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).

Figure 1

Sedeen viewing program. A whole-mount breast section is annotated, regions of interest are defined, and coordinates are stored for quantitative analysis.

Figure 2

Selected serial whole-mount sections (Case A) in IDC NOS, diffuse pattern. The orientation is consistent for all of the images (A = anterior; P = posterior; S = superior; I = inferior). Invasive tumour is digitally contoured in green. The cyan boxes represent areas which would be sampled in the conventional pathology evaluation, as assessed by the pathology assistant on optical images aided by palpation of tissue slices. There are 14 whole-mount sections in total.

Figure 3

3D tumour visualization for Case A: (a) volume rendering and projection views through the following dimensions: (a) SI, (b) ML, and (c) AP.

Figure 4

Selected serial whole-mount sections (Case B) in IDC NOS, localized pattern with in situ component extending away from the tumour. The orientation is consistent for all of the images (A = anterior; P = posterior; S = superior; I = inferior). Invasive tumour is contoured in green, in situ in red. The cyan boxes represent areas which would be sampled in the conventional pathology evaluation, as assessed by the pathology assistant on optical images aided by palpation of tissue slices. There are 23 whole-mount sections in total for this case.

Figure 5

3D tumour visualization for Case B: (a) volume rendering and projection views through the following dimensions: (a) SI, (b) ML, and (c) AP. Regions of invasive tumour are shown in red, and in situ disease in green.