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Assessment of Serosal Invasion and Criteria for the Classification of Pathological (p) T4 Staging in Colorectal Carcinoma: Confusions, Controversies and Criticisms.

Stewart CJ, Hillery S, Platell C, Puppa G - Cancers (Basel) (2011)

Bottom Line: However, controversy persists regarding the most appropriate criteria for diagnosis and there are also practical difficulties associated with histological assessment in some cases.The examination of multiple microscopic sections combined with ancillary studies such as cytology preparations, elastin stains, and immunohistochemistry may prove beneficial in selected problematic cases, but these are not used routinely.Further studies are required to demonstrate whether recent adjustments to the TNM staging of pT4 tumors are appropriate.

View Article: PubMed Central - PubMed

Affiliation: Department of Histopathology, SJOG Hospital, Perth, Western Australia. colin.stewart@health.wa.gov.au.

ABSTRACT
Transmural spread by colorectal carcinoma can result in tumor invasion of the serosal surface and, hence, more likely dissemination within the peritoneal cavity and potentially to additional metastatic sites. The adverse prognostic significance of serosal invasion is widely accepted and its presence may be considered an indication for chemotherapy in patients with node negative disease. However, controversy persists regarding the most appropriate criteria for diagnosis and there are also practical difficulties associated with histological assessment in some cases. Therefore, serosal invasion may be under-diagnosed in a significant proportion of tumors, potentially leading to sub-optimal treatment of high-risk patients. The examination of multiple microscopic sections combined with ancillary studies such as cytology preparations, elastin stains, and immunohistochemistry may prove beneficial in selected problematic cases, but these are not used routinely. The relative prognostic significance of serosal invasion and of direct tumor spread to other organs, both of which are incorporated within the pT4 category of the AJCC/UICC TNM staging system, remains unclear. Further studies are required to demonstrate whether recent adjustments to the TNM staging of pT4 tumors are appropriate.

No MeSH data available.


Related in: MedlinePlus

Histological image of colorectal carcinoma infiltrating the subserosal fat. (A) At low magnification there is no obvious relationship between the tumor and the serosal surface but note arrowed focus of malignant glands (×40). (B) At higher magnification the same tumor focus (short arrow) is adjacent to an inconspicuous serosal cleft lined by mesothelium (long arrow) (×100). (C) The mesothelium is highlighted by immunohistochemical staining for cytokeratin 7 (×100).
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f5-cancers-03-00164: Histological image of colorectal carcinoma infiltrating the subserosal fat. (A) At low magnification there is no obvious relationship between the tumor and the serosal surface but note arrowed focus of malignant glands (×40). (B) At higher magnification the same tumor focus (short arrow) is adjacent to an inconspicuous serosal cleft lined by mesothelium (long arrow) (×100). (C) The mesothelium is highlighted by immunohistochemical staining for cytokeratin 7 (×100).

Mentions: It might appear that the histological diagnosis of serosal invasion would be straightforward since this would be defined by transgression of the serosal surface (i.e., the mesothelial layer) by malignant cells. Unfortunately several factors complicate such microscopic assessment. First, the mesothelial cells are relatively fragile and they may be stripped from the peritoneal surface during surgery, fixation, or post-operative handling. Therefore, in some instances it can be difficult to identify residual mesothelium overlying a tumor. Second, the normal peritoneal surface is not smooth and flat but follows the undulating contour of the pericolic/perirectal fat with clefts that invaginate from the external aspect of the bowel towards the muscle coat. Identification of these serosal clefts can be difficult, especially in the pathological setting, since they may be distorted by adjacent tumor infiltration or by inflammatory and fibrotic changes. Therefore, it is not always readily apparent that subserosal tumor cells are close to, or in continuity with, the peritoneal lining (Figure 5). This is an important issue since peritoneal clefts and areas of peritoneal reflection probably represent the most frequent site of serosal invasion by colorectal neoplasms [12-14]. Finally, and like many other types of carcinoma, CRC frequently elicit a prominent stromal reaction that includes fibroblasts/myofibroblasts, inflammatory and immune cells, proliferating vessels, and non-cellular matrix components. Indeed, these non-neoplastic elements are increasingly recognized to play an important role in cancer progression [15]. Even in the absence of direct tumor spread, these reactive stromal components can disrupt or efface normal anatomic structures including the peritoneum making it difficult to determine whether tumor cells have actually breached the serosal surface [16].


