Three Dimensional Breast Pathology Imaging for Reducing Sampling Errors: A Case Study
JT Zubovits, G Clarke, L Sun, D Wang, A Moskaluk, C Peressotti, M Yaffe. Sunnybrook Health Sciences Centre, Toronto, Canada
Background: Conventional pathological specimen evaluation may fail to accurately demonstrate tumour extent and closest margin in cases with multifocal or diffuse distribution of disease. These cases include multifocal in-situ ductal carcinoma [DCIS], locally advanced breast cancer [LABC] following neoadjuvant chemotherapy [NAC], or those in which tumor is impalpable (e.g., lobular carcinoma). Positive margins may be missed, the presence of multifocal disease may not be identified, or the tumor size or extent can be underestimated. Secondary treatments may be inadequate and disease can recur.
Design: We developed an efficient method for 3D, whole-specimen histology using whole-mount serial sections and digital imaging techniques. This approach does not require the usual gross sampling techniques, and total fixation and processing time for a mastectomy is a rapid 36 hours. We summarize the technique and present examples to illustrate its clinical utility. We apply the technique to: (1) lobular carcinoma, (2) LABC treated with NAC, 3) multifocal DCIS, and (4) a close or involved margin. To show its potential as a research tool we apply it to study the heterogeneity of biomarkers with established or potential prognostic significance; estrogen receptor and tumour stem cell markers. Digital imaging and display techniques render inspection of a vastly increased amount of histology data feasible.
Results: The specimen preparation and processing techniques yield diagnostic-quality whole-mount serial section images in a feasible timeframe. Comparison between simulated standard sampling technique and the 3D method for two DCIS cases resulted in multifocal disease and an involved margin being identified only with the 3D technique. The full extent of lobular carcinoma was appreciated only using the 3D technique. A more accurate assessment of pathological complete response to chemotherapy can be obtained by applying this technique. Biomarker distribution is readily visualized using whole-mount section images.
Conclusions: The 3D approach is highly amenable for cases which may require more extensive sampling (e.g. lobular carcinoma and DCIS, and LABC following NAC) by providing more accurate estimates of margins, or tumour burden when disease is multifocal or diffuse. This new technique allows more accurate tumor measurements and better information regarding the presence and distribution of prognostic and predictive markers.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 216, Wednesday Afternoon