Colorectal Polyps and Polyposis Syndromes

• Colorectal polyps and polyposis syndromes are the topic of the notes.

Colorectal Polyps

• Polyps denote mucosa elevation.
• Polyps result from an imbalance between replication and exfoliation of the luminal epithelium.
• Most colorectal polyps occur as isolated lesions on otherwise normal colorectal mucosa.
• Polyps are subdivided based upon their attachment to the bowel wall i.e diminitive, sessile, or pedunculated.
• Polyps are subdivided based upon their histopathological appearance i.e hyperplastic or adenomatous.
• Polyps are subdivided based upon their neoplastic potential i.e benign or malignant.
• Neoplastic polyps include adenomas and carcinomas.
• Non-neoplastic polyps include hyperplastic, juvenile, inflammatory, and harmatomatous polyps.
• The three commonest colorectal polyps are adenomatous, hyperplastic, and inflammatory.

Adenomatous Polyps

• Adenomatous polyps (adenomas) are benign neoplasms that arise from mucosal epithelium.
• Adenomatous polyps are composed of neoplastic epithelial cells that have migrated to the surface.
• The epithelial cells accumulate beyond the needs for replacement of the cells sloughed into the lumen.
• Adenomatous polyps are the most common pathologic type of colorectal polyps.
• Adenomatous polyps are the precursor lesion for colorectal adenocarcinomas.
• Prevalence is highest in Western countries.
• Diet, particularly one rich in animal fat and low in fiber, as well as high alcohol intake and cigarette smoking, is a consistent factor.
• Diet is an environmental difference between high-risk and low-risk populations.
• In adults over 65, 50-60% have colorectal adenomas detected at autopsy.
• It rarely occurs in children without familial adenomatous polyposis.
• There is a slight male predominance at a ratio of 1.4:1.
• Blacks have a higher proportion of right-sided adenomas and cancers.
• Almost half of all adenomatous polyps of the colon in the US are in the rectosigmoid region.
• Adenomatous polyps can be detected by digital examination or sigmoidoscopy.
• They vary from diminutive to small pedunculated to large sessile adenomas.
• Adenomatous polyps are classified by architecture into tubular, villous, and tubolovillous types.

Tubular Adenomas

• Tubular adenomas are >75% tubular arch.
• Tubular adenomas constitute two thirds of benign large bowel adenomas.
• Tubular adenomas will usually be less than 2cm in diameter, and often attached to the mucosa by a stalk.
• The risk of invasive carcinoma correlates with the size of the tubular adenoma.
• Only 1% of tubular adenomas smaller than 1cm across contain invasive carcinoma at resection.
• Tubular adenomas between 1 and 2cm across contain invasive carcinoma 10% of the time.
• Tubular adenomas greater than 2cm across contain invasive carcinoma 35% of the time.

Villous Adenomas

• Villous Adenomas are >50% villous.
• Villous adenomas constitute one tenth of colonic adenomas.
• Villous adenomas are found predominantly in the rectosigmoid region.
• They are usually large, broad-based, elevated lesions with a shaggy, cauliflower-like surface.
• They can be small and pedunculated.
• More than half are larger than 2cm in diameter, and can reach 10-20cm across.
• In villous adenomas less than 1cm in diameter, the risk is 10 times higher than comparably sized tubular adenomas.
• 50% prevalence of invasive carcinoma in villous adenomas greater than 2cm.

Tubulovillous Adenoma

• Tubulovillous adenomas manifest both tubular and villous features.
• Polyps with between 25% to 50% villous architecture are termed tubulovillous adenomas.
• One forth to one third are larger than 2cm across.
• They are also intermediate between tubular and villous adenomas in the risk of invasive carcinoma.

Pathogenesis of Adenoma Formation

• This involves a neoplastic alteration of crypt epithelial homeostasis characterized by diminished apoptosis.
• Pathogenesis involves a neoplastic alteration of crypt epithelial homeostasis characterized by the persistence of cell replication.
• Pathogenesis involves a neoplastic alteration of crypt epithelial homeostasis characterized by the failure of maturation and differentiation in the epithelial cells that migrate toward the surface of the crypts.
• DNA synthesis normally ceases when cells reach the upper third of the crypts.
• Cells then mature, migrate to the surface and become senescent, then undergo apoptosis and are sloughed.
• Adenoma arises from a focal disruption of this orderly sequence.

Polyposis Syndromes

• A large number of syndromes are characterized by the presence of multiple colorectal polyps.
• They are classified by the pathologic types of polyps into harmatomatous and adenomatous polyposis syndromes.
• The incidence of adenocarcinoma is low in the hamartomatous polyposis versus the adenomatous polyposis.

Adenomatous Polyposis Syndromes

• They are characterized by the inheritance of a single abnormal gene.
• They result in the presence of multiple colorectal adenomatous polyps.
• FAP, Gardner’s syndrome, and Turcot’s syndrome are three variant syndromes
• FAP, also termed adenomatous polyposis coli (APC), is a rare, autosomal dominant inherited trait.
• FAP is characterized by the progressive development of uncountable adenomatous polyps of the colorectum, particularly in the rectosigmoid region.
• FAP reflects a germ-line mutation of the APC gene on the long arm of chromosome 5 (5q21).
• APC codes for a 2843 amino acid protein, which has a tumor suppressor function.
• APC protein interacts with microtubules and B-cathenin.
• B-cathenin is a protein involved in cell adhesion.
• Genetic testing is commercially available to detect the germline defect in FAP.
• Young patients with FAP have no polyps, but in a matter of few years, the colorectal mucosa becomes carpeted with 100-1000 of adenomas.
• Carcinoma of the colon is inevitable, often by age 40 years, unless a total colectomy is performed.

