3D Pathology Volumetric Technique: A Method for Calculating Breast Tumour Volume from Whole-Mount Serial Section Images

Abstract

Tumour size, most commonly measured by maximum linear extent, remains a strong predictor of survival in breast cancer. Tumour volume, proportional to the number of tumour cells, may be a more accurate surrogate for size. We describe a novel “3D pathology volumetric technique” for lumpectomies and compare it with 2D measurements. Volume renderings and total tumour volume are computed from digitized whole-mount serial sections using custom software tools. Results are presented for two lumpectomy specimens selected for tumour features which may challenge accurate measurement of tumour burden with conventional, sampling-based pathology: (1) an infiltrative pattern admixed with normal breast elements; (2) a localized invasive mass separated from the in situ component by benign tissue. Spatial relationships between key features (tumour foci, close or involved margins) are clearly visualized in volume renderings. Invasive tumour burden can be underestimated using conventional pathology, compared to the volumetric technique (infiltrative pattern: 30% underestimation; localized mass: 3% underestimation for invasive tumour, 44% for in situ component). Tumour volume approximated from 2D measurements (i.e., maximum linear extent), assuming elliptical geometry, was seen to overestimate volume compared to the 3D volumetric calculation (by a factor of 7x for the infiltrative pattern; 1.5x for the localized invasive mass).

Optimized SIFTFlow for registration of whole-mount histology to reference optical images

“…Clarke et al 13 demonstrated that manually identified landmarks can be used to align a whole-mount lumpectomy histology image with a specimen cone-beam computed tomography slice and used this manual alignment to compare 3-D with 2-D tumor measurements, 12 but this is a laborious and imprecise process. Booth et al 4 investigated the use of automated 3-D reconstruction of small breast tissue WSIs in the study of the biology of DCIS.…”

“…The second problem is that there are no clear boundaries to help guide the registration; this is especially true of lumpectomy specimens where the surgeon removes the tumor together with as little of the surrounding breast tissue as possible. Manual methods of reconstructing 3-D lumpectomy specimens have been described 12,13 but they are very time-consuming and inaccurate.…”

3D chemical imaging of the brain using quantitative IR spectro-microscopy

“…A common limit to all chemical imaging techniques that might be used for 3D volume rendering is that, at microscopic scale, 3D reconstruction is considerably more challenging relative to two-dimensional imaging because sectioning artifacts such as tissue tears, bends, folds, and cracks become unmanageable. 12 Moreover, in 3D pathology, it is also mandatory to consider soft tissue distortions due to organ removal by surgery or biopsy. The shape of the tissue is considerably altered via cryomicrotomy, and the final 3D reconstruction model that is created from serial 2D sections will be significantly distant from reality.…”

Cost-Effectiveness Analysis of Whole-Mount Pathology Processing for Patients with Early Breast Cancer Undergoing Breast Conservation

“…The fresh specimen is suspended in a gel to reduce tissue collapse and distortion, and then serially sectioned into uniform 4-mm slices suitable for processing, staining, and interpretation 8,11 . The method has been refined and demonstrates preservation of cellular morphology, reduction in specimen shrinkage, compatibility with standard breast cancer immunohistochemistry, and superiority to standard processing with respect to evaluating specimen orientation and volumetric extent of disease [12][13][14][15] . Furthermore, the wm process is the backbone for slide digitization and three-dimensional reconstructive imaging, thus providing unparalleled interpretation of the entire resected specimen.…”