Rare B-Cell Non-Hodgkin’s Lymphomas in Childhood and Adolescence

  • Auke BeishuizenEmail author
  • Vasiliki Tzotzola
  • Lena Uzunova
  • Amos Burke


Non-Hodgkin’s lymphoma (NHL) results from malignant proliferation of lymphocytes and is generally restricted to lymphoid tissue such as lymph nodes, Peyer’s patches, and spleen. However, pediatric NHL can rarely and solely arise in other anatomical sites, such as the kidney, skin, lung, eye, bone, stomach, or cavities as an effusion. Adult-type lymphomas (chronic lymphocytic leukemia and multiple myeloma) have scarcely been reported in children. Understanding of these rare pediatric B-NHLs is mainly based on small pediatric case series or adult studies. Due to the limited number of cases the exact prevalence of the abovementioned NHL types cannot be easily estimated. Moreover, the index of suspicion is usually low because of the rarity, resulting sometimes in late diagnosis with a significant impact on prognosis. Since these NHL types are often more well-studied in adult population, adult-based therapeutic approaches are also applied in children. Prognosis in pediatric patients may be different from that of adults. So, more international collaborative efforts are needed in order to identify specific prognostic factors, including molecular and cytogenetic variables and define specific pediatric treatment protocols.


Rare B-NHL Primary extra-nodal B-NHL Adult B-NHL 


  1. 1.
    Airaghi L, et al. Unusual presentation of large B cell lymphoma: a case report and review of literature. Clin Lab Haematol. 2006;28:338–42. Scholar
  2. 2.
    Tefekli A, Baykal M, Binbay M, Barut M, Muslumanoglu AY. Lymphoma of the kidney: primary or initial manifestation of rapidly progressive systemic disease? Int Urol Nephrol. 2006;38:775–8. Scholar
  3. 3.
    Torrecilla Garcia-Ripoll JR, et al. Primary renal lymphoma. Actas Urol Esp. 2003;27:555–8.CrossRefGoogle Scholar
  4. 4.
    Ahmad AH, Maclennan GT, Listinsky C. Primary renal lymphoma: a rare neoplasm that may present as a primary renal mass. J Urol. 2005;173:239. Scholar
  5. 5.
    Baran A, Küpeli S, Doğru Ö. A pediatric renal lymphoma case presenting with central nervous system findings. Turkish Journal of Hematology. 2013;30:191–3. Scholar
  6. 6.
    Dhull VS, et al. Bilateral primary renal lymphoma in a pediatric patient: staging and response evaluation with (1)(8)F-FDG PET/CT. Rev Esp Med Nucl Imagen Mol. 2015;34:49–52. Scholar
  7. 7.
    Karadeniz C, et al. Primary renal lymphoma and xanthogranulomatous pyelonephritis in childhood. J Nephrol. 2002;15:597–600.PubMedGoogle Scholar
  8. 8.
    Malbrain ML, et al. Acute renal failure due to bilateral lymphomatous infiltrates. Primary extranodal non-Hodgkin’s lymphoma (p-EN-NHL) of the kidneys: does it really exist? Clin Nephrol. 1994;42:163–9.PubMedGoogle Scholar
  9. 9.
    Stallone G, et al. Primary renal lymphoma does exist: case report and review of the literature. J Nephrol. 2000;13:367–72.PubMedGoogle Scholar
  10. 10.
    Okuno SH, Hoyer JD, Ristow K, Witzig TE. Primary renal non-Hodgkin’s lymphoma. An unusual extranodal site. Cancer. 1995;75:2258–61.CrossRefGoogle Scholar
  11. 11.
    Sieniawska M, Bialasik D, Jedrzejowski A, Sopylo B, Maldyk J. Bilateral primary renal Burkitt lymphoma in a child presenting with acute renal failure. Nephrol Dial Transplant. 1997;12:1490–2. Scholar
  12. 12.
    Hagihara M, Hua J, Iwaki Y, Inoue M, Sato T. Primary renal lymphoma: a case report and literature review. Intern Med. 2015;54:2655–9. Scholar
  13. 13.
    Estrella C-C, et al. Role of 18F-FDG-PET/CT in the management of Burkitt lymphoma. Eur J Haematol. 2015;94:23–30. Scholar
  14. 14.
