Synonyms
Definition
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma (HL) with distinct clinical, morphological, immunophenotypical, and molecular features.
Clinical Features
Incidence: HL has an incidence of 3:100,000 (Küppers et al. 2012). NLPHL constitutes between 5% and 16% of all HL cases (Saarinen et al. 2013), depending on locoregional differences.
Age: NLPHL affects patients of a broad age range. This includes pediatric patients from the age of approximately 5 years up to elderly patients around 80 years (Anagnostopoulos et al. 2000; Shankar et al. 2015). The median age is 40 years.
Sex: NLPHL shows an important predominance of the male gender with around 75% of patients being males (Anagnostopoulos et al. 2000). Male patients have a sixfold increased risk of relapse (Hartmann et al. 2013b).
Site: NLPHL affects primarily lymph nodes. Most frequently axillary, cervical, and inguinal lymph nodes are affected. Patients...
References and Further Reading
Al-Mansour, M., Connors, J. M., Gascoyne, R. D., Skinnider, B., & Savage, K. J. (2010). Transformation to aggressive lymphoma in nodular lymphocyte-predominant Hodgkin’s lymphoma. Journal of Clinical Oncology, 28, 793–799.
Anagnostopoulos, I., Hansmann, M. L., Franssila, K., Harris, M., Harris, N. L., Jaffe, E. S., Han, J., van Krieken, J. M., Poppema, S., Marafioti, T., Franklin, J., Sextro, M., Diehl, V., & Stein, H. (2000). European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: Histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes. Blood, 96, 1889–1899.
Bakhirev, A. G., Vasef, M. A., Zhang, Q. Y., Reichard, K. K., & Czuchlewski, D. R. (2014). Fluorescence immunophenotyping and interphase cytogenetics (FICTION) detects BCL6 abnormalities, including gene amplification, in most cases of nodular lymphocyte-predominant Hodgkin lymphoma. Archives of Pathology & Laboratory Medicine, 138, 538–542.
Biasoli, I., Stamatoullas, A., Meignin, V., Delmer, A., Reman, O., Morschhauser, F., Coiffier, B., Bosly, A., Divine, M., & Brice, P. (2010). Nodular, lymphocyte-predominant Hodgkin lymphoma: A long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group. Cancer, 116, 631–639.
Braeuninger, A., Küppers, R., Strickler, J. G., Wacker, H. H., Rajewsky, K., & Hansmann, M. L. (1997). Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells. Proceedings of the National Academy of Sciences of the United States of America, 94, 9337–9342.
Brune, V., Tiacci, E., Pfeil, I., Doring, C., Eckerle, S., van Noesel, C. J., Klapper, W., Falini, B., von Heydebreck, A., Metzler, D., Brauninger, A., Hansmann, M. L., & Kuppers, R. (2008). Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis. The Journal of Experimental Medicine, 205, 2251–2268.
Carbone, A., Gloghini, A., Gaidano, G., Franceschi, S., Capello, D., Drexler, H. G., Falini, B., & Dalla-Favera, R. (1998). Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin’s disease. Blood, 92, 2220–2228.
Chen, B. J., Chapuy, B., Ouyang, J., Sun, H. H., Roemer, M. G., Xu, M. L., Yu, H., Fletcher, C. D., Freeman, G. J., Shipp, M. A., & Rodig, S. J. (2013). PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clinical Cancer Research, 19, 3462–3473.
Churchill, H. R., Roncador, G., Warnke, R. A., & Natkunam, Y. (2010). Programmed death 1 expression in variant immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma: Comparison with CD57 and lymphomas in the differential diagnosis. Human Pathology, 41, 1726–1734.
Eichenauer, D. A., Fuchs, M., Pluetschow, A., Klimm, B., Halbsguth, T., Boll, B., von Tresckow, B., Nogova, L., Borchmann, P., & Engert, A. (2011). Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: A report from the German Hodgkin Study Group. Blood, 118, 4363–4365.
