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PATHOLOGY OF COLORECTAL POLYPS :
An Overview
Arun R Chitale
*Hon. Con. Surgon; **Hon. Asst. Cons. Surgeon, Bombay Hospital, Mumbai 400 020.
Polyp is a gross description or a clinical term used to describe a sessile or pedunculated mass protruding above the surface of mucosa and into the lumen. The polyp can be inflammatory or neoplastic, benign or malignant. Polyps occur throughout the gastrointestinal tract but are particularly common in the large bowel. It is universally agreed that adenocarcinomas of the large bowel often arise from an adenomatous polyp. In fact, adenoma-carcinoma sequence in the large intestine has been used as a model to study the sequence of genetic changes that occur in the evolution of cancer. An accurate histological diagnosis and classification of polyps is important for a correct therapeutic approach.During a 30 year period a total of 8194 biopsies and resected specimens of the large bowel were studied. There were 562 polyps and 1568 adenocarcinomas.
Adenomatous Polyps 260 Villous Adenoma 28 Familial Polyposis 6 Juvenile Polyps 203 Hyperplastic polyp 31 Inflammatory Polyp 34 Total 562
The gross and histopathological features of the various polyps will be described and the clinical implications and biological behaviour of the various types of polyps discussed.
HYPERPLASTIC POLYP
This is a small (3-6 mm) flat or dome shaped usually sessile polyp having same colour as the surrounding mucosa. Hyperplastic polyps are asymptomatic, typically seen in rectum and less commonly in sigmoid colon, detected on routine proctoscopic or colonoscopic study. Histologically, these reveal serrated saw-toothed appearance with papillary infoldings in the tall crypts (Fig. 1). The altered crypts are lined by a mixed population of absorptive and goblet cells with basal bland nuclei. A rare case of large or multiple polyps with symptoms has been reported.[1]
PEUTZ-JEGHERS POLYP
This is a hamartomatous lesion that occurs in any part of gastrointestinal tract. The Peutz-Jegher syndrome is an autosomal dominant disorder characterized by mucocutaneous pigmentation (Fig. 2), gastrointestinal hamartomatous, polyp and ovarian or testicular sex cord tumours. P-J polyp can occur without the syndrome. It varies in size from 1 to 3.5 cm and may be pedunculated or sessile (Fig. 3). Microscopic appearance is of groups of normal mucosal glands separated by branching smooth muscle network arising from muscularis mucosae (Fig. 4). Adenocarcinoma rarely arises from these polyps but, the prevalence of cancer in various organs in patients with P-J syndrome has been shown to vary from 22 to 50%.[2]
INFLAMMATORY POLYP
These polyps are invariably associated with chronic inflammatory bowel disease like ulcerative colitis or Crohn’s disease, solitary ulcers, surgical anastomotic sites etc. The polyps are small, innumerable (Fig. 5) and composed of inflammatory granulation and overlying ulcerated mucosa.
Uncommonly, ‘inflammatory fibroid polyp’ (inflammatory pseudotumour) can occur in the large bowel. This is a solitary polyp about 3-4 cm in size and has a broad base (Fig. 6). It has a predominant mesenchymal stromal component and variable vascular and inflammatory response. The stromal cells may contain large bizarre nuclei and this should not be mistaken for a sarcoma.
JUVENILE POLYP
This polyp is common in children and young adults (first two decades) but not uncommon in adults. It is usually solitary and occurs in the rectum. It is pedunculated, 2-3 cm in size, red-tan in colour, smooth and always shows fluid filled cystic spaces on cut surface (Fig. 7). Microscopically, it is composed of large cystic mucous glands and acutely inflamed lamina propria. Rupture of cystic glands with foreign body reaction and replacement by granulation tissue do occur. Juvenile polyp is non-neoplastic and is also called as retention polyp with obvious reference to the presence of cystically dilated glands. A polyposis syndrome (juvenile polyposis coli) exists. There is increased colonic cancer in this syndrome[3] but it must be emphasized that solitary juvenile polyp is not a precancerous lesion and no follow up investigation is required.
ADENOMATOUS POLYP
Adenomatous polyp also called as tubular adenoma is the most common type of polyp of neoplastic origin. It is of great interest to both clinicians and pathologists because it has been unanimously accepted to be the forerunner of most adenocarcinomas of the large bowel. Its frequency varies greatly in different parts of the world, the autopsy incidence showing a prevalence as high as 60% in the industrialized nations and as low as 5% in the developing countries.[4],[5] Similarly the incidence of adenocarcinoma is far higher in Europeans and Americans than in most Asian populations. These polyps are usually about 1 cm in diameter and possess a pedicle of variable length (Fig. 8). Some are sessile. More than one polyp can occur in different parts of the large intestine in the same patient but this is different from the polyposis syndromes.
Microscopically, adenomatous polyp consists of compactly arranged glands larger than normal mucosal glands and with diminished mucin secretions. The nuclei are slightly hyperchromatic, stratified and display mitosis. The stalk is composed of normal mucosa including muscularis mucosae and submucosal tissue in continuity with the bowel wall. Some polyps are partly glandular and partly villous. These are called villo-glandular polyps or tubulo-villous adenomas. Adenomatous polyp often shows dysplastic changes of various degrees in the glands near the surface. The villo-glandular pattern is usually seen in polyps larger than 1 cm and these show dysplastic changes more frequently.