    Kumar D, et al. Pediatric renal non-hodgkin lymphoma with inferior vena cava thrombosis. J Pediatr Hematol Oncol. 2010;32:147–9. Scholar
  15. 15.
    Paladugu S, Garro R, Schrijver I, Kambham N, Higgins JPT. A 30-month-old child with acute renal failure due to primary renal cytotoxic T-cell lymphoma. Am J Surg Pathol. 2010;34:1066–70. Scholar
  16. 16.
    Shetty S, Singh AC, Babu V. Primary renal lymphoma - a case report and review of literature. J Clin Diagn Res. 2016;10:XD05–7. Scholar
  17. 17.
    Swerdlow SH, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90.CrossRefGoogle Scholar
  18. 18.
    Simonelli C, et al. Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J Clin Oncol. 2003;21:3948–54. Scholar
  19. 19.
    Karadeniz C, et al. Primary pleural lymphoma: an unusual presentation of childhood non-Hodgkin lymphoma. Pediatr Hematol Oncol. 2000;17:695–9. Scholar
  20. 20.
    Ravikumar G, Tirumalae R, Das K. Primary pleural non-Hodgkin lymphoma in a child--an exceedingly rare disease. J Pediatr Surg. 2012;47:e29–31. Scholar
  21. 21.
    Okada S, Goto H, Yotsumoto M. Current status of treatment for primary effusion lymphoma. Intractable Rare Dis Res. 2014;3:65–74.CrossRefGoogle Scholar
  22. 22.
    Boulanger E, et al. Prognostic factors and outcome of human herpesvirus 8-associated primary effusion lymphoma in patients with AIDS. J Clin Oncol. 2005;23:4372–80. Scholar
  23. 23.
    Luppi M, et al. Treatment of herpesvirus associated primary effusion lymphoma with intracavity cidofovir. Leukemia. 2005;19:473–6. Scholar
  24. 24.
    Siddiqi T, Joyce RM. A case of HIV-negative primary effusion lymphoma treated with bortezomib, pegylated liposomal doxorubicin, and rituximab. Clin Lymphoma Myeloma. 2008;8:300–4. Scholar
  25. 25.
    Terasaki Y, et al. Disappearance of malignant cells by effusion drainage alone in two patients with HHV-8-unrelated HIV-negative primary effusion lymphoma-like lymphoma. Int J Hematol. 2011;94:279–84. Scholar
  26. 26.
    Servitje O, et al. Primary cutaneous marginal zone B-cell lymphoma: a clinical, histopathological, immunophenotypic and molecular genetic study of 22 cases. Br J Dermatol. 2002;147:1147–58.CrossRefGoogle Scholar
  27. 27.
    Kimura H, et al. EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases. Blood. 2012;119:673–86. Scholar
  28. 28.
    Soda R, et al. Systemic therapy of primary cutaneous B-cell lymphoma, marginal zone type, with rituximab, a chimeric anti-CD20 monoclonal antibody. Acta Derm Venereol. 2001;81:207–8.CrossRefGoogle Scholar
  29. 29.
    Senff NJ, et al. European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas. Blood. 2008;112:1600–9. Scholar
  30. 30.
    Kempf W, Denisjuk N, Kerl K, Cozzio A, Sander C. Primary cutaneous B-cell lymphomas. J Dtsch Dermatol Ges. 2012;10:12–22; quiz 23. Scholar
  31. 31.
    Kempf W, Sander CA. Classification of cutaneous lymphomas - an update. Histopathology. 2010;56:57–70. Scholar
  32. 32.
    Abdul-Wahab A, et al. Chromosomal anomalies in primary cutaneous follicle center cell lymphoma do not portend a poor prognosis. J Am Acad Dermatol. 2014;70:1010–20. Scholar
  33. 33.
    Ghislanzoni M, Gambini D, Perrone T, Alessi E, Berti E. Primary cutaneous follicular center cell lymphoma of the nose with maxillary sinus involvement in a pediatric patient. J Am Acad Dermatol. 2005;52:S73–5. Scholar
  34. 34.