Eichenauer, D. A., Plutschow, A., Fuchs, M., von Tresckow, B., Boll, B., Behringer, K., Diehl, V., Eich, H. T., Borchmann, P., & Engert, A. (2015). Long-term course of patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma: A report from the German Hodgkin Study Group. Journal of Clinical Oncology, 33, 2857–2862.
Fan, Z., Natkunam, Y., Bair, E., Tibshirani, R., & Warnke, R. A. (2003). Characterization of variant patterns of nodular lymphocyte predominant Hodgkin lymphoma with immunohistologic and clinical correlation. The American Journal of Surgical Pathology, 27, 1346–1356.
Hartmann, S., Doring, C., Jakobus, C., Rengstl, B., Newrzela, S., Tousseyn, T., Sagaert, X., Ponzoni, M., Facchetti, F., de Wolf-Peeters, C., Steidl, C., Gascoyne, R., Kuppers, R., & Hansmann, M. L. (2013a). Nodular lymphocyte predominant Hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma – Endpoints of a spectrum of one disease? PLoS One, 8, e78812.
Hartmann, S., Eichenauer, D. A., Plutschow, A., Mottok, A., Bob, R., Koch, K., Bernd, H. W., Cogliatti, S., Hummel, M., Feller, A. C., Ott, G., Moller, P., Rosenwald, A., Stein, H., Hansmann, M. L., Engert, A., & Klapper, W. (2013b). The prognostic impact of variant histology in nodular lymphocyte-predominant Hodgkin lymphoma: A report from the German Hodgkin Study Group (GHSG). Blood, 122, 4246–4252.
Hartmann, S., Eichenauer, D. A., Plutschow, A., Mottok, A., Bob, R., Koch, K., Bernd, H. W., Cogliatti, S., Hummel, M., Feller, A. C., Ott, G., Moller, P., Rosenwald, A., Stein, H., Hansmann, M. L., Engert, A., & Klapper, W. (2014a). Histopathological features and their prognostic impact in nodular lymphocyte-predominant Hodgkin lymphoma – A matched pair analysis from the German Hodgkin Study Group (GHSG). British Journal of Haematology, 167, 238–242.
Hartmann, S., Eray, M., Doring, C., Lehtinen, T., Brunnberg, U., Kujala, P., Vornanen, M., & Hansmann, M. L. (2014b). Diffuse large B cell lymphoma derived from nodular lymphocyte predominant Hodgkin lymphoma presents with variable histopathology. BMC Cancer, 14, 332.
Hartmann, S., Doring, C., Vucic, E., Chan, F. C., Ennishi, D., Tousseyn, T., de Wolf-Peeters, C., Perner, S., Wlodarska, I., Steidl, C., Gascoyne, R. D., & Hansmann, M. L. (2015a). Array comparative genomic hybridization reveals similarities between nodular lymphocyte predominant Hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma. British Journal of Haematology, 169, 415–422.
Hartmann, S., Winkelmann, R., Metcalf, R. A., Treetipsatit, J., Warnke, R. A., Natkunam, Y., & Hansmann, M. L. (2015b). Immunoarchitectural patterns of progressive transformation of germinal centers with and without nodular lymphocyte-predominant Hodgkin lymphoma. Human Pathology, 46, 1655–1661.
Hartmann, S., Schuhmacher, B., Rausch, T., Fuller, L., Doring, C., Weniger, M., Lollies, A., Weiser, C., Thurner, L., Rengstl, B., Brunnberg, U., Vornanen, M., Pfreundschuh, M., Benes, V., Kuppers, R., Newrzela, S., & Hansmann, M. L. (2016). Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma. Leukemia, 30, 844–853.
Huppmann, A. R., Nicolae, A., Slack, G. W., Pittaluga, S., Davies-Hill, T., Ferry, J. A., Harris, N. L., Jaffe, E. S., & Hasserjian, R. P. (2014). EBV may be expressed in the LP cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in both children and adults. The American Journal of Surgical Pathology, 38, 316–324.
