FREQUENCY OF DOUBLE EXPRESSOR LYMPHOMA IN A TERTIARY CARE HOSPITAL

Authors

  • Masroor Hassan Khyber Teaching Hospital Peshawar
  • Maria Tasneem Khattak Rehman Medical Institute Peshawar
  • Muhammad Ashraf Qamar Rehman Medical Institute Peshawar
  • Sarah Javed Rehman Medical Institute Peshawar
  • Syeda Uzma Saeed Rehman Medical Institute Peshawar

Abstract

Background: Accounting for 30% cases of all lymphoid neoplasms, Diffuse large B cell lymphoma (DLBCL) is the commonest lymphoma worldwide. It occurs over a wide age range and has diverse morphology, immunophenotype and clinical outcome. Objectives of the study were to determine the frequency of Double expressor lymphoma (DEL) in a tertiary care hospital. Methods: This descriptive cross-sectional study was carried out in the Department of Histopathology, Rehman Medical Institute Peshawar from June 1st to December 1st, 2018. A total of 88 newly diagnosed cases of diffuse large B-cell lymphoma (DLBCL); diagnosed on incisional or excisional biopsies were included in the study by non-probability consecutive sampling. Statistical analysis was carried out using SPSS-23. Quantitative variables were calculated as mean±SD. Qualitative variables were computed as frequency and percentages. Post stratification chi-square test was applied keeping p value equal or less than 0.05 as significance. Results: In our 88 cases of DLBCL, 56 (63.6%) were males and 32 (36.4%) were females. Age of patients ranged from 15yrs to 84yrs. Mean age was 50.8±15.2SD. Activated B-cell like (ABC) subtype of DLBCL constitute 51 cases (58%) while 37 cases (42%) were of germinal centre B-cell like (GCB) subtype. Nineteen cases (21.6%) were of DEL. Cervical node was the commonest site of involvement (n=17, 19.3%) followed by stomach (n=10, 11.4%) and tonsil (n=6, 6.8%). Out of 19 cases of DEL, 17 cases (89.5%) were of ABC type. DEL was found to have significant correlation with ABC subtype of DLBCL (p=0.002).  DEL had no correlation with gender (p=0.6), age (p=0.27), Mib-1 (p=0.36) and tumour site (p=0.42). Conclusion: The frequency of DEL in our study was 21.6% which is comparable to other studies who used similar cut-offs for c-Myc and BCL2 and similar criteria of inclusion as in our study. Significant association was found between DEL and ABC subtype of DLBCL. Keywords: Double protein lymphoma; Double expressor lymphoma; Diffuse large B cell lymphoma; Double hit lymphoma, Frequency

Author Biographies

Masroor Hassan, Khyber Teaching Hospital Peshawar

Assistant Professor, Department of Pathology

Maria Tasneem Khattak, Rehman Medical Institute Peshawar

Assistent professor and consultant histopathologist, Depatment of pathology

Muhammad Ashraf Qamar, Rehman Medical Institute Peshawar

Professor and consultant histopathologist, Depatment of pathology

Sarah Javed, Rehman Medical Institute Peshawar

Postgraduate Resident, Department of Pathology and blood bank

Syeda Uzma Saeed, Rehman Medical Institute Peshawar

Postgraduate Resident, Department of Pathology and blood bank

References

REFERENCES:

Hunt KE, Reichard KK. Diffuse Large B-Cell Lymphoma. Arch Pathol Lab Med. 2008;132:118-24.

Nowakowski GS, Czuczman MS. ABC, GCB, and Double-Hit Diffuse Large B-Cell Lymphoma: Does Subtype Make a Difference in Therapy Selection? Am Soc Clin Oncol Educ Book. 2015:e449-57.

Edwards L, Krakow EF, Bhagirath VC, Keng C, Lytwyn A, Ross C, Cheng J, et al. B-Cell Lymphoma Unclassifiable with Features Intermediate between Diffuse Large B-Cell Lymphoma and Burkitt’s Lymphoma: Comparison Study of Clinical Outcome and Treatment Response. J Clin Anat Pathol 2015;2:1-8.

