Is Investing Additional Time on Mitotic Counts in Neuroendocrine Neoplasm Clinically Relevant?
Mohammad Shahid, Lawrence R Zukerberg, Vikram Deshpande. Massachusetts General Hospital, Boston, MA
Background: Mitotic activity is a robust prognostic factor in pancreatic neuroendocrine neoplasms (PanNEN). Grading of NENs is based on mitotic counts and Ki67 labeling index. It is widely accepted that mitotic counts are performed on proliferation 'hotspots', however, the impact of the time expended on mitotic count has not been evaluated. We assess the impact of an extended evaluation of mitotic index on survival in PanNEN.
Design: The mitotic index in 130 PanNET was evaluated by two methods: (1) extended mitotic evaluation - identified all mitotic figures in one tumor bearing slide and used the 10 fields with the highest mitotic count, (2) abbreviated '3 minute' count to mirror routine clinical practice - the 10 fields with the highest counts were recorded. We compared mitotic counts from the two methodologies to overall survival. We used the 2010 WHO grading system with a modification - to critically assess the impact of mitotic counts we did not consider Ki67 labeling index.
Results: The 'extended' method of mitotic counts revealed significantly higher number of mitotic figures (6.7 vs 2.2, p=0.0001). For tumors less than 4 cm, the WHO grade on both the extended and 3 minute mitotic counts correlated with disease specific survival (p=0.0001 and 0.001). Most significantly, based on 'extended' counts the tumor deaths for grade 1, grade 2 and grade 3 tumors were 0/41, 4/30 and 2/5, respectively.
The tumor related deaths based on the '3 minute' counts: 3 deaths in grade 1 and 3 deaths in grade 2. There were no grade 3 tumors identified on the '3 minute' count. Interestingly, among tumors > 4 cm there was no correlation between the WHO grade based on either of the two methods and disease specific survival.
Conclusions: For tumors under 4 cm, an extended mitotic count provides a more robust separation of the 3 tumor grades and identifies an unrecognized group of grade 3 tumors whose behavior mirrors grade 3 tumors identified on 'conventional' mitotic counts. The lack of correlation between extended mitotic counts and outcome for tumors > 4 cm may be related to the greater heterogeneity in proliferation of larger tumors.
Tuesday, March 5, 2013 1:15 PM
Proffered Papers: Section F, Tuesday Afternoon