Küppers, R. (2009). The biology of Hodgkin’s lymphoma. Nature Reviews. Cancer, 9, 15–27.
Küppers, R., Engert, A., & Hansmann, M. L. (2012). Hodgkin lymphoma. The Journal of Clinical Investigation, 122, 3439–3447.
Liso, A., Capello, D., Marafioti, T., Tiacci, E., Cerri, M., Distler, V., Paulli, M., Carbone, A., Delsol, G., Campo, E., Pileri, S., Pasqualucci, L., Gaidano, G., & Falini, B. (2006). Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma. Blood, 108, 1013–1020.
Mauz-Korholz, C., Gorde-Grosjean, S., Hasenclever, D., Shankar, A., Dorffel, W., Wallace, W. H., Schellong, G., Robert, A., Korholz, D., Oberlin, O., Hall, G. W., & Landman-Parker, J. (2007). Resection alone in 58 children with limited stage, lymphocyte-predominant Hodgkin lymphoma-experience from the European network group on pediatric Hodgkin lymphoma. Cancer, 110, 179–185.
Moroch, J., Copie-Bergman, C., de Leval, L., Plonquet, A., Martin-Garcia, N., Delfau-Larue, M. H., Molinier-Frenkel, V., Belhadj, K., Haioun, C., Audouin, J., Swerdlow, S. H., Marafioti, T., & Gaulard, P. (2012). Follicular peripheral T-cell lymphoma expands the spectrum of classical Hodgkin lymphoma mimics. The American Journal of Surgical Pathology, 36, 1636–1646.
Mottok, A., Renne, C., Willenbrock, K., Hansmann, M. L., & Brauninger, A. (2007). Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6. Blood, 110, 3387–3390.
Nicolae, A., Pittaluga, S., Venkataraman, G., Vijnovich-Baron, A., Xi, L., Raffeld, M., & Jaffe, E. S. (2013). Peripheral T-cell lymphomas of follicular T-helper cell derivation with Hodgkin/Reed-Sternberg cells of B-cell lineage: Both EBV-positive and EBV-negative variants exist. The American Journal of Surgical Pathology, 37, 816–826.
Prakash, S., Fountaine, T., Raffeld, M., Jaffe, E. S., & Pittaluga, S. (2006). IgD positive L&H cells identify a unique subset of nodular lymphocyte predominant Hodgkin lymphoma. The American Journal of Surgical Pathology, 30, 585–592.
Quintanilla-Martinez, L., Fend, F., Moguel, L. R., Spilove, L., Beaty, M. W., Kingma, D. W., Raffeld, M., & Jaffe, E. S. (1999). Peripheral T-cell lymphoma with Reed-Sternberg-like cells of B-cell phenotype and genotype associated with Epstein-Barr virus infection. The American Journal of Surgical Pathology, 23, 1233–1240.
Rahemtullah, A., Reichard, K. K., Preffer, F. I., Harris, N. L., & Hasserjian, R. P. (2006). A double-positive CD4+CD8+ T-cell population is commonly found in nodular lymphocyte predominant Hodgkin lymphoma. American Journal of Clinical Pathology, 126, 805–814.
Rahemtullah, A., Harris, N. L., Dorn, M. E., Preffer, F. I., & Hasserjian, R. P. (2008). Beyond the lymphocyte predominant cell: CD4+CD8+ T-cells in nodular lymphocyte predominant Hodgkin lymphoma. Leukemia & Lymphoma, 49, 1870–1878.
Renné, C., Martin-Subero, J. I., Hansmann, M. L., & Siebert, R. (2005). Molecular cytogenetic analyses of immunoglobulin loci in nodular lymphocyte predominant Hodgkin’s lymphoma reveal a recurrent IGH-BCL6 juxtaposition. The Journal of Molecular Diagnostics, 7, 352–356.
