Document Type : Original Research


Department of Pathology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India



Primary extra nodal lymphoma (pENL) is a malignant lymphoid neoplasm that presents with the main bulk of disease at an extra nodal site. The incidence of primary pENL has risen sharply in recent years due to the advent of better diagnostic modalities. Diagnosing pENL can be challenging due to its morphological overlap with other tumours native to the site of origin. This study aims to establish the anatomic distribution, clinical presentations, possible etiologic correlations, and histological subtypes of pENL in a tertiary care centre located in South India.

This is a retrospective study of 109 patients with pENL (69 males, 40 females, M: F = 1.7:1) over 5 years (October 2012 to September 2017). The tumors were reclassified according to WHO classification of Haematolymphoid tumors, 5th edition, 2022.
pENL constituted 109/481 cases (22.6%) of all NHL cases, with the highest incidence in 7th decade. The gastrointestinal tract (39%) was the predominant site involved, followed by head and neck (26%). Diffuse large B cell lymphoma (DLBCL) was the most common histomorphological variant followed by Follicular lymphoma (FL). The majority of the patients were immunocompetent (89%) and presented with stage IV disease (31.1%) at diagnosis.
This study presents an overview of the diverse distribution patterns of both common and rare pENL within a tertiary care center. The accurate diagnosis of pENL necessitates the elimination of secondary extranodal involvement. It is important to note that the accurate diagnosis of pENL requires careful evaluation and exclusion of other possible causes.


