The Utility of Phosphohistone H3 (PHH3) in Follicular Lymphoma Grading: A Comparative Study With Ki-67 and H&E Mitotic Count

Am J Clin Pathol. 2019 May 3;151(6):542-550. doi: 10.1093/ajcp/aqz003.

Abstract

Objectives: To determine the utility of phosphohistone H3 (PHH3) mitotic count (MC) in grading follicular lymphoma (FL).

Methods: FL cases were identified (2005-2017). Three hematopathologists recorded their average Ki-67 proliferation index, MC/high-power field (hpf) using PHH3 and H&E stains, and number of centroblasts/hpf. Results were assessed for correlations and interobserver variability.

Results: Forty-three cases of FL were studied. PHH3 MC resulted in the strongest correlation to grade (r = 0.701, P < .0001) compared with Ki-67 proliferation index (PI) (r = 0.681, P < .0001) and H&E MC (r = 0.536, P = .0002) and the strongest linear relationship to centroblast count (R2 = 0.453). Agreement among pathologists was strongest for PHH3 (intraclass correlation coefficient [ICC] = 0.86) followed by Ki-67 PI (ICC = 0.85) and H&E MC (ICC = 0.78).

Conclusions: PHH3 correlates best to histologic grade and has less interobserver variability compared with Ki-67 PI and H&E MC. These results support using PHH3 as an adjunct in FL grading.

Keywords: Follicular; Grading; Lymphoma; PHH3; Phosphohistone H3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Histones / analysis*
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis*
  • Lymphoma, Follicular / pathology*
  • Middle Aged
  • Mitotic Index
  • Neoplasm Grading
  • Observer Variation
  • Young Adult

Substances

  • Histones
  • Ki-67 Antigen