Lymph node staging in colorectal cancer: Old controversies and recent advances

Table 1 Parameters affecting the clinical significance of lymph node staging in colorectal cancer

Extent of surgical lymph node removal

Thoroughness of the pathologist in dissecting the resection specimen

Technical methods to increase lymph node yield

Methylene blue injection

Fat clearing

Acetone compression

Changing definitions of lymph nodes, involved lymph nodes, and tumor deposits in different editions of the AJCC/UICC TNM staging system

History of neoadjuvant treatment

Absolute number of retrieved lymph nodes

Absolute number of positive lymph nodes

Lymph node ratio

Presence of extracapsular invasion

Sentinel node biopsy

Number of histological sections

Use of immunohistochemistry to identify micrometastasis and/or isolated tumor cells

Use of molecular techniques to identify minimal tumor disease in lymph node tissue

AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control; TNM: Tumor node metastasis.

Table 2 Changing definitions of lymph nodes, involved lymph nodes, and tumor deposits in different editions of the American Joint Committee on Cancer/Union for International Cancer Control tumor node metastasis staging system

TNM-5	A tumor nodule greater than 3 mm in diameter in perirectal or pericolic adipose tissue without histological evidence of a residual lymph node in the nodule is classified as regional lymph node metastasis. However, a tumor nodule up to 3 mm in diameter is classified in the T category as discontinuous extension,i.e., T3
TNM-6	A tumor nodule in the pericolic/perirectal adipose tissue without histological evidence of residual lymph node in the nodule is classified in the pN category as a regional lymph node metastasis if the nodule has the form and smooth contour of a lymph node. If the nodule has an irregular contour, it should be classified in the T category and also coded as V1 (microscopic venous invasion) or V2, if it was grossly evident, because there is a strong likelihood that it represents venous invasion.
TNM-7	Tumor deposits (satellites),i.e., macroscopic or microscopic nests or nodules, in the pericolorectal adipose tissue’s lymph drainage area of a primary carcinoma without histological evidence of residual lymph node in the nodule, may represent discontinuous spread, venous invasion with extravascular spread (V1/2) or a totally replaced lymph node (N1/2). If such deposits are observed with lesions that would otherwise be classified as T1 or T2, then the T classification is not changed, but the nodule(s) is recorded N1c. If a nodule is considered by the pathologist to be a totally replaced lymph node (generally having a smooth contour), it should be recorded as a positive lymph node and not as a satellite, and each nodule should be counted separately as lymph node in the final pN determination.

TNM: Tumor node metastasis.

Table 3 Markers for molecular lymph node staging

Keratin 20

Keratin 19 (including one-step nucleic acid amplification technique)

Mucin apoprotein 2

Guanylyl cylase C

Carcinoembryonic antigen

CEACAM6

CEACAM1-S

CEACAM1-L

CEACAM7-1

CEACAM7-2

c-Met

K-rasmutation

Estrogen receptor promoter methylation