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Three-dimensional tumor visualization of invasive breast carcinomas using whole-mount serial section histopathology: implications for tumor size assessment

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Abstract

Purpose

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.

Methods

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.

Results

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].

Conclusions

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.

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Data Availability

The datasets created and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

TNM:

Tumor Node Metastasis

AJCC/UICC:

American Joint Committee on Cancer/Union for International Cancer Control

3-D:

Three-dimensional

WMSS:

Whole-mount serial sections

WM:

Whole-mount

H&E:

Hematoxylin and eosin

SCS:

Simulated conventional sections

AP:

Anterior–posterior

SI:

Superior–inferior

ML:

Medial–lateral

BI:

Border Index

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Acknowledgements

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.

Funding

This work was supported by the Canadian Breast Cancer Research Alliance/Canadian Cancer Society Research Institute.

Author information

Author notes

  1. J. T. Zubovits

    Present address: Department of Pathology, Scarborough and Rouge Hospital, 3030 Birchmount Road, Toronto, ON, M1W 3W3, Canada

Authors and Affiliations

  1. Physical Sciences Platform, Sunnybrook Research Institute, Room C7-27c 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    G. M. Clarke

  2. Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada

    C. M. B. Holloway

  3. Department of Surgery, Sunnybrook Health Sciences Centre, Room T2-015 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    C. M. B. Holloway

  4. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada

    J. T. Zubovits & S. Nofech-Mozes

  5. Sunnybrook Health Sciences Centre, Room E423a 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    S. Nofech-Mozes

  6. Physical Sciences Platform, Sunnybrook Research Institute, Room C7-48a 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    M. Murray

  7. Physical Sciences Platform, Sunnybrook Research Institute, Room C7-27a 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    K. Liu & D. Wang

  8. Research Design and Biostatistics, Sunnybrook Research Institute, Toronto, ON, Canada

    A. Kiss

  9. Institute of Health Policy, Management and Evaluation, University of Toronto, Room G106 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    A. Kiss

  10. Departments of Medical Biophysics and Medical Imaging, Faculty of Medicine, University of Toronto, Toronto, Canada

    M. J. Yaffe

  11. Physical Sciences Platform, Sunnybrook Research Institute, Room S6-57 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    M. J. Yaffe

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  1. G. M. Clarke
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Corresponding author

Correspondence to M. J. Yaffe.

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The authors do not have a conflict of interest.

Ethical approval

This study was conducted in full compliance with the applicable, current Canadian law.

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Clarke, G.M., Holloway, C.M.B., Zubovits, J.T. et al. Three-dimensional tumor visualization of invasive breast carcinomas using whole-mount serial section histopathology: implications for tumor size assessment. Breast Cancer Res Treat 174, 669–677 (2019). https://doi.org/10.1007/s10549-018-05122-7

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  • DOI: https://doi.org/10.1007/s10549-018-05122-7

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