Clinical manifestations, pathologic features, and diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
- Ann S LaCasce, MD
Ann S LaCasce, MD
- Associate Professor of Medicine
- Harvard Medical School
- Section Editors
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- George P Canellos, MD
George P Canellos, MD
- Editor-in-Chief — Oncology
- Section Editor — Miscellaneous Tumors
- Professor of Medicine
- Harvard Medical School
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma (HL). This disorder is differentiated from all other forms of HL, which are commonly referred to as classical HL, by characteristic pathologic and clinical features.
NLPHL represents a more indolent disease than classical HL, and is therefore managed uniquely. Since this disease is so uncommon, most information concerning treatment and outcome has come from reports of single institutions or pooled, multi-institutional retrospective analyses.
The epidemiology, pathogenesis, clinical presentation, pathology, diagnosis, and differential diagnosis of NLPHL are reviewed here. Treatment and prognosis of NLPHL are discussed separately as is the diagnosis of classical HL. (See "Treatment of nodular lymphocyte-predominant Hodgkin lymphoma" and "Epidemiology, pathologic features, and diagnosis of classical Hodgkin lymphoma".)
Approximately 5 percent of patients initially diagnosed with HL have the uncommon variant NLPHL . The incidence of NLPHL in the United States and Europe has been stable at approximately 8 to 9 cases per 10,000,000 people per year [2,3]. For unknown reasons, an increase in incidence among children has been noted.
Approximately 75 percent of patients with NLPHL are male . The age distribution has two peaks: one in children and one in adults, the latter with a median age of 30 to 40 years [4,5]. Unlike classical HL, NLPHL is more common in the United States among African-Americans compared with Caucasians .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
- Morton LM, Wang SS, Devesa SS, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood 2006; 107:265.
- Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010; 116:3724.
- 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 1999; 17:776.
- Saarinen S, Pukkala E, Vahteristo P, et al. High familial risk in nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol 2013; 31:938.
- Braeuninger A, Küppers R, Strickler JG, et al. Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells. Proc Natl Acad Sci U S A 1997; 94:9337.
- Marafioti T, Hummel M, Anagnostopoulos I, et al. Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B cells. N Engl J Med 1997; 337:453.
- Ohno T, Stribley JA, Wu G, et al. Clonality in nodular lymphocyte-predominant Hodgkin's disease. N Engl J Med 1997; 337:459.
- Liso A, Capello D, Marafioti T, et al. Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma. Blood 2006; 108:1013.
- Wlodarska I, Nooyen P, Maes B, et al. Frequent occurrence of BCL6 rearrangements in nodular lymphocyte predominance Hodgkin lymphoma but not in classical Hodgkin lymphoma. Blood 2003; 101:706.
- Mottok A, Renné C, Willenbrock K, et al. Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6. Blood 2007; 110:3387.
- Hartmann S, Schuhmacher B, Rausch T, et al. Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma. Leukemia 2016; 30:844.
- Schmitz R, Stanelle J, Hansmann ML, Küppers R. Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma. Annu Rev Pathol 2009; 4:151.
- Brune V, Tiacci E, Pfeil I, et al. Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis. J Exp Med 2008; 205:2251.
- Miettinen M, Franssila KO, Saxén E. Hodgkin's disease, lymphocytic predominance nodular. Increased risk for subsequent non-Hodgkin's lymphomas. Cancer 1983; 51:2293.
- Boudová L, Torlakovic E, Delabie J, et al. Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma. Blood 2003; 102:3753.
- Rüdiger T, Gascoyne RD, Jaffe ES, et al. Workshop on the relationship between nodular lymphocyte predominant Hodgkin's lymphoma and T cell/histiocyte-rich B cell lymphoma. Ann Oncol 2002; 13 Suppl 1:44.
- Weiss LM, Chen YY, Liu XF, Shibata D. Epstein-Barr virus and Hodgkin's disease. A correlative in situ hybridization and polymerase chain reaction study. Am J Pathol 1991; 139:1259.
- Uccini S, Monardo F, Stoppacciaro A, et al. High frequency of Epstein-Barr virus genome detection in Hodgkin's disease of HIV-positive patients. Int J Cancer 1990; 46:581.
- Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
- Regula DP Jr, Hoppe RT, Weiss LM. Nodular and diffuse types of lymphocyte predominance Hodgkin's disease. N Engl J Med 1988; 318:214.
- Mauch PM, Kalish LA, Kadin M, et al. Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis. Cancer 1993; 71:2062.
