Polyposis Coli – A Premalignant Condition
Introduction
Polyposis coli or Familial Adenomatous polyposis (FAP) is an inherited disorder characterized by hundreds of polyps in the bowel. This inherited condition shows autosomal dominant inheritance with high degree of penetrance. If left untreated one or more carcinomas will develop in the large bowel in nearly every instance, often before the age of 40 years. We present a case of Polyposis coli in a middle aged man.
Case history
A forty-nine year old male presented to our hospital with black stools for five days and a history of loose motions associated with weakness for one year. He did not have a history of rectal bleeding prior to this episode. There was no family history of cancer or any other systemic disease. Patient was a non-smoker and did not consume alcohol. General physical examination showed no significant findings except pallor. On per- abdomen examination, no abnormality was found whereas on per-rectal examination multiple polyps were felt 3 cm above the anal verge.
On investigations he was found to be anaemic (Hb-7.5 g/dl). Ultrasound and CT of the abdomen were normal. Upper gastrointestinal endoscopy showed a lax oesophageal sphincter and gastric biopsy done was reported to have non-specific chronic inflammation. Colonoscopy revealed multiple polyps in the entire colon suggestive of polyposis coli (Fig I). Biopsy from one of the polyps showed Adenomatous polyps with moderate dysplasia.
Management
The case was discussed in the multidisciplinary tumor board of the hospital and a plan for total colectomy and ileorectalanastomis with surveillance endoscopic polypectomy of remnant rectum, was advised.
At laparotomy, bowel loops were dilated and sigmoid colon showed one indurated area measuring 4x4 cm. A few mesentriclymphnodes were found. Intraoperative colonoscopy by the gastroenterologist revealed the whole colon and rectum full of varying sized polyps, extending till the anal verge. Colon was mobilized, colic vessels ligated, rectum dissected (leaving 3 cm of rectum as stump) and 10 cm of ileum was resected and the specimen removed. Single layered ileorectal anastomosis was done and complete haemostasis achieved. Post-operative recovery was satisfactory and patient was discharged on eighth day in a stable condition.
Histopathology
Gross examination of the colectomy specimen included 107 cm long colon, ileocolic junction and 8 cm of ileum with unremarkable appendix. The colonic mucosa was studded by numerous sessile and pedunculated polyps, extending from cecum to distal resected margin ( Fig II).
The largest polyp measured 3x2.2x1.8cm. A thickened area with ulceration measuring 3x2.6cm was seen 19cm from distal margin which on cut section showed a grey-white tumor infiltrating the bowel wall. Histopathology showed a well-differentiated Adenocarcinoma infiltrating the muscle coat (Fig III) and the pericolic tissue with metastasis in two out of thirty- four pericoliclymphnodes (02/34) dissected from the specimen. Remaining colon had multiple villous adenomas with moderate to severe dysplasia. A diagnosis of well differentiated adenocarcinoma with multiple villous adenomas (Pathological stagepT1 pN1b) was made.
Discussion
Polyposis coli or FAP is a rare familial colorectal cancer syndrome characterized by striking phenotype in colon i.e. multifocal colorectal cancer in a background of thousands of adenomatous polyps. It is transmitted as autosomal dominant trait .It is now recognized that FAP phenotype is diverse and the number of colonic polyps can vary markedly. Accordingly, classical FAP is now diagnosed when an individual develops at least 100 adenomatous polyps during lifetime, while attenuated FAP (AFAP) is a term applied to a patient whose lifetime polyp burden is in the range of 20 to 100 polyps. The disorder (both FAP and AFAP) is caused by germline mutations in APC (adenomatous polyposis coli) gene, which is a tumor suppressor gene. Germline APC mutations are carried by 1/10,000 to 1/5000 individuals, most inherited from similarly affected parent but 20 to 30% are de-novo mutations and our patient belonged to this category.
The colonic polyps generally appear after puberty and are evident by age 25. If polyposis is not treated surgically colorectal cancer will develop in almost all patients before age 40. Polyposis coli results from defect in the colonic mucosa, leading to an abnormal proliferative pattern and impaired DNA repair mechanism. To facilitate early diagnosis screening sigmoidoscopies should be started at age of ten years in families with history of FAP. Once multiple polyps are detected patient should undergo prophylactic total colectomy. For AFAP screening may begin later in the teens, and colectomy is performed when polyp burden is no longer manageable by polypectomy. NSAIDS such as Sulindac and Cyclooxygenase inhibitors like Celecoxib can decrease the number and size of polyps temporarily. NSAIDS are not proven to reduce the risk of cancer. Upper gastrointestinal surveillance is also indicated since gastric and small bowel polyps can develop, especially in the periampullary region, where there is 5 to 12 % risk of progression to cancer in FAP.
Polyposis coli is the most common cause of hereditary colorectal cancer. At least 100 polps are necessary diagnosis of classic FAP. Except for their remarkable numbers these growths are morphologically indistinguishable from sporadic adenomas. Colorectal adenocarcinomas develop in 10 percent of untreated FAP patients sometimes even before 30 years age. Colectomy remains the primary modality for therapy and prevention. Colectomy prevents colorectal cancer but patients remain at risk of neoplasia at other sites in gastrointestinal tract particularly adjacent to ampulla of Vater and stomach.
Early recognition of these conditions is not only vital for management in affected individuals, but also for prevention and early detection in at-risk relatives. Molecular techniques can be used for the pre-symptomatic diagnosis of this disorder through demonstration of germ line mutations in the relevant genes.
