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low-grade colorectal adenoma

Tuesday 13 March 2012

Low-grade denomas of the colon and the rectum

At least half of adults in Western countries will have an adenomatous polyp in their lifetime and one-tenth of these lesions will progress to adenocarcinoma. The risk increases after the age of 50.

Endoscopically, adenomas can be pedunculated or sessile.

By definition, adenomas are clonal lesions that show at least low grade dysplasia characterized by enlarged, hyperchromatic and elongated (pencillate) nuclei arranged in a stratified configuration along the basement membrane.

The adenomatous cells may show mucin depletion and increased apoptotic activity. Interestingly, adenomatous polyps appear to develop through a “top-down” mechanism.

As such, small lesions will often only have adenomatous epithelium in their superficial portions.

Conventional adenomas are subclassified as tubular, tubulovillous and villous based on their architectural features:
- Tubular adenomas are composed of simple crypt-like dysplastic glands and contain @<@25% villous component.
- Villous adenomas consist of >75% villous component that resemble finger-like projections.
- Tubulovillous adenomas are intermediate lesions with 25-75% villous component.

Adenomas that are large in size (>1 cm) or predominantly villous, or contain high grade dysplasia are considered “advanced adenomas”, which require more aggressive endoscopic surveillance.


The histologic features of adenomas may be defined as low-and high-grade dysplasia, carcinoma in situ, intramucosal carcinoma, and invasive carcinoma.

Low-grade Dysplasia

By definition, all adenomas contain at least low-grade dysplasia.

Low-grade dysplasia consists of stratified dysplastic epithelium that retains its columnar shape.

The nuclei are spindle or oval shaped. The stratified nuclei tend to remainin the basal epithelium extending no more than three quarters ofthe height of the epithelium.

There is minimal nuclear hyperchromasia. Minor cytologic variations,such as variations in mucin content, nuclear pleomorphism, differencesin chromatin distribution, and variations in cell size and shape, frequently occur in adenomatous epithelium, especially in larger lesions.

These findings represent features of the underlying neoplastic process and, in the absence of significant atypia or architectural alterations, have no clinical significance.

Such changes are insufficient to warrant a diagnosis of high-grade dysplasia.

Occasionally,it is difficult to distinguish a small tubular adenoma from reactive epithelium present in an inflamed mucosa.

One approach is to examine the degree of differentiation of the epithelium along the length of the tubular crypt.

Reactive glands appear more basophilic than normal, and the nuclei may exhibit pseudostratification.

These changes extend from the crypt base toward the luminal surface. Mitotic activity is present in the basophilic regenerating cells.

If the entire gland is not replaced by basophilic epithelium, then its restriction to the bottom portion of the crypt serves to identify the epithelium as regenerative.

Conversely, in small adenomas the adenomatous glands appear more basophilic at the surface of the lesion and non-neoplastic epithelium lies below it.

The mitotic activity is at the surface.

Ki-67 immunostains help highlight the proliferating compartments.

When the entire crypt appears immature, the epithelium may be either regenerative or adenomatous.

Then one must rely on the histologic context in which the glands are found to distinguish between these two possibilities.

In a setting of active inflammation, the glands are most likely to be regenerative. The one disorder in which these distinctions are particularly difficult is ulcerative colitis.

High-grade dysplasia

High-grade dysplasia consists of cytologically malignant cells that remain confined within the basement membrane of the original colonic crypt.

It is recognizable by the presence of marked cytologic atypia, the loss of cellular polarity, and the occasional formation of solid nests of
dysplastic cells, sometimes including dystrophic goblet cells.

Extension of the neoplastic cells through the basement membrane of the crypt into the surrounding lamina propria can be designated an
intramucosal carcinoma.

Areas of intramucosal carcinoma show greater glandular irregularity and greater glandular density than carcinoma in situ.

Intramucosal carcinoma may occupy the entire mucosal thickness, or it may represent a small focal area within the adenoma.

Once intramucosal carcinomas reach the deep mucosa, the neoplastic cells may mingle with frayed fibers of the muscularis mucosae and may gain access to lymphatics and may theoretically metastasize. This is extraordinarily rare.

Invasion into, but not through, the muscularis mucosae is still intramucosal carcinoma.

Since neither intra-epithelial neoplasia nor intra-mucosal carcinoma has a clinically significant potential for metastasis (if all neoplastic tissue is removed), the lesions do not require additional treatment.

In fact, we rarely use the term "intramucosal carcinoma" because of the clinical misinterpretation of the significance ofthe lesion that can occur as a result of the word carcinoma.

A carcinoma of the large bowel is not considered to be invasive and clinically significant until it invades through the muscularis mucosae into the underlying submucosa.

Submucosal invasion is most easily recognized by the intermingling of the malignant glands with normal submucosal structures, including medium-sized blood vessels, fat, nerves and ganglia, and larger lymphatics.

A prominent desmoplastic response often accompanies even early invasion.

The Adenoma–Carcinoma Sequence

Adenomas constitute the obligate precursor lesion for most colorectal carcinomas.

The earliest lesions consist of pseudo-stratified immature, mildly dysplastic, adenomatous cells.

The adenoma may be ofany of the types dis-cussed in previous sections.

In some cases,one may see a continuous histologic spectrum of increasing degrees of dysplasia culminating in the development of an invasive carcinoma.

This neoplastic continuum can be diagrammed schematically and can also be shown histologically.

Carcinomas are more likely to arise in larger adenomas than smaller ones.

Molecular pathology

- DNA methylation

  • Distinct patterns of DNA methylation in conventional adenomas involving the right and left colon. (23868178)


- Adenoma and Adenocarcinoma Arising in Adenoma. UNDERSTANDING YOUR PATHOLOGY REPORT: A FAQ SHEET