    Amitay-Laish I, et al. Juvenile onset of primary low-grade cutaneous B-cell lymphoma. Br J Dermatol. 2009;161:140–7. Scholar
  35. 35.
    Willemze R. Primary cutaneous B-cell lymphoma: classification and treatment. Curr Opin Oncol. 2006;18:425–31. Scholar
  36. 36.
    Black CL, Foster-Smith E, Lewis ID, Faull RJ, Sidhu SK. Post-transplant plasmablastic lymphoma of the skin. Australas J Dermatol. 2013;54:277–82. Scholar
  37. 37.
    Hernandez C, Cetner AS, Wiley EL. Cutaneous presentation of plasmablastic post-transplant lymphoproliferative disorder in a 14-month-old. Pediatr Dermatol. 2009;26:713–6. Scholar
  38. 38.
    Apichai S, et al. Multifocal cutaneous and systemic plasmablastic lymphoma in an infant with combined living donor small bowel and liver transplant. Pediatr Transplant. 2009;13:628–31. Scholar
  39. 39.
    Liebow AA, Carrington CRB, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol. 1972;3:457–558. Scholar
  40. 40.
    Guinee D Jr, et al. Pulmonary lymphomatoid granulomatosis. Evidence for a proliferation of Epstein-Barr virus infected B-lymphocytes with a prominent T-cell component and vasculitis. Am J Surg Pathol. 1994;18(8):753.CrossRefGoogle Scholar
  41. 41.
    Tacke ZC, et al. Childhood lymphomatoid granulomatosis: a report of 2 cases and review of the literature. J Pediatr Hematol Oncol. 2014; Scholar
  42. 42.
    Lee S, Kang M-J, Kim H-J, Kim H-B, Lee J. Pulmonary lymphomatoid granulomatosis in a 4-year-old girl. Pediatr Radiol. 2015;45:1082–5. Scholar
  43. 43.
    Aboobaker S, Tinley C. Primary orbital lymphomatoid granulomatosis in a 1-year-old child. Middle East Afr J Ophthalmol. 2015;22:517–9.CrossRefGoogle Scholar
  44. 44.
    Ghosh S, Bienemann K, Boztug K, Borkhardt A. Interleukin-2-inducible T-Cell Kinase (ITK) deficiency - clinical and molecular aspects. J Clin Immunol. 2014;34:892–9. Scholar
  45. 45.
    Hernandez-Marques C, et al. Rituximab in lymphomatoid granulomatosis. J Pediatr Hematol Oncol. 2014;36:e69–74. Scholar
  46. 46.
    Desai A, et al. Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study. Blood. 2017;129:324–32.CrossRefGoogle Scholar
  47. 47.
    Ponzoni M, et al. A reappraisal of the diagnostic and therapeutic management of uncommon histologies of primary ocular adnexal lymphoma. Oncologist. 2013;18:876–84. Scholar
  48. 48.
    Ferry JA, et al. Lymphoma of the ocular adnexa: a study of 353 cases. Am J Surg Pathol. 2007;31:170–84. Scholar
  49. 49.
    Sjö LD, et al. Increasing incidence of ophthalmic lymphoma in Denmark from 1980 to 2005. Invest Ophthalmol Vis Sci. 2008;49:3283–8. Scholar
  50. 50.
    Verdijk RM. Lymphoproliferative tumors of the ocular adnexa. Asia Pac J Ophthalmol (Phila). 2017;6:132–42. Scholar
  51. 51.
    Kalogeropoulos D, Papoudou-Bai A, Kanavaros P, Kalogeropoulos C. Ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue. Clin Exp Med. 2018;18:151–63. Scholar
  52. 52.
    Schalenbourg A, Mantel I. The eye and cancer. Rev Med Suisse. 2015;11:2395–8.PubMedGoogle Scholar
  53. 53.
    Eckardt AM, Lemound J, Rana M, Gellrich N-C. Orbital lymphoma: diagnostic approach and treatment outcome. World J Surg Oncol. 2013;11:73. Scholar
  54. 54.
    Hochberg FH, Miller DC. Primary central nervous system lymphoma. J Neurosurg. 1988;68:835–53. Scholar
  55. 55.