Polyposis coli or Familial Adenomatous polyposis (FAP) is an inherited disorder characterized by hundreds of polyps in the bowel. This inherited condition shows autosomal dominant inheritance with high degree of penetrance. If left untreated one or more carcinomas will develop in the large bowel in nearly every instance, often before the age of 40 years. We present a case of Polyposis coli in a middle aged man.
Case history
A forty-nine year old male presented to our hospital with black stools for five days and a history of loose motions associated with weakness for one year. He did not have a history of rectal bleeding prior to this episode. There was no family history of cancer or any other systemic disease. Patient was a non-smoker and did not consume alcohol. General physical examination showed no significant findings except pallor. On per- abdomen examination, no abnormality was found whereas on per-rectal examination multiple polyps were felt 3 cm above the anal verge.
On investigations he was found to be anaemic (Hb-7.5 g/dl). Ultrasound and CT of the abdomen were normal. Upper gastrointestinal endoscopy showed a lax oesophageal sphincter and gastric biopsy done was reported to have non-specific chronic inflammation. Colonoscopy revealed multiple polyps in the entire colon suggestive of polyposis coli (Fig I). Biopsy from one of the polyps showed Adenomatous polyps with moderate dysplasia.
Management
The case was discussed in the multidisciplinary tumor board of the hospital and a plan for total colectomy and ileorectalanastomis with surveillance endoscopic polypectomy of remnant rectum, was advised.
At laparotomy, bowel loops were dilated and sigmoid colon showed one indurated area measuring 4x4 cm. A few mesentriclymphnodes were found. Intraoperative colonoscopy by the gastroenterologist revealed the whole colon and rectum full of varying sized polyps, extending till the anal verge. Colon was mobilized, colic vessels ligated, rectum dissected (leaving 3 cm of rectum as stump) and 10 cm of ileum was resected and the specimen removed. Single layered ileorectal anastomosis was done and complete haemostasis achieved. Post-operative recovery was satisfactory and patient was discharged on eighth day in a stable condition.
Histopathology
Gross examination of the colectomy specimen included 107 cm long colon, ileocolic junction and 8 cm of ileum with unremarkable appendix. The colonic mucosa was studded by numerous sessile and pedunculated polyps, extending from cecum to distal resected margin ( Fig II).
The largest polyp measured 3x2.2x1.8cm. A thickened area with ulceration measuring 3x2.6cm was seen 19cm from distal margin which on cut section showed a grey-white tumor infiltrating the bowel wall. Histopathology showed a well-differentiated Adenocarcinoma infiltrating the muscle coat (Fig III) and the pericolic tissue with metastasis in two out of thirty- four pericoliclymphnodes (02/34) dissected from the specimen. Remaining colon had multiple villous adenomas with moderate to severe dysplasia. A diagnosis of well differentiated adenocarcinoma with multiple villous adenomas (Pathological stagepT1 pN1b) was made.
Discussion
Polyposis coli or FAP is a rare familial colorectal cancer syndrome characterized by striking phenotype in colon i.e. multifocal colorectal cancer in a background of thousands of adenomatous polyps. It is transmitted as autosomal dominant trait .It is now recognized that FAP phenotype is diverse and the number of colonic polyps can vary markedly. Accordingly, classical FAP is now diagnosed when an individual develops at least 100 adenomatous polyps during lifetime, while attenuated FAP (AFAP) is a term applied to a patient whose lifetime polyp burden is in the range of 20 to 100 polyps. The disorder (both FAP and AFAP) is caused by germline mutations in APC (adenomatous polyposis coli) gene, which is a tumor suppressor gene. Germline APC mutations are carried by 1/10,000 to 1/5000 individuals, most inherited from similarly affected parent but 20 to 30% are de-novo mutations and our patient belonged to this category.
The colonic polyps generally appear after puberty and are evident by age 25. If polyposis is not treated surgically colorectal cancer will develop in almost all patients before age 40. Polyposis coli results from defect in the colonic mucosa, leading to an abnormal proliferative pattern and impaired DNA repair mechanism. To facilitate early diagnosis screening sigmoidoscopies should be started at age of ten years in families with history of FAP. Once multiple polyps are detected patient should undergo prophylactic total colectomy. For AFAP screening may begin later in the teens, and colectomy is performed when polyp burden is no longer manageable by polypectomy. NSAIDS such as Sulindac and Cyclooxygenase inhibitors like Celecoxib can decrease the number and size of polyps temporarily. NSAIDS are not proven to reduce the risk of cancer. Upper gastrointestinal surveillance is also indicated since gastric and small bowel polyps can develop, especially in the periampullary region, where there is 5 to 12 % risk of progression to cancer in FAP.
Polyposis coli is the most common cause of hereditary colorectal cancer. At least 100 polps are necessary diagnosis of classic FAP. Except for their remarkable numbers these growths are morphologically indistinguishable from sporadic adenomas. Colorectal adenocarcinomas develop in 10 percent of untreated FAP patients sometimes even before 30 years age. Colectomy remains the primary modality for therapy and prevention. Colectomy prevents colorectal cancer but patients remain at risk of neoplasia at other sites in gastrointestinal tract particularly adjacent to ampulla of Vater and stomach.
Early recognition of these conditions is not only vital for management in affected individuals, but also for prevention and early detection in at-risk relatives. Molecular techniques can be used for the pre-symptomatic diagnosis of this disorder through demonstration of germ line mutations in the relevant genes.
