DIFFUSE LARGE B CELL LYMPHOMA

Krisna Murti

doi:10.32539/mks.v53i3.20435

DIFFUSE LARGE B CELL LYMPHOMA

Krisna Murti

Abstract

Diffuse large B cell lymphoma is a neoplasm arising from B lymphocytes and having a diffuse growth pattern. The nuclei cells showed a medium or similar or larger than the sizes of normal macrophages. This entity is the most common type of non-Hodgkin lymphoma (NHL) with incidence 30-40% from all NHL types. In Indonesia DLBCL cases was 68.2%, much higher than that in western countries (37%) and slightly higher than in other Asian countries (30-60%). Another data showed that in Indonesia there was 16.125 new NHL cases in 2020. This entity has diversity of molecular pathogenesis causes DLBCL showed some heterogeneity and similarities of clinical sign and symptoms, morphology and immunopheno types with other non-Hodgkin lymphomas. Therefore, some other molecular analysis such mutation events should be performed to achieve a correct diagnosis. All clinical data, morphologic immunhistochemical foundings have to be collected and analyzed and some additional molecular examination should be also conducted such as FISH analysis, PCR-based assay to exclude differential diagnosis. Some patients can be cured with a standard regimen Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (R-CHOP). However, 40% of patients is refractory or relapse.

Keywords

Diffuse large B cell lymphoma, Non Hodgkin lymphoma, R-CHOP, refractory or relapse

Full Text:

PDF

References

Ott G. Aggressive B-cell lymphomas in the update of the 4th edition of the World Health Organization classification of haematopoietic and lymphatic tissues: Refinements of the classification, new entities and genetic findings. Br. J. Haematol. 2017; 178(6):871–887. http://dx.doi.org/10.1111/bjh.14744.

Xie Y, Pittaluga S, Jaffe ES. The histological classification of diffuse large B-cell lymphomas. Semin Hematol. 2015;52(2):57-66. http://dx.doi.org/10.1053/j.seminhematol.2015.01.006.

Reksodiputro AH. Multicentre Epidemiology and Survival Study of B Cell Non Hodgkin Lymphoma Patients In Indonesia. J Blood Disorder Transf. 2015; 6(2):1-5. http://dx.doi.org/10.4172/2155-9864.1000257.

GLOBOCAN 2020. The Global Cancer Observatory : Indonesia

[Internet]. March 2021. Available from:https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf

Liu Y and Barta SK. Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2019; 94(5):604-616. http://dx.doi.org/10.1002/ajh.25460.

Rosenwald A, Delabie J, Medeiros LJ, Klapper W, Gujral S, Kikkeri N, et al. Diffuse large B cell lymphoma In: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours [Internet; beta version ahead of print]. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chaptercontent/63/157.

Perry AM, Diebold J, Nathwani BN, MacLennan KA, Müller-Hermelink HK, Bast MM, et al. Non-Hodgkin lymphoma in the developing world: review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project. Haematologica. 2016:101(10):1244-1250. http://dx.doi.org/10.3324/haematol.2016.148809.

Gouveia GR, Siqueira SA, Pereira J. Pathophysiology and molecular aspects of diffuse large B-cell lymphoma. Rev Bras Hematol Hemoter. 2012; 34(6):447-51. http://dx.doi.org/10.5581/1516-8484.20120111.

Azzaoui I, Uhel F, Rosille D, Pangault C, Dulong J, Le Priol J, et al. T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells. Blood.2016;128(8):1081–1092. http://dx.doi.org/10.1182/blood-2015-08-662783.

Yin X, Xu A, Fan F, Huang Z, Cheng Q, Zhang L, et al. Incidence and Mortality Trends and Risk Prediction Nomogram for Extranodal Diffuse Large B-Cell Lymphoma: An Analysis of the Surveillance, Epidemiology, and End Results Database. Front. Oncol. 2019;9:1198. http://dx.doi.org/10.3389/fonc.2019.01198.