    Auw-Haedrich C, et al. Long term outcome of ocular adnexal lymphoma subtyped according to the REAL classification. Br J Ophthalmol. 2001;85:63–9.CrossRefGoogle Scholar
  56. 56.
    Glotzbecker MP, et al. Primary non-Hodgkin’s lymphoma of bone in children. J Bone Joint Surg Am. 2006;88:583–94.PubMedGoogle Scholar
  57. 57.
    Maruyama D, et al. Primary bone lymphoma: a new and detailed characterization of 28 patients in a single-institution study. Jpn J Clin Oncol. 2007;37:216–23.CrossRefGoogle Scholar
  58. 58.
    Krishnan A, et al. Primary bone lymphoma: radiographic-MR imaging correlation. Radiographics. 2003;23:1371–83. ; discussion 1384-1377. Scholar
  59. 59.
    Milks KS, McLean TW, Anthony EY. Imaging of primary pediatric lymphoma of bone. Pediatr Radiol. 2016;46:1150–7.CrossRefGoogle Scholar
  60. 60.
    Borst AJ, States LJ, Reilly AF, Rheingold SR. Determining response and recurrence in pediatric B-cell lymphomas of the bone. Pediatr Blood Cancer. 2013;60:1281–6.CrossRefGoogle Scholar
  61. 61.
    Moschovi M, Menegas D, Stefanaki K, Constantinidou CV, Tzortzatou-Stathopoulou F. Primary gastric Burkitt lymphoma in childhood: associated with Helicobacter pylori? Med Pediatr Oncol. 2003;41:444–7.CrossRefGoogle Scholar
  62. 62.
    Kassira N, Pedroso FE, Cheung MC, Koniaris LG, Sola JE. Primary gastrointestinal tract lymphoma in the pediatric patient: review of 265 patients from the SEER registry. J Pediatr Surg. 2011;46:1956–64.CrossRefGoogle Scholar
  63. 63.
    Bethel CA, Bhattacharyya N, Hutchinson C, Ruymann F, Cooney DR. Alimentary tract malignancies in children. J Pediatr Surg. 1997;32:1004–8. ; discussion 1008-1009.CrossRefGoogle Scholar
  64. 64.
    Kuo SH, Cheng AL. Helicobacter pylori and mucosa-associated lymphoid tissue: what’s new. Hematology Am Soc Hematol Educ Program. 2013;2013:109–17. Scholar
  65. 65.
    Burger JA, O’Brien S. Evolution of CLL treatment - from chemoimmunotherapy to targeted and individualized therapy. Nat Rev Clin Oncol. 2018; Scholar
  66. 66.
    Dores GM, et al. Chronic lymphocytic leukaemia and small lymphocytic lymphoma: overview of the descriptive epidemiology. Br J Haematol. 2007;139:809–19. Scholar
  67. 67.
    Demir HA, et al. Chronic lymphocytic leukemia in a child: a challenging diagnosis in pediatric oncology practice. Pediatr Blood Cancer. 2014;61:933–5.CrossRefGoogle Scholar
  68. 68.
    Rollig C, Knop S, Bornhauser M. Multiple myeloma. Lancet. 2015;385:2197–208. Scholar
  69. 69.
    Ludwig H, et al. Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group. Blood. 2008;111:4039–47. Scholar
  70. 70.
    Crusoe EDQ, et al. Multiple myeloma: a rare case in an 8-year-old child. Clin Lymphoma Myeloma Leuk. 2015;15:e31–3. Scholar
  71. 71.
    Blade J, Kyle RA, Greipp PR. Multiple myeloma in patients younger than 30 years. Report of 10 cases and review of the literature. Arch Intern Med. 1996;156:1463–8.CrossRefGoogle Scholar
  72. 72.
    Dearden C. Management of prolymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2015;2015:361–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Auke Beishuizen
    • 1
    Email author
  • Vasiliki Tzotzola
    • 1
  • Lena Uzunova
    • 2
  • Amos Burke
    • 2
  1. 1.Department of Pediatric Oncology and HematologyPrincess Máxima Center for Pediatric OncologyUtrechtThe Netherlands
  2. 2.Department of Paediatric Haematology, Oncology and Palliative CareCambridge University Hospitals NHS Foundation Trust, Addenbrooke’s HospitalCambridgeUK

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