Colorectal Carcinoma: Selected Issues in Pathologic Examination and Staging and Determination of Prognostic Factors

Archives of Pathology & Laboratory Medicine, Oct 2008 by Washington, Mary Kay

Context.-Colorectal carcinoma is one of the most common types of cancer in Western countries and is consistently ranked among the top 3 causes of cancer-related deaths, with approximately 150 000 new cases in the United States and 55 000 deaths in 2006. The pathologist's assessment of tumor stage and stage-independent morphologic features, such as vascular/lymphatic invasion, influences treatment strategies for the individual patient, such as the decision to offer adjuvant therapy after surgery. However, although the pathologist influences clinical care in colorectal cancer, certain aspects of staging and evaluation of prognostic factors remain challenging and confusing.

Objectives.-To present the currently used colorectal cancer staging system; to address challenging areas in pathologic staging, including T category considerations and recommendations for the minimum number of lymph nodes sampled; and to discuss assessment of selected stage-independent prognostic factors, such as vascular/ lymphatic invasion.

Data Sources.-This review is based on the current staging manual from the American Joint Committee on Cancer, the College of American Pathologists Protocol for Examination of Specimens From Patients With Primary Carcinomas of the Colon and Rectum, and selected articles pertaining to colorectal carcinoma staging and prognostic factors accessible through Ovid Medline (National Library of Medicine, Bethesda, Md).

Conclusions.-Proper assessment of pathologic staging for colorectal cancer and of morphologic prognostic factors requires a thorough understanding of staging guidelines and careful specimen dissection and sampling.

(Arch Pathol Lab Med. 2008;132:1600-1607)

Pathologic assessment of the colorectal carcinoma resection specimen is of critical importance for a number of reasons: it remains the gold standard for determining local extent of disease, decisions made regarding adjuvant therapy are based upon the pathologic findings,1 and important prognostic factors may be gleaned from the pathologic examination (Table 1). In addition, pathologic assessment provides quality control data for surgery and radiology. However, despite pathologists' collective familiarity with resections for colorectal cancer and the importance of pathologic assessment, questions regarding accurate TNM staging of these specimens still arise. In particular, controversies and pitfalls in pathologic assessment include the subjective nature of some of the elements assessed and the need for standardized examination protocols and reporting. Although there is agreement that the data elements reported should be evidence based,2 data regarding validation of specific elements are sometimes limited, and there remains the perception of a gap between the recommendations and the realities of surgical pathology practice.3 In addition, publications designed to provide recommendations to clarify areas of uncertainty are sometimes contradictory.2

The frequency of incomplete pathology reports varies among institutions, with larger hospitals and those with higher volumes of the specimen of interest showing greater adherence to published guidelines for colorectal cancer reporting.4 Most critical elements, such as microscopic extent of tumor invasion, are reported in more than 90% of cases; however, venous and lymphatic invasion, often a determinant of whether adjuvant therapy will be given for stage II cancer, was absent in roughly 64% of reports in one survey.4 Completeness of reporting is improved, in general, with the use of a checklist (synoptic) reporting format5 with one study reporting an approximately 25% increase in the number of complete reports when synoptic reporting for breast and colorectal cancer was instituted.5 Web-based systems designed to minimize text editing and allow for efficient retrieval of data further facilitate tumor reporting and data management.6

Important morphologic prognostic factors for colorectal carcinoma determined from examination of the specimen are listed in Table 1. The most powerful predictor of outcome for colorectal cancer remains anatomic extent of disease, 7 as determined by pathologic examination of the resection specimen. The most widely used staging system, used by national, state, and local tumor registries in the United States and Canada, is the TNM staging system of the American Joint Committee on Cancer (AJCC)8 and the International Union Against Cancer (Table 2). Significant differences for 5-year survival are demonstrated using the stage groupings for colorectal cancer from the AJCC Cancer Staging Manual, 6th edition8 (Table 3),9 with the exception of stage IIIa patients having better survival than stage IIb, likely because of the adverse impact of tumor serosal involvement on survival, even in the setting of node-negative disease.

TUMOR CATEGORY ISSUES

The designations in the pathologic tumor size (pT) category describe the deepest point of penetration of tumor in the bowel wall, with pTis (in situ carcinoma) including both high-grade dysplasia (tumor cells confined within the basement membrane of the involved crypt) and intramucosal carcinoma (tumor cells that invade the lamina propria but do not extend beyond the muscularis mucosae). 8 However, designation of high-grade dysplasia of glandular epithelium as in situ carcinoma of the colon and rectum is not well accepted as standard terminology among gastrointestinal pathologists, most of whom prefer the terms adenoma with high-grade dysplasia or adenoma with intramucosal carcinoma. Distinction between high-grade dysplasia and intramucosal carcinoma is not made for AJCC staging purposes because colorectal carcinomas confined to the mucosa essentially have no associated risk of nodal metastases.