Protocol for the Examination of Specimens From Patients With Primary Carcinoma of the Colon and Rectum

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the "Surgical Pathology Cancer Case Summary (Checklist) " portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document. This protocol applies to all primary carcinomas of the colon and rectum. Well-differentiated neuroendocrine neoplasms (carcinoid tumors) are not included. The seventh edition TNM staging system for carcinoma of the colon and rectum of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended. Select a Single Response Unless Otherwise Indicated* Data elements with asterisks are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. Tumor Site (note A) __ Cecum__ Right (ascending) colon__ Hepatic flexure__ Transverse colon__ Splenic flexure__ Left (descending) colon__ Sigmoid colon__ Rectum__ Other (specify): ______ Not specified*Specimen Integrity*__ Intact*__ Fragmented*Polyp Size* Greatest dimension: __ cm* Additional dimensions: __ × __ cm*__ Cannot be determined (see Comment) *Polyp Configuration*__ Pedunculated with stalk * Stalk length: __ cm*__ SessileSize of Invasive CarcinomaGreatest dimension: __ cm* Additional dimensions: __ × __ cm__ Cannot be determined (see Comment) Histologic Type (note B) __ Adenocarcinoma__ Mucinous adenocarcinoma__ Signet-ring cell carcinoma__ Small cell carcinoma__ Squamous cell carcinoma__ Adenosquamous carcinoma__ Medullary carcinoma__ Undifferentiated carcinoma__ Other (specify): ______ Carcinoma, type cannot be determinedHistologic Grade (note C) __ Not applicable__ Cannot be determined__ Low grade (well differentiated to moderately differentiated) __ High grade (poorly differentiated to undifferentiated) Microscopic Tumor Extension (note D) __ Cannot be determinedInvasion (deepest): __ Lamina propria __ Muscularis mucosae __ Submucosa __ Muscularis propriaMargins (select all that apply) Deep Margin (Stalk Margin) __ Cannot be assessed__ Uninvolved by invasive carcinoma Distance of invasive carcinoma from margin: __ mm__ Involved by invasive carcinomaMucosal/Lateral Margin__ Not applicable__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinoma__ Involved by adenomaLymph-Vascular Invasion (notes D and E) __ Not identified__ Present__ Indeterminate*Type of Polyp in Which Invasive Carcinoma Arose (note F) *__ Tubular adenoma*__ Villous adenoma*__ Tubulovillous adenoma*__ Traditional serrated adenoma*__ Sessile serrated adenoma*__ Hamartomatous polyp*__ Indeterminate*Additional Pathologic Findings (select all that apply) *__ None identified*__ Inflammatory bowel disease *__ Active *__ Quiescent*__ Other (specify): ____*Ancillary Studies* Specify: ____*__ Not performed*Comment (s): ___Select a Single Response Unless Otherwise Indicated* Data elements with asterisks are not required. However, these elements may be clinically important but are not yet validated or regularly used in patient management. Specimen (select all that apply) (note A) __ Terminal ileum__ Cecum__ Appendix__ Ascending colon__ Transverse colon__ Descending colon__ Sigmoid colon__ Rectum__ Anus__ Other (specify): ______ Not specifiedProcedure__ Right hemicolectomy__ Transverse colectomy__ Left hemicolectomy__ Sigmoidectomy__ Rectal/rectosigmoid colon (low anterior resection) __ Total abdominal colectomy__ Abdominoperineal resection__ Transanal disk excision (local excision) __ Other (specify): ______ Not specified*Specimen Length (if applicable) * Specify: __ cmTumor Site (select all that apply) (note A) __ Cecum__ Right (ascending) colon__ Hepatic flexure__ Transverse colon__ Splenic flexure__ Left (descending) colon__ Sigmoid colon__ Rectosigmoid__ Rectum__ Colon, not otherwise specified__ Cannot be determined (see Comment) Tumor SizeGreatest dimension: __ cm* Additional dimensions: __ × __ cm__ Cannot be determined (see Comment) Macroscopic Tumor Perforation (note G) __ Present__ Not identified__ Cannot be determined*Macroscopic Intactness of Mesorectum (note H) *__ Not applicable*__ Complete*__ Near complete*__ Incomplete*__ Cannot be determinedHistologic Type (note B) __ Adenocarcinoma__ Mucinous adenocarcinoma__ Signet-ring cell carcinoma__ Small cell carcinoma__ Squamous cell carcinoma__ Adenosquamous carcinoma__ Medullary carcinoma__ Undifferentiated carcinoma__ Other (specify): ______ Carcinoma, type cannot be determinedHistologic Grade (note C) __ Not applicable__ Cannot be assessed__ Low grade (well differentiated to moderately differentiated) __ High grade (poorly differentiated to undifferentiated) __ Other (specify): ____*Histologic Features Suggestive of Microsatellite Instability (note I) *Intratumoral Lymphocytic Response (tumor-infiltrating lymphocytes) *__ None*__ Mild to moderate (0–2 per high-power ×400 field) *__ Marked (3 or more per high-power field) *Peritumor Lymphocytic Response (Crohn-like response) *__ None*__ Mild to moderate*__ Marked*Tumor