Whole slide scanning and virtual microscopy in prostate pathology

Reference: Camparo P, Egevad L, Algaba F, et al. Utility of whole slide imaging and virtual microscopy in prostate pathology. APMIS 2012; 120: 298-304

WSI = Whole slide scanning

VM = Virtual microscopy

Advantages of WSI / VM:

- The slide can be examined at in-between magnifications rather than being limited by the objective lenses fitted to the microscope

- Allow examination of the section at extreme low-power, thereby aiding identification of general architecture as well as reducing the risk of missing separate fragments as in TURP chippings.

- Most viewers show an overview image that aids orientation and navigation when viewing at higher power.

- Remove problems such as the need to transport slides and issues with slide breakages and fading

- In medical education and international meetings, it removes the need for multiple copies of the slide or microscopes that require maintenance and storage as well as enabling annotating of slides with labels and comments.

- Permit simultaneous viewing of a single slide at multiple locations, facilitating specialist second opinion.

- In research, it allow slides to be shared by researchers in different cities, countries or even continents.

- May also facilitate automated image analysis for quantification of immunostaining

- Can help in proficiency testing such as external quality assurance (EQA) schemes as it obviates the necessity for complicated time consuming manual slide circulations and the need to produce multiple identical copies of the section, which is difficult if the lesional focus is small or there is only limited tissue available.

- Can be used for digital archiving that would address issues with space required for storing glass slides as well as removing the risks of slide breakage and manual misfiling. It woul also make retrieval of old slides easier and allow simultaneous access to archival material by multiple users in different locations.

Problems with WSI / VM:

- High-quality slide scanners required for WSI, and high resolution colour monitors for VM are currently expensive

- With many scanners, scanning slides particularly at 40x magnification can still be quite slow limiting their utility in routine diagnostic practice.

- The time it takes to load WSI images onto the computer screen depends on the speed of the Internet connectionand the location of the image server (local or distant). Even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of microscopic slides.

- Changes in histopathology practice including issues related to work flow patterns and ergonomics such as preventing carpal tunnel syndrome and other repetitive use computer injuries. Navigating virtual slides by moving a computer mouse as opposed to a microscope stage would have a very different fell. Non-mouse options such as track balls, touch screens and keyboard options may reduce the risk of repetitive use computer injuries.

- Optimizing monitor resolution as well as brightness and contrast settings is important, and many displays still suffer from off-angle viewing problems resulting in changes in colour hues.

- Firewalls installed by some hospital computer networks can also cause difficulty.

- Many pathologists are currently more comfortable evaluating histological material through microscopes rather than on computer monitor screens.

- Outsourcing of surgical pathology work to other countries (as has been the case with diagnostic radiology) resulting in clinical governance issues. A major limiting factor to histopathology outsourcing is the larger size of the pathology digital files when compared with the simpler black and whiter radiology images.

Advantages of WSI/VM in prostate pathology:

- Prostate biopsies are in some ways particularly well suited to VM, as the suspect area is often very small, enabling quicker scanning with smaller digital files.

- VM is superior to static images, as prostatic lesions requieres careful assessment of architecture at low and medium magnifications followed by assessment of cytological features at medium to high power.

- Facilitates Gleason grading of prostatic adenocarcinoma, as it requires assessment of all the cancer in the core or cores to determine the relative predominance of the various grades.

- Can also facilitate measurement of tumour volume in prostate biopsies.

- Particulary useful when correlating morphology with basal cell immunoreactivity in prostate needle biopsies, which may be critical when seeking to distinguish entrapped benign glands in cancer from the typical patchy immunoreactivity seen in adenosis.

- Lesions in prostate biopsies are often very small and 'cut out' in deeper levels, making it difficult to prepare multiple copies of glass slides for teaching. The difficulty in preparing multiple copies of focal lesions in glass slides of prostate biopsies in also an issue for external quality assurance schemes that test the professional competency of pathologists. Use of WSI/VM would overcome this problem.

- Identical foci are viewed by all participants in proficiency testing schemes in contrast to the minor (sometimes major) differences observed in glass slides prepared from different levels of a prostate biopsy.

- Using appropriate software with VM would also allow participants to annotate the images.

- Used to study the degree of inter-observer variation in prostate pathology. It is a good tool for teaching and standardizing Gleason grading.

- Can pemit accurate remote interpretation of prostatic immunohistochemistry by adequately trained pathologists, and facilitate outsourcing of immunohistochemistry by laboratories with insufficient volume to validate some in-house tests.

Problems with WSI/VM in prostate pathology:

- Identification of subtle features such as nucleolar prominence in suspect glands often requires focusing up and down the section. Z-scanning of the prostate biopsy slides would be particularly useful. However, this would significantly increase the size of the digital files resulting in longer scanning times and issues related to data storage.

- As each set of prostate biopsies consists of many cores examined through multiple levels, each case would have numerous slides, especially if each core is processed separately. This would greatly increase the time required for scanning and the size of the digital file for each case, which would be a major problem if WSI/VM is used for routine reporting or digital archiving.

- Similarly, prostatectomy specimens that are submitted in total for histological examination would have numerous slides requiring scanning.

- If the specimen is embedded in large blocks, this can cause additional problems as few of the currently available scanners can scan large tissue blocks.

- Screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing

- Routine use of biopsy core analysis would be time consuming, as it requires scanning of large series of slides, as in the case of sextant prostate biopsy cores.

- Potential overlook of small atypical foci on the digital slides for a variety of reasons such as lack of familiarity with WSI/VM slide viewing or becoming frustrated with the prolonged time of slide navigation in their Internet connection with a sub-optimal server.