Gardner's Syndrome

• Gardner’s syndrome is a variant of FAP with extracolonic lesions.
• Extracolonic lesions may include osteomas of the skull, mandible, and long bones,
• Extracolonic lesions may include soft tissue tumors of the skin including epidermoid cysts and fibromas, supernumerary teeth.
• Extracolonic lesions may include congenital hypertrophy of the retinal pigmented epithelium (CHRPE).

Turcot's Syndrome

• Turcot’s Syndrome is intestinal polyposis associated with CNS neoplasms.
• Turcot’s syndrome is not a homogenous entity.
• Two thirds of cases are caused by APC gene mutations, developing primitive neuroectodermal tumors, medulloblastomas, malignant astrocytomas, and ependymomas.
• One third of cases are caused by mutation of mismatch repair genes that characterised HNPCC.

Harmatomatous Polyposis Syndrome

• Harmatomas are mass lesions resulting from a disorderly proliferation of tissue elements normally present at that site.
• Intestinal harmatomas are usually composed of disordered crypts.
• Intestinal harmatomas show varying degrees of hyperplasia and cystic change and smooth muscle proliferation.

Peutz-Jeghers Syndrome

• Peutz-Jeghers syndrome is characterized by gastrointestinal hamartomatous polyps.
• Peutz-Jeghers syndrome is associated with pigmented macules on the skin around the mouth and eyes and in the buccal mucosa.
• More rarely, macules can present in extremities and perianal area.
• The brown macules appear in early childhood and are 1-2mm in size.
• Histologically, the macules show increased melanin pigment in the basal layer of the epidermis and increased dermal melanophages.
• Peutz-Jeghers syndrome is inherited as autosomal-dorminant trait.
• The genetic defect or the chromosomal location of the abnormal gene has not been determined.
• Multiple polyps are found throughout the gastrointestinal tract.
• Polyps occur with maximal frequency in the jejunum, the colon, and stomach.
• Smaller polyps are sessile, whereas the large ones are pedunculated with a typical frond-like appearance and long slender stalk.
• Histology shows the polyps are a complex mass of disorganized and hyperplastic mucosal glands, containing secretory and absorptive enterocytes and Paneth cells.
• Bundles of smooth muscle arborize through the polyp, dividing the glandular element into lobules.
• Dysplasia is rare.
• Patients commonly present in the 2nd and 3rd decades of life with recurrent bouts of intussusception associated with abdominal pain.
• Extraintestinal manifestations apart from pigmented macules are benign ovarian sex cord tumor and well differentiated adenocarcinoma of the endocervix in females,
• Extra intestinal manifestations apart from from pigmented macules include a bilateral Sertoli cell tumor of the testis in males.
• There is a general increased incidence of malignant neoplasms of breast, ovarian, pancreatic carcinomas.
• There's about a 2-3% risk of developing gastrointestinal malignancies.

Familial Juvenile Polyposis

• Familial Juvenile Polyposis is rare and accounts for a third of juvenile polyposis.
• FJP is inherited as autosomal-dorminant trait. The affected gene is not known.
• FJP patients have an increased incidence of colorectal adenocarcinoma that can be as high as 2-3%.
• Juvenile polyposis is diagnosed when a patient has more than 6 polyps or polyps in the stomach and small bowel in addition to the colorectum.
• Diagnosis occurs when a patient in a family with FJP develops any juvenile polyps.

Cronkhite-Canada Syndrome

• Cronkhite-Canada Syndrome is a nonfamilial condition characterized by the presence of juvenile polyps of the GIT, brown skin macules, generalized alopecia, and atrophy of the nails.

Cowden's Disease

• Cowden’s Disease is a rare disease inherited as an autosomal-dorminant trait.
• Cowden’s Disease is characterized by multiple harmatomas of the skin.
• Additional symptoms include multiple verrucoid squamous papillomas in the oral mucosa and harmatomatous polyps in the GIT occurring in 30-60% of cases.
• There is no increased risk of GIT cancer in Cowden’s disease.
• 50% of patients develop breast cancer, 10%-thyroid cancer, over 50% have goiters.

Non-Neoplastic Polyps

• These include hyperplastic polyps, which are the most common polypoid lesions of the colon particularly the rectum.
• They are remarkably common, being present in 40% of rectal specimens in persons younger than 40 years and in 75% of older persons.
• Ras mutation and overexpression of Bcl-2 have found in a substantial minority of hyperplastic polyps.
• Juvenile polyps are most common in children younger than 10 years, although one third occur in adults.
• Inflammatory polyps are found in IIBD, and also in cases of amebic colitis and bacillary dysentery.
• Lymphoid polyps are more common in female than in male subjects, and are seen in persons of any age, including children.