Nodular lymphocyte-predominant Hodgkin’s lymphoma: Principles of diagnosis and treatment


Aim. To describe the clinical and morphological features of the rare Hodgkin’s lymphoma (HL) subtype — nodular lymphocyte-predominant HL (NLPHL). Subjects and methods. Forty-two patients were diagnosed with NLPHL in 2010 to 2014. The male to female ratio was 2.2:1; the median age was 37 years (range 17—68 years). NLPHL was diagnosed on the basis of the histological and immunohistochemical examinations of tumor biopsy specimens; disease stages were determined by standard HL studies. Results. Before NLPHL was detected, 23 (55%) patients were diagnosed as having HL in 13 cases, follicular lymphoma in 2, lymphofollicular hyperplasia in 3, angioimmunoblastic lymphoma in 1, diffuse large B-cell lymphoma in 3, and B-cell lymphoma (non-HL) in 1. Long-term (3—21-year; median 8 years) persistent lymphadenopathy was observed in 16 (38%) patients. Seventeen (40.5%) patients had early (I—II) stages of the disease and 25 (59.5%) had advanced stages. B symptoms were noted in 24% of cases. There was involvement of extranodal sites (salivary gland, tonsil) in 2 patients, spleen in 14 (33%), bone marrow in 8, and bulky disease in 2. Cycles of ABVD ± rituximab ± radiotherapy (RT) were used in early-stage NLPHL; those of R-ВЕАСОРР-14 ± RT were performed in the advanced stages of the disease or its transformation to diffuse large B-cell lymphoma with excessive T cells. Conclusion. When patients have a history of long-term asymptomatic lymphadenopathy, it is necessary to rule out NLPHL, for which purpose an immunohistochemical examination of a biopsy specimen and its reexamination in a laboratory having experience in diagnosing NLPHL must necessarily be done. Lower RT doses and rituximab incorporated into the cycle of treatment are indicated to reduce its toxicity and to preserve therapeutic efficiency.


