EBV-positive Diffuse Large B-Cell Lymphoma, NOS in a Filipino Patient
Mimickers and Essential Ancillary Studies
DOI:
https://doi.org/10.21141/PJP.2021.15Keywords:
immunohistochemistry, Philippines, DLBCL, Epstein-Barr virus, EBV DLBCLAbstract
Epstein-Barr virus positive diffuse large B-cell lymphoma (EBV+ DLBCL) is prevalent among Asians but is underreported in the Philippine setting. We report the case of an 88-year-old male who presented with difficulty swallowing. CT scan showed an ill-defined soft tissue focus with calcifications in the supraglottic to hypopharyngeal region measuring approximately 2.6 x 1.7 x 1.5 cm, and multiple lymphadenopathies in the head and neck. Biopsy of the masses at the left tonsil, left arytenoid mucosa, pyriform sinus, and aryepiglottic fold showed large lymphoid cells with several Reed-Sternberg-like cells in a background of small lymphocytes, neutrophils, few eosinophils and histiocytes. A panel of immunohistochemical stains and EBER-ish were performed to differentiate among six entities that were morphologically similar to the patient’s case, namely, classic Hodgkin lymphoma, T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), DLBCL, NOS, anaplastic variant, B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic HL (gray zone lymphoma), and infectious mononucleosis (IM). The neoplastic cells expressed CD20, CD30, CD45, PAX5, CD10, MUM-1, BCL6, BCL2, and c-myc, while CD3, CD15 and ALK-1 were negative. The cells of interest also showed nuclear staining (30-40%) on Epstein-Barr virus encoding RNA in-situ hybridization (EBER-ish). The Ki-67 showed a proliferation index of 40-50%. Given the differences in prognosis and treatment among these diseases, judicious use of immunostains and EBER-ish is recommended for accurate diagnosis.
Downloads
Download data is not yet available.
References
1. Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011 Nov;105(11):1684-92. https://pubmed.ncbi.nlm.nih.gov/22045184. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242607. https://doi.org/10.1038/bjc.2011.450.
2. Swerdlow SH, Campo E, Harris NL, et al., eds. WHO Classification of tumors of hematopoietic and lymphoid tissues, revised 4th ed, vol. 2. IARC: Lyon; 2017.
3. Oyama T, Ichimura K, Suzuki R, et al. Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol. 2003;27(1):16-26. https://pubmed.ncbi.nlm.nih.gov/12502924. https://doi.org/10.1097/00000478-200301000-00003.
4. Castillo JJ, Beltran BE, Miranda RN, Young KH, Chavez JC, Sotomayor EM. EBV‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2018 update on diagnosis, risk‐stratification and management. Am J Hematol. 2018;93(7):953–62. https://pubmed.ncbi.nlm.nih.gov/29984868. https://doi.org/10.1002/ajh.25112.
5. Sato A, Nakamura N, Kojima M, et al. Clinical outcome of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in the rituximab era. Cancer Sci. 2014;105(9):1170-5. https://pubmed.ncbi.nlm.nih.gov/24974976. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462402. https://doi.org/10.1111/cas.12467.
6. Lu TX, Liang JH, Miao Y, et al. Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age. Sci Rep. 2015;5:12168. https://pubmed.ncbi.nlm.nih.gov/26202875. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511873. https://doi.org/10.1038/srep12168.
7. Hong JY, Yoon DH, Suh C, et al. EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity? Ann Oncol. 2015;26(3):548-55.https://pubmed.ncbi.nlm.nih.gov/25475080. https://doi.org/10.1093/annonc/mdu556.
8. Hoeller S, Tzankov A, Pileri SA, Went P, Dirnhofer S. Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly patients is rare in Western populations. Hum Pathol. 2010;41(3):352-7. https://pubmed.ncbi.nlm.nih.gov/19913281. https://doi.org/10.1016/j.humpath.2009.07.024.
9. Hofscheier A, Ponciano A, Bonzheim I, et al. Geographic variation in the prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population. Mod Pathol. 2011;24(8):1046-54. https://pubmed.ncbi.nlm.nih.gov/21499229. https://doi.org/10.1038/modpathol.2011.62.
