Association of Morphology and Immunophenotype in Diffuse Large B-Cell Lymphomas with Bone Marrow Infiltration in a Sample Mexican Population

Abstract

Introduction: Diffuse large B-cell lymphoma (DLBCL), not otherwise specified, is a large B-cell lymphoma with a diffuse growth pattern and aggressive clinical course. It is divided in subgroups according to its morphology, immunophenotype, and primary site. Dissemination to bone marrow occurs in 11% to 35% of cases and can be of concordant or discordant morphology. Objective: To examine the association, the type of bone marrow involvement in relation to the primary site, morphology, immunohistochemistry of DLBCLs and to determine the cases of Epstein-Barr virus positive DLBCLs. Materials and Methods: We reviewed lymph node and extranodal biopsies as well as the respective bone marrow biopsies in all cases of DLBCL diagnosed in the Hospital General de México during the period from 2002 to 2010. We used immunohystochemistry for immunophenotype identification (Hans’s algorithm) and an in-situ hybridization technique to detect presence of Epstein Barr encoded RNA (EBER). Results: We included 108 patients with a mean age of 51.9 years, 59 (55%) were men. DLBCL involved lymph nodes in 60% of cases and palatine tonsils in 13%. The centroblastic variant predominated (80%) and 58% originated from activated B-cells. Infiltration of bone marrow was present in 30% of cases and was discordant in 55% of these cases. Correlation between morphology and bone marrow infiltration was statistically significant (P = 0.0003). Presence of Epstein-Barr virus was demonstrated in 15% of patients older than 50 years. Conclusions: Dissemination to bone marrow occurred in 30% of cases and discordant involvement was most common. DLBCL originating from activated B-lymphocytes predominated and the most common extranodal sites were palatine tonsils, suggesting that our population has a clinical behavior similar to Asiatic populations.

Share and Cite:

