Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC

3 factors in margin assessment 1. Knowing the margins 2. Handling the specimen correctly 3. Reporting of all the data related to the margins (Minimal Pathology Data Set) Focus will be on rectal cases. They require a little more TLC and the information is a little newer.

Part 1: Knowing the Margins 1.Mucosal 2.Serosal 3.Mesenteric radial 4.Radial 5.CRM

Serosal Margin Peritonealized surface near bowel wall 3 levels of involvement with different prognoses ◦2 of those levels are micro level ◦Take more sections if close Grave prognosis if involved Some institutions doing intraoperative serosal scrapings if tumor appears to approach surface

Mesenteric Margin aka mesenteric radial m. Cecum, Transverse, Sigmoid Point where the mesentary vessel root is cut by the surgeon Specimen should be surrounded by peritoneum at the level of the tumor Measure distance from deepest tumor penetration to resection line – usually > 5 cm

Mesenteric margin

Radial Margin aka adventitial m., lateral m. Retroperitoneal or perineal adventitial soft tissue closest to deepest penetration of tumor Created by blunt dissection during surgery Ascending, Descending, Upper rectum (partially encased by peritoneum) = radial margin Distal rectum (not encased) = circumferential radial margin (CRM)

Part 2: Assessing and Measuring Dr. Phil Quirke from Leeds University is leading professor, researcher and honorary consultant on colorectal cancer reporting and CRM data Second interest is digital pathology ◦GI specialist + avid photographer = amazing instruction on dissecting of colorectal specimens Publication titles include: ◦Local recurrence of rectal adeno CA is caused by inadequate surgical resection (1986) ◦Who to treat with adjuvent therapy in Stage II colorectal CA? The need for high quality pathology (2007)

Quirke’s Protocol Grade the surgery quality of the specimen 2. Fix for 2 days minimum! 3. Serially section 4. Collect Minimal Data Pathology Set (MPD)

1. Mesorectum Quality Assessment Grades 3-1 Intact > Moderate > Incomplete Great indicator of the patient’s prognosis 3-Good : “intact, bulky mesorectum”

Grade 3 intact, smooth, complete

Grade 3

Grade 3 bulky up to levators

Grade 2 - Moderate irregularity of the mesorectal surface w/ >5 mm defects. Moderate coning. No visible m.propria “received is a 12 cm length segment of recto sigmoid colon with a moderate (ragged but no visible m.propria) excision of the mesorectum”

Grade 2 not intact

Is it possible for the entire mesorectum to be removed even though it has a ragged appearance? Is it possible for the entire mesorectum to be removed even though it has a ragged appearance? Yes, but it doesn't matter. Once the mesorectum has been violated the risk for spillage of tumor from lymphatics exists. A ragged specimen without a smooth surface must therefore be a grade 2.

Grade 1: Poor Little bulk with defects down onto m.propria and/or very irregular CRM “The mesorectum is incomplete with defects exposing m.propria.” TAKE PICTURES!

Grade 1

Quirke’s Protocol 1. Grade surgery quality 2. Ink, Partially cut, Fix for 2 days minimum! 3. Serially section 4. Collect Minimal Data Pathology Set (MPD)

2. Don’t cut tumor area

3. Serially section 3-5 mm slices 2 cm above and 2 cm below tumor area

Quirke’s Protocol 1. Grade surgery quality 2. Fix for 2 days minimum! 3. Serially section 4. Collect Minimal Data Pathology Set (MPD)

4. Measure limit of tumor extension (yellow) and distance of tumor, deposit, or node to CRM (red) 4. Measure limit of tumor extension (yellow) and distance of tumor, deposit, or node to CRM (red)

Minimal Pathology Data Set 1. Extent of local invasion (w distance beyond m. propria given) 2. # LNs retrieved 3. Nodal Stage 4. Extramural vascular invasion (EMVI) 5. Peritoneal or serosal involvement 6. CRM involvement (distance of tumor, deposit, or +LN to margin) 7. Quality of mesorectum Together the 7 bits help provide a more accurate prognosis and make retrospective analysis better

Part 3: Reporting the Data Sounds like the easy part but it’s actually the most difficult to accomplish.

