Pathol Int. 2021 Oct;71(10):674-681. doi: 10.1111/pin.13148. Epub 2021 Aug 02.

Diagnostic utility and prognostic significance of the Ki-67 labeling index in diffuse large B-cell lymphoma transformed from follicular lymphoma: a study of 76 patients.

Pathology international

Akiko Miyagi Maeshima, Hirokazu Taniguchi, Yoshikazu Hori, Hanae Ida, Rika Hosoba, Shinichi Makita, Suguru Fukuhara, Wataru Munakata, Tatsuya Suzuki, Dai Maruyama, Koji Izutsu

PMID: 34339560 DOI: 10.1111/pin.13148

Abstract

The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki-67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B-cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki-67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression-free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki-67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes.

© 2021 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Keywords: Ki-67; diffuse large B-cell lymphoma; follicular lymphoma; transformation

References

1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2017. - PubMed
2. Aoki R, Karube K, Sugita Y, Nomura Y, Shimizu K, Kimura Y, et al. Distribution of malignant lymphoma in Japan: analysis of 2260 cases, 2001-2006. Pathol Int. 2008;58:174-8. - PubMed
3. Fischer T, Zing NPC, Chiattone CS, Federico M, Luminari S. Transformed follicular lymphoma. Ann Hematol. 2018;97:17-29. - PubMed
4. Al-Tourah AJ, Gill KK, Chhanabhai M, Hoskins PJ, Klasa RJ, Savage KJ, et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. J Clin Oncol. 2008;26:5165-9. - PubMed
5. Davies AJ, Rosenwald A, Wright G, Lee A, Last KW, Weisenburger DD, et al. Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms. Br J Haematol. 2007;136:286-93. - PubMed
6. Maeshima AM, Omatsu M, Nomoto J, Maruyama D, Kim SW, Watanabe T, et al. Diffuse large B-cell lymphoma after transformation from low-grade follicular lymphoma: morphological, immunohistochemical, and FISH analyses. Cancer Sci. 2008;99:1760-8. - PubMed
7. Maeshima AM, Taniguchi H, Ida H, Hosoba R, Fujino T, Saito Y, et al. Non-diffuse large B-cell lymphoma transformation from follicular lymphoma: a single-institution study of 19 cases. Hum Pathol. 2020;102:33-43. - PubMed
8. Maeshima AM, Taniguchi H, Toyoda K, Yamauchi N, Makita S, Fukuhara S, et al. Clinicopathological features of histological transformation from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue to diffuse large B-cell lymphoma: an analysis of 467 patients. Br J Haematol. 2016;174:923-31. - PubMed
9. Shichijo T, Maruyama D, Yamauchi N, Maeshima AM, Sugano M, Yuda S, et al. Transformation Scoring System (TSS): a new assessment index for clinical transformation of follicular lymphoma. Cancer Med. 2020;9:8864-74. - PubMed
10. Noy A, Schöder H, Gönen M, Weissler M, Ertelt K, Cohler C, et al. The majority of transformed lymphomas have high standardized uptake values (SUVs) on positron emission tomography (PET) scanning similar to diffuse large B-cell lymphoma (DLBCL). Ann Oncol. 2009;20:508-12. - PubMed
11. Kridel R, Sehn LH, Gascoyne RD. Can histologic transformation of follicular lymphoma be predicted and prevented? Blood. 2017;130:258-66. - PubMed
12. González-Rincón J, Méndez M, Gómez S, García JF, P, Bellas C, et al. Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma. PLoS One. 2019;14:e0212813. - PubMed
13. Maeshima AM, Taniguchi H, Fukuhara S, Maruyama D, Kim SW, Watanabe T, et al. Clinicopathological prognostic indicators in 107 patients with diffuse large B-cell lymphoma transformed from follicular lymphoma. Cancer Sci. 2013;104:952-7. - PubMed
14. Rusconi C, Anastasia A, Chiarenza A, Marcheselli L, Cavallo F, Rattotti S, et al. Outcome of transformed follicular lymphoma worsens according to the timing of transformation and to the number of previous therapies. A retrospective multicenter study on behalf of Fondazione Italiana Linfomi (FIL). Br J Haematol. 2019;185:713-7. - PubMed
15. Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13-20. - PubMed
16. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984;133:1710-5. - PubMed
17. Miller TP, Grogan TM, Dahlberg S, Spier CM, Braziel RM, Banks PM, et al. Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group Trial. Blood. 1994;83:1460-6. - PubMed
18. Broyde A, Boycov O, Strenov Y, Okon E, Shpilberg O, Bairey O. Role and prognostic significance of the Ki-67 index in non-Hodgkin's lymphoma. Am J Hematol. 2009;84:338-43. - PubMed
19. Samols MA, Smith NE, Gerber JM, Vuica-Ross M, Gocke CD, Burns KH, et al. Software-automated counting of Ki-67 proliferation index correlates with pathologic grade and disease progression of follicular lymphomas. Am J Clin Pathol. 2013;140:579-87. - PubMed
20. Kawaguchi Y, Shiozawa E, Shimada S, Sasaki Y, Abe M, Murai S, et al. Ki-67 expression of immunohistochemistry using computerized image analysis is a useful prognostic marker in follicular lymphomas. Int J Clin Exp Pathol. 2018;11:3366-74. - PubMed
21. Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med. 2007;48:932-45. - PubMed
22. Werner M, Chott A, Fabiano A, Battifora H. Effect of formalin tissue fixation and processing on immunohistochemistry. Am J Surg Pathol. 2000;24:1016-9. - PubMed

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