M. Romero-Guadarrama, F. Jiménez Ponce, A. Medina Cruz, E. Lorena Durán Ramírez and I. Palma Lara, "Association of Morphology and Immunophenotype in Diffuse Large B-Cell Lymphomas with Bone Marrow Infiltration in a Sample Mexican Population," Open Journal of Pathology, Vol. 2 No. 2, 2012, pp. 29-37. doi: 10.4236/ojpathology.2012.22007.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] E. Campo, S. H. Swerdlow, N. L. Harris, S. Pileri, H. Stein and E. S. Jaffe, “The 2008 WHO Classification of Lymphoid Neoplasms and Beyond: Evolving Concepts and Practical Applications,” Blood, Vol. 117, No. 19, 2011, pp. 5019-5032. doi:10.1182/blood-2011-01-293050
[2] E. Zucca, E. Roggero, F. Bertoni, et al., “Primary Extranodal Non-Hodgkin’s Lymphomas. Part I: Gastrointestinal, Cutaneous and Genitourinary Lymphomas,” Annals of Oncology, Vol. 8, No. 8, 1997, pp. 727-737. doi:10.1023/A:1008282818705
[3] M. B. Romero-Guadarrama, M. M. Hernández-González, M. A. Durán-Padilla, et al., “Linfoma B difuso de Células Grandes. Características Patológicas y de Inmunofenotipo en 148 Pacientes Estudiados en el Hospital General de México,” Revisa Medica Hospital General de México, SS, Vol. 69, No. 4, 2006, pp. 192-198.
[4] A. C. Feller and J. Diebold, “Histopathology of Nodal and Extranodal Non-Hodkgin’s Lymphomas: Based on the WHO Classification,” 3rd Edition, Springer-Verlag, Berlin-Heidelberg, 2004, pp. 75-99.
[5] K. Offit, F. Lococo, D. C. Lovie, N. Z. Parsa, D. Leung, et al., “Rearrangement of the bcl-6 Gene as a Prognostic Marker in Diffuse Large-Cell Lymphoma,” The New England Journal of Medicine, Vol. 331, 1994, pp. 74-80. doi:10.1056/NEJM199407143310202
[6] M. G. Tibiletti, V. Martin, B. Bermasconi, B. Del Curto, L. Pecciarin, et al., “BCL2, BCL6, MYC, MALT 1 and BCL10 Rearrangements in Nodal Diffuse Large B-Cell Lymphomas: A Multicenter Evaluation of a New Set of Fluorescent in Situ Hybridization Probes and Correlation with Clinical Outcome,” Human Pathology, Vol. 40, No. 5, 2009, pp. 645-652. doi:10.1016/j.humpath.2008.06.032
[7] C. P. Hans, D. D. Weissenburger, T. C. Greiner, et al., “Confirmation of the Molecular Classification of Diffuse Large B-Cell Lymphoma by Immunohistochemistry Using a Tissue Microarray,” Blood, Vol. 103, No. 1, 2003, pp. 275-282. doi:10.1182/blood-2003-05-1545
[8] D. Talaulikar, J. E. Dahlstrom, B. Shadbolt, M. McNiven, A. Broomfeld, et al., “Occult Bone Marrow Involvement in Patients with Diffuse Large B-Cell Lymphoma Results of a Pilot Study,” Pathology, Vol. 39, No. 6, 2007, pp. 580-585. doi:10.1080/00313020701684417
[9] M. G. Conlan, M. Bast, J. O. Armitage and D. D. Weisenburger, “Bone Marrow Involvement by NonHodgkin’s Lymphoma: The Clinical Significance of Morphologic Discordance between the Lymph Node and Bone Marrow. Nebraska Lymphoma Study Group,” Journal of Clinical Oncology, Vol. 8, No. 7, 1990, pp. 1163-1172.
[10] J. Campbell, J. F. Seymour, J. Matheews, M. Wolf, J. Stone and S. Juneja, “The Prognostic Impact of Bone Marrow Involvement in Patients with Diffuse Large Cell Lymphoma Varies According to the Degree of Infiltration and Presence of Discordant Marrow Involvement,” European Journal of Haematology, Vol. 76, No. 6, 2006, pp. 473-480. doi:10.1111/j.1600-0609.2006.00644.x
[11] D. A. Arber and T. I. George, “Bone Marrow Biopsy Involvement by Non-Hodgkin’s Lymphoma: Frequency of Lymphoma Types, Patterns, Blood Involvement, and Discordance with Other Sites in 450 Specimens,” The American Journal of Surgical Pathology, Vol. 29, No. 12, 2005, pp. 1549-1557. doi:10.1097/01.pas.0000182405.65041.8b
[12] R. Chung, R. Lai, P. Wei, et al., “Concordant but Not Discordant Bone Marrow Involvement in Diffuse Large B-Cell Lymphoma Predicts a Poor Clinical Outcome Independent of the International Prognostic Index,” Blood, Vol. 110, No. 4, 2007, pp. 1278-1282. doi:10.1182/blood-2007-01-070300
[13] C. Palacio, G. Acevedo, M. Navarrete, et al., “Flow Cytometry in the Bone Marrow Evaluation of Follicular and Diffuse Large B-Cell Lymphomas,” Haematologica, Vol. 86, No. 9, 2001, pp. 934-940.
[14] T. Dipti and J. E. Dahlstrom, “Staging Bone Marrow in Diffuse Large B-Cell Lymphoma: The Role of Ancillary Investigations,” Pathology, Vol. 41, No. 3, 2009, pp. 214-222. doi:10.1080/00313020902756295
[15] S. H?ller, H. Horn, A. Lohr, U. M?der, T. Katzenberger, et al., “A Cytomorphological and Immunohistochemical Profile of Aggressive B-Cell Lymphoma: High Clinical Impact of a Cumulative Immunohistochemical Outcome Predictor Score,” Journal of Hematopathology, Vol. 2, No. 4, 2009, pp. 187-194. doi:10.1007/s12308-009-0044-x
[16] K. K. Wong, N. Prepageran and S. C. Peh, “Prognostic Subgroup Distribution in Diffuse Large B-Cell Lymphoma of the Upper Aerodigestive Tract,” Pathology, Vol. 41, No. 2, 2009, pp. 133-139. doi:10.1080/00313020802436790
[17] J. E. Kim, J. A. Kim, Y. K. Jeon, S. S. Park, D. S. Heo and C.W. Kim, “Comparative Analysis or NK/T Cell Lymphoma and Peripheral T-Cell Lymphoma in Korea: Clinicopathological Correlations and Analysis of EBV Strain Type and 30-bp Deletion Variant LMO1,” Pathology International, Vol. 53, 2003, pp. 735-743.