Subtype and Differentiation (select all that apply) *__ Mucinous tumor component (specify percentage: __) *__ Medullary tumor component*__ High histologic grade (poorly differentiated) Microscopic Tumor Extension__ Cannot be assessed__ No evidence of primary tumor__ Intramucosal carcinoma, invasion of lamina propria__ Tumor invades submucosa__ Tumor invades muscularis propria__ Tumor invades through the muscularis propria into the subserosal adipose tissue or the nonperitonealized pericolic or perirectal soft tissues but does not extend to the serosal surface__ Tumor penetrates to the surface of the visceral peritoneum (serosa) __ Tumor is adherent to other organs or structures (specify: ____) __ Tumor directly invades adjacent structures (specify: ____) __ Tumor penetrates to the surface of the visceral peritoneum (serosa) and directly invades adjacent structures (specify: ____) Margins (select all that apply) (note J) Proximal Margin__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinoma__ Intramucosal carcinoma/adenoma not identified at proximal margin__ Intramucosal carcinoma/adenoma present at proximal marginDistal Margin__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinoma__ Intramucosal carcinoma/adenoma not identified at distal margin__ Intramucosal carcinoma/adenoma present at distal marginCircumferential (Radial) or Mesenteric Margin__ Not applicable__ Cannot be assessed__ Uninvolved by invasive carcinoma__ Involved by invasive carcinoma (tumor present 0– 1 mm from margin) If all margins uninvolved by invasive carcinoma: Distance of invasive carcinoma from closest margin: __ mm or __ cm Specify margin: _Lateral Margin (for noncircumferential transanal disk excision) __ Cannot be assessed__ Uninvolved by invasive carcinoma Distance of invasive carcinoma from closest lateral margin: __ mm * Specify location (eg, o'clock position), if possible: ______ Involved by invasive carcinoma * Specify location (eg, o'clock position), if possible: ______ Uninvolved by adenoma__ Involved by adenomaTreatment Effect (applicable to carcinomas treated with neoadjuvant therapy) (note K) __ No prior treatment__ Present *__ No residual tumor (complete response, grade 0) *__ Moderate response (grade 1, minimal residual cancer) *__ Minimal response (grade 2) __ No definite response identified (grade 3, poor response) __ Not knownLymph-Vascular Invasion (note E) __ Not identified__ Present__ IndeterminatePerineural Invasion (note E) __ Not identified__ Present__ IndeterminateTumor Deposits (Discontinuous Extramural Extension) (note L) __ Not identified__ Present__ Indeterminate*Type of Polyp in Which Invasive Carcinoma Arose (note F) *__ None identified*__ Tubular adenoma*__ Villous adenoma*__ Tubulovillous adenoma*__ Traditional serrated adenoma*__ Sessile serrated adenoma*__ Hamartomatous polyp*__ IndeterminatePathologic Staging (pTNM) (note M) TNM Descriptors (required only if applicable) (select all that apply) __ m (multiple primary tumors) __ r (recurrent) __ y (posttreatment) Primary Tumor (pT) __ pTX: Cannot be assessed__ pT0: No evidence of primary tumor__ pTis: Carcinoma in situ, intraepithelial (no invasion) __ pTis: Carcinoma in situ, invasion of lamina propria__ pT1: Tumor invades submucosa__ pT2: Tumor invades muscularis propria__ pT3: Tumor invades through the muscularis propria into pericolorectal tissues__ pT4a: Tumor penetrates the visceral peritoneum__ pT4b: Tumor directly invades or is adherent to other organs or structuresRegional Lymph Nodes (pN) __ pNX: Cannot be assessed__ pN0: No regional lymph node metastasis__ pN1a: Metastasis in 1 regional lymph node__ pN1b: Metastasis in 2 to 3 regional lymph nodes__ pN1c: Tumor deposit (s) in the subserosa, or nonperitonealized pericolic or perirectal tissues without regional lymph node metastasis__ pN2a: Metastasis in 4 to 6 regional lymph nodes__ pN2b: Metastasis in 7 or more regional lymph nodesSpecify: Number examined: __ Number involved: _Distant Metastasis (pM) __ Not applicable__ pM1: Distant metastasis * Specify site (s): ______ pM1a: Metastasis to single organ or site (eg, liver, lung, ovary, nonregional lymph node) __ pM1b: Metastasis to more than one organ/site or to the peritoneum*Additional Pathologic Findings (select all that apply) *__ None identified*__ Adenoma (s) *__ Chronic ulcerative proctocolitis*__ Crohn disease*__ Dysplasia arising in inflammatory bowel disease*__ Other polyps (types): ____*__ Other (specify): ____*Ancillary Studies (select all that apply) (note N) *__ Microsatellite instability (specify testing method: ____) *__ Stable *__ Low *__ High* Immunohistochemistry Studies for Mismatch Repair Proteins *__ MLH1 *__ Intact nuclear positivity, tumor cells *__ Loss of nuclear positivity, tumor cells *__ Pending *__ Other (specify): ____ *__ MSH2 *__ Intact nuclear positivity, tumor cells *__ Loss of nuclear positivity, tumor cells *__ Pending *__ Other (specify): ____ *__ MSH6 *__ Intact nuclear positivity, tumor cells *__ Loss of nuclear positivity, tumor cells *__ Pending *__ Other (specify): ____ *__ PMS2 *__ Intact nuclear positivity, tumor cells *__ Loss of nuclear positivity, tumor cells *__ Pending *__ Other (specify): ____*__ BRAF V600E mutational analysis (specify testing method: ____) *__ Mutant BRAF detected *__ No mutant BRAF detected (wild-type BRAF allele) *__ Other (specify): ____*__ KRAS mutational analysis (specify testing method: ____) *__ Mutant KRAS detected (specify mutation ____) *__ No mutant KRAS detected (wild-type KRAS allele) *__ Other (specify): ___Other, specify: ____*__ Not performed*Comment (s): ___The protocol applies to all carcinomas arising in the colon and rectum. 1 It excludes carcinomas of the vermiform appendix and low-grade neuroendocrine neoplasms (carcinoid tumors). The colon is divided as shown in Figure 1. The right colon is subdivided into the cecum and the ascending colon. 2 The left colon is subdivided into the descending colon and sigmoid colon (see Table). 1The transition from sigmoid to rectum is marked by the fusion of the tenia coli of the sigmoid to form the circumferential longitudinal muscle of the rectal wall approximately 12 to 15 cm from the dentate line. The rectum is defined clinically as the distal large intestine commencing opposite the sacral promontory and ending at the anorectal ring, which corresponds to the proximal border of the puborectalis muscle palpable on digital rectal examination1 (Figure 2). When measuring below with a rigid sigmoidoscope, it extends 16 cm from the anal verge. Tumors located at the border between 2 subsites of the colon (eg, cecum and ascending colon) are registered as tumors of the subsite that is more involved. If 2 subsites are involved to the same extent, the tumor is classified as an "overlapping" lesion. A tumor is classified as rectal if its inferior margin lies less than 16 cm from the anal verge or if any part of the tumor is located at least partly within the supply of the superior rectal artery. 3 A tumor is classified as rectosigmoid when differentiation between rectum and sigmoid according to the previously mentioned guidelines is not possible. 4For consistency in reporting, the histologic classification proposed by the World Health Organization (WHO) is recommended and follows. 5AdenocarcinomaMucinous (colloid) adenocarcinoma (greater than 50% mucinous) Signet-ring cell carcinoma (greater than 50% signet-ring cells) *Squamous cell carcinomaAdenosquamous carcinomaMedullary carcinoma†Small cell carcinoma# (high-grade neuroendocrine carcinoma) Undifferentiated carcinoma*Other (specify) ‡* By convention, signet-ring cell carcinomas, small cell carcinomas, and undifferentiated carcinomas are high grade (see note C). The only histologic types of colorectal carcinoma that have been shown to have adverse prognostic significance independent of stage are signet-ring cell carcinoma6 and small cell carcinoma (high-grade neuroendocrine carcinoma). 7† Medullary carcinoma is a distinctive histologic type strongly associated with high levels of microsatellite instability (MSI-H), indicative of defects in normal DNA repair gene function. Medullary carcinoma may occur either sporadically8 or in association with hereditary nonpolyposis colon cancer (HNPCC). 9 This tumor type is characterized by solid growth in nested, organoid, or trabecular patterns, with no immunohistochemical evidence of neuroendocrine differentiation. Medullary carcinomas are also characterized by numerous tumor infiltrating lymphocytes (see note I). ‡ The term "carcinoma, NOS" (not otherwise specified) is not part of the WHO classification. A number of grading systems for colorectal cancer have been suggested, but a single widely accepted and uniformly used standard for grading is lacking. Most systems stratify tumors into 3 or 4 grades as follows: Grade 1: Well differentiatedGrade 2: Moderately differentiatedGrade 3: Poorly differentiatedGrade 4: UndifferentiatedDespite a significant degree of interobserver variability, 10 histologic grade has repeatedly been shown by multivariate analysis to be a stage-independent prognostic factor. 11 Specifically, it has been demonstrated that high tumor grade is an adverse prognostic factor. It is noteworthy that in most studies documenting the prognostic power of tumor grade, the number of grades has been collapsed to produce a 2-tiered stratification for data analysis as follows: Low grade: Well differentiated and moderately differentiatedHigh grade: Poorly differentiated and undifferentiatedThe widest variations in grading concern the stratification of low-grade tumors into well- or moderately differentiated categories, while interobserver variability in diagnosing high-grade carcinoma is relatively small. Therefore, in light of its proven prognostic value, relative simplicity, and reproducibility, a 2-tiered grading system