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Better see to better agree: phosphohistone H3 increases interobserver agreement in mitotic count for meningioma
Eleonora Duregon1, Adele Cassenti1, Alessandra Pittaro1
1Department of Medical Sciences, University of Torino, Turin, Italy (A.C., A.P., R.S., P.C.); Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Italy (E.D.); Department of Statistical Sciences, University of Padua, Padova, Italy (L.V.); Department of Neuro-Oncology, University and City of Health and Science Hospital of Turin, Turin, Italy (R.R.).
Background:
Mitotic count on hematoxylin and eosin (H&E)-stained slides is a crucial diagnostic criterion in meningioma grading. However, mitosis assessment on H&E slides can be impaired by technical factors and by pathologist's experience. Phosphohistone H3 (PHH3) serine-10 is a mitosis-specific antibody that has proven to facilitate mitotic count in various tumors.
Methods:
A series of 70 meningiomas (15 grade I, 40 grade II, 15 grade III) was used to validate PHH3 intra- and interobserver reproducibility and to identify PHH3-specific mitotic thresholds. Four pathologists with different experience in neuropathology counted mitoses on both H&E- and PHH3-stained slides.
Results:
H&E and PHH3 mitotic rates were highly correlated (Pearson's r = 0.92, P < .0001). PHH3 mitotic counts had both a good mean interobserver correlation (R(m) = 0.83) and a good intraclass correlation (0.78), higher than H&E mitotic indices (R(m) = 0.77, intraclass correlation = 0.71). After further stratification of meningiomas according to World Health Organization grade, PHH3 performed better in terms of interobserver concordance (Kendall's W = 0.761) compared with H&E (Kendall's W = 0.697). Referring to the same meningioma groups identified by World Health Organization grade as the gold standard, the volume under the receiver operator characteristic surface was 0.91, indicating a very good diagnostic ability of PHH3 scores in discriminating the 3 meningioma groups. The 2 optimal PHH3-specific cutoff values were 6.61 and 22.02.
Conclusion:
PHH3 staining is a useful diagnostic complementary tool to standard H&E mitotic count, optimizing intra- and interobserver reproducibility. PHH3-specific mitotic thresholds should be adopted to avoid overgrading of meningioma when ancillary methods are employed.
Insights
Phosphohistone H3 (PHH3) staining improves the accuracy of meningioma grading by enhancing mitosis count reproducibility. Adopting PHH3-specific thresholds can prevent overgrading, leading to more reliable diagnoses.
Area of Science:
- Neuropathology
- Oncology
- Histopathology
Background:
- Mitotic count on hematoxylin and eosin (H&E)-stained slides is crucial for meningioma grading.
- H&E mitosis assessment can be affected by technical factors and pathologist experience.
- Phosphohistone H3 (PHH3) serine-10 is a mitosis-specific antibody aiding mitotic count in various tumors.
Purpose of the Study:
- Validate PHH3 intra- and interobserver reproducibility in meningioma grading.
- Identify PHH3-specific mitotic thresholds for improved diagnostic accuracy.
- Compare PHH3 performance against standard H&E staining.
Main Methods:
- A series of 70 meningiomas (grades I, II, III) were analyzed.
- Four pathologists with varying experience assessed mitoses on both H&E and PHH3-stained slides.
- PHH3 intra- and interobserver reproducibility and mitotic thresholds were evaluated.
Main Results:
- PHH3 and H&E mitotic rates were highly correlated (Pearson's r = 0.92).
- PHH3 showed higher interobserver (R(m) = 0.83) and intraclass (0.78) correlations than H&E (R(m) = 0.77, 0.71).
- PHH3 demonstrated superior interobserver concordance (Kendall's W = 0.761) compared to H&E (Kendall's W = 0.697) for WHO grading, with a diagnostic ability of 0.91.
Conclusions:
- PHH3 staining is a valuable adjunct to H&E for meningioma grading, enhancing reproducibility.
- PHH3-specific mitotic thresholds should be implemented to prevent meningioma overgrading.
- PHH3 improves diagnostic accuracy and interobserver agreement in meningioma classification.