Armitage JO, Gascoyne RD, Lunning, MA, Cavalli F. Non-Hodgkin lymphoma. Lancet. 2017; 390(10091):298-310. http://dx.doi.org/10.1016/S0140-6736(16)32407-2.

Ollila TA, Olszewski AJ. Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence. Curr Treat Options Oncol. 2018;19(8):38. http://dx.doi.org/10.1007/s11864-018-0555-8.

Pasqualucci L and Dalla-Favera R. Genetics of diffuse large B-cell lymphoma. Blood. 2018;131(21):2307-2319. http://dx.doi.org/10.1182/blood-2017-11-764332.

De Silva NS and Klein U. Dynamics of B cells in germinal centres. Nat Rev Immunol. 2015;15(3):137-48. http://dx.doi.org/10.1038/nri3804.

Song S and Matthias PD. The Transcriptional Regulation of Germinal Center Formation. Front Immunol. 2018;9(2026):1-9. http://dx.doi.org/10.3389/fimmu.2018.02026.

Calado DP, Sasaki Y, Godinho SA, Pellerin A, Köchert K, Sleckman BP, et al. The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers. Nat Immunol. 2012;13(11):1092-100. http://dx.doi.org/10.1038/ni.2418.

Dominguez-Sola D, Kung J, Holmes AB, Wells VA, Mo T, Basso K, Dalla-Favera R. The FOXO1 Transcription Factor Instructs the Germinal Center Dark Zone Program. Immunity. 2015; 43(6):1064-74. http://dx.doi.org/10.1016/j.immuni.2015.10.015.

Heise, N, De Silva NS, Silva K, Carette A, Simonetti G, Pasparakis M, Klein U. Germinal center B cell maintenance and differentiation are controlled by distinct NF-?B transcription factor subunits. J Exp Med 2014;211(10):2103-18. http://dx.doi.org/10.1084/jem.20132613.

Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, et al. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Engl J Med. 2018;378(15):1396-1407. http://dx.doi.org/10.1056/NEJMoa1801445.

Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, et al. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell. 2017;171(2):481-494.e15. http://dx.doi.org/10.1016/j.cell.2017.09.027.

Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, et al. Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937-47. http://dx.doi.org/10.1056/NEJMoa012914.

Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24(5):679-690. http://dx.doi.org/10.1038/s41591-018-0016-8.

Lacy SE, Barrans SL, Beer PA, Painter D, Smith AG, Roman E, et al. Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report. Blood. 2020;135(20): 1759-1771. http://dx.doi.org/10.1182/blood.2019003535.

Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, et al. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020;37(4):551-568.e14. http://dx.doi.org/10.1016/j.ccell.2020.03.015.

Hübschmann D, Kleinheinz K, Wagener R, Bernhart SH, López C, Toprak UH, et al. Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas. Leukemia. 2021;35(7):2002-2016. http://dx.doi.org/10.1038/s41375-021-01251-z.

Pasqualucci L and Ott G. Pathology and Molecular Pathogenesis of DLBCL and Related Entities. In: Lenz, G., Salles, G. (eds) Aggressive Lymphomas. Hematologic Malignancies. Springer Cham. 2019;41-73. http://dx.doi.org/10.1007/978-3-030-00362-3_2

Koh Y. Genomics of diffuse large B cell lymphoma. Blood. 2021;56(S1): S75-S79. http://dx.doi.org/10.5045/br.2021.2021049.

Alsaadi M, Khan MY, Dalhat MH, Bahashwan S, Khan MU, Albar A, et al. Dysregulation of miRNAs in DLBCL: Causative Factor for Pathogenesis, Diagnosis and Prognosis. Diagnostics. 2021;11(1739):1-7. http://dx.doi.org/10.3390/diagnostics11101739.

Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359(22):2313-2323. http://dx.doi.org/10.1056/NEJMoa0802885.

Onaindia A, Santiago-Quispe N, Iglesias-Martinez E, Romero-Abrio C. Molecular update and evolving classification of large B-cell lymphoma. Cancers (Basel). 2021;13(3352):1-24. http://dx.doi.org/10.3390/cancers13133352.