Saarinen, S., Aavikko, M., Aittomaki, K., Launonen, V., Lehtonen, R., Franssila, K., Lehtonen, H. J., Kaasinen, E., Broderick, P., Tarkkanen, J., Bain, B. J., Bauduer, F., Unal, A., Swerdlow, A. J., Cooke, R., Makinen, M. J., Houlston, R., Vahteristo, P., & Aaltonen, L. A. (2011). Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma. Blood, 118, 493–498.
Saarinen, S., Pukkala, E., Vahteristo, P., Makinen, M. J., Franssila, K., & Aaltonen, L. A. (2013). High familial risk in nodular lymphocyte-predominant Hodgkin lymphoma. Journal of Clinical Oncology, 31, 938–943.
Sattarzadeh, A., Diepstra, A., Rutgers, B., van den Berg, A., & Visser, L. (2015). CD57+ T-cells are a subpopulation of T-follicular helper cells in nodular lymphocyte predominant Hodgkin lymphoma. Experimental Hematology & Oncology, 4, 27.
Schmid, C., Sargent, C., & Isaacson, P. G. (1991). L and H cells of nodular lymphocyte predominant Hodgkin’s disease show immunoglobulin light-chain restriction. The American Journal of Pathology, 139, 1281–1289.
Shankar, A. G., Kirkwood, A. A., Hall, G. W., Hayward, J., O’Hare, P., & Ramsay, A. D. (2015). Childhood and adolescent nodular lymphocyte predominant Hodgkin lymphoma – A review of clinical outcome based on the histological variants. British Journal of Haematology, 171, 254–262.
Shankar, A. G., Roques, G., Kirkwood, A. A., Lambilliotte, A., Freund, K., Leblanc, T., Hayward, J., Abbou, S., Ramsay, A. D., Schmitt, C., Gorde-Grosjean, S., Pacquement, H., Haouy, S., Boudjemaa, S., Aladjidi, N., Hall, G. W., & Landman-Parker, J. (2017). Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: Clinical characteristics and treatment outcome – A report from the SFCE & CCLG groups. British Journal of Haematology, 177, 106–115.
Stein, H., Marafioti, T., Foss, H. D., Laumen, H., Hummel, M., Anagnostopoulos, I., Wirth, T., Demel, G., & Falini, B. (2001). Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription. Blood, 97, 496–501.
Tedoldi, S., Mottok, A., Ying, J., Paterson, J. C., Cui, Y., Facchetti, F., van Krieken, J. H., Ponzoni, M., Ozkal, S., Masir, N., Natkunam, Y., Pileri, S., Hansmann, M. L., Mason, D., Tao, Q., & Marafioti, T. (2007). Selective loss of B-cell phenotype in lymphocyte predominant Hodgkin lymphoma. The Journal of Pathology, 213, 429–440.
Torlakovic, E., Tierens, A., Dang, H. D., & Delabie, J. (2001). The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin’s disease. The American Journal of Pathology, 159, 1807–1814.
Wlodarska, I., Nooyen, P., Maes, B., Martin-Subero, J. I., Siebert, R., Pauwels, P., De Wolf-Peeters, C., & Hagemeijer, A. (2003). Frequent occurrence of BCL6 rearrangements in nodular lymphocyte predominance Hodgkin lymphoma but not in classical Hodgkin lymphoma. Blood, 101, 706–710.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this entry
Cite this entry
Hartmann, S. (2019). Hodgkin Lymphoma, Nodular Lymphocyte Predominant. In: van Krieken, J. (eds) Encyclopedia of Pathology. Encyclopedia of Pathology. Springer, Cham. https://doi.org/10.1007/978-3-319-28845-1_3856-1
Download citation
DOI: https://doi.org/10.1007/978-3-319-28845-1_3856-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-28845-1
Online ISBN: 978-3-319-28845-1
eBook Packages: Springer Reference MedicineReference Module Medicine