Colon and Rectal Cancers: Pathologic Staging and Assessment

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Pathologic Staging: Assessing pT

The T category codifies the degree of radial extension of the primary untreated tumor at its deepest point of invasion. For colorectal carcinoma, size has no prognostic importance and is not a factor in staging.3

The T category for primary tumor in colorectal cancer staging is subclassified as follows:

TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ: intraepithelial or invasion of the lamina propria (intramucosal)
T1
Tumor invades submucosa
T2
Tumor invades muscularis propria
T3
Tumor invades pericolorectal tissues
T3a
Tumor invades through the muscularis propria into the subserosa or into non-peritonealized pericolonic or perirectal tissues
T3b
T1 or T2 tumor with satellite deposits in pericolorectal tissues
T4a
Tumor penetrates the visceral peritoneum
T4b
Tumor directly invades or is adherent to other organs or structures

Details related to the pathological assignment of the T category are discussed below.

pTis

For colorectal carcinomas, the staging category pTis (carcinoma in situ) includes both malignant cells that are confined within the glandular basement membrane (intraepithelial carcinoma) and those that invade the mucosal lamina propria (intramucosal carcinoma). Intramucosal carcinoma that extends into but not through the muscularis mucosae also is included in the pTis category. Penetration of the muscularis mucosae and invasion of the submucosa is classified as pT1. High grade (severe) dysplasia and intraepithelial carcinoma sometimes may be used synonymously, especially in cases of inflammatory bowel disease.3,9

It is noteworthy that for all organ systems other than the large intestine, "carcinoma in situ" refers exclusively to malignancy that has not yet penetrated the basement membrane of the epithelium from which it arose, and "invasive carcinoma" encompasses all tumors that penetrate the underlying stroma. Stromal invasion of any degree is a feature of extreme importance in all non-colorectal sites because of the possible access of tumor cells to stromal lymphatic or blood vessels and the consequent risk of metastasis. In colorectal cancer, however, the designation "pTis" (i.e., carcinoma in situ) is used to refer both to intraepithelial malignancies and intramucosal carcinomas because the colonic mucosa is biologically unique. In contrast to the mucosa elsewhere in the gastrointestinal tract (or, indeed, in the rest of the human body), tumor invasion of the lamina propria of the colorectal mucosa has no associated risk of regional nodal metastasis. Therefore, inclusion of intramucosal carcinoma in the pTis category of the colorectal cancer is justified. Nevertheless, the term "carcinoma in situ" in reference to colorectal cancer can be confusing, depending upon whether it is used to refer to the T category of the TNM staging system or to intraepithelial tumor only, as it does in all other epithelial systems. Therefore, the terms "intraepithelial carcinoma" and "intramucosal carcinoma" may be preferred descriptive terms for colorectal tumors in the pTis category.3,9

pT1

This category encompasses tumor invasion deep to the muscularis mucosae but confined to the submucosa. The deepest aspect of the tumor must have breached the fibers of the muscularis mucosae to be considered pT1, as discussed above. If, however, the deepest aspect of the tumor is seen to invade the muscularis propria, no matter how superficially, the tumor would be categorized as pT2.

pT2

Mural invasion that is confined to the muscularis propria at its deepest point is categorized as pT2. If no muscle fibers are observed between the deepest point of tumor invasion and the extramural soft tissue or subserosa, then assignment of pT3 is justified.

pT3

This category refers to transmural penetration that falls short of involvement of the overlying serosa or the deep adjacent organs or structures (e.g., prostate, vagina, etc.). The extent of extramural penetration within the T3 category has been shown in some studies to substratify outcome with penetration of 5 mm or less outside the wall having a better outcome than deeper extension. However, the degree of extramural extension may be difficult to determine to this degree of precision microscopically due to mural distortion and/or destruction by tumor.

pT4

The highest category of local extent is pT4, which includes both extension into adjacent organs or structures and penetration of the parietal peritoneum with or without gross perforation of the wall or involvement of an adjacent structure. Serosal involvement may be determined either histopathologically from sections taken through the area of deepest tumor penetration observed grossly or cytopathologically from touch preparation specimens of the serosa overlying the primary tumor.

Involvement of the serosa may occur in the presence or absence of involvement of adjacent organs. Conversely, involvement of adjacent organs may occur in the presence or absence of serosal involvement, depending on the anatomic location of the involved structure. Direct invasion of other segments of the colorectum by way of (radial) extension through the visceral peritoneum (e.g., invasion of the sigmoid by a cecal carcinoma) should be classified as pT4. In contrast, intramural (longitudinal) extension of tumor from one subsite (segment) of the large intestine into an adjacent subsite or into the ileum (e.g. for a cecal carcinoma) or anal canal (e.g., for a rectal carcinoma) does not affect the pT classification.11

Among the features that define T4 tumors, serosal penetration had been considered the most dire until recent data from the National Cancer Data Base showed that extension into an adjacent organ or structure was associated with a worse outcome, prompting corresponding changes to the TNM stage groupings.1 Either subcategory of T4 may be challenging for pathological diagnosis, however. Even direct extension into an adjacent organ or structure that may be evident to the surgeon at operation may prove difficult or impossible to confirm pathologically unless a portion of the involved organ/structure also is resected and can be definitively identified under the microscope. Invasion of the colorectal serosa (parietal peritoneum) also may be difficult to diagnose definitively under the microscope due to obfuscation by the fibro-inflammatory response often observed at the leading edge of colorectal carcinomas. Thus, serosal involvement is often underdiagnosed by pathologists. Documentation of peritoneal involvement by tumor demands meticulous pathologic analysis and may require extensive sampling and/or serial sectioning, thus such involvement can be missed on routine histopathologic examination.10,11 In fact, cytological examination of serosal scrapings has been shown to reveal malignant cells in as many as 26% of tumor specimens categorized as pT3 by histological examination alone.13

Viewed under the microscope, peritoneal involvement by tumor may be associated with a spectrum of pathologic features. Three types of local peritoneal involvement have been defined: 1) a mesothelial inflammatory and/or hyperplastic reaction with tumor close to (but not at) the serosal surface; 2) tumor present at the serosal surface with inflammatory reaction, mesothelial hyperplasia, and/or erosion/ulceration; and 3) free tumor cells on the serosal surface (in the peritoneum) with underlying ulceration of the visceral peritoneum. All three (and especially the latter two) types of local peritoneal involvement have been shown to be associated with decreased survival compared to pT3 tumor well clear of the serosal surface.12 Therefore, it has been recommended that the definition of T4 be modified to encompass the last two reactions outlined above.9 As mentioned above, tumor also may be classified as pT4 based on positive cytological specimens obtained by scraping or touching the serosa overlying the primary tumor.

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