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colorectal adenocarcinoma staging

Friday 15 February 2013

colorectal adenocarcinoma staging system; colon cancer staging; colonic carcinoma staging

Tumor staging is by far the most important prognostic predictor of clinical outcome for patients with colorectal carcinoma.

Tumor invasion (T)

Histologic examination of surgically resected specimens serves an irreplaceable role in determining the depth of tumor invasion (T) and the extent of nodal metastasis (N).

The histologic determination of T1 (tumor invades submucosa), T2 (tumor invades muscularis propria) and T3 (tumor invades through the muscularis propria into pericolorectal tissues) is usually straightforward when using the AJCC TNM staging system.

However, determination of T4a (tumor penetrates to the surface of the visceral peritoneum) and T4b (tumor directly invades or is adherent to other organs or structures) can sometimes be problematic:
- First, serosal surface (visceral peritoneum) involvement can be missed if the specimen is not adequately sampled for histologic examination.
- Second, the serosal surface may be confused with the circumferential margin (radial margin) or mesenteric margin, which is a nonperitonealized surface created surgically by blunt or sharp dissection. A T3 tumor may involve the radial margin and a T4 tumor may have a negative radial margin.
- Third, a surgically induced perforation at the tumor site may be confused with true tumor perforation, which requires clarification from surgeons.
- Fourth, adherence of other organs or structures at the tumor site does not necessarily qualify for T4b. Histologically, the adherent site may show only inflammatory changes, abscess formation and/or fibrosis, but without direct tumor involvement.
- Finally, there is some confusion about the definition of visceral peritoneum involvement.

Clearly, the interpretation of T4a can be unequivocal if,

  • (I) tumor cells are present at the serosal surface with inflammatory reaction, mesothelial hyperplasia, and/or erosion;
  • or (II) free tumor cells are seen on the serosal surface with underlying ulceration of the visceral peritoneum.

Tumor cells close to, but not at, the serosal surface, with mesothelial inflammatory and hyperplastic reactions, which may be considered T4a by some investigators.

However, identification of tumor cells close to, but not at, the serosal surface would be considered T4a by some investigators if there are associated mesothelial inflammatory and/or hyperplastic reactions.

Apparently, the application of this third criterion is prone to subjective judgment and lacks reproducibility.

It is noted that in the updated cancer protocols and checklists by College of American Pathologists (CAP), only the first two criteria are listed as the diagnostic features of T4a, and the third criterion is deleted.

Nodal metastasis (N)

Minimal 12 nodes

It is pathologists’ obligation to retrieve as many lymph nodes as possible from surgical specimens. The vast majority of pathologists follow the guidelines of a minimum of 12 nodes. It is recommended that pathologists document the degree of diligence of their efforts to find lymph nodes in a specimen in pathology reports, if @<@12 nodes are retrieved.

Extra efforts will be made if @<@12 nodes are retrieved, although this will increase the turnaround time for pathology reports. The extra efforts may include repeated manual searches, submitting more sections, utilizing fat clearance techniques, or ex vivo injection of methylene blue.

The application of fat clearance techniques has several potential disadvantages, such as further delay in signout of the pathology reports, cost, toxicity and disposal of clearing solutions, and unknown effect on immunohistochemistry. As a result, fat clearance has not become a standard practice in pathology laboratories.

Methylene blue injection is a relatively new method for colorectal cancer. There have been only a few publications in this area, mostly from the same study group. Its clinical application needs further investigation.

It should be realized that the total number of nodes retrieved is not only dissector-dependent, but also influenced by a number of specimen and patient variables.

Studies have shown a positive correlation with the specimen length, pericolorectal fat width, female gender and tumor size; and a negative correlation with the age of patient and the rectosigmoid location of tumors.

Not surprisingly, fewer than 12 nodes may be expected if patients have received preoperative neoadjuvant therapies.

Discrete tumor deposits

One of the interesting issues in nodal staging is the interpretation of discrete tumor deposits in pericolorectal fat away from the main tumor but without identifiable residual lymph node tissue.

In AJCC Cancer Staging Manual 5th edition, a tumor nodule >3 mm was counted as a positive node, whereas a nodule ≤3 mm was classified in the category of discontinuous extension.

In the 6th edition, tumor deposits were considered as positive nodes if they are round and have a smooth contour irrespective of size, but classified in the T category as well as venous invasion if they are irregular in shape.

The current edition (7th edition) recognizes the fact that tumor deposits may represent discontinuous extension, venous invasion with extravascular spread, or truly totally replaced lymph nodes.

Given their association with reduced disease-free and overall survival, these tumor deposits are now considered nodal metastasis, irrespective of size or contour, and are designated N1c in the absence of regional lymph node metastasis to favor additional postoperative treatment.

Single positive lymph node

However, if a single positive lymph node is also identified, the N stage will be changed from N1c to N1a. The presence of discontinuous tumor deposits does not change the T stage in the 7th edition.

Isolated tumor cells (ITCs)

The prognostic significance of isolated tumor cells (ITCs), defined as single tumor cells or small clusters of tumor cells ≤0.2 mm, detected by either immunohistochemical staining or standard hematoxylin and eosin staining in regional lymph nodes remains unclear at present.

In the absence of overt nodal metastasis, ITCs are classified as N0 but annotated as N0 (i+) with “i” standing for “isolated tumor cells”.

On the other hand, micrometastasis (>0.2 mm but ≤2.0 mm) is reported as N1(mic). The number of lymph nodes involved by ITCs or micrometastasis should be stated.




- Histologic features and cytologic techniques that aid pathologic stage assessment of colonic adenocarcinoma. Panarelli NC, Schreiner AM, Brandt SM, Shepherd NA, Yantiss RK. Am J Surg Pathol. 2013 Aug;37(8):1252-8. doi : 10.1097/PAS.0b013e3182960e7c PMID: 23774176