Main Subjects

  1. Feller AC, Diebold J. Extranodal Lymphoma. In: Feller AC, Diebold J, editors. Histopathology of Nodal and Extranodal Non-Hodgkin's Lymphomas. Berlin, Heidelberg: Springer; 2004. p. 186-363. [DOI:10.1007/978-3-642-18653-0_6]
  2. Krol ADG, le Cessie S, Snijder S, Kluin-Nelemans JC, Kluin PM, Noordijk EM. Primary extranodal non-Hodgkin's lymphoma (NHL): the impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry. Ann Oncol Off J Eur Soc Med Oncol. 2003;14(1):131-9. [DOI:10.1093/annonc/mdg004] [PMID]
  3. Zucca E, Roggero E, Bertoni F, Cavalli F. Primary extranodal non-Hodgkin's lymphomas. Part 1: Gastrointestinal, cutaneous and genitourinary lymphomas. Ann Oncol Off J Eur Soc Med Oncol. 1997 Aug;8(8):727-37. [DOI:10.1023/A:1008282818705] [PMID]
  4. Dawson IM, Cornes JS, Morson BC. Primary malignant lymphoid tumours of the intestinal tract. Report of 37 cases with a study of factors influencing prognosis. Br J Surg. 1961;49:80-9. [DOI:10.1002/bjs.18004921319] [PMID]
  5. Sabharwal R, Sircar K, Sengupta S, Sharma B. Update on classification of lymphomas. Dent Hypotheses. 2013;4(1):4. [DOI:10.4103/2155-8213.110180]
  6. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90. [DOI:10.1182/blood-2016-01-643569] [PMID]
  7. Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IB de O, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022 Jul;36(7):1720-48.
  8. Sapkota S, Shaikh H. Non-Hodgkin Lymphoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
  9. Wright DH. Pathology of extra-nodal non Hodgkin lymphomas. Clin Oncol R Coll Radiol G B. 2012 Jun;24(5):319-28. [DOI:10.1016/j.clon.2012.02.004] [PMID]
  10. Alevizos L, Gomatos IP, Smparounis S, Konstadoulakis MM, Zografos G. Review of the molecular profile and modern prognostic markers for gastric lymphoma: How do they affect clinical practice? Can J Surg. 2012 Apr;55(2):117-24. [DOI:10.1503/cjs.002310] [PMID]
  11. Pai A, Kannan T, Balambika RG, Vasini V. A Study of Clinical Profile of Primary Extranodal Lymphomas in a Tertiary Care Institute in South India. Indian J Med Paediatr Oncol Off J Indian Soc Med Paediatr Oncol. 2017;38(3):251-5. [DOI:10.4103/ijmpo.ijmpo_82_16] [PMID]
  12. Mishra P, Prashar M, Rehman N, Sinha A, Raman DK. Primary extranodal lymphomas: five-year experience from a tertiary care center of North India. Indian J Cancer. 2023 May 2; [DOI:10.4103/ijc.IJC_1267_20]
  13. Vasudevan JA, Jacob RAN Priya Mary, Sukumaran R, Narayanan G. Primary Extranodal Lymphomas: A Five Year Retrospective Study from a Tertiary Care Cancer Centre, Kerala, India. J Clin Diagn Res. 2022; [DOI:10.7860/JCDR/2022/53164.16323]
  14. Aparna C, Renuka IV, Rajani M, Sailabala G, Annapurna P. Primary extranodal lymphomas - spectrum of distribution and morphology with immunophenotyping: A 3-year institutional study. Med J Dr Patil Univ. 2015 Mar 1;8(2):138. [DOI:10.4103/0975-2870.153137]
  15. Mertsoylu H, Muallaoglu S, Besen AA, Erdogdu S, Sezer A, Sedef AM, et al. Primary extranodal non-Hodgkin's lymphoma: clinicopathological features, survival and treatment outcome in two cancer centers of southern Turkey. Asian Pac J Cancer Prev APJCP. 2014;15(17):7207-11. [DOI:10.7314/APJCP.2014.15.17.7207] [PMID]
  16. Fujita A, Tomita N, Fujita H, Motohashi K, Hyo R, Yamazaki E, et al. Features of primary extranodal lymphoma in Kanagawa, a human T-cell leukemia virus type 1 nonendemic area in Japan. Med Oncol Northwood Lond Engl. 2009;26(1):49-54. [DOI:10.1007/s12032-008-9080-0] [PMID]
  17. Babu SJ, Krishna HN, Dattatreya PS, Nirni SS, Vasini V. A Retrospective Study of the Clinico-pathological Profile of Primary Extra Nodal Lymphomas in a Tertiary Care Hospital. Glob J Hematol Blood Transfus. 2019 Jan 30;6(1):1-5. [DOI:10.15379/2408-9877.2019.06.01.01]
  18. Padhi S, Paul TR, Challa S, Prayaga AK, Rajappa S, Raghunadharao D, et al. Primary extra nodal non Hodgkin lymphoma: a 5 year retrospective analysis. Asian Pac J Cancer Prev APJCP. 2012;13(10):4889-95. [DOI:10.7314/APJCP.2012.13.10.4889] [PMID]
  19. Mehta J, Thakrar MP, Meena M, Mittal A, Gupta K. Primary Extranodal Non-Hodgkin Lymphoma: A 2-Year Retrospective Analysis from a Tertiary Care Centre in Rajasthan. Int J Med Res Prof. 2016;2(4). [DOI:10.21276/ijmrp.2016.2.4.018]
