demonstrated. Objective.—To explore the epidemiology of Hodgkin lymphoma and its relationship with EBV in Argentine pa- tients. Methods.—The presence of EBV was assessed by Epstein- Barr encoded RNA in situ hybridization and latent mem- brane protein 1 immunohistochemistry. We studied 92 pe- diatric and 42 adult Hodgkin lymphoma cases from a pub- lic center as well as 39 adult cases from a private center. Results.—The mixed cellularity Hodgkin lymphoma had a prevalence of 52% in the pediatric group, while similar frequencies of both nodular sclerosis Hodgkin lymphoma (47%) and mixed cellularity Hodgkin lymphoma (44%) were observed in adults. As for Epstein-Barr encoded RNAs, 55% of the pediatric cases and 31% of the adult cases were positive. Among adult EBV  cases, 38% were from the public hospital, and 23% were from the private center. EBV was present in 77% of the pediatric mixed cellularity Hodgkin lymphoma cases when compared with the other histologic subtypes of Hodgkin lymphoma. EBV was mainly detected in mixed cellularity cases (39% in the adult group). Conclusion.—Our findings strengthen the argument that EBV is involved in the pathogenesis of Hodgkin lymphoma in most children younger than 10 years. Our findings of EBV prevalence, along with both childhood and second- decade peaks as well as comparable frequencies for Hodg- kin lymphomas of mixed cellularity and nodular sclerosis, distinguish our population from others in developing coun- tries. (Arch Pathol Lab Med. 2003;127:1325–1329) H odgkin lymphoma is a malignant lymphoma whose unusual heterogeneous clinical, histologic, and epi- demiologic features have suggested either a single disease entity with a complex host response or more than one possible distinct etiology. A definite bimodal age peak, absent in most other lym- phomas, is present in the incidence of Hodgkin lympho- ma. In developing countries, the early peak occurs in childhood, whereas in developed countries, it occurs in young adults; the second peak occurs in late adulthood in both groups. 1,2 Furthermore, in developing countries, there is usually a marked male preponderance and a high pro- portion of the mixed cellularity histologic subtype. Nod- ular sclerosis, the predominant histologic subtype in the Accepted for publication May 19, 2003. From the Pathology Division (Dr De Matteo) and the Laboratory of Virology (Mr Chabay and Dr Preciado), Ricardo Gutie ´rrez Children’s Hospital, the Private Pathology Centre (Dr Vijnovich Baro ´n), and the Pathology Service, Marie Curie Hospital (Drs Vijnovich Baro ´n, Porta, and Dragosky), Buenos Aires, Argentina. Part of this work was presented at the United States and Canadian Academy of Pathology Spring Meeting, Chicago, Ill, February 23– March 1, 2002. Reprints: Marı ´a Victoria Preciado, PhD, Laboratorio de Virologia, Hospital de Nin ˜ os Ricardo Gutie ´rrez, Gallo 1330, CP (1425) Capital Federal, Argentina (e-mail: preciado@conicet.gov.ar). United States and western Europe, is generally much less common in developing countries. 3 Growing evidence points to an etiologic role for Ep- stein-Barr virus (EBV), a ubiquitous herpesvirus associ- ated with several lymphoid malignancies and certain ep- ithelial tumors. Early suggestions of EBV and Hodgkin lymphoma association were based on the finding of an altered pattern of serum antibodies to EBV antigens be- fore tumor development. 4 Furthermore, a role for EBV in the pathogenesis of Hodgkin lymphoma has been sup- ported by the identification of clonal EBV DNA in a subset of Hodgkin lymphoma on the basis of Southern blot DNA hybridization. 5,6 The EBV genome was subsequently local- ized to Reed-Sternberg cells by in situ hybridization 3,7,8 ; these cells were also shown to express high levels of latent membrane protein 1 (LMP-1) in the absence of EBNA-2. 9 Moreover, EBV infection occurs at different ages, depend- ing on the developmental status of the country. In devel- oping countries, EBV infection occurs very early in life. In Argentina, 90% of children have had their first EBV infec- tion before the age of 6 years, 10 whereas in developed countries, only 30% to 40% are seropositive by that age. 11 The purpose of this study was to analyze the Hodgkin lymphoma histologic subtype distribution and its associ- ation with EBV in different age groups of Argentine pa- tients.