1. Geraldine O’Dowd Consultant Pathologist NHS Lanarkshire 18 th November 2014 Colorectal Cancer Pathology: Impact of new guidelines for the laboratory

2. Introduction Colorectal cancer is common in Scotland Important part of workload in most laboratories New developments: New RCPath. guidelines Colorectal screening ICC and molecular testing

3. Plan Focus on new RCPath. guideline 2014 Gross dissection Venous invasion Cases without obvious cancer Colorectal screening impact ICC and molecular testing developments

4. RCPath. Minimum Dataset

5. Background Changes in pathology reporting requirements and in clinical expectations occur with time Major impact for lab and consultant workload The report…..

6. Pathology Reports

7. IN THE PAST: Minimalist reporting Block of tumour, block of lymph nodes, maybe margins (max. around 5 blocks) Very brief report…..

14. NOW: Requires use of ‘minimum’ dataset More tumour blocks All lymph nodes Complex margin assessment Use of ICC and routine special stains Many blocks (often more than 40) Additional molecular testing

19. Dissection

20. Specimen dissection Hemicolectomies, anterior resections and abdominoperineal resections Colorectal trimming is time consuming macroscopic assessment and handling is critical identification of anterior peritoneal reflection assessment of mesorectal plane quality marking of non peritonealised ( ‘ circumferential ’ ) margin

22. From RCPath ‘ Dataset for Colorectal Cancer ’, 3rd edition, July 2014.

23. .

24. Specimen dissection Specimen photography- time consuming Ink to mark non-peritonealised circumferential margin Open specimen and clean but, where possible, avoid opening through tumour Good fixation (College recommends at least 48h) Careful cutting into thin transverse slices (around 3 to 6mm), arranged to preserve anatomical orientation

25. PROXIMAL DISTAL POSTERIOR ANTERIOR R L LEVEL OF APR 1 2 3 4 5 6 7 8 9 10

26. PROXIMAL DISTAL POSTERIOR ANTERIOR R L LEVEL OF APR 1 2 3 4 5 6 7 8 9 10 6 7

27. From RCPath ‘ Dataset for Colorectal Cancer ’, 3rd edition, July 2014.

31. Specimen dissection Selection of blocks for histological examination standard versus ‘ macro ’ blocks relationship to peritoneum (determines pT3 or pT4) relationship to layers of bowel wall (good sampling to avoid understaging) proximity to margins venous or perineural invasion role of special staining to improve detection discontinuous deposits of tumour in mesorectum

32. From RCPath ‘ Dataset for Colorectal Cancer ’, 3rd edition, July 2014.

34. Specimen dissection Lymph node examination apical node (nearest to surgical vascular tie) sequential sections through mesorectal fat to retrieve ALL lymph nodes if nodes are bisected in this process, care is required to avoid over staging (many pathologists process one node per block to avoid problems)

35. Histological reporting Tumour type, differentiation and stage Other pathological changes, e.g. polyps, IBD, diverticular disease, etc. Lymph node status Presence or absence of venous and perineural invasion extramural versus intramural veins elastic staining to aid recognition

38. Venous Invasion

40. Extramural vein Elastic layer below serosal surface

41. Extramural vein

43. Intramural venous invasion

44. Identifying the Tumour Site

45. Where’s the cancer?!? Problems in 2 main settings: Pre-operative chemoradiotherapy Previous polypectomy with cancer Must identify correct part of bowel to process Need good clinical and radiological information May need many blocks and levels Must identify tumour bed or scar site

46. College guidance “Rectal tumours that have undergone pre-operative therapy may undergo regression such that no definite residual tumour can be recognised. In such cases, at least five blocks from the site of the original mass should be taken in the first instance. If these do not show residual tumour on microscopic examination (after examining sections from three levels) then the whole of the tumour site and/or the scarred area should be blocked for histology. If still no tumour is found, three levels should be cut on all blocks from the tumour site and, if still negative, a pathology complete response can then be recorded.” From RCPath ‘ Dataset for Colorectal Cancer ’, 3rd edition, July 2014.

49. Molecular Testing

50. Molecular testing Evidence that some genes predict response to certain forms of chemotherapy, e.g. cetuximab K-RAS BRAF NRAS Testing of formalin-fixed, paraffin embedded tissue At present, usually requested for specific patients May allow curative treatment when irresectable disease Known prognostic value and may affect risk for other family members

51. College guidance “Mismatch repair (MMR) protein immunohistochemistry now has several well-recognised applications in colorectal carcinoma..... We now consider MMR immunohistochemistry a core dataset item for patients under 50 years at time of diagnosis and for patients, in whom an assessment of prognosis is appropriate, with adenocarcinomas classified as poorly differentiated morphologically or tumours showing other morphological features of MMR deficiency. It should also be available upon request by either oncologist or geneticist on individual cases..” From RCPath ‘ Dataset for Colorectal Cancer ’, 3rd edition, July 2014.

52. Consequences for the lab…

53. Consequences More time dissecting: photos, inking, macro blocks, etc. More blocks produced and so more sections to cut and stain Routine use of elastica staining on all tumour blocks More blocks and levels from cases without obvious cancer After Bowel Screening polypectomy After pre-operative chemoradiotherapy More use of ICC and molecular testing

54. Summary New guidelines have important consequences for workload at every level More time trimming More blocks More sections More special stains and ICC More molecular testing Longer reports to produce and to type Those involved in planning must consider likely future service developments

55. Any questions? END!