ADENOMATOUS POLYP WITH MALIGNANT CHANGE
Numerous published reports support the concept of transition of benign adenomatous epithelium to intraepithelial carcinoma to intramucosal carcinoma, and finally to invasive carcinoma.[6-9] The presence of dysplasia in the polyp does not imply malignancy (Figs. 9 and 10). In the past, severe degree of dysplastic changes in the glands of the polyp were labelled carcinoma in situ. This term has now been abandoned because its usage at times leads to misinterpretation and unnecessary colectomies. Surgical pathologist must exercise caution in proper interpretation of dysplastic changes in adenomatous polyps. Only high grade dysplasia (“carcinoma in situ”) should be accorded a precancerous status and a complete polypectomy is curative. If adenomatous polyp with severe dysplasia is diagnosed on biopsy fragments a thorough histological study of the completely excised polyp is necessary to rule out invasive carcinoma.
The next event in the adenoma-carcinoma sequence is the invasion of the lamina propria by glands or carcinomatous cells. Carcinoma invading only upto muscularis mucosae is termed as intramucosal carcinoma. It can not be too strongly stressed that intramucosal carcinomas are usually incapable of metastasizing as the lamina propria of normal colonic mucosa as well as adenomatous polyp is devoid of lymphatics.[10] Thus, a polyp containing invasive carcinoma, thus defined, is also treated by only polypectomy. On the other hand, if resection margin of the polyp is involved or tumour is poorly differentiated or lymphatic invasion is present, colonic resection is necessary. The risk of developing adenocarcinoma is 1% in adenomas of upto 1 cm in size, 10% in adenomas from 1 to 2 cm in diameter and as high as 50% in those greater than 2 cm in diameter.[11]
FLAT ADENOMA
A special subgroup of adenomas that has received attention recently is the so called “flat adenoma”. These are small plaques of tubular adenomatous mucosa, unassociated with inflammatory bowel disease that have a high grade dysplasia and higher association with synchronous or metachronous adenocarcinoma.[12-14]
VILLOUS ADENOMA
This is a distinctive polypoid tumour presenting as a single mass in the rectum or recto-sigmoid region. It is quite rare and in the author’s experience accounted for only 26 out of 562 polyps (5%). It is characterized by villous or finger-like projections arising directly from the mucosa (Fig. 11). This tumour is attached by a wide base (Fig. 12) but is occasionally pedunculated. Over a period of time, the villous adenomas become malignant and the reported incidence varies from 29 to 70%.[15-17] In few cases, a large population of mucin producing cells occur in the villous adenomas and this is the type that is associated with symptom producing potassium loss.
FAMILIAL POLYPOSIS COLI (FAMILIAL ADENOMATOUS POLYPOSIS, FAP)
It is an autosomal dominant disorder in which the large bowel is studded with close crops of polyps (Fig. 13). It manifests around average age of 35 years and all untreated invariably develop a colorectal adenocarcinoma. In patients surveyed because of family history the average age of detection is around 25 years. The polyps have typical histological features of an adenomatous polyp. One of the diagnostic features is the presence of adenomatous change in a single crypt (single crypt adenomas). The genetic defect relates to interstitial deletion on the long arm of chromosome 5.[18],[19] There are adenomatous polyposis syndromes namely: Gardner’s syndrome, Turcot’s syndrome, attenuated FAP, Muir-Torre syndrome, hereditary mixed polyposis syndrome etc. Apart from some variation in the number and type of colonic polyps, neoplasms of different organs occur. These syndromes are extemely rare and will not be discussed further.
ADENOMA-CARCINOMA SEQUENCE
Even before the use of molecular biology techniques, the role of adenoma in the genesis of adenocarcinoma was firmly established on the basis of epidemiological, histological and clinical data. The various findings supporting the adenoma-carcinoma sequence are as follows:
1. The incidence of adenocarcinoma parallels that of adenoma in the different populations in the world and in different parts of large bowel.2. All untreated patients with polyposis syndrome invariably develop an adenocarcinoma.
3. Histologically, transition of adenomatous epithelium to various grades of dysplasia and finally adenocarcinoma has been demonstrated.
4. Adenomas are frequently seen alongside a full-blown growth of an adenocarcinoma.
5. Polypectomy and follow up colonoscopies have brought down the incidence of symptomatic adenocarcinoma considerably, as shown by the National Polyp Study.[20]
Molecular biology studies have shown that a series of genetic alterations in the colonic adenoma lead to colorectal adenocarcinoma. The genetic abnormalities include mutation in k-ras or N-ras oncogenes, duplications, deletions and rearrangements at certain locations on chromosome 5, 17 and 18 and loss of heterozygosity in tumour suppressor genes (p53 and DCC). In short, the multistep evolution of adenoma-carcinoma sequence involves mutational activation of oncogenes coupled with loss of tumour suppressor genes.[21]REFERENCES
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