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Adult Hodgkin Lymphoma Treatment (PDQ®)

Cellular Classification of Adult HL

Pathologists currently use the World Health Organization (WHO) modification of the Revised European-American Lymphoma (REAL) classification for the histologic classification for adult Hodgkin lymphoma (HL).[1,2]

WHO/REAL classification

  • Classical HL.
    • Nodular sclerosis HL.
    • Mixed-cellularity HL.
    • Lymphocyte depletion HL.
    • Lymphocyte-rich classical HL.
  • Nodular lymphocyte–predominant HL.

Among 10,019 patients who underwent central expert pathology review for the German Hodgkin Study Group, 84 patients (<1%) were identified as having lymphocyte-depleted classical HL.[3] These patients present with more advanced-stage HL and usually with B symptoms.

Nodular Lymphocyte–Predominant HL

Nodular lymphocyte–predominant HL is a clinicopathologic entity of B-cell origin that is distinct from classic HL.[4-6] The typical immunophenotype for lymphocyte-predominant disease is CD15-, CD20+, CD30-, CD45+, while the profile for classic HL is CD15+, CD20-, CD30+, CD45-. Patients with lymphocyte-predominant disease have earlier-stage disease, longer survival, and fewer treatment failures than those with classic HL.[7] Despite a usually favorable prognosis, there is a tendency for histologic transformation to diffuse large B-cell lymphoma in around 10% of patients by 10 years.[8] Lymphocyte-predominant HL is usually diagnosed in asymptomatic young males with cervical or inguinal lymph nodes but usually without mediastinal involvement. Based on retrospective analyses spanning several decades and because of the rarity of this histology, limited-field radiation therapy is the most common treatment approach for patients with early-stage disease.[9-11]

The REAL Classification of Lymphoid Neoplasms proposed separating nodular lymphocyte–predominant HL (CD15-, CD20+, CD30-) from lymphocyte-rich classical HL (CD15+, CD20-, CD30+), on the basis of these immunophenotypic differences.[2,12] The largest retrospective report of 426 cases showed no significant difference in clinical response or outcome to standard therapies for these two subgroups.[13][Level of evidence: 3iiiA] Of interest, with a median follow-up of 7 to 8 years, more patients died of treatment-related toxic effects (acute and long-term) than from Hodgkin recurrence. Limitation of radiation dose and fields and avoidance of leukemogenic chemotherapeutic agents, along with watchful waiting policies, should be investigated for these subgroups.[14,15] For patients with advanced-stage nodular lymphocyte–predominant HL, chemotherapy regimens designed for non-HLs may be preferred, based on a retrospective review.[16][Level of evidence: 3iiiDii]


  1. Lukes RJ, Craver LF, Hall TC, et al.: Report of the Nomenclature Committee. Cancer Res 26 (1): 1311, 1966.
  2. Harris NL: Hodgkin's lymphomas: classification, diagnosis, and grading. Semin Hematol 36 (3): 220-32, 1999. [PUBMED Abstract]
  3. Klimm B, Franklin J, Stein H, et al.: Lymphocyte-depleted classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin study group. J Clin Oncol 29 (29): 3914-20, 2011. [PUBMED Abstract]
  4. von Wasielewski R, Mengel M, Fischer R, et al.: Classical Hodgkin's disease. Clinical impact of the immunophenotype. Am J Pathol 151 (4): 1123-30, 1997. [PUBMED Abstract]
  5. Bodis S, Kraus MD, Pinkus G, et al.: Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease. J Clin Oncol 15 (9): 3060-6, 1997. [PUBMED Abstract]
  6. Orlandi E, Lazzarino M, Brusamolino E, et al.: Nodular lymphocyte predominance Hodgkin's disease: long-term observation reveals a continuous pattern of recurrence. Leuk Lymphoma 26 (3-4): 359-68, 1997. [PUBMED Abstract]
  7. Nogová L, Reineke T, Brillant C, et al.: Lymphocyte-predominant and classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin Study Group. J Clin Oncol 26 (3): 434-9, 2008. [PUBMED Abstract]
  8. Al-Mansour M, Connors JM, Gascoyne RD, et al.: Transformation to aggressive lymphoma in nodular lymphocyte-predominant Hodgkin's lymphoma. J Clin Oncol 28 (5): 793-9, 2010. [PUBMED Abstract]
  9. Chen RC, Chin MS, Ng AK, et al.: Early-stage, lymphocyte-predominant Hodgkin's lymphoma: patient outcomes from a large, single-institution series with long follow-up. J Clin Oncol 28 (1): 136-41, 2010. [PUBMED Abstract]
  10. Nogová L, Reineke T, Eich HT, et al.: Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG). Ann Oncol 16 (10): 1683-7, 2005. [PUBMED Abstract]
  11. Wilder RB, Schlembach PJ, Jones D, et al.: European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease. Cancer 94 (6): 1731-8, 2002. [PUBMED Abstract]
  12. Shimabukuro-Vornhagen A, Haverkamp H, Engert A, et al.: Lymphocyte-rich classical Hodgkin's lymphoma: clinical presentation and treatment outcome in 100 patients treated within German Hodgkin's Study Group trials. J Clin Oncol 23 (24): 5739-45, 2005. [PUBMED Abstract]
  13. Diehl V, Sextro M, Franklin J, 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 17 (3): 776-83, 1999. [PUBMED Abstract]
  14. Aster JC: Lymphocyte-predominant Hodgkin's disease: how little therapy is enough? J Clin Oncol 17 (3): 744-6, 1999. [PUBMED Abstract]
  15. Pellegrino B, Terrier-Lacombe MJ, Oberlin O, et al.: Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology. J Clin Oncol 21 (15): 2948-52, 2003. [PUBMED Abstract]
  16. Canellos GP, Mauch P: What is the appropriate systemic chemotherapy for lymphocyte-predominant Hodgkin's lymphoma? J Clin Oncol 28 (1): e8, 2010. [PUBMED Abstract]
  • Updated: April 2, 2015