Whole-mount histopathology and technique development

The biomarker imaging research lab specializes in whole-mount histopathology, which captures an entire cross-section of a surgical tissue specimen. These tissue sections are up to 120mm x 170mm in size and, once stained and scanned, can be analysed and co-registered with in vivo images. We produce these digital whole-mount serial sections at diagnostic quality, which can be used in clinical studies. Since its inception, the lab has processed over 110 lumpectomy, 40 mastectomy, 23 prostate, and 19 tongue specimens. Other pilot projects include several whole-mount brain samples and a sample of colorectal cancer.

Left: breast cancer lumpectomy with multi-focal cancer, middle: prostate cancer, right: brain whole-specimen section for neurological research.

We use large field-of-view microscopes and tissue scanners like the TissueScope 4000 and Leica SCN400 to take high-resolution digital images of the slides. These images can be converted into 2-D and 3-D datasets and analyzed using digital pathology tools and software that are either developed by our lab or commercially available. Another application of this technique is to study disease characterization and progression, like spatial heterogeneity and progression of cancer.

The advantages of whole-mount histopathology are:

• improved sampling through preserving spatial arrangement of the tissue;
• more accurate margin assessment;
• volumetric assessment of tumour burden; and
• secondary disease foci identification.

We have published several studies in these areas of whole-mount pathology. We are continuing our work on the improvement and automation of the whole-mount process by optimizing laboratory procedures, using advanced equipment and applying automation to the workflow.

Tissue processing equipment (click to enlarge)

We have developed a prototype automated stainer for whole-mount slides to reduce further the cost and time associated with the method, and validated it on several clinical whole-mount hematoxylin and eosin slides.

Other examples of automation include automated microwave processing methods that significantly reduce overall processing time. For example, an optimized microwave whole-mount breast cancer tissue fixation protocol is 16 hours, compared to 59 hours for conventional processing. For prostate cancer tissue, the processing time is reduced to nine hours from 20 hours using the automatic microwave-based processing protocol on the Milestone Delta Ultra Rapid Microwave Tissue Processor that is available in the lab.

Tissue slicer (click to enlarge)

Finally, we have developed an alternative gel formulation that allows rapid and accurate slicing and sampling of the tissue. A tissue slicer developed in the lab is also used routinely to render accurate slicing of the specimens to produce serial sections at equal intervals.

Tissue processing equipment

Tissue slicer