Part 3: Reporting the data Updating the dynamic TNM system depends on outcome studies and the collection of outcome data by the NCDB (National Cancer Data Base). 3 parts of the MPD are being collected with the TNM system and it’s been useful: ◦The first 5 ed. of the AJCC staging manual classified stage III in a single group but now has subcategories in the 6 th ed. because of prognostic figures from NCDB analysis from ‘87-’93. ◦Subgroup survival rates were 59.8%, 42%, and 27.3%,respectively when assessing both depth of penetration and difference btwn <4 nodes or ≥4 nodes (+) 7 th ed. comes out in June with changes going in to effect Jan. 1, 2010

And there are more issues… TNM system is good for staging and thus giving prognosis based on studies already performed. But streamlined reporting often omits data (MPD) needed for prognosis and treatment of the patients and omits data needed to assess possible future staging changes. Eg. TNM (+) radial margin definition: 0mm A pt with tumor at the CRM has a 22% chance of local recurrence. But it’s the same prognosis if distance from CRM to tumor is 1mm. Chance of local recurrence doesn’t significantly drop til distance is greater than 2 mm (5%). Europe reports CRM as positive if tumor is 1mm or less from the inked radial margin. Places in the US fail to even report on CRM distance.

Problem: According to several journals on the staging and prognosis of colorectal cancer, many centers, especially the US, are omitting data (MPD) pertinent to prognosis and data analysis! 1. Poor assessment of specimen (informed PAs can fix that issue!) 2. No comprehensive report of data set (pull out the easy button for the pathologists) ‘

Example comments about specimen assessment: “Frequency of margin involvement is related to the interest of the pathologist. [Dept.] with high LN yields, a good indicator of high quality pathology, are more likely to reflect the true incidence of CRM involvement.” Examination of additional slides has led to an increase in CRM (+) pts from 6% to 27%. And they keep going…

..and going… Centers not having a special interest in GI pathology reported extramural vascular invasion findings in 17.8% of cases. In centers with special GI interest, EMVI rates of 30% are seen. If the oncologist is not aware that a pt. is potentially at risk then treatment could be withheld with a concomitant increase in the risk of death.

Get the picture? “In North America, the clinical importance of the CRM has not been widely recognized by pathologists and routine pathological evaluation of the CRM has been lacking. Assessment of data from 3 treatment protocols conducted between ‘79-’92 by North Central Cancer Treatment Group shows the CRM was evaluated pathologically in only 21% of cases.”

Shout out to the PAs One pathologist said that NAACLS trained PAs perform gross pathology and dissection duties better than most pathologists. “It is doubtful that any path dept. where dissections are performed by pathologists can match [their] quality of work. But the use of PAs is not universal.” (Dr. Goldstien of William Beaumont Hospt., Royal Oaks MI)

Solution Incorporate all necessary data in to the gross report. Talk with your pathologists about including all the data. The report reflects on your skills, the pathologist’s, the dept’s and the hospital. Most importantly, it affects the patient! Patients have been refused into a trial based on lack of information. Become…

Magnum G.I.

Conclusion Take all the necessary measurements Comment on the serosa and mesocolon and back up assessment with photos Take extra sections if necessary Fix the specimen for best cutting and measurements Find all the lymph nodes (12-15+) Talk to your pathologists about getting the data in to the report Go to tumor board so the surgeons are familiar with you

PS. Positive node AT mesenteric margin: no research on it yet. But Dr. Quirke says it’s similar to a Dukes C2 (+ln at high tie). So margin now is reported (-) but note should be included in the report stating that a + LN was at the margin.

References 1. Anderson C, Uman G, Pigazzi A. Oncological outcomes of laparoscopic surgery for rectal cancer: A systematic review and meta-analysis of the literature. EJSO 34 (2008) Compton, C. Colorectal Carcinoma: Diagnostic, Prognostic, and Molecular Features. Mod Pathol 2003; 16(4): Compton C, Greene F. The staging of colorectal cancer: 2004 and beyond. Cancer J Clin 2004; 54; Fleshman Jr, J. The effect of the surgeon and the pathologist on patient survival after resection of colon and rectal cancer. Annals of Surgery V235N4, Goldstein N.S. Recent pathology related advances in colorectal adenocarcinomas. EJSO : Greene, F. Current TNM staging of colorectal cancer. The Lancet Oncology, V8I Maughan NJ, Morris E, Forman D, Quirke P. The validity of the Royal College of Pathologists’ colorectal cancer minimum dataset within a population. British J of Cancer , Nagtegaal I, Quirke P. What is the role for the circumferential margin in the modern treatment of rectal cancer. J Clin Onc : Parfitt J, Driman D. The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment. J Clin Pathol 2007; 60: West N, Morris E, Rotimi O, Cairns A, Finan P, Quirke P. Pathology grading of colon cancer surgical resection and its association with survival: a retrospective study. The Lancel Oncology V9I9: 11. Wibe A, Rendedal PR, Svensson E, Norstein J, Eide TJ, Myrvold HE, Prognostic significance of the CRM folowing TME for rectal cancer. British Journal of Surg 2002, 89,