for colorectal carcinoma (ie, low grade and high grade) is recommended. The following criteria for grading based on gland formation alone are suggested12: Low grade: Greater than or equal to 50% gland formationHigh grade: Less than 50% gland formationColorectal adenomas containing invasive adenocarcinoma that extends through the muscularis mucosae into the submucosa have been defined as "malignant polyps. "13 This term encompasses cases in which the entire polyp head is replaced by carcinoma and adenomas with focal malignancy, but the definition excludes adenomas with high-grade dysplasia (intraepithelial carcinoma) or intramucosal carcinoma (invasive carcinoma limited to the lamina propria or invading no deeper than the muscularis mucosae) because these polyps possess negligible biologic potential for metastasis14 (see Tis in note M). Malignant polyps removed by endoscopic polypectomy require evaluation of histologic factors related to the risk of adverse outcome (ie, lymph node metastasis or local recurrence from residual malignancy) following polypectomy. 1315 Factors shown to have independent prognostic significance and are important in determining the need for further surgical treatment include: An increased risk of adverse outcome has been shown to be associated with: Venous invasion has been demonstrated by multivariate analysis to be an independent adverse prognostic factor. 11 Invasion of extramural veins, in particular, has been shown to be an independent indicator of unfavorable outcome and increased risk of occurrence of hepatic metastasis. 16 The significance of intramural venous invasion is less clear, because data specific to this issue are lacking. In several studies, both lymphatic invasion17 and perineural invasion18 have been shown by multivariate analysis to be independent indicators of poor prognosis. The prognostic significance, if any, of the anatomic location of these structures is not defined. Furthermore, it is not always possible to distinguish lymphatic vessels from postcapillary venules because both are small, thin-walled structures. Thus, the presence or absence of tumor invasion of small, thin-walled vessels should be reported in all cases. Distinction should be made between traditional serrated adenomas, which exhibit cytologic features of adenomas, and the newly described sessile serrated adenomas. 19 The sessile serrated adenoma may be the precursor lesion for colorectal carcinomas with MSI-H; they are more commonly found in the right colon and are characterized by serrated architecture with bulbous dilatation of deep crypts and lack of overt nuclear atypia, in most cases. Tumor perforation is an uncommon complication of colorectal cancer, but one that is associated with a poor outcome, including high in-hospital mortality and morbidity. 20 Perforation of the uninvolved colon proximal to an obstructing tumor is also associated with high mortality because of generalized peritonitis and sepsis. Reported perforation rates range from 2. 6% to 9%. Perforation is more likely to occur in older patients. The quality of the surgical technique is a key factor in the success of surgical treatment for rectal cancer, both in the prevention of local recurrence and in long-term survival. Numerous studies have demonstrated that total mesorectal excision (TME) improves local recurrence rates and the corresponding survival by as much as 20%. This surgical technique entails precise sharp dissection within the areolar plane outside (lateral to) the visceral mesorectal fascia to remove the rectum. This plane encases the rectum, its mesentery, and all regional nodes and constitutes Waldeyer fascia. High-quality TME surgery reduces local recurrence from 20% to 30%, to 8% to 10% or less, and increases 5-year survival from 48% to 68%. 2122 Adjuvant therapy in the presence of a high-quality TME may further reduce local recurrence (from 8% to 2. 6%). 22Pathologic evaluation of the resection specimen has been shown to be a sensitive means of assessing the quality of rectal surgery. It is superior to indirect measures of surgical quality assessment, such as perioperative mortality, rates of complication, number of local recurrences, and 5-year survival. It has been shown that macroscopic pathologic assessment of the completeness of the mesorectum of the specimen, scored as complete, partially complete, or incomplete, accurately predicts both local recurrence and distant metastasis. 22 Microscopic parameters, such as the status of the circumferential resection margin, the distance between the tumor and nearest circumferential margin (ie, "surgical clearance"), and the distance between the tumor and the closest distal margin, are all important predictors of local recurrence and may be affected by surgical technique. There is strong evidence that the status of the circumferential resection margin is a powerful predictor of local recurrence but is inconsistently evaluated and underreported. The nonperitonealized surface of the fresh specimen is examined circumferentially, and the completeness of the mesorectum is scored as described in the following. 