Assessment of Serosal Invasion and Criteria for the Classification of Pathological (p) T4 Staging in Colorectal Carcinoma: Confusions, Controversies and Criticisms.

Stewart CJ, Hillery S, Platell C, Puppa G - Cancers (Basel) (2011)

Histological image of colorectal carcinoma infiltrating the subserosal fat. (A) At low magnification there is no obvious relationship between the tumor and the serosal surface but note arrowed focus of malignant glands (×40). (B) At higher magnification the same tumor focus (short arrow) is adjacent to an inconspicuous serosal cleft lined by mesothelium (long arrow) (×100). (C) The mesothelium is highlighted by immunohistochemical staining for cytokeratin 7 (×100).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756354&req=5

f5-cancers-03-00164: Histological image of colorectal carcinoma infiltrating the subserosal fat. (A) At low magnification there is no obvious relationship between the tumor and the serosal surface but note arrowed focus of malignant glands (×40). (B) At higher magnification the same tumor focus (short arrow) is adjacent to an inconspicuous serosal cleft lined by mesothelium (long arrow) (×100). (C) The mesothelium is highlighted by immunohistochemical staining for cytokeratin 7 (×100).
Mentions: It might appear that the histological diagnosis of serosal invasion would be straightforward since this would be defined by transgression of the serosal surface (i.e., the mesothelial layer) by malignant cells. Unfortunately several factors complicate such microscopic assessment. First, the mesothelial cells are relatively fragile and they may be stripped from the peritoneal surface during surgery, fixation, or post-operative handling. Therefore, in some instances it can be difficult to identify residual mesothelium overlying a tumor. Second, the normal peritoneal surface is not smooth and flat but follows the undulating contour of the pericolic/perirectal fat with clefts that invaginate from the external aspect of the bowel towards the muscle coat. Identification of these serosal clefts can be difficult, especially in the pathological setting, since they may be distorted by adjacent tumor infiltration or by inflammatory and fibrotic changes. Therefore, it is not always readily apparent that subserosal tumor cells are close to, or in continuity with, the peritoneal lining (Figure 5). This is an important issue since peritoneal clefts and areas of peritoneal reflection probably represent the most frequent site of serosal invasion by colorectal neoplasms [12-14]. Finally, and like many other types of carcinoma, CRC frequently elicit a prominent stromal reaction that includes fibroblasts/myofibroblasts, inflammatory and immune cells, proliferating vessels, and non-cellular matrix components. Indeed, these non-neoplastic elements are increasingly recognized to play an important role in cancer progression [15]. Even in the absence of direct tumor spread, these reactive stromal components can disrupt or efface normal anatomic structures including the peritoneum making it difficult to determine whether tumor cells have actually breached the serosal surface [16].

Bottom Line: However, controversy persists regarding the most appropriate criteria for diagnosis and there are also practical difficulties associated with histological assessment in some cases.The examination of multiple microscopic sections combined with ancillary studies such as cytology preparations, elastin stains, and immunohistochemistry may prove beneficial in selected problematic cases, but these are not used routinely.Further studies are required to demonstrate whether recent adjustments to the TNM staging of pT4 tumors are appropriate.

View Article: PubMed Central - PubMed

Affiliation: Department of Histopathology, SJOG Hospital, Perth, Western Australia. colin.stewart@health.wa.gov.au.

ABSTRACT
Transmural spread by colorectal carcinoma can result in tumor invasion of the serosal surface and, hence, more likely dissemination within the peritoneal cavity and potentially to additional metastatic sites. The adverse prognostic significance of serosal invasion is widely accepted and its presence may be considered an indication for chemotherapy in patients with node negative disease. However, controversy persists regarding the most appropriate criteria for diagnosis and there are also practical difficulties associated with histological assessment in some cases. Therefore, serosal invasion may be under-diagnosed in a significant proportion of tumors, potentially leading to sub-optimal treatment of high-risk patients. The examination of multiple microscopic sections combined with ancillary studies such as cytology preparations, elastin stains, and immunohistochemistry may prove beneficial in selected problematic cases, but these are not used routinely. The relative prognostic significance of serosal invasion and of direct tumor spread to other organs, both of which are incorporated within the pT4 category of the AJCC/UICC TNM staging system, remains unclear. Further studies are required to demonstrate whether recent adjustments to the TNM staging of pT4 tumors are appropriate.

No MeSH data available.


Related in: MedlinePlus