Case 5 -

Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Judith Ferry Massachusetts General Hospital Boston, MA

Case History: 20-year-old male with a 3 cm left neck mass. Within the large, ill-defined nodules filling the node are numerous small B cells (CD20+) and scattered large atypical B cells (CD20+, CD15-, CD30-, bcl6+). Also present are many T cells (CD3+), including many co-expressing CD57. T cells cluster around the large B cells. CD21 highlights expanded dendritic networks of follicular dendritic cells. Case 5 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). Discussion NLPHL comprises 5% of all cases of Hodgkin's lymphoma. There is a male:female ratio of 3:1. Patients are affected over a wide age range with a median in the thirties and a unimodal age distribution, in contrast to classical Hodgkin's lymphoma. The typical presentation is with localized disease involving peripheral lymph nodes, most often cervical, followed by axillary and then by inguinal nodes. Typically there are long disease-free intervals but relapses are common. NLPHL is indolent, with excellent survival in most cases [1]. Those patients who present with high-stage disease may not have a favorable outcome [2]. In approximately 3% of all cases there is an associated diffuse large B-cell lymphoma that may represent outgrowth of the neoplastic cells of the original Hodgkin's lymphoma [3]. Lymph nodes are replaced by an infiltrate that is entirely or partially nodular. The nodules are large, poorly circumscribed and expansile and they contain scattered neoplastic cells (L&H cells or popcorn cells). The large, pale lobated popcorn cells are CD20+ bcl-6+, CD15-, CD30-, CD45+ and Epstein-Barr virus-negative. Single L&H cells that have been extracted and analyzed by PCR are clonal with ongoing mutation of the Ig variable region genes, analogous to normal follicle center cells. The normal counterpart of the L&H cell is believed to be the follicle center centroblast. Reactive cells include lymphocytes, histiocytes and follicular dendritic cells. The lymphocytes in most cases are mostly B-cells with an admixture of T-cells. T-cells tend to cluster around the popcorn cells and in some cases T cells co-express CD57. Nodules are delimited by expanded, motheaten networks of follicular dendritic cells. In addition to this classic pattern, some cases have variant patterns: 1. The nodules may contain small cells that are predominantly T cells (T-cell rich nodular pattern), 2. L&H cells may be found around but outside the nodules (nodular with prominent extranodular L&H cell pattern), 3. Nodules may be serpiginous and interconnected (serpiginous/interconnected nodular pattern), 4. Nodularity can be vague and difficult to appreciate but with a B-cell rich background (diffuse B-cell rich pattern), or 5. There may be diffuse areas with small cells that are mostly T cells, resembling T-cell rich large B-cell lymphoma (T-cell rich large B-cell-like pattern). The presence of a TCR-BCL-like component may indicate a higher risk for recurrence [4]. The differential diagnosis of NLPHL includes classical Hodgkin's lymphoma, especially nodular lymphocyte-rich classical Hodgkin's lymphoma which has a background similar to that of NLPHL [2], T-cell/histiocyte rich large B-cell lymphoma, follicular lymphoma and reactive hyperplasia with prominent progressive transformation of germinal centers [5]. References Wirth A, Yuen K, Barton M, Roos D, Gogna K, Pratt G, et al. Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma: a retrospective multicenter study of the Australasian Radiation Oncology Lymphoma Group. Cancer 2005;104(6):1221-1229. Diehl V, Sextro M, Franklin J, Hansmann M, Harris N, Jaffe E, et al. Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on lymphocyte-predominant Hodgkin's disease. J Clin Oncol 1999;17:776-783. Hansmann M, Stein H, Fellbaum C, Hui P, Parwaresch M, Lennert K. Nodular paragranuloma can transform into high-grade malignant lymphoma of B type. Hum Pathol 1989;20:1169-1175. Fan Z, Natkunam Y, Bair E, Tibshirani R, Warnke R. Characterization of variant patterns of nodular lymphocyte predominant Hodgkin lymphoma with immunohistologic and clinical correlation. Am J Surg Pathol 2003;27:1346-1356. Ferry JA, Zukerberg LR, Harris NL. Florid progressive transformation of germinal centers. A syndrome affecting young men, without early progression to nodular lymphocyte predominance Hodgkin's disease. Am J Surg Pathol 1992;16:252-258.