22 The entire specimen is scored according to the worst area. Little bulk to the mesorectumDefects in the mesorectum down to the muscularis propriaAfter transverse sectioning, the circumferential margin appears very irregularModerate bulk to the mesorectumIrregularity of the mesorectal surface with defects greater than 5 mm, but none extending to the muscularis propriaNo areas of visibility of the muscularis propria at the site of the mesorectum with a of the mesorectal surface defects greater than 5 mm in the distal margin of the transverse sectioning, the circumferential margin appears of colorectal tumors is as repair may as a prognostic of patient outcome, a of response to and as a tool for guidelines for testing colorectal tumors for the following cancer in a patient is than of or other tumors and small and tumors and adenomas and of cancer with in a patient is than cancer in 1 or more with an with 1 of the in a than cancer in 2 or more or with of histologic features are defined as presence of cell or growth lymphocytes are associated with and architecture (see and should be from or are the tumor not associated with lymph have not been only and lymphocytes 3 or more per high-power should be pathologic features associated with status in colorectal carcinomas high-grade and lack of may be to the closest to the tumor with following of the serosal surface for and other of tumor marked by should be in the macroscopic of the surgical pathology report. The serosal surface does not a surgical to the proximal and distal the circumferential margin (Figure 3, A through be for any either (Figure 3, or by peritoneum (Figure 3, (see note The circumferential margin the soft tissue margin closest to the of tumor and is by or sharp dissection of the or analysis has that tumor of the circumferential margin is the most factor in local recurrence in rectal A circumferential margin in rectal cancer increases the risk of recurrence by and the risk of from this the circumferential margin should be in all rectal carcinomas as as with nonperitonealized The distance between the tumor and circumferential margin should be reported (see note The circumferential margin is if the tumor is more than 1 mm from the nonperitonealized surface but should be as if tumor is located 1 mm or less from the nonperitonealized surface because local recurrence rates are with of to 1 This assessment tumor within a lymph node as as tumor but if circumferential margin is based on this should be resection margin is the only relevant circumferential margin in by peritoneum (eg, transverse of this margin should be reported even if tumor does not the serosal to the proximal and distal resection margins be either by longitudinal to the margin or by to the The distance from the tumor to the closest resection may also be for low anterior these a distal resection margin of 2 cm is for and 1 cm may be distal are when the distance to the closest transverse margin is 5 cm or cases of carcinoma arising in a of inflammatory bowel proximal and distal resection margins should be evaluated for dysplasia and therapy in rectal cancer is associated with significant tumor response and of the as detected by pathologic of the specimen, is associated with a from neoadjuvant should be with of the tumor Minimal residual disease has been shown to have a than residual several grading systems for tumor response have been a tumor grade has been shown to interobserver with and to prognostic should be only in the primary lymph node should not be in the of in from patient neoadjuvant therapy are to tumor and are not used to stage or as lymph tumor in pericolic or perirectal from the of the tumor and no evidence of residual lymph node but within the lymphatic of the primary carcinoma, are or and are not as lymph nodes replaced by Most are to more perineural these tumor are associated with and their number should be in the surgical pathology report. If tumor are in that otherwise be classified as (tumor to or (tumor to muscularis the primary tumor classification is not but the is in a as (see note resection the most effective therapy for colorectal carcinoma, and the of is from the pathologic on the resection The anatomic of disease is by the most important prognostic factor in colorectal protocol the TNM staging system of the and the but does not the use of other staging convention, the to a primary tumor that has not been previously The to the pathologic classification of the as to the and is based on and entails a resection of the primary tumor or to the entails or of nodes to lymph node and of distant classification is by the treatment evaluation of the patient or when pathologic classification is not of cases of TNM or the and and are