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Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma
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The Utility of Phosphohistone H3 (PHH3) in Follicular Lymphoma Grading: A Comparative Study With Ki-67 and H&E

Michelle L Khieu1, Devin R Broadwater1, James K Aden1

  • 1Department of Pathology, Brooke Army Medical Center, San Antonio, TX.

American Journal of Clinical Pathology
|February 22, 2019
PubMed
Abstract

Insights

Phosphohistone H3 (PHH3) mitotic count (MC) is a superior marker for grading follicular lymphoma (FL). PHH3 MC demonstrates stronger correlation and less variability than Ki-67 and H&E stains, supporting its use in FL diagnosis.

Area of Science:

  • Hematopathology
  • Oncology
  • Immunohistochemistry

Background:

  • Follicular lymphoma (FL) grading is crucial for patient management.
  • Current grading methods using Ki-67 and H&E stains have limitations in accuracy and interobserver agreement.

Purpose of the Study:

  • To evaluate the utility of phosphohistone H3 (PHH3) mitotic count (MC) as a reliable marker for grading follicular lymphoma (FL).
  • To compare the performance of PHH3 MC with Ki-67 proliferation index and H&E MC in FL grading.

Main Methods:

  • Retrospective analysis of 43 FL cases diagnosed between 2005 and 2017.
  • Hematopathologists assessed average Ki-67 proliferation index, PHH3 MC, H&E MC, and centroblast count per high-power field.
  • Statistical analysis included correlation and interobserver variability assessments.

Main Results:

  • PHH3 MC showed the strongest correlation with FL grade (r = 0.701, P < .0001) compared to Ki-67 PI (r = 0.681) and H&E MC (r = 0.536).
  • PHH3 MC exhibited the highest interobserver agreement (ICC = 0.86), surpassing Ki-67 PI (ICC = 0.85) and H&E MC (ICC = 0.78).
  • PHH3 MC demonstrated the strongest linear relationship with centroblast count (R2 = 0.453).

Conclusions:

  • PHH3 mitotic count is a highly reliable marker for follicular lymphoma grading.
  • PHH3 MC offers superior correlation to histologic grade and reduced interobserver variability compared to Ki-67 PI and H&E MC.
  • PHH3 staining should be considered as an adjunct tool for accurate FL grading.
Keywords:
FollicularGradingLymphomaPHH3Phosphohistone H3

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