  20. Mishra P, Das S, Kar R, Jacob SE, Basu D. Primary extranodal non-Hodgkin lymphoma: A 3-year record-based descriptive study from a tertiary care center in Southern India. Indian J Pathol Microbiol. 2015 Jul 1;58(3):296. [DOI:10.4103/0377-4929.162834] [PMID]
  21. Yang QP, Zhang WY, Yu JB, Zhao S, Xu H, Wang WY, et al. Subtype distribution of lymphomas in Southwest China: Analysis of 6,382 cases using WHO classification in a single institution. Diagn Pathol. 2011 Aug 22;6:77. [DOI:10.1186/1746-1596-6-77] [PMID]
  22. Parikh K, Dhotre SV, Patel M, Barot H, Satasiya AH. Retrospective study of primary extranodal abdominal lymphoma from a tertiary healthcare centre. In 2018.
  23. Arora N, Manipadam MT, Pulimood A, Ramakrishna BS, Chacko A, Kurian SS, et al. Gastrointestinal lymphomas: pattern of distribution and histological subtypes: 10 years experience in a tertiary centre in South India. Indian J Pathol Microbiol. 2011;54(4):712-9.
  24. Shirsat HS, Vaiphei K. Primary gastrointestinal lymphomas - A study of 81 Cases from a Tertiary Healthcare Centre. Indian J Cancer. 2014;51(3):290-2. [DOI:10.4103/0019-509X.146777] [PMID]
  25. Narayana S, Premalata C, Amirtham U, Kurlekar G, Kumar R. Histomorphological and anatomical analysis of primary extra nodal non-Hodgkin lymphoma - ten years study from a tertiary cancer centre in South India. In 2017.
  26. Tran T, Vu TH, Vo HQ, Thi Nguyen H, Van Nguyen H. Primary gastrointestinal non-Hodgkin lymphoma: a retrospective study in Vietnam. Ann Med Surg 2012. 2023 Jun;85(6):2390-4. [DOI:10.1097/MS9.0000000000000858] [PMID]
  27. Economopoulos T, Papageorgiou S, Rontogianni D, Kaloutsi V, Fountzilas G, Tsatalas C, et al. Multifocal extranodal non-hodgkin lymphoma: a clinicopathologic study of 37 cases in Greece, a Hellenic Cooperative Oncology Group study. The Oncologist. 2005 Oct;10(9):734-8. [DOI:10.1634/theoncologist.10-9-734] [PMID]
  28. Thomas AS A, Schwartz M, Quigley E. Gastrointestinal lymphoma: the new mimic. BMJ Open Gastroenterol. 2019;6(1):e000320. [DOI:10.1136/bmjgast-2019-000320] [PMID]
  29. Papaxoinis G, Papageorgiou S, Rontogianni D, Kaloutsi V, Fountzilas G, Pavlidis N, et al. Primary gastrointestinal non-Hodgkin's lymphoma: a clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG). Leuk Lymphoma. 2006 Oct;47(10):2140-6. [DOI:10.1080/10428190600709226] [PMID]
  30. Vannata B, Zucca E. Primary extranodal B-cell lymphoma: current concepts and treatment strategies. Chin Clin Oncol. 2015 Mar;4(1):10.
  31. Sorrentino A, Ferragina F, Barca I, Arrotta A, Cristofaro MG. Extra-Nodal Lymphomas of the Head and Neck and Oral Cavity: A Retrospective Study. Curr Oncol Tor Ont. 2022 Sep 29;29(10):7189-97. [DOI:10.3390/curroncol29100566] [PMID]
  32. Biagi JJ, Seymour JF. Insights into the molecular pathogenesis of follicular lymphoma arising from analysis of geographic variation. Blood. 2002 Jun 15;99(12):4265-75. [DOI:10.1182/blood.V99.12.4265] [PMID]
  33. Devi A, Sharma T, Singh Y, Sonia H. Clinicopathological profile of patients with non-hodgkin's lymphoma at a regional cancer center in Northeast India. J Sci Soc. 2017;44(3):140. [DOI:10.4103/jss.JSS_42_17]
  34. Berhan A, Bayleyegn B, Getaneh Z. HIV/AIDS Associated Lymphoma: Review. Blood Lymphat Cancer Targets Ther. 2022 Apr 29;12:31-45. [DOI:10.2147/BLCTT.S361320] [PMID]
  35. Srinivasan S, Takeshita K, Holkova B, Czuczman MS, Miller K, Bernstein ZP, et al. Clinical characteristics of gastrointestinal lymphomas associated with AIDS (GI-ARL) and the impact of HAART. HIV Clin Trials. 2004 May;5(3):140-5. [DOI:10.1310/BDHX-D9BC-YWVU-9NBR] [PMID]
  36. Gupta V, Singh V, Bajwa R, Meghal T, Sen S, Greenberg D, et al. Site-Specific Survival of Extra Nodal Diffuse Large B-Cell Lymphoma and Comparison With Gastrointestinal Diffuse Large B-Cell Lymphoma. J Hematol. 2022 Apr;11(2):45-54. [DOI:10.14740/jh984] [PMID]
  37. Lal A, Bhurgri Y, Vaziri I, Rizvi NB, Sadaf A, Sartajuddin S, et al. Extranodal non-Hodgkin's lymphomas--a retrospective review of clinico-pathologic features and outcomes in comparison with nodal non-Hodgkin's lymphomas. Asian Pac J Cancer Prev APJCP. 2008;9(3):453-8.