[18] S.-C. Peh, G.-G. Gan, L.-K. Lee and G.-I. Eow, “Clinical Relevance of CD 10, BCL6 and Multiple Myeloma-1 Expression in Diffuse Large B-Cell Lymphomas in Malaysia,” Pathology International, Vol. 58, No. 9, 2008, pp. 572-579. doi:10.1111/j.1440-1827.2008.02273.x
[19] M. Engelhard, G. Brittinger, D. Huhn, et al., “Subclassification of Diffuse Large B-Cell Lymphomas According to the Kiel Classification: Distinction of Centroblastic and Immunoblastic Lymphomas Is a Significant Prognostic Risk Factor,” Blood, Vol. 89, No. 7, 1997, pp. 2291-2297.
[20] J. Diebold, J. R. Anderson, J. O. Armitage, J. M. Connors, K. A. MacLennan, et al., “Diffuse Large B-Cell Lymphoma: A Clinicopathologic Analysis of 444 Cases Classified According to the Updated Kiel Classification,” Leukemia and Lymphoma, Vol. 43, No. 1, 2002, pp. 97104. doi:10.1080/10428190210173
[21] J. W. Sweetenham, “Molecular Signatures in the Diagnsis and Management of Diffuse Large B-Cell Lymphoma,” Current Opinion in Hematology, Vol. 18, No. 4, 2011, pp. 288-292. doi:10.1097/MOH.0b013e32834706ee
[22] Y. Chen, T. Han, J. Iqbal, R. Irons, C. C Wing, et al., “Diffuse Large B-Cell Lymphoma in Chinese Patients. Immunophenotypic and Cytogenetic Analyses of 124 Cases,” American Journal of Clinical Pathology, Vol. 133, No. 2, 2010, pp. 305-313. doi:10.1309/AJCP4H6ADGYDZMOA
[23] S. Camilleri-Broet, E. Criniere, P. Broet, et al., “A Uniform Activated B-Cell-Like Immunophenotype Might Explain the Poor Prognosis of Primary Central Nervous System Lymphomas: Analysis of 83 Cases,” Blood, Vol. 107, No. 1, 2006, pp. 190-196. doi:10.1182/blood-2005-03-1024
[24] M. A. Al-Abbadi, E. M. Hattab, M. S. Tarrawneh, et al., “Primary Testicular Diffuse Large B-Cell Lymphoma Shows a Non-Germinal Center B-Cell-Like Subgroup: A Study of 18 Cases,” Modern Pathology, Vol. 19, No. 12, 2006, pp. 1521-1527. doi:10.1038/modpathol.3800691
[25] G. Paone, E. Itti, C. Haioun, P. Gaulard, J. Dupuis, et al., “Bone Marrow Involvement in Diffuse Large B-Cell Lymphoma: Correlation between FDG-PET Uptake and Type of Cellular Infiltrate,” European Journal of Nuclear Medicine and Molecular Imaging, Vol. 36, No. 5, 2009, pp. 745-750. doi:10.1007/s00259-008-1021-9
[26] Y. Yan, W. C. Chan, D. D. Weisenburger, J. R. Anderson, M. A. Bast, et al., “Clinical and Prognostic Significance of Bone Marrow Involvement in Patients with Diffuse Aggressive B-Cell Lymphoma,” Journal of Clinical Oncology, Vol. 13, No. 6, 1995, pp. 1336-1342.
[27] D. Talaulikar, J. E. Dahistrom, B. Shadholt, A. Broomfield and A. Mc Donald, “Role of Immunohistochemistry in Staging Diffuse Large B-Cell Lymphoma,” Journal of Histochemistry and Cytochemistry, Vol. 56, No. 10, 2008, pp. 893-900. doi:10.1369/jhc.2008.951087
[28] A. Hagenbeek, R. D. Gascoyne, M. Dreyling, P. Kluin, A. Engert and G. Salles, “Biomarkers and Prognosis in Malignant Lymphomas,” Clinical Lymphoma Myeloma and Leukemia, Vol. 9, No. 2, 2009, pp. 160-166.
[29] A. Nussenzweig and M. C. Nussenzweig, “Origin of Chromosomal Translocations in Lymphoid Cancer,” Cell, Vol. 141, No. 1, 2010, pp. 27-38. doi:10.1016/j.cell.2010.03.016
[30] L. Pasqualucci, G. Bhagat, M. Jankovic, et al., “AID Is Required for Germinal Center-Derived Lymphomagenesis,” Nature Genetics, Vol. 40, No. 1, 2008, pp. 108-112. doi:10.1038/ng.2007.35
[31] O. A. O’Connor, L. E. Toner, R. Vrhovac, T. BudakAlpdogan, E. A. Smith and P. Bergman, “Comparative Animal Models for the Study of Lymphohematopoietic Tumors: Strengths and Limitations of Present Approaches,” Leukemia and Lymphoma, Vol. 46, No. 7, 2005, pp. 973-992. doi:10.1080/10428190500083193
[32] T. Oyama, K. Ichimura, R. Suzuki, J. Suzumiya, K. Ohshima, et al., “Age-Related EBV-Associated B-Cell Lymphoproliferative Disorders Constitute a Distinct Clinicopathologic Group: A study of 96 Patients,” Clinical Cancer Research, Vol. 13, No. 17, 2007, pp. 5124-5132. doi:10.1158/1078-0432.CCR-06-2823
[33] A. Hofscheier, A. Ponciano, I. Bonzheim P. Adam, C. Lome-Maldonado, 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 German Population,” Modern Pathology, Vol. 24, No. 8, 2011, pp. 1046-1054. doi:10.1038/modpathol.663-667.62
[34] B. E. Beltran, J. J. Castillo, D. Morales., F. H. de Mendoza, P. Qui?ones, et al., “EBV-Positive Diffuse Large B-Cell Lymphoma of the Elderly: A Case Series from Peru,” American Journal of Hematology, Vol. 86, No. 8, 2011, pp. 663-667. doi:10.1002/ajh.22078
[35] S. Park, J. Lee, Y. H. Ko, et al., “The Impact of Epstein-Barr Virus Status on Clinical outcome in Diffuse Large B-Cell Lymphoma,” Blood, Vol. 110, No. 3, 2007, pp. 972-978. doi:10.1182/blood-2007-01-067769
[36] B. E. Beltran, P. Qui?ones, D. Morales, J. C. Revilla, et al., “Diffuse Large B-Cell Lymphoma in Human T-Lymphotropic Virus Type 1 Carriers,” Leukemia Research and Treatment, Vol. 2012, 2012, 4 pages. doi:10.1155/2012/262363

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.