10. Laurini JA, Perry AM, Boilesen E, et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood. 2012;120(24):4795-801. https://pubmed.ncbi.nlm.nih.gov/23086753. https://doi.org/10.1182/blood-2012-07-440073
11. Gibson S, Hsi E. Epstein-Barr virus–positive B-cell lymphoma of the elderly at a United States tertiary medical center: an uncommon aggressive lymphoma with a nongerminal center B-cell phenotype. Hum Pathol. 2009;40(5):653-61. https://pubmed.ncbi.nlm.nih.gov/19144386. https://doi.org/10.1016/j.humpath.2008.10.007.
12. Yap MG, Tiangco B. Clinicopathologic profile of Filipino patients with malignant lymphomas. Philipp J Intern Med. 2014;42(6):289-96. https://www.herdin.ph/index.php/component/herdin/?view=research&cid=36236. Accessed March 8, 2021.
13. Paulino AF, Medeiros LJ, Paulino-Cabrera E, Weiss LM. Hodgkins disease in the Philippines. Mod Pathol. 1996. https://www.herdin.ph/index.php/component/herdin/?view=research&cid=28735. Accessed March 8, 2021.
14. Nicolae A, Pittaluga S, Abdullah S, et al. EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment. Blood. 2015;126(7):863-72. https://pubmed.ncbi.nlm.nih.gov/25999451. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536540. https://doi.org/10.1182/blood-2015-02-630632.
15. Cohen M, Narbaitz M, Metrebian F, De Matteo E, Preciado MV, Chabay PA. Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients. Int J Cancer. 2014;135(12):2816-24. https://pubmed.ncbi.nlm.nih.gov/24789501. https://doi.org/10.1002/ijc.28942.
16. Beltran BE, Morales D, Quiñones P, Medeiros LJ, Miranda RN, Castillo JJ. EBV-positive diffuse large b-cell lymphoma in young immunocompetent individuals. Clin Lymphoma Myeloma Leuk. 2011;11(6):512-6. https://pubmed.ncbi.nlm.nih.gov/21889434. https://doi.org/10.1016/j.clml.2011.07.003.
17. Medeiros LJ, Miranda RN. Diagnostic pathology: lymph nodes and extranodal lymphomas, 2nd ed. Second. Salt Lake City, UT: Elsevier; 2017.
18. Adam P, Bonzheim I, Fend F, Quintilla-Martinez L. Epstein-Barr virus-positive diffuse large B-cell lymphomas of the elderly. Adv Anat Pathol. 2011;18(5):349-55. https://pubmed.ncbi.nlm.nih.gov/21841405. https://doi.org/10.1097/PAP.0b013e318229bf08.
19. Wang E, Papavassiliou P, Sebastian S. A malignant lymphoma with histological features and immunophenotypic profile intermediate between EBV-positive diffuse large B-cell lymphoma and EBV-positive classical Hodgkin lymphoma in a 67-year-old female: a "gray zone" lymphoma associated with Epstein-Barr virus in the elderly. Pathol Res Pract. https://pubmed.ncbi.nlm.nih.gov/22572037. https://doi.org/10.1016/j.prp.2012.04.003.
20. Medeiros LJ, Ioachim HL. Ioachim's lymph node pathology. 4th ed. Philadelphia, PA: Wolters Kluwer Health; 2009.
21. Kanderi T, Khoory MS. Infectious mononucleosis mimicking Epstein–Barr virus positive diffuse large B-cell lymphoma not otherwise specified. Int J Hematol Oncol. 2020;9(2):IJH25. https://pubmed.ncbi.nlm.nih.gov/33005328. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510517. https://doi.org/10.2217/ijh-2020-0002.
22. Louissaint A, Ferry JA, Soupir CP, Hasserjian RP, Harris NL, Zukerberg LR. Infectious mononucleosis mimicking lymphoma: distinguishing morphological and immunophenotypic features. Mod Pathol. 25(8):1149-59. https://pubmed.ncbi.nlm.nih.gov/22627742. https://doi.org/10.1038/modpathol.2012.70.