- Borg-Grech A, Radford JA, Crowther D, et al. A comparative study of the nodular and diffuse variants of lymphocyte-predominant Hodgkin's disease. J Clin Oncol 1989; 7:1303.
- 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 2005; 23:5739.
- Bodis S, Kraus MD, Pinkus G, et al. Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease. J Clin Oncol 1997; 15:3060.
- Ha CS, Kavadi V, Dimopoulos MA, et al. Hodgkin's disease with lymphocyte predominance: long-term results based on current histopathologic criteria. Int J Radiat Oncol Biol Phys 1999; 43:329.
- Leibenhaut MH, Hoppe RT, Efron B, et al. Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease. J Clin Oncol 1989; 7:81.
- Khoury JD, Jones D, Yared MA, et al. Bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma. Am J Surg Pathol 2004; 28:489.
- Li G, Hansmann ML. Lymphocyte predominant Hodgkin's disease of nodular subtype combined with pulmonary lymphoid infiltration and hypogammaglobulinaemia. Virchows Arch A Pathol Anat Histopathol 1989; 415:481.
- Jackson HJ, Parker FJ. Hodgkin's disease. II. Pathology N Engl J Med 1944; 231:35.
- WRIGHT CJ. The "benign" form of Hodgkin's disease (Hodgkin's paragranuloma). J Pathol Bacteriol 1960; 80:157.
- SMETANA HF, COHEN BM. Mortality in relation to histologic type in Hodgkin's disease. Blood 1956; 11:211.
- HANSON TA. HISTOLOGICAL CLASSIFICATION AND SURVIVAL IN HODGKIN'S DISEASE; A STUDY OF 251 CASES WITH SPECIAL REFERENCE TO NODULAR SCLEROSING HODGKIN'S DISEASE. Cancer 1964; 17:1595.
- Lukes RJ, Butler JJ. The pathology and nomenclature of Hodgkin's disease. Cancer Res 1966; 26:1063.
- Morton LM, Turner JJ, Cerhan JR, et al. Proposed classification of lymphoid neoplasms for epidemiologic research from the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph). Blood 2007; 110:695.
- Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84:1361.
- Swerdlow SH, Campo E, Harris NL, et al. WHO classification of Tumors of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Falini B, Bigerna B, Pasqualucci L, et al. Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease. Blood 1996; 87:465.
- Nogová L, Rudiger T, Engert A. Biology, clinical course and management of nodular lymphocyte-predominant hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2006; :266.
- Hartmann S, Eichenauer DA, Plütschow A, et al. Histopathological features and their prognostic impact in nodular lymphocyte-predominant Hodgkin lymphoma--a matched pair analysis from the German Hodgkin Study Group (GHSG). Br J Haematol 2014; 167:238.
- Hicks J, Flaitz C. Progressive transformation of germinal centers: review of histopathologic and clinical features. Int J Pediatr Otorhinolaryngol 2002; 65:195.
- Verma A, Stock W, Norohna S, et al. Progressive transformation of germinal centers. Report of 2 cases and review of the literature. Acta Haematol 2002; 108:33.
- Maes B, Anastasopoulou A, Kluin-Nelemans JC, et al. Among diffuse large B-cell lymphomas, T-cell-rich/histiocyte-rich BCL and CD30+ anaplastic B-cell subtypes exhibit distinct clinical features. Ann Oncol 2001; 12:853.
- de Jong D, Bosq J, MacLennan KA, et al. Lymphocyte-rich classical Hodgkin lymphoma (LRCHL): clinico-pathological characteristics and outcome of a rare entity. Ann Oncol 2006; 17:141.
- Carbone PP, Kaplan HS, Musshoff K, et al. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 1971; 31:1860.
- Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7:1630.
- Pappa VI, Norton AJ, Gupta RK, et al. Nodular type of lymphocyte predominant Hodgkin's disease. A clinical study of 50 cases. Ann Oncol 1995; 6:559.
- Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol 2014; 32:3048.
- Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32:3059.
- CLINICAL MANIFESTATIONS
- Classification schemes
- - REAL classification
- - WHO classification
- - L&H variant
- - Background cells
- - Growth pattern
- DIFFERENTIAL DIAGNOSIS
- Reactive hyperplasia or PTGC
- T cell/HRBCL
- Lymphocyte-rich classical HL
- History and physical examination
- Blood studies
- Computed tomography (CT)
- Bone marrow exam
- Staging laparotomy
- PET scan
- SUMMARY AND RECOMMENDATIONS