Hereditary gastrointestinal polyposis - Comparative study!
Hereditary gastrointestinal polyposis syndromes are clubbed into hamartomatous, adenomatous and serrated types depending upon histological subtype of polyp present.
 Adenomatous polyp
Familial Adenomatous Polyposis (FAP) and Variants
(a) Classic form of FAP ( > 100 Polyp)
(b) Attenuated FAP ( < 30 polyp )
(c) Gardner syndrome
(d) Turcot syndrome
(e) MYH-associated polyposis
 Hamartomatous polyp www.pgmeeuploads.com
A. Peutz-Jeghers Syndrome
B. Juvenile Polyposis Syndrome
[ Note - Sporadic Juvenile polyps also occur in rectum ]
C. PTEN Hamartoma Tumor Syndrome
(a) Cowden syndrome
(b) Bannayan Riley-Ruvalcaba syndrome
 Serrated Polyp
Serrated Polyposis Syndrome
 Mixed Types
Hereditary Mixed Polyposis Syndrome
Familial Adenomatous Polyposis = APC gene (5q21-22)
Peutz-Jeghers Syndrome = STK11 (also known as LKB1)
Juvenile Polyposis Syndrome = SMAD4/DPC4 > BMPR1A
PTEN Hamartoma Tumor Syndrome = PTEN
Serrated Polyposis Syndrome = Yet to be established.
NOTE = Approximately 20% of patients with a SMAD4 mutation have a combined syndrome of hereditary hemorrhagic telangiectasia and Juvenile Polyposis Syndrome.
Site of Polyp in GIT
Familial Adenomatous Polyposis = Colorectal polyps > Duodenum
Peutz-Jeghers Syndrome = Small Bowel > Colon > Stomach
Juvenile Polyposis Syndrome = Rectum (Colorectum) www.pgmeeuploads.com
Cowden Syndrome = Stomach > Colon > Esophagus > Duodenum
Serrated Polyposis Syndrome = Colon
Familial Adenomatous Polyposis www.pgmeeuploads.com
 GIT = FAP is associated with an essentially 100% lifetime risk of colorectal carcinoma at an average age of 39 years. [ Highest malignant Potential among all]
 GIT = Increased GIT Carcinoma. Also Note - Colon cancers can also develop at sites without Peutz-Jeghers polyps.
 Peutz-Jeghers syndrome is associated with a markedly increased risk of several malignancies. Sex cord tumors of the testes, gastric and small intestinal cancers, colon, pancreatic, breast, lung, ovarian, and uterine cancers.
Juvenile Polyposis Syndrome = 30% to 50% of patients with juvenile polyposis develop colonic adenocarcinoma by age 45 and appears to arise in adenomatous epithelium "within" the polyps.
NOTE = Dysplasia is extremely rare in "sporadic" juvenile polyps and risk of malignant transformation is low as compared to Syndromic ones. www.pgmeeuploads.com
 Among PTEN mutation carriers 13% develop colorectal carcinoma before the age of 50. www.pgmeeuploads.com
 These patients also have an increased risk of breast cancer (25-50%), thyroid cancer (10%), and endometrial cancer (10%)
Serrated Polyposis Syndrome
 There is a 25-40% risk of colorectal carcinoma.
 No risk of extracolonic malignancy and no extracolonic manifestations
 Hyperplastic polyps histologically have a serrated “saw tooth” appearance, while grossly they tend to be small and have a “dewdrop” appearance. www.pgmeeuploads.com
 Juvenile (retention) polyps contain abundant stroma and dilated glands filled with mucus.
 Peutz-Jeghers polyps are similar to juvenile polyps, but they also contain arborising smooth muscle bundles = Arborizing polyps* www.pgmeeuploads.com
 (a) Intestinal Polyps + Multiple Osteomas = Gardner syndrome
(b) Intestinal Polyps + Multiple epidermoid cysts = Gardner syndrome
(Gardner syndrome refers to the polyposis syndrome plus other extracolonic manifestations including fibromatosis (desmoid tumors), osteomas of the skull and mandible, epidermal inclusion cysts, nasopharyngeal angiofibroma, dentigerous cysts, and abnormal dentition)
 Adenomatous polyposis and cerebellar medulloblastomas = FAP/Turcot syndrome www.pgmeeuploads.com
 Hamartomatous polyps of the GIT, mucocutaneous pigmentation, and an elevated risk for a wide variety of malignancies = Peutz-Jeghers Syndrome
 Hamartomatous polyp + Pulmonary arteriovenous malformations = JPS
 Hamartomatous polyp + trichilemmomas = Cowden Syndrome
 Lhermitte-Duclos disease is a pathognomonic feature of Cowden Syndrome and consists of mental retardation and cerebellar dysplastic gangliocytomas.
 All are Autosomal Dominant except = MYH-associated polyposis [ Autosomal Recessive ] www.pgmeeuploads.com
 Juvenile polyps are prone to self-amputation, and patients may find them floating in the toilet.
 Nonhereditary syndromic Hamartomatous polyps of stomach, small intestine, colon = Cronkhite-Canada syndrome www.pgmeeuploads.com
Some OTHER Important points about Familial Adenomatous Polyposis (FAP) www.pgmeeuploads.com
 FAP is associated with an essentially 100% lifetime risk of colorectal carcinoma at an average age of 39 years.
 By definition, the classic form of FAP has greater than 100 colonic adenomatous polyps.
 Congenital hypertrophy of the retinal pigment epithelium is present in over 90% of FAP patients; this characteristic can be used clinically as a diagnostic marker of the syndrome.
 The attenuated form of FAP (AFAP), as the name implies, is
associated with fewer polyps, averaging approximately 30 colorectal adenomas.
 The APC gene is a large tumor suppressor gene involved in the Wnt signaling pathway.
 Approximately 75% of mutations are inherited and the remaining 25% are new mutations in patients with no family history of the disease.
NOW LETS PRACTICE
Q1. A 45-year-old woman presents with 2-cm mass in the left side of his colon having an “apple core” appearance and a 2-cm mass in the right colon which histologically shows adenocarcinoma. She had undergone successful treatment for endometrial adenocarcinoma 3 years back. She has no previous history of colon polyps however several of her relatives have a history of colon cancer. Germ line mutations present in this situation is?www.pgmeeuploads.com
Ans =  MSH2
Multiple colonic adenocarcinoma + Family H/O - ie Hereditary + No Polyp + Endometrial carcinoma = Hereditary nonpolyposis colon carcinoma (HNPCC) syndrome, is characterized by an increased risk of colorectal cancer (often multiple) and is not preceded by Polyp.
Lynch syndrome type I is associated with colorectal carcinoma only (predominately of the right side)
Lynch syndrome type II is associated with extraintestinal cancer, particularly of the endometrium.
The HNPCC syndrome is associated with germ-line mutations involving any of the five genes that are involved in DNA repair, but the majority of mutations involve either the MSH2 or MLH1 genes.
Q2. The type of polyp depicted in image given below is ?www.pgmeeuploads.com
Ans = Histologic examination demonstrates a characteristic arborizing network of connective tissue, smooth muscle,lamina propria, and glands lined by normal-appearing intestinal epithelium = Arborizing polyps = “Christmas tree” appearance at low power