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

Dec 15, 2015

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Page 1: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Assessment of Margins in Colorectal Cancer

SpecimensHolly Brunner, PA(ASCP)Sibley Memorial Hospital

Washington, DC

Page 2: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

3 factors in margin assessment1. Knowing the margins2. Handling the specimen correctly3. 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.

Page 3: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Part 1: Knowing the Margins

1. Mucosal

2. Serosal

3. Mesenteric radial

4.Radial 5.CRM

Page 4: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Serosal Margin

Peritonealized surface near bowel wall3 levels of involvement with different

prognoses◦2 of those levels are micro level◦Take more sections if close

Grave prognosis if involvedSome institutions doing intraoperative

serosal scrapings if tumor appears to approach surface

Page 5: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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

Page 6: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Mesenteric margin

Page 7: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Radial Margin aka adventitial m., lateral m.

Retroperitoneal or perineal adventitial soft tissue closest to deepest penetration of tumor

Created by blunt dissection during surgeryAscending, Descending, Upper rectum

(partially encased by peritoneum) = radial marginDistal rectum (not encased) = circumferential

radial margin (CRM)

Page 8: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Part 2: Assessing and MeasuringDr. 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)

Page 9: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Quirke’s Protocol

http://www.ualberta.ca/~rmclean/crdiss.htm

http://philquirke.weebly.com/index.html

1. Grade the surgery quality of the specimen

2. Fix for 2 days minimum!3. Serially section4. Collect Minimal Data Pathology Set (MPD)

Page 10: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

1. Mesorectum Quality Assessment

Grades 3-1 Intact > Moderate > IncompleteGreat indicator of the patient’s prognosis

3-Good:

“intact, bulky mesorectum”

Page 11: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Grade 3 intact, smooth, complete

Page 12: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Grade 3

Page 13: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Grade 3 bulky up to levators

Page 14: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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”

Page 15: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Grade 2 not intact

Page 16: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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.

Page 17: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Grade 1: PoorLittle bulk with defects down onto

m.propria and/or very irregular CRM

“The mesorectum is incomplete with defects exposing m.propria.”

TAKE PICTURES!

Page 18: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Grade 1

Page 19: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Quirke’s Protocol1. Grade surgery quality

2. Ink, Partially cut, Fix for 2 days minimum!

3. Serially section

4. Collect Minimal Data Pathology Set (MPD)

Page 20: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

2. Don’t cut tumor area

Page 21: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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

Page 22: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Quirke’s Protocol

1. Grade surgery quality2. Fix for 2 days minimum!3. Serially section4. Collect Minimal Data Pathology Set

(MPD)

Page 23: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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

Page 24: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Minimal Pathology Data Set1. Extent of local invasion (w distance beyond

m. propria given)2. # LNs retrieved3. Nodal Stage4. Extramural vascular invasion (EMVI)5. Peritoneal or serosal involvement6. 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

Page 25: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Part 3: Reporting the DataSounds like the easy part but it’s actually

the most difficult to accomplish.

Page 26: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Part 3: Reporting the dataUpdating 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 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

Page 27: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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.

Page 28: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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)

Page 29: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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…

Page 30: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

..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.

Page 31: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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.”

Page 32: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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)

Page 33: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

SolutionIncorporate 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…

Page 34: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Magnum G.I.

Page 35: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

Conclusion

Take all the necessary measurementsComment on the serosa and mesocolon and back

up assessment with photosTake extra sections if necessaryFix the specimen for best cutting and

measurementsFind all the lymph nodes (12-15+)Talk to your pathologists about getting the data in

to the reportGo to tumor board so the surgeons are familiar

with you

Page 36: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

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.

Page 37: Assessment of Margins in Colorectal Cancer Specimens Holly Brunner, PA(ASCP) Sibley Memorial Hospital Washington, DC.

References1. 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.

2. Compton, C. Colorectal Carcinoma: Diagnostic, Prognostic, and Molecular Features. Mod Pathol 2003; 16(4): 376-388.

3. Compton C, Greene F. The staging of colorectal cancer: 2004 and beyond. Cancer J Clin 2004; 54;295-308.

4. 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.

5. Goldstein N.S. Recent pathology related advances in colorectal adenocarcinomas. EJSO 2001. 27:446-450.

6. Greene, F. Current TNM staging of colorectal cancer. The Lancet Oncology, 2007. V8I7. 572-573.

7. 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. 97,1393-1398.

8. 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.

9. 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.

10. 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:

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, 327-334.