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Chapter 2:
Subgross Morphology Parameters in Breast Cancer and Their Prognostic and Predictive Power

2.1 Introduction

Subgross morphology represents a common basis for all imaging methods. While radiological methods generate and analyze images of breast tissue, pathology examines the tissue itself after it is sliced and processed for microscopic assessment. In general, radiology has far less resolution capacity compared to microscopy, but in turn, radiology methods give a perfect overview of the lesion(s) and surrounding tissue. Radiology can also generate images in different projections, allowing a 3D reconstruction and exact localization of the lesion(s). Furthermore, in contrast to histopathology, radiological examinations can be repeated, allowing physicians to follow the lesion(s) during development and progression.

Histopathology, however, is still the gold standard in breast diagnostics, as it can confirm or rule out radiological diagnoses with the exactness of microscopic analysis. In addition, histological analysis generates morphological prognostic parameters (not only tumor size, histology grade, and lymph node status, but also lesion distribution, disease extent, and status of the resection margins), representing the basis of current grading and staging systems. Furthermore, special methods of histological analysis provide parameters predictive of a tumor's response to adjuvant therapy. The most established of these parameters are estrogen and progesterone receptor (ER and PR) status, HER-2 status, proliferative activity of the tumor cells, and most recently, genetic and immunohistochemical phenotyping of the tumor (ER positive, HER-2 positive, triple negative, and basal-like).

Subgross morphology represents a level midway between low-resolution radiological imaging methods and high-resolution microscopic analyses. It does not correspond to macroscopic (naked eye) assessment of the surgical specimen and its slices; as such, an assessment is minimally more sensitive than radiology methods. Subgross morphology is best assessed in large-format histological preparations, preferably including entire cross sections of the specimen. These large-format histology slides are of the same thickness (3-5 μm) as traditional small slides but are prepared without fragmentation of the specimen slices. This preserves the in vivo relation between different components of the tumor. The same large-format slide can be viewed under a microscope or projected as an overhead and can be directly compared to mammography, ultrasound, or magnetic resonance images. This method opens the possibility of correlating radiological and histological findings, and additionally can show subtle changes and minute lesions, even if they are radiologically or macroscopically occult.

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