23. Ding Y, Zhang L (eds). Practical oncologic molecular pathology: frequently asked questions. 1st ed. Springer; 2021.
24. Zhou Y, Xu Z, Lin W, et al. Comprehensive genomic profiling of EBV-positive diffuse large B-cell lymphoma and the expression and clinicopathological correlations of some related genes. Front Oncol. 2019;9:683. https://pubmed.ncbi.nlm.nih.gov/31403034. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669985. https://doi.org/10.3389/fonc.2019.00683.
25. Gebauer N, Künstner A, Ketzer J, et al. Genomic insights into the pathogenesis of Epstein–barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing. Blood Cancer J. 2021;11(5):102. https://pubmed.ncbi.nlm.nih.gov/34039950. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155002. https://doi.org/10.1038/s41408-021-00493-5.
26. Park S, Lee J, Ko YH, et al. The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma. Blood. 2007;110(3):972-8. https://pubmed.ncbi.nlm.nih.gov/17400912. https://doi.org/10.1182/blood-2007-01-067769.
27. Rosenberg SA, Kaplan HS. Evidence for an orderly progression in the spread of hodgkin’s disease. Cancer Res. 1966;26(6):1225-31. https://pubmed.ncbi.nlm.nih.gov/5947346.
28. NCCN Clinical Practice Guidelines in Oncology. Hodgkin lymphoma, Ver 3.2021. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf. Accessed March 7, 2021.
29. Hasenclaver D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med. 1998;339(1):1506-14. https://pubmed.ncbi.nlm.nih.gov/9819449. https://doi.org/10.1056/NEJM199811193392104.
30. Pilichowska M, Kritharis A, Evens M. Gray zone lymphoma: current diagnosis and treatment options. Hematol Oncol Clin North Am. 2016;30(6):1251–60. https://pubmed.ncbi.nlm.nih.gov/27888879. https://doi.org/10.1016/j.hoc.2016.07.006.
31. Wilson W, Pittaluga S, Nicolae A, et al. A prospective study of mediastinal gray zone lymphoma. Blood. 2014;124(10):1563–19. https://pubmed.ncbi.nlm.nih.gov/25024303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155269. https://doi.org/10.1182/blood-2014-03-564906.
32. International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non- Hodgkin’s lymphoma. N Engl J Med. 1993; 329(14):987–94. https://pubmed.ncbi.nlm.nih.gov/8141877. https://doi.org/10.1056/NEJM199309303291402.
33. NCCN Clinical Practice Guidelines in Oncology. B - cell lymphomas, ver 3.2021. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed March 7, 2021.
34. Kanakry J, Ambinder R. EBV related lymphomas: new approaches to treatment. Curr Treat Options Oncol. 2013;14(2):224-36. https://pubmed.ncbi.nlm.nih.gov/23549980. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670765. https://doi.org/10.1007/s11864-013-0231-y.
2. Swerdlow SH, Campo E, Harris NL, et al., eds. WHO Classification of tumors of hematopoietic and lymphoid tissues, revised 4th ed, vol. 2. IARC: Lyon; 2017.
3. Oyama T, Ichimura K, Suzuki R, et al. Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol. 2003;27(1):16-26. https://pubmed.ncbi.nlm.nih.gov/12502924. https://doi.org/10.1097/00000478-200301000-00003.
4. Castillo JJ, Beltran BE, Miranda RN, Young KH, Chavez JC, Sotomayor EM. EBV‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2018 update on diagnosis, risk‐stratification and management. Am J Hematol. 2018;93(7):953–62. https://pubmed.ncbi.nlm.nih.gov/29984868. https://doi.org/10.1002/ajh.25112.
5. Sato A, Nakamura N, Kojima M, et al. Clinical outcome of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in the rituximab era. Cancer Sci. 2014;105(9):1170-5. https://pubmed.ncbi.nlm.nih.gov/24974976. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462402. https://doi.org/10.1111/cas.12467.
6. Lu TX, Liang JH, Miao Y, et al. Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age. Sci Rep. 2015;5:12168. https://pubmed.ncbi.nlm.nih.gov/26202875. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511873. https://doi.org/10.1038/srep12168.
