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EBV May Be Expressed in the LP Cells of Nodular Lymphocyte–predominant Hodgkin Lymphoma (NLPHL) in Both Children and Adults

Huppmann, Alison R. MD; Nicolae, Alina MD, PhD; Slack, Graham W. MD; Pittaluga, Stefania MD, PhD; Davies-Hill, Theresa; Ferry, Judith A. MD; Harris, Nancy Lee MD; Jaffe, Elaine S. MD; Hasserjian, Robert P. MD

The American Journal of Surgical Pathology: March 2014 - Volume 38 - Issue 3 - p 316–324
doi: 10.1097/PAS.0000000000000107
Original Articles

Nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (CHL) are classified separately because of their distinct clinical and pathologic features. Whereas Epstein-Barr virus (EBV) is detected in the neoplastic cells of 25% to 70% of CHL, NLPHL is generally considered to be EBV. We assessed EBV status in 302 pediatric and adult cases of NLPHL. A total of 145 pediatric (age 18 y or younger) and 157 adult cases of NLPHL were retrieved from 3 North American centers and tested for EBV by in situ hybridization (EBV-encoded small RNA). Clinical and pathologic features were analyzed. Five (3.4%) pediatric and 7 (4.5%) adult NLPHL cases contained EBV+ lymphocyte-predominant (LP) cells. Although all 12 cases met the criteria for diagnosis of NLPHL, atypical features were present, including capsular fibrosis, atrophic germinal centers, and pleomorphic or atypical LP cells. CD20 and OCT-2 were strongly and diffusely positive in all except 1 case. However, PAX5 and CD79a were weak and/or variable in 7/8 and 6/6 cases tested, respectively. EBV+ cases were more likely to be CD30+ (75%) compared with EBV cases (25%) (P=0.0007); CD15 was negative in all cases. Our results show that EBV+ LP cells may occur in NLPHL. Distinguishing EBV+ NLPHL from CHL can be challenging, as EBV+ NLPHL can have partial expression of CD30 and weak PAX5 staining as well as pleomorphic-appearing LP cells. However, the overall appearance and maintenance of B-cell phenotype, with strong and diffuse CD20 and OCT-2 expression, support the diagnosis of NLPHL in these cases.

*National Cancer Institute, Bethesda, MD

Massachusetts General Hospital, Boston, MA

British Columbia Cancer Agency, Vancouver, BC, Canada

A.R.H. and A.N. contributed equally.

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Elaine S. Jaffe, MD, National Institutes of Health/National Cancer Institute, 10 Center Drive, Bldg 10, Room 2B42, Bethesda, MD 20892 (e-mail:

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