Tumor deposits in colorectal cancer: Refining their definition in the TNM system

Abstract

Tumor deposits (TDs) are discontinuous tumor spread in the mesocolon/mesorectum which is found in approximately 20% of colorectal cancer (CRC) and negatively affects survival. We have a history of repeated revisions on TD definition and categorization in the tumor-node-metastasis (TNM) system leading to stage migration. Since 1997, TDs have been categorized as T or N factors depending on their size (TNM5) or contour (TNM6). In 2009, TNM7 provided the category of N1c for TDs in a case without positive lymph nodes (LNs), which is also used in TNM8. However, increasing evidence suggests that these revisions are suboptimal and only "partially" successful. Specifically, the N1c rule is certainly useful for oncologists who are having difficulty with TDs in a case with no positive LNs. However, it has failed to maximize the value of the TNM system because of the underused prognostic information of individual TDs. Recently, the potential value of an alternative staging method has been highlighted in several studies using the "counting method." For this method, all nodular type TDs are individually counted together with positive LNs to derive the final pN, yielding a prognostic and diagnostic value that is superior to existing TNM systems. The TNM system has long stuck to the origin of TDs in providing its categorization, but it is time to make way for alternative options and initiate an international discussion on optimal treatment of TDs in tumor staging; otherwise, a proportion of patients end up missing an opportunity to receive the optimal adjuvant treatment.

Keywords: Extramural cancer deposits without lymph node structure (EX); Lymph node metastasis; Tumor deposits (TDs); Tumor‐node‐metastasis (TNM) system; tumor stage.

FIGURE 1

Area of adipose tissue harboring tumor deposit (TD). TDs exist in extramural adipose tissue attached to the bowel wall with the primary tumor (A) and in a lump of adipose tissue postoperatively harvested for pathologic examination of LN metastasis (B). Regarding the length of discontinuity to define peritumoral TD (two‐headed arrow in [A]), a yardstick of 5‐mm discontinuity is used as a criterion for judging a peritumoral TD in the Japanese classification of colorectal, appendiceal, and anal carcinoma (third English edition), i.e., only a deposit discontinuously located at ≥5 mm from the main body of the primary tumor is attributed to the final pathological stage (see Figure 5). LN, Lymph node; MP, Muscularis propria; TD, Tumor deposit

FIGURE 2

Tumor nodules in the pericolorectal adipose tissue lymph drainage area of a primary carcinoma. In TNM6, tumor nodules without histological evidence of residual lymph node in the nodule are classified in the pN category as a regional lymph node metastasis if the nodule has a smooth contour (A). A nodule with an irregular contour (B) is classified in the T category and also coded as V1 or V2. In TNM7 and TNM8, tumor nodules are no longer treated as a T category. A nodule considered by the pathologists as a totally replaced lymph node is regarded as a positive lymph node, and otherwise, it may change the node status to pN1c depending on some conditions defined differently in TNM7 and TNM8. No specific criteria for a nodule that should be diagnosed as a totally replaced lymph node are being provided other than a short explanatory note that it is “generally having a smooth contour”. (A and B), hematoxylin and eosin staining; Bar, 1 mm

FIGURE 3

Non‐nodular type tumor deposits in the pericolorectal adipose tissue lymph drainage area of a primary carcinoma. An intravascular tumor deposit located near a non‐metastatic lymph node (A) and a perineural tumor deposit (B) in the regional lymph node area. (A and B), hematoxylin and eosin stain; Bar, 500 mm

FIGURE 4

Stage migration caused by different categorizations of a tumor deposit (TD) depending on staging systems. The picture in the upper‐left panel indicates a peritumoral TD with a diameter of approximately 3.5 mm with an irregular contour and an identifiable vascular structure. Under TNM5, this nodule is classified as an LN because it is >3 mm in diameter. On the contrary, this nodule is considered a lesion of the T category because of its contour and is also coded as venous invasion under TNM6. The category N1c is used for this nodule in the absence of regional LN metastasis under TNM7, whereas under TNM8, the tumor stage does not change by this nodule which is regarded as venous invasion because the vascular structure is evident (arrow). Since 2013, this nodule has been invariably treated the same as LN metastasis to derive the final N stage in Japan. Picture, hematoxylin and eosin staining; bar, 1 mm. The inset illustrates the magnification of the part of the nodule that is indicated with an arrow (Victoria blue–hematoxylin and eosin staining). LN, Lymph node; MP, Muscularis propria; TD: Tumor deposit

FIGURE 5

The distance of peritumoral TDs to be located from the body of the primary tumor. The UICC defines tumor deposits (TDs) as discrete macroscopic or microscopic nodules of cancer in the pericolorectal adipose tissue's lymph drainage area of a primary carcinoma that are discontinuous from the primary, but the objective judgment is difficult for the discontinuity. (A) A nodule located at 7.5 mm from the body of the primary tumor; (B) a nodule that is located just below the body of the primary tumor and some streaks of fibrous tissue connecting them; (C) a nodule that is connected to the body of the primary tumor with cancerous tissue. In Japan, among these nodules, only the nodule (A) is regarded as a TD that should be recorded and treated as an N factor according to the “5‐mm” rule for the discontinuity of TDs (Japanese classification of colorectal, Appendiceal, and anal carcinoma, third English edition). (A–C), hematoxylin and eosin staining; Bar, 1 mm