Zeng D, Desai A, Yan F, Gong T, Ye H, Ahmed M, et al. Challenges and Opportunities for High-grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangement (Double-hit Lymphoma). Am J Clin Oncol. 2018;2:111-23.

Ye Q, Xu-Monette ZY, Tzankov A, Deng L, Wang X, Manyam GC, et al. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. Oncotarget 2015;7(3):2401-16.

Lu TX, Fan L, Wang L, Wu JZ, Miao KR, Liang JH, et al. MYC or BCL2 copy number aberration is a strong predictor of outcome in patients with diffuse large B-cell lymphoma. Oncotarget 2015;6(21):18374-88.

Sarkozy C, Traverse-Glehen A, Coiffier B. Double-hit and double-protein-expression lymphomas: aggressive and refractory lymphomas. Lancet Oncol. 2015;16(15):e555-e567.

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;127(20):2375-90.

Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer 2008;8:976–90.

Raess PW, Moore SR, Cascio MJ, Dunlap J, Fan G, Gatter K, et al. MYC immunohistochemical and cytogenetic analysis are required for identification of clinically relevant aggressive B cell lymphoma subtypes. Leuk Lymphoma. 2018;59(6):1391-98.

Yan L-X, Liu Y-H, Luo D-L, Zhang F, Cheng Y, et al. (2014)MYC Expression in Concert with BCL2 and BCL6 Expression Predicts Outcome in Chinese Patients with Diffuse Large B-Cell Lymphoma, Not Otherwise Specified. PLoS ONE 2014;9(8):e104068.

Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15(17):5494-502.

Gutierrez-García G, Cardesa-Salzmann T, Climent F, Gonza´lez-Barca E, Mercadal S, Mate JL, et al. Gene expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood. 2011;117(18):4836-43.

Rosenthal A, Younes A. High grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6: Double hit and triple hit lymphomas and double expressing lymphoma. Blood Rev. 2017;31(2):37-42.

Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol 2012;30:3452–59.

Smith SM. Aggressive B-cell lymphoma: the double-hit and double-expressor phenotypes. Clin Adv Hematol Oncol. 2017;15(1):40-2.

Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A, et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013;121(20):4021-31.

Green TM, Young KH, Visco C, Xu-Monette ZY, Orazi A, Go RS, et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30:3460–67.

Herrera AF, Mei M1, Low L1, Kim HT1, Griffin GK1, Song JY, et al. Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation. J Clin Oncol. 2017;35(1):24-31.

Miura K, Takahashi H, Nakagawa M, Izu A, Sugitani M, Kurita D, et al. Clinical significance of co-expression of MYC and BCL2 protein in aggressive B-cell lymphomas treated with a second line immunochemotherapy. Leuk Lymphoma. 2016;57(6):1335-41.

Kawashima I, Inamoto Y, Maeshima AM, Nomoto J, Tajima K, Honda T, et al. Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2018;24(2):294-300.

Allen J, Ruano Mendez AL, Rybicki L, Sawalha Y, Jagadeesh D, Dean R, et al. Co-expression of MYC and BCL2 predicts poorer outcomes for relapsed/refractory diffuse large B-cell lymphoma with R-ICE and intent to transplant. Ther Adv Hematol. 2018;9(4):81-7.

Takahashi H, Miura K, Nakagawa M, Sugitani M, Amano Y, Kurita D, et al. Negative impact of concurrent overexpression of MYC and BCL2 in patients with advanced diffuse large B-cell lymphoma treated with dose-intensified immunochemotherapy. Leuk Lymphoma. 2016;57(12):2784-90.

Kawamoto K, Miyoshi H, Yoshida N, Nakamura N, Ohshima K, Sone H, et al. MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B-cell lymphoma. Cancer Sci. 2016;107(6):853-61.

Petrella T, Copie-Bergman C, Brière J, Delarue R, Jardin F, Ruminy P, et al. BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial. Ann Oncol. 2017;28(5):1042-49.

Savage KJ, Slack GW, Mottok A, Sehn LH, Villa D, Kansara R, et al. Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL. Blood. 2016;127(18):2182-88

Published

2021-02-20