title: IgD positive L&H cells identify a unique subset of nodular lymphocyte predominant Hodgkin lymphoma.
abstract: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell lymphoma considered to be of germinal center (GC) derivation. Studies on immunoglobulin expression have been few, and post-switch immunoglobulin (IgG) has been identified in the majority of cases examined thus far. We reviewed 180 cases of NLPHL and observed the unexpected expression of IgD in 27% of cases. IgD is usually coexpressed with IgM in naive B cells but can also be seen as IgD-only in centroblasts (CD38-positive) or memory B cells (CD27-positive). We asked whether IgD-positive NLPHL differed from cases of NLPHL negative for IgD. Clinically, the IgD-positive cases presented at a younger median age (21 vs. 44 years) and had a striking male predominance (male-to-female ratio, 23:1 vs. 1.5:1). Cervical lymph nodes were more frequently involved (56% vs. 18.2%). L&H cells were localized in a predominantly extrafollicular distribution in the majority of IgD-positive cases (69%). The IgD-positive cases did not coexpress IgM or CD27 (a marker associated with memory B cells), and nearly all (93%) were weakly positive for CD38, supporting a GC derivation. The expression of Bcl-6, BOB.1, Oct2, and SWAP-70 was similar in the two groups. However, PU.1 expression was seen in 60% of the IgD-positive cases in contrast to 86% of the IgD-negative cases. The absence of PU.1 staining correlated with more L&H cells in an extrafollicular distribution, weakening the use of this marker in the differential diagnosis with T-cell rich/histiocyte rich B-cell lymphomas. To study IgD expression in "de-novo" T-cell rich/histiocyte rich B-cell lymphomas, we analyzed 20 cases and all but one were negative. In conclusion, cases of IgD-positive NLPHL do not differ from IgD-negative cases regarding cellular derivation and most other immunophenotypic characteristics. However, IgD-positive NLPHL exhibits distinctive clinical features, and more often involves the interfollicular region in a background relatively rich in T cells. IgD positivity may represent an additional useful marker in the diagnosis of NLPHL.
authors.affiliation: Laboratory of Pathology, Hematopathology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. stefpitt@mail.nih.gov
authors.forename: Sonam
authors.initials: S
authors.lastname: Prakash
authors.forename: Thomas
authors.initials: T
authors.lastname: Fountaine
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D002648:Child; D005260:Female; D006644:Histiocytes / Q000378:metabolism*; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis*; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
chemical_list: D014408:Biomarkers, Tumor; D007072:Immunoglobulin D