Ki67 Proliferation Index in Germinal and Non-Germinal Subtypes of Diffuse Large B-Cell Lymphoma

Atif A Hashmi; Syeda N Iftikhar; Gul Nargus; Omer Ahmed; Ishaq Azeem Asghar; Umme Aiman Shirazi; Anoshia Afzal; Muhammad Irfan; Javaria Ali

doi:10.7759/cureus.13120

Ki67 Proliferation Index in Germinal and Non-Germinal Subtypes of Diffuse Large B-Cell Lymphoma

Cureus. 2021 Feb 4;13(2):e13120. doi: 10.7759/cureus.13120.

Authors

Atif A Hashmi¹, Syeda N Iftikhar¹, Gul Nargus², Omer Ahmed³, Ishaq Azeem Asghar⁴, Umme Aiman Shirazi¹, Anoshia Afzal⁵, Muhammad Irfan⁶, Javaria Ali¹

Affiliations

¹ Pathology, Liaquat National Hospital and Medical College, Karachi, PAK.
² Pathology, Khyber Medical University, Peshawar, PAK.
³ Internal Medicine, Liaquat National Hospital and Medical College, Karachi, PAK.
⁴ Pathology, Ascension St. John Hospital, Detroit, USA.
⁵ Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
⁶ Statistics, Liaquat National Hospital and Medical College, Karachi, PAK.

Abstract

Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma. The 2016 World Health Organization (WHO) update on hematopoietic tumors suggested that all DLBCL cases should be subtyped into germinal and non-germinal center phenotypes. Ki67 immunohistochemistry is a maker of cell proliferation and thus is used as a prognostic and predictive marker in various tumors of human body. Only a few studies evaluated the proliferative index of DLBCL subtypes in our population. Therefore, in this study, we evaluated the frequency of subtypes of DLBCL in our population and K67 index in each subtype. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2018 till December 2020, over a period of three years. A total of 101 cases with a histopathological diagnosis consistent DLBCL were included in the study. Immunohistochemical (IHC) stains CD10, B-cell lymphoma 6 (Bcl-6), and multiple myeloma oncogene 1 (MUM1) were applied for the further sub-categorization of DLBCL into germinal center B-cell-like (GCB) and non-GCB subtypes according to the Hans algorithm. The Ki67 index was interpreted in hot spots of the tumor and reported as an average percentage. Results Out of 101 DLBCL cases, 47.5% of DLBCL were GCB, while 52.5% were non-GCB subtypes. Bcl-2, Bcl-6, MUM1, c-Myc, CD10, and CD30 expression were noted in 62.4%, 45.5%, 42.6%, 44.6%, 39.6%, and 7.9% cases, respectively. The mean Ki67 index was 72.94±16.69%. The mean Ki67 index in non-GCB-type DLBCL was 77.67±14.80%, which was significantly higher than the mean Ki67 index in GCB-type DLBCL (67.70±17.22%) with a significant p-value (p=0.002). Cervical lymph node was the most common site of DLBCL, while the stomach was the most common extra-nodal site. A significant association of Ki67 index was noted with subtypes of DLBCL. A higher proportion of non-GCB-type DLBCL exhibited greater than 80% Ki67 index than GCB subtype DLBCL. Moreover, a significant association Ki67 index was noted with c-Myc positivity. A higher proportion of c-Myc-positive DLBCL had greater than 80% Ki67 index. Conclusion We found that non-GCB-type DLBCL had a higher Ki67 index than GCB subtype DLBCL, portending a poor prognostic significance of non-GCB subtype of DLBCL. Moreover, c-Myc expression was associated with a higher Ki67 index.

Keywords: diffuse large b-cell lymphoma (dlbcl); germinal center b-cell-like (gcb); hans algorithm; ki67 index; proliferative index.