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

Abstract

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor node metastasis (TNM) system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer. For affected patients, the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis. In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen, several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging. These include changing definitions of lymph nodes, involved lymph nodes, and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected. Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression. Outcome prediction based on the lymph node ratio, defined as the number of positive lymph nodes divided by the total number of retrieved nodes, may be superior to the absolute numbers of involved nodes. Extracapsular invasion has been identified as additional prognostic factor. Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis. The clinical value of more recent technical advances, such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.

Keywords: Colon cancer; Extracapsular invasion; Immunohistochemistry; Lymph node metastasis; Lymph node ratio; Molecular analysis; Prognosis; Rectum cancer; Sentinel lymph node; Tumor staging.

Figure 1

Manual dissection with subsequent histological assessment based on routinely hematoxylin and eosin stained slides is the standard approach in the examination of regional lymph nodes in cancer specimens. A: Rectum cancer specimen of a 56-year-old female; B: Ulcerated primary tumor, measuring 5 cm in largest diameter; C: After preparation of the primary tumor (including the fatty tissue underneath the lesion and the circumferential margin) the remaining perirectal/mesocolic fatty tissue is carefully removed; D: Specimen for subsequent manual lymph node dissection; E: 36 presumed lymph nodes are isolated, of which the largest four are cut into halves and embedded on their own, respectively (lower right); F: 31 lymph nodes are confirmed on hematoxylin and eosin stained slides, one of which with metastatic cancer tissue (encircled).

Figure 2

Lymph node metastases and tumor deposits in patients with colorectal cancer. A: Metastatic adenocarcinoma within a mesocolic lymph node [hematoxylin and eosin (HE) original magnification, × 100]; B: Mesocolic lymph node totally replaced by metastatic cancer tissue, note the smooth contour of the lesion (HE, original magnification, × 150); C: Tumor deposit (satellite) within the mesocolic fatty tissue, note the irregular contour of the lesion (HE, original magnification, × 250); D: Mesocolic lymph node metastasis with extracapsular extension of cancer tissue (original magnification, × 250).

Figure 3

Value of immunohistochemistry in the evaluation of lymph nodes from patients with colorectal cancer. A: Micrometastasis in the subcapsular sinus of a mesocolic sentinel node evaluated by standard hematoxylin and eosin (HE) staining (original magnification, × 400); B: Micrometastasis in the subcapsular sinus of a mesocolic sentinel node evaluated by immunohistochemistry using an antibody preparation directed against pankeratin (serial section to A, original magnification, × 400); C: Atrophic perirectal lymph node with marked fibrosis after neoadjuvant treatment (original magnification, × 100); D: Identification of residual cancer cells by pankeratin immunostaining (original magnification, × 400).