  1. Rosenthal SR. Signnificanse of tissue lymphocytes in prognosis of lymphogranulomatosis. Arch Pathol. 1936;21:628-646.
  2. Jakson H, Parker F. Hodgkin’s disease. I. General considerations. NEngl J Med. 1944;230:108.
  3. Jakson H, Parker F. Hodgkin’s disease. II. Pathology. N Engl JMed. 1944;231:35-44.
  4. Jaffe E. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program. 2009:523-531.
  5. Eichenauer D, Engert A. Management of nodular lymphocyte-predominant Hodgkin Lymphoma. Hematol Oncol. 2013;203: 31(Suppl. I):47-50.
  6. Lee A, LaCasle A. Nodular Lymphocyte Predominant Hodgkin Lymphoma. The Oncologist. 2009;14:739-751.
  7. Bazzeh F, Rihani R, Howard S, Sultan I. Comparing adult and pediatric Hodgkin Lymphoma in Surveillance, Epidemiology and End Results Programs Program, 1988—2005: an analysis of 21 734 cases. Leuk Lymphoma. 2010;51(12):2198-2207. doi: 10.3109/10428194.2010.525724.
  8. Diehl V, Sextro M, Franklin J, Hansmann ML, Harris N, Jaffe E, Poppema S, Harris M, Franssila K, van Krieken J, Marafioti T, Anagnostopoulos I, Stein H. Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin’s disease: report from the European Task Forse on lymphocyte-Predominant Hodgkin’s Disease. J Clin Oncol. 1999;17:766-783.
  9. Brune V, Tiacci E, Pfeil I, Döring C, Eckerle S, van Noesel CJ, Klapper W, Falini B, von Heydebreck A, Metzler D, Bräuninger A, Hansmann ML, Küppers R. Origin and pathogenesis of nodular lymphocyte predominant Hodgkin Lymphoma as revealed by global gene expression analysis. J Exper Med. 2008;205:2251-2268. doi: 10.1084/jem.20080809.
  10. Hartmann S, Eichenauer DA, Plütschow A, Mottok A, Bob R, Koch K, Bernd HW, Cogliatti S, Hummel M, Feller AC, Ott G, Möller P, Rosenwald A, Stein H, Hansmann ML, Engert A, Klapper W. The prognostic impact of variant histology in nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG). Blood. 2013;122(26): 4246-4252.
  11. Kuppers R, Rajewsky K, Zhao M, Simons G, Laumann R, Fischer R, Hansmann ML. Hodgkin disease: Hodgkin and Reed-Stenberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci USA. 1994;91:10962-10966.
  12. Rdiger T, Gascoyne RD, Jaffe ES, de Jong D, Delabie J, De Wolf-Peeters C, Poppema S, Xerri L, Gisselbrecht C, Wiedenmann S, Müller-Hermelink HK. Workshop on the relationship between nodular lymphocyte predominant Hodgkin’s lymphoma and T cell/histocyte-rich B cell lymphoma. ANN Oncol. 2002;13(Suppl. 1):44-51. doi: 10.3324/haematol.2009.016931.
  13. Franke S, Wlodarska I, Maes B, Vandenberghe P, Delabie J, Hagemeijer A, De Wolf-Peeters C. Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic imbalances. Blood. 2001;97:1845-1853.
  14. Falini B, Bigerna B, Pasqualucci L, Fizzotti M, Martelli MF, Pileri S, Pinto A, Carbone A, Venturi S, Pacini R, Cattoretti G, Pescarmona E, Lo Coco F, Pelicci PG, Anagnastopoulos I, Dalla-Favera R, Flenghi L. Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin’s disease. Blood. 1996;87:465-471.
  15. Anagnostopoulos I, Hansmann M, Fransilla K, Harris M, Harris NL, Jaffe ES, Han J, van Krieken JM, Poppema S, Marafioti T, Franklin J, Sextro M, Diehl V, Stein H. 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 grouth pattern and abundant lymphocytes. Blood. 2000;96:1889-1899.
  16. Ковригина А.М., Пробатова Н.А. Лимфома Ходжкина и крупноклеточные лимфомы. М.: МИА; 2007:61-62.
  17. Nagova L, Reineke T, Brillant C, Sieniawski М, Rüdiger T, Josting A, Bredenfeld H, Skripnitchenko R, Müller RP, Müller-Hermelink HK, Diehl V, Engert A. German Hodgkin Study Group. Lymphocyte-predominant and classical Hodgkin’s Lymphoma: a comprehensive analysis from German Hodgkin Study Group. J ClinOncol. 2008;26(3):434-439.
  18. Bodis S, Kraus MD, Pinkus G, Silver B, Kadin ME, Canellos GP, Shulman LN, Tarbell NJ, Mauch PM. Clinical presentation and outcome in lymphocyte-predominant Hodgkin’s disease. J Clin Oncol. 1997;26:359-368.
  19. Biasoli I, Stamatoullas A, Meignin V, Delmer A, Reman O, Morschhauser F, Coiffier B, Bosly A, Diviné M, Brice P. Nodular lymphocyte-predominant Hodgkin lymphoma: a long-term stady and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group. Cancer. 2010;116:631-639. doi: 10.1002/cncr.24819.
  20. Al-Mansour M, Connors JM, Cascoune RD, Skinnider B, Savage KJ. Transformation to aggressive lymphoma in nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol. 2010;28: 793-799. doi: 10.1200/jco.2009.24.9516.
  21. Appel BE, Ehrlich P, Chen L, Hutchinson RE, Hodgson DC, Constine LS, Schwartz CL. Treatment of pediatric stage IA lymphocyte-predominant Hodgkin lymphoma with surgical resection alone: A report from the Children Oncology Group. ASCO Meeting abstracts. 2012;30(15-suppl):9524.
  22. Engert A, Plutschow A, Eich H, Lohri A, Dörken B, Borchmann P, Berger B, Greil R, Willborn KC, Wilhelm M, Debus J, Eble MJ, Sökler M, Ho A, Rank A, Ganser A, Trümper L, Bokemeyer C, Kirchner H, Schubert J, Král Z, Fuchs M, Müller-Hermelink HK, Müller RP, Diehl V. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Eng J Med. 2010;363:640-652. doi: 10.1056/nejmoa1000067.
  23. Bierman P, Naushad H, Loberiza F. High-dose chemotherapy followed by autologous hematopoetic stem cell transplantation (AHSCT) for lymphocyte predominance Hodgkin’s disease. ASH Annual Meeting Abstr. 2006;108(11):3061.
  24. Jackson C, Sirohi B, Cunningham D, Horwich A, Thomas K, Wotherspoon A. Lymphocyte-predominant Hodgkin lymphoma — clinical features and treatment outcomes from a 30-yer experience. Ann Oncol. 2010;21:2061-2068. doi: 10.1093/annonc/mdq063.
  25. Ekstrand B, Lucas J, Horwitz S, Fan Z, Breslin S, Hoppe RT, Natkunam Y, Bartlett NL, Horning SJ. Rituximab in lymphocyte predominant Hodgkin disease: Results of phase 2 trial. Blood. 2003;101:4285-4289.
  26. Eichenauer D, Fuchs M, Pluetchow A, Klimm B, Halbsguth T, Böll B, von Tresckow B, Nogová L, Borchmann P, Engert A. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011;118(16):4363-4365. doi: 10.1182/blood-2011-06-361055.
  27. Advani RH, Horning SJ, Hoppe RT, Daadi S, Allen J, Natkunam Y, Bartlett NL. Mature results of a phase II study of rituximab therapy for nodular lymphocyte predominant Hodgkin lymphoma. JClin Oncol. 2014;32(9):912-918. doi: 10.1200/jco.2013.53.2069.

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