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Wednesday, December 15, 2010

Clinical Case: Old Man With Colonoscopic Findings Of Small Pedunculated Polyps In The Right Colon

Clinical Vignette: A 45-year-old man with a family history of colon cancer undergoes a screening colonoscopy. No invasive carcinomas are identified, but two small pedunculated tubular adenomas are removed and one villous adenoma measuring 5 mm in diameter is biopsied. 


◆    What is the most likely diagnosis? 


◆    What are the syndromes that could predispose this individual 
     to colon cancer? 


◆    What other dietary factors could play a role in the
     development 
     of colon cancer? 


Summary:A 45-year-old man with a family history of colon cancer underwent colonoscopy for rectal bleeding. Colonoscopic findings included several small pedunculated polyps in the right colon, all measuring less than 5 mm.

Most likely diagnosis: Hyperplastic polyps or tubular adenomas.

Syndromes predisposing to colon cancer: Familial adenomatous
   polyposis (FAP) and hereditary nonpolyposis colon cancer
  (HNPCC)are two common inherited colon cancer syndromes.

Dietary factors that play a role in the development of colon
  cancer:Diets rich in fat and red meat and low in fiber may
  contribute to the development of colon cancer.

CLINICAL CORRELATION

Learn it for your USMLE..... Another Clinical Vignette with lots of explanation...

Colon cancer is the third most common malignant neoplasm worldwide and the second leading cause of cancer death in the United States. The peak incidence is in the seventh decade of life. Recommended screening for colon cancer for patients without increased risk starts at age 50, but for at-risk patients with a positive family history, screening should start at age 40 (some recommend 10 years earlier than the age at which the youngest
index case presents). Annual fecal occult blood tests should be performed as well as digital rectal examination and flexible sigmoidoscopy every 5 years.

Additional screening can be done by colonoscopy every 10 years, or a double contrast barium enema can be done every 5 to 10 years. These recommended screening intervals may be maintained after a negative examination. For patients at high risk for cancer or with polyps, rescreening by colonoscopy at 3-year intervals is recommended. New technologies such as virtual colonography and genetic testing of stool specimens are being examined for their appropriate clinical settings. In this patient, the colonic polyps showed proliferation of tubular glands, arising from a fibromuscular base with normal
colonic epithelium consistent with a polyp stalk. The polyps showed no evidence of malignant transformation (i.e., carcinoma). The diagnosis was multiple tubular adenomas of the colon.

APPROACH TO COLON ADENOMAS

Objectives
Describe the adenoma-dysplasia-carcinoma sequence.
List the risk factors for colon cancer.
Describe the hereditary polyp disorders.

Definitions
Adenoma: Neoplastic proliferation of colonic epithelium that results in the formation of a polyp.

Neoplasia: Usually implies abnormal, often clonal proliferation of cells that results in the formation of a tumor.

Dysplasia: Usually the result of additional genetic abnormalities in cells that lead to further dysfunction or abnormal cell maturation.

Adenoma-dysplasia-carcinoma sequence: Model for colon cancer development that outlines the genetic pathway involved in the progression from a benign neoplastic polyp (adenoma) to frankly invasive cancer (carcinoma).

Familial adenomatous polyposis syndrome: The prototypic inherited
colon cancer phenotype; affected patients have hundreds to thousands of polyps and are at high risk for cancer development.

Hereditary nonpolyposis colorectal cancer: Also known as Lynch syndrome. Often presents as right-sided colon cancer and involves mutation in mismatch repair genes. It is inherited in an autosomal dominant fashion, and affected individuals are also at high risk for extracolonic malignancies such as endometrial carcinomas.

DISCUSSION
Polyps of the colon can be classified broadly into inflammatory /reactive, hyperplastic, and neoplastic. Inflammatory polyps can be seen in chronic colitides such as ulcerative colitis and Crohn disease. Hyperplastic polyps are some of the more frequently encountered polyps and are thought to represent nonneoplastic proliferation of colonic epithelium. There is accumulating evidence that some hyperplastic polyps may transform to adenomas through a serrated adenoma pathway. Adenomas are truly neoplastic proliferations and have the potential to transform and progress to carcinomas.
With increasing age, there is an increased incidence of adenoma formation. Approximately 50 percent of patients who have one adenoma have additional synchronous adenomas present. Most polyps are present in the rectosigmoid colon, but with increasing age, there is a tendency to see more  right-sided involvement by polyps.

Types of Adenomas
Adenomas can be classified on the basis of the pattern of growth: whether they are flat, sessile, and broad without a stalk, or pedunculated and on a stalk.
Histologically, depending on the extent of tubular gland formation versus fingerlike villous projections, they are classified as tubular adenomas, villous adenomas, or tubulovillous adenomas.

Adenoma-carcinoma sequence



Polyposis and Inherited Colon Cancer Syndromes

Syndromes that involve the formation of multiple gastrointestinal polyps occur infrequently. Some, such as Peutz-Jeghers syndrome and Cowden disease, are autosomal dominant, resulting in the formation of  nonneoplastic hamartomatous polyps; others, such as Canada-Cronkhite syndrome, are not hereditary and result in multiple juvenile polyps. Other clinically significant polyposis or colon cancer syndromes include familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.
The autosomal dominant FAP gene on chromosome 5q21 contains the
tumor suppressor gene APC (adenomatous polyposis coli). Affected individuals have hundreds to  thousands of polyps, typically presenting in the  left colon.
Almost all individuals with APC gene mutations eventually develop colon cancer. Hence, carriers usually are candidates for  prophylactic colectomy.
Recent studies have shown that cyclooxygenase inhibitors can suppress polyp formation and possibly carcinoma development in patients with FAP.

Adenoma-Dysplasia-Carcinoma Sequence

A variant of FAP is Gardner syndrome, which involves the formation of osteomas of the bone,  desmoid fibromatosis. HNPCC also is known as Lynch syndrome, named after the gastroenterologist Dr. Henry Lynch. The autosomal dominant inherited disease presents early in life, often with right-
sided cancer, and can be associated with polyps, although much less numerous (usually fewer than 10) than what is seen in FAP. Patients with HNPCC are also at risk for extra–gastrointestinal tract tumors.
There are also less-well-defined familial cancer syndromes involving glandular elements (adenocarcinomas) that are ssociated with a family history or personal history of breast, ovarian, endometrial, or colon cancer.
The development of colon cancer is a multifactorial process involving not only predisposition genes but also factors such as diet (low-fiber foods, red meat, and refined carbohydrates are nonfavorable),  obesity, and inactivity.
Genetically, it is known that adenomas can progress and transform through additional mutations (i.e., genetic “hits”) and progressively grow in size, increase in the degree of dysplasia, and acquire full malignant potential (carcinoma). Additional genes that have been shown to be involved in this process include the K-ras oncogene, the DCC (deleted in colon cancer) adhesion molecule gene, and the p53 tumor suppressor gene.