Horn H, Staiger AM, Vöhringer M, Hay U, Campo E, Rosenwald A, et al. Diffuse large B-cell lymphomas of immunoblastic type are a major reservoir for MYC-IGH translocations. Am. J. Surg. Pathol. 2015;39(1):61–66. http://dx.doi.org/10.1097/PAS.0000000000000319.

Gong QX, Wang Z, Liu C, Li X, Lu TX, Liang JH, et al. CD30 expression and its correlation with MYC and BCL2 in de novo diffuse large B-cell lymphoma. J. Clin. Pathol. 2018;71(9): 795–801. http://dx.doi.org/10.1136/jclinpath-2018-205039.

Li M, Liu Y, Wang Y, Chen G, Chen, Q, Xiao H, et al. Anaplastic Variant of Diffuse Large B-cell Lymphoma Displays Intricate Genetic Alterations and Distinct Biological Features. Am. J. Surg. Pathol. 2017;41(10):1322–1332. http://dx.doi.org/10.1097/PAS.0000000000000836.

Cerroni L, El-Shabrawi-Caelen L, Fink-Puches R, LeBoit PE, Kerl H. Cutaneous spindle-cell B-cell lymphoma: a morphologic variant of cutaneous large B-cell lymphoma. Am J Dermatopathol. 2000;22(4):299-304. http://dx.doi.org/10.1097/00000372-200008000-00001.

Nozawa Y, Wang J, Weiss LM, Kikuchi S, Hakozaki H, Abe M. Diffuse large B-cell lymphoma with spindle cell features. Histopathology. 2021;38(2):177-186. http://dx.doi.org/10.1046/j.1365-2559.2001.01072.x.

Elsaghayer WA, Jewaid A, Topov Y, Anthoni D, Abdalla FB. Case Report Diffuse Large B-cell Lymphoma with Clear Cells Morphology: A rare Variant. Journal of Medical Science. 2014;1(1):85-91.

Stein H, Warnke RA, Chan WC, Jaffe ES, Chan JKC, Gatter KC, et al. Diffuse large B-cell lymphoma, not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, et al., eds. WHO Classification of Tumours of Haemotopoietic and Lymphoid Tissues. Revised 4th ed. Lyon, France: IARC Press; 2017.

Cho J. Basic immunohistochemistry for lymphoma diagnosis. Blood. 2022;57(S1):S55-S61. http://dx.doi.org/10.5045/br.2022.2022037

Xu J, Li P, Chai J, Yu K, Xu T, Zhao D, et al. The clinicopathological and molecular features of sinusoidal large B-cell lymphoma. Mod Pathol. 2021;34(5):922-933. http://dx.doi.org/10.1038/s41379-020-00685-7.

Roschewski M, Phelan JD, Wilson WH. Molecular Classification and Treatment of Diffuse Large B-Cell Lymphoma and Primary Mediastinal B-Cell Lymphoma. Cancer J. 2020;26(3):195-205. http://dx.doi.org/10.1097/PPO.0000000000000450.

Salles G, Barret M, Foa R, Maurer J, O’Brien S, Valente N, et al. Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience. Adv Ther. 2017;34(10):2232-2273. http://dx.doi.org/10.1007/s12325-017-0612-x.

Miao Y, Medeiros LJ, Xu-Monette ZY, Li J, Young KH. Dysregulation of Cell Survival in Diffuse Large B Cell Lymphoma: Mechanisms and Therapeutic Targets. Front Oncol. 2019;9(107):1-17. http://dx.doi.org/10.3389/fonc.2019.00107.

Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, et al. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2020;394(10216):2271–2281. http://dx.doi.org/10.1016/S0140-6736(19)33008-9.

Crump M, Neelapu SS, Farooq U, Neste EVD, Kuruvilla J, Westin J, et al. Outcomes in refractory diffuse large B-cell lymphoma:results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–1808. http://dx.doi.org/10.1182/blood-2017-03-769620.

DOI: https://doi.org/10.32539/mks.v53i3.20435