Malignant polyps

Therapeutic polypectomy if the adenocarcinoma is:

(a) well or moderately differentiated

(b) clear of the stalk base

(c) without lymphovascular invasion.

Resection if the adenocarcinoma is:

(a) poorly differentiated (22%)*

(c) shows lymphovascular invasion (18%)*.

Resection is more likely if the patient is young and medically fit to obviate the risk of nodal metastases which can occasionally occur with pT1 lesions (4%). A not uncommon finding is stalked adenomas in the sigmoid colon that twist and prolapse, resulting in glandular herniation into submucosa mimicking invasive carcinoma—the presence of haemosiderin, lack of stromal desmoplasia, surrounding lamina propria and cytoarchitectural abnormalities similar to those of the overlying adenoma are helpful pointers to a benign lesion.

Sessile adenomas with invasion: resection is indicated as this represents invasion of actual mural submucosa (Haggitt level 4) rather than just stalk submucosa (Haggitt levels 1, 2 and 3). Local transanal resection is considered for the very elderly and medically unfit. Indications for more radical surgery are: a lesion >3 cm diameter, incomplete tumour excision, deep submucosal (sm 3) or muscularis propria invasion, lymphovas-cular invasion or the presence of a poorly differentiated invasive component.

Flat adenomas: uncommon with a different genetic basis from usual adenomas and difficult to identify endoscopically on gross examination without magnification and dye spray techniques. Defined as up to twice the height of the adjacent mucosa with a height usually less than half its diameter (<10 mm across)—proportionately (x10 risk) higher grades of dysplasia and frequency of carcinoma. Depressed variants harbour carcinoma in up to 25% of cases, overexpress p53 and the DNA aneuploidy rate is increased.

Hereditary non-polyposis colorectal cancer (HNPCC, syn. hereditary mismatch repair deficiency syndrome; hMSH2 and hMLH1 are the two most frequently mutated genes): autosomal dominant with 90% penetrance, this forms 2% of colorectal cancer cases requiring three affected family members across two generations with at least one <50 years of age at presentation. Numbers of adenomas are low but they progress more quickly, forming carcinomas tending to be right-sided and multiple. Although mucinous or poorly/undifferentiated (medullary-like) in character, they are of better prognosis (66% vs. 44% 5-year survival). They have expanding or circumscribed margins, intra- and peritumoral lymphocytes, show loss of hMSH2/hMLH1 expression and are less likely to show distant spread. There is often a family history of cancer in other

*The risk of lymph node metastases being present.

Level 0

Level 1 Level 2 Level 3

Level 4

Adenocarcinoma

Submucosa

Muscularis propria

Subserosal connective tissue

Adenomatous epithelium

Normal colonic mucosa

Muscularis mucosae

Adenocarcinoma

Adenocarcinoma

Muscularis propria

Subserosal connective tissue

Pedunculated adenoma

Sessile adenoma

Figure 5.5. Malignant colorectal polyp. Levels of invasion in a pedunculated adenoma (left) and a sessile adenoma (right). The stippled areas represent zones of carcinoma. Note that any invasion below the muscularis mucosae in a sessile lesion represents level 4 invasion, i.e. invasion into the submucosa of the bowel wall. In contrast, invasive carcinoma in a pedunculated adenoma (left) must traverse a considerable distance before it reaches the submucosa of the underlying bowel wall. The dotted line in the head of the pedunculated adenoma represents the zone of level 1 invasion. (Haggit RC, et al. Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polyectomy. Gastroenterology 1985;89:328-336. Copyright 1985, with permission from American Gastroenterological Association) Therapeutic polypectomy:

— carcinoma of well or moderate differentiation

— no lymphovascular invasion

— no involvement of the stalk resection margin

Resection indicated:

— sessile lesion with invasion (level 4)

— pedunculated lesion with level 4 invasion

— carcinoma poorly differentiated

— lymphovascular invasion

— involvement of the stalk resection margin.

viscera, e.g. stomach, small intestine, endometrium, breast, ovary, renal pelvis, and the risk of colonic cancer in a first-degree relative of an affected individual is about 50%. The tumours have a high level of microsatellite instability (MSI-H) but this applies to only a small minority (15%) of sporadic colorectal cancers, most of which show more exten sive chromosomal abnormalities and are microsatellite stable. Most sporadic colorectal cancers arise on the basis of the p53/APC adenome-carcinoma pathway but those with MSI-H are associated with the serrated pathway, viz, sessile serrated adenoma/mixed polyps (serrated and tubular adenoma)/sporadic MSI-H cancer. Therefore, although the vast majority of hyperplastic polyps are innocuous, large sessile serrated right-sided lesions in a young patient may be instrumental in the development of a minority of cancers.

Familial adenomatous polyposis coli: sporadic or familial and autosomal dominant with a high degree of penetrance (chromosome 5q21). The site of gene mutation can determine the phenotype and type of surgery required. A minimum of 100 colorectal polyps is required for a morphological diagnosis and these can vary from unicryptal dysplasia to macroscopic lesions. Usually thousands of polyps are present and, if left untreated, one or more cancers occur on average 20 years earlier than usual colorectal carcinomas. FAPC is also associated with adenomas and periampullary carcinoma in the duodenum (a significant cause of mortality), gastric fundic gland cyst polyps and desmoid tumours (fibromatosis).

Rates for synchronous and metachronous carcinomas range from 5 to 15%.

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