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

Abstract

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (CHL) are classified separately because of their distinct clinical and pathological features. While EBV is detected in the neoplastic cells of 25-70% of CHL, NLPHL is generally considered to be EBV-negative. We assessed EBV status in 302 pediatric and adult cases of NLPHL. A total of 145 pediatric (age ≤18) and 157 adult cases of NLPHL were retrieved from 3 North American centers and tested for EBV by in situ hybridization (EBER). Clinical and pathological features were analyzed. Five (3.4%) pediatric and 7 (4.5%) adult NLPHL cases contained EBV-positive LP cells. While all 12 cases met criteria for the diagnosis of NLPHL, atypical features were present, including capsular fibrosis, atrophic germinal centers and pleomorphic or atypical lymphocyte predominant (LP) cells. Both CD20 and OCT-2 expression were strong and diffuse in all except one case. However, PAX5 and CD79a were weak and/or variable in 7/8 and 6/6 cases tested, respectively. EBV-positive cases were more likely to be CD30-positive (75%) than EBV-negative cases (25%) (p=0.0007); CD15 was negative in all cases. Our results show that EBV-positive LP cells may occur in NLPHL. Distinguishing EBV+ NLPHL from CHL can be challenging, since 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.

Histopathological features and their prognostic impact in nodular lymphocyte‐predominant Hodgkin lymphoma – a matched pair analysis from the German Hodgkin Study Group (GHSG)

“…A recent study reconfirmed EBV positivity as rare event in NLPHL with only 4% of patients presenting with this feature (Huppmann et al , ). This low overall incidence of EBV‐positive NLPHL probably represents the main reason for the lack of EBV‐positive cases observed in the present study.…”

Epstein-Barr virus–positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus–positive diffuse large B-cell lymphoma of the elderly

“…In a recent study of 302 cases of NLPHL occurring in the United States and Canada, it was found that 12 cases (4%) contained EBV+ LP cells [24]. Five of the 12 EBV+ NLPHL cases were pediatric; all of them were male, and in 2 of 5 cases, LP cells were IgD+.…”

“…Criteria for the differential diagnosis were previously proposed for EBV+ DLBCL of the elderly [3,4,[22][23][24] and consisted in more than 50% tumor cells expressing B-cell antigens, in a high number of CD20+/CD79a+/CD30+ medium-sized tumor cells, and in the absence or poor expression of CD15. All these criteria were satisfied in our cases.…”

Contribution of the Epstein-Barr Virus to the Pathogenesis of Hodgkin Lymphoma

“…While L&H cells retain the expression of typical B-cell antigens such as CD20 and CD19, HRS cells of classical HL have an unusual phenotype in which the B-cell gene expression programme is largely extinguished. Although recent studies suggest that a small proportion of NLPHL cases harbour the Epstein-Barr virus (EBV) (Wang et al 2014;Huppmann et al 2014), here we focus on classical HL in which the link with EBV is well established.…”