7. Hong JY, Yoon DH, Suh C, et al. EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity? Ann Oncol. 2015;26(3):548-55.https://pubmed.ncbi.nlm.nih.gov/25475080. https://doi.org/10.1093/annonc/mdu556.
8. Hoeller S, Tzankov A, Pileri SA, Went P, Dirnhofer S. Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly patients is rare in Western populations. Hum Pathol. 2010;41(3):352-7. https://pubmed.ncbi.nlm.nih.gov/19913281. https://doi.org/10.1016/j.humpath.2009.07.024.
9. Hofscheier A, Ponciano A, Bonzheim I, et al. Geographic variation in the prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population. Mod Pathol. 2011;24(8):1046-54. https://pubmed.ncbi.nlm.nih.gov/21499229. https://doi.org/10.1038/modpathol.2011.62.
10. Laurini JA, Perry AM, Boilesen E, et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood. 2012;120(24):4795-801. https://pubmed.ncbi.nlm.nih.gov/23086753. https://doi.org/10.1182/blood-2012-07-440073
11. Gibson S, Hsi E. Epstein-Barr virus–positive B-cell lymphoma of the elderly at a United States tertiary medical center: an uncommon aggressive lymphoma with a nongerminal center B-cell phenotype. Hum Pathol. 2009;40(5):653-61. https://pubmed.ncbi.nlm.nih.gov/19144386. https://doi.org/10.1016/j.humpath.2008.10.007.
12. Yap MG, Tiangco B. Clinicopathologic profile of Filipino patients with malignant lymphomas. Philipp J Intern Med. 2014;42(6):289-96. https://www.herdin.ph/index.php/component/herdin/?view=research&cid=36236. Accessed March 8, 2021.
13. Paulino AF, Medeiros LJ, Paulino-Cabrera E, Weiss LM. Hodgkins disease in the Philippines. Mod Pathol. 1996. https://www.herdin.ph/index.php/component/herdin/?view=research&cid=28735. Accessed March 8, 2021.
14. Nicolae A, Pittaluga S, Abdullah S, et al. EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment. Blood. 2015;126(7):863-72. https://pubmed.ncbi.nlm.nih.gov/25999451. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536540. https://doi.org/10.1182/blood-2015-02-630632.
15. Cohen M, Narbaitz M, Metrebian F, De Matteo E, Preciado MV, Chabay PA. Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients. Int J Cancer. 2014;135(12):2816-24. https://pubmed.ncbi.nlm.nih.gov/24789501. https://doi.org/10.1002/ijc.28942.
16. Beltran BE, Morales D, Quiñones P, Medeiros LJ, Miranda RN, Castillo JJ. EBV-positive diffuse large b-cell lymphoma in young immunocompetent individuals. Clin Lymphoma Myeloma Leuk. 2011;11(6):512-6. https://pubmed.ncbi.nlm.nih.gov/21889434. https://doi.org/10.1016/j.clml.2011.07.003.
17. Medeiros LJ, Miranda RN. Diagnostic pathology: lymph nodes and extranodal lymphomas, 2nd ed. Second. Salt Lake City, UT: Elsevier; 2017.
18. Adam P, Bonzheim I, Fend F, Quintilla-Martinez L. Epstein-Barr virus-positive diffuse large B-cell lymphomas of the elderly. Adv Anat Pathol. 2011;18(5):349-55. https://pubmed.ncbi.nlm.nih.gov/21841405. https://doi.org/10.1097/PAP.0b013e318229bf08.
19. Wang E, Papavassiliou P, Sebastian S. A malignant lymphoma with histological features and immunophenotypic profile intermediate between EBV-positive diffuse large B-cell lymphoma and EBV-positive classical Hodgkin lymphoma in a 67-year-old female: a "gray zone" lymphoma associated with Epstein-Barr virus in the elderly. Pathol Res Pract. https://pubmed.ncbi.nlm.nih.gov/22572037. https://doi.org/10.1016/j.prp.2012.04.003.
