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

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.

Histologic transformation of follicular lymphoma: pathologists’ viewpoint

“…1A and 1B ), and for the diagnosis of challenging cases, Ki-67 index ≥50% is used as a reference. 34 However, judgment of the size of lymphoma cells is also unclear. Simple and objective criteria for HT are required in routine examination in the future.…”

“…Using the abovementioned criteria, the Ki‐67 index of a DLBCL component transformed from FL ranges from 16.8% to 98.4%, with a median of 60.6%, and a Ki‐67 index of ≥70% is an adverse prognostic factor for patients with HT of FL (P = 0.024; 5-year overall survival rates, 53% and 85%, respectively). 34 Broyde et al 35 reported that the appropriate cutoff value for the Ki‐67 labeling index (LI) to distinguish between low‐grade B‐cell lymphoma and DLBCL was 45%, and among the de novo DLBCL cases, patients with a Ki‐67 LI of >70% had a poor outcome (3‐year overall survival rate, 75% vs. 56%; P = 0.015). The Ki‐67 LI and FL grade are mildly correlated: the Ki‐67 LI of FL grades 1–2 is usually ≤40%, and that of FL grades 3A–3B is 30%–60%.…”