Three-dimensional tumor visualization of invasive breast carcinomas using whole-mount serial section histopathology: implications for tumor size assessment
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Linear tumor size (T-size) estimated with conventional histology informs breast cancer management. Previously we demonstrated significant differences in margin and focality estimates using conventional histology versus digital whole-mount serial sections (WMSS). Using WMSS we can measure T-size or volume. Here, we compare WMSS T-size with volume, and with T-size measured conventionally. We also compare the ellipsoid model for calculating tumor volume to direct, WMSS measurement.
Two pathologists contoured regions of invasive carcinoma and measured T-size from both WMSS and (simulated) conventional sections in 55 consecutive lumpectomy specimens. Volume was measured directly from the contours. Measurements were compared using the paired t-test or Spearman’s rank-order correlation. A five-point ‘border index’ was devised and assigned to each case to parametrize tumor shape considering ‘compactness’ or cellularity. Tumor volumes calculated assuming ellipsoid geometry were compared with direct, WMSS measurements.
WMSS reported significantly larger T-size than conventional histology in the majority of cases [61.8%, 34/55; means = (2.34 cm; 1.99 cm), p < 0.001], with a 16.4% (9/55) rate of ‘upstaging’. The majority of discordances were due to undersampling. T-size and volume were strongly correlated (r = 0.838, p < 0.001). Significantly lower volume was obtained with WMSS versus ellipsoid modeling [means = (1.18 cm3; 1.45 cm3), p < 0.001].
Significantly larger T-size is measured with WMSS than conventionally, due primarily to undersampling in the latter. Volume and linear size are highly correlated. Diffuse tumors interspersed with normal or non-invasive elements may be sampled less extensively than more localized masses. The ellipsoid model overestimates tumor volume.
KeywordsBreast cancer Lumpectomy Whole-mount serial sections Large-format histology Histologic size Tumor volume
Tumor Node Metastasis
American Joint Committee on Cancer/Union for International Cancer Control
Whole-mount serial sections
Hematoxylin and eosin
Simulated conventional sections
The authors are grateful to Ms Anoma Gunasekara for her assistance with recruitment, and together with Ms Yulia Yerofeyeva with organizing all aspects of the study logistics and patient tracking. Finally we acknowledge the co-operation of pathologist assistants Ms Anna-Marie Moskaluk, Mr Ian Cooper. Dr Laibao Sun and Dr Peter Leventis for performing the virtual sampling and overseeing the research protocol, and Adebayo Adeeko for assistance with specimen preparation.
This work was supported by the Canadian Breast Cancer Research Alliance/Canadian Cancer Society Research Institute.
Compliance with ethical standards
Conflict of interest
The authors do not have a conflict of interest.
This study was conducted in full compliance with the applicable, current Canadian law.
- 9.Lester S, Bose S, Chen Y-Y et al (2013) Protocol for the examination of specimens from patients with invasive carcinoma of the breast protocol applies to all invasive carcinomas of the breast, including ductal. Arch Pathol Lab Med 133(10):1515–1538Google Scholar
- 14.Dekker TJA, van de Velde CJH, van Pelt GW et al (2013) Prognostic significance of the tumor-stroma ratio: validation study in node-negative premenopausal breast cancer patients from the EORTC perioperative chemotherapy (POP) trial (10854). Breast Cancer Res Treat 139:371–379. https://doi.org/10.1007/s10549-013-2571-5 CrossRefGoogle Scholar
- 24.Clarke GM, Peressotti C, Constantinou P et al (2010) Increasing specimen coverage using digital whole-mount breast pathology: implementation, clinical feasibility and application in research. Comput Med Imaging Graph 35:531–541. https://doi.org/10.1016/j.compmedimag.2011.05.002 CrossRefGoogle Scholar
- 31.Foster MR, Harris L, Biesemier KW (2012) Large format histology may aid in the detection of unsuspected pathologic findings of potential clinical significance: a prospective multiyear single institution study. Int J Breast Cancer 2012:532547. https://doi.org/10.1155/2012/532547 CrossRefGoogle Scholar