Assessment of Margins in Colorectal Cancer Specimens

Assessment of Margins in Colorectal Cancer Specimens

Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC 3 factors in margin assessment 1. 2. 3.

Knowing the margins Handling the specimen correctly 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 Cecum, aka mesenteric radial m. 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 Retroperitoneal aka adventitial m., lateral m. 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) Quirkes Protocol http://www.ualberta.ca/~rmclean/crdiss.ht m http://philquirke.weebly.com/index.html 1. 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 patients 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? 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 Quirkes 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. Dont cut tumor area 3. Serially section 3-5 mm slices 2 cm above and 2 cm below tumor area Quirkes 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) Minimal Pathology Data Set 1. 2. 3. 4.

5. 6. 7. Extent of local invasion (w distance beyond m. propria given) # LNs retrieved Nodal Stage Extramural vascular invasion (EMVI) Peritoneal or serosal involvement CRM involvement (distance of tumor,

deposit, or +LN to margin) 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 its 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 its been useful:

The first 5 ed. of the AJCC staging manual classified stage III in a single group but now has subcategories in the 6th 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 (+) 7th ed. comes out in June with changes going in to effect Jan. 1, 2010

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 its the same prognosis if distance from CRM to tumor is 1mm. Chance of local recurrence doesnt 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. And there are more issues 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 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. ..and going 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. Get the picture? 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) Shout out to the PAs 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 pathologists, the depts 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.

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 Conclusion PS. Positive node AT mesenteric margin: no research on it yet. But Dr. Quirke says its 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. 2. 3. 4. 5. 6. 7.

8. 9. 10. 11. 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) 1135-1142. Compton, C. Colorectal Carcinoma: Diagnostic, Prognostic, and Molecular Features. Mod Pathol 2003; 16(4): 376-388.

Compton C, Greene F. The staging of colorectal cancer: 2004 and beyond. Cancer J Clin 2004; 54;295-308. Fleshman Jr, J. The effect of the surgeon and the pathologist on patient survival after resection of colon and rectal cancer. Annals of Surgery 2002. V235N4, 464-465. Goldstein N.S. Recent pathology related advances in colorectal adenocarcinomas. EJSO 2001. 27:446-450. Greene, F. Current TNM staging of colorectal cancer. The Lancet Oncology, 2007. V8I7. 572573. 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 2007. 97,13931398. Nagtegaal I, Quirke P. What is the role for the circumferential margin in the modern treatment of rectal cancer. J Clin Onc 2008. 26:303-312.

Parfitt J, Driman D. The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment. J Clin Pathol 2007; 60:849-855. 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 2008. V9I9: 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, 327-334.

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