20. Medeiros LJ, Ioachim HL. Ioachim's lymph node pathology. 4th ed. Philadelphia, PA: Wolters Kluwer Health; 2009.
21. Kanderi T, Khoory MS. Infectious mononucleosis mimicking Epstein–Barr virus positive diffuse large B-cell lymphoma not otherwise specified. Int J Hematol Oncol. 2020;9(2):IJH25. https://pubmed.ncbi.nlm.nih.gov/33005328. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510517. https://doi.org/10.2217/ijh-2020-0002.
22. Louissaint A, Ferry JA, Soupir CP, Hasserjian RP, Harris NL, Zukerberg LR. Infectious mononucleosis mimicking lymphoma: distinguishing morphological and immunophenotypic features. Mod Pathol. 25(8):1149-59. https://pubmed.ncbi.nlm.nih.gov/22627742. https://doi.org/10.1038/modpathol.2012.70.
23. Ding Y, Zhang L (eds). Practical oncologic molecular pathology: frequently asked questions. 1st ed. Springer; 2021.
24. Zhou Y, Xu Z, Lin W, et al. Comprehensive genomic profiling of EBV-positive diffuse large B-cell lymphoma and the expression and clinicopathological correlations of some related genes. Front Oncol. 2019;9:683. https://pubmed.ncbi.nlm.nih.gov/31403034. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669985. https://doi.org/10.3389/fonc.2019.00683.
25. Gebauer N, Künstner A, Ketzer J, et al. Genomic insights into the pathogenesis of Epstein–barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing. Blood Cancer J. 2021;11(5):102. https://pubmed.ncbi.nlm.nih.gov/34039950. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155002. https://doi.org/10.1038/s41408-021-00493-5.
26. Park S, Lee J, Ko YH, et al. The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma. Blood. 2007;110(3):972-8. https://pubmed.ncbi.nlm.nih.gov/17400912. https://doi.org/10.1182/blood-2007-01-067769.
27. Rosenberg SA, Kaplan HS. Evidence for an orderly progression in the spread of hodgkin’s disease. Cancer Res. 1966;26(6):1225-31. https://pubmed.ncbi.nlm.nih.gov/5947346.
28. NCCN Clinical Practice Guidelines in Oncology. Hodgkin lymphoma, Ver 3.2021. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf. Accessed March 7, 2021.
29. Hasenclaver D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med. 1998;339(1):1506-14. https://pubmed.ncbi.nlm.nih.gov/9819449. https://doi.org/10.1056/NEJM199811193392104.
30. Pilichowska M, Kritharis A, Evens M. Gray zone lymphoma: current diagnosis and treatment options. Hematol Oncol Clin North Am. 2016;30(6):1251–60. https://pubmed.ncbi.nlm.nih.gov/27888879. https://doi.org/10.1016/j.hoc.2016.07.006.
31. Wilson W, Pittaluga S, Nicolae A, et al. A prospective study of mediastinal gray zone lymphoma. Blood. 2014;124(10):1563–19. https://pubmed.ncbi.nlm.nih.gov/25024303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155269. https://doi.org/10.1182/blood-2014-03-564906.
32. International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non- Hodgkin’s lymphoma. N Engl J Med. 1993; 329(14):987–94. https://pubmed.ncbi.nlm.nih.gov/8141877. https://doi.org/10.1056/NEJM199309303291402.
33. NCCN Clinical Practice Guidelines in Oncology. B - cell lymphomas, ver 3.2021. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed March 7, 2021.
34. Kanakry J, Ambinder R. EBV related lymphomas: new approaches to treatment. Curr Treat Options Oncol. 2013;14(2):224-36. https://pubmed.ncbi.nlm.nih.gov/23549980. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670765. https://doi.org/10.1007/s11864-013-0231-y.
Published
11/23/2021
How to Cite
Sasis, K., Lee, D., Arevalo, A., Tiangco, B., & Agbay, R. L. M. (2021). EBV-positive Diffuse Large B-Cell Lymphoma, NOS in a Filipino Patient: Mimickers and Essential Ancillary Studies. PJP, 6(2), 47–54. https://doi.org/10.21141/PJP.2021.15
Issue
Section
Case Reports
License
The Philippine Journal of Pathology is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Based on works made open access at http://philippinejournalofpathology.org
@philippinepathologyjournal