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GIT - 7
Dr.CSBR.Prasad, M.D.,
What are the possibilities?A 59-year-old woman presented with: h/o20-year history of papules on the dorsa of the hands and
feetBenign tumor of the breast at age 16 Bone cyst of the femur at age 21Breast cancer at age 45At age 46, she developed hyperthyroidism Breast cancer in the contralateral breast at age 52 Five years later, bilateral partial nephrectomies were
performed for renal cell carcinoma
What is the abnormality?What is your suspicion?
What is the abnormality?What is your diagnosis?
What is the abnormality?What is your diagnosis?
Some questions• What is the important criterion in the definition
of adenoma in GIT?• What is a Hamartoma?• What do you understand by the term familial?• How do you define a polyp?• How a polyp is different from adenoma?• What do you understand by the terms:
– Sessile– Pedunculated
Polyps of Polyps of Small & Large intestinesSmall & Large intestines
Dr.CSBR.Prasad, M.D.,
Polyps - terms
• Sessile / Pedunculated
INFLAMMATORY POLYPS
• Example: Solitary rectal ulcer syndrome • CF: Triad
– Rectal bleeding– Mucus discharge and – Inflammatory lesion of the anterior rectal wall
• Pathology: Impaired relaxation of the anorectal sphincter
Solitary rectal ulcer syndrome
Histologic features - SRU• Mucosal prolapse and include lamina propria • Fibromuscular hyperplasia • Mixed inflammatory infiltrates • Erosion and epithelial hyperplasia
HAMARTOMATOUS POLYPS
What is hamartoma?•Jumbled mixture of tissue native to the site
HAMARTOMATOUS POLYPS
• Occurrence:– Sporadically or – As components of Syndromes
• Rare• Importance:
– Intestinal and extra-intestinal manifestations– May be present in other family members
Gastrointestinal polyposis syndromes
Juvenile Polyps
• Focal malformations of the mucosal epithelium and lamina propria
• Age: < 5 years• Types:
– Sporadic – solitary– Juvenile polyposis syndrome (> 3 polyps)
Morphology• Gross:
– <3 cm – Pedunculated– Surface ulceration– c/s cystic spaces
• Microscopy:– Dilated glands– Neutrophilic debris in the
lumen– Lamina propria –
inflammatory cells– Muscularis mucosa - normal
Juvenile Polyps
Pathogenesis:• Incompletely understood• In AD juvenile polyposis:
– TGF-β signaling pathway (50% cases) • SMAD1• BMPR1A
– Other genesImportance: Increased risk of colonic carcinoma
Peutz-Jeghers Syndrome
Dr. Johannes Peutz, 1951 Dr. Harold M Jeghers
Peutz-Jeghers Syndrome
• AD• Age of presentation: ~11yrs• Multiple polyps and mucocutaneous
hyperpigmentation • Increased risk for several malignancies
– colon, pancreas, breast, lung, ovaries, uterus, and testicles, sex cord tumors
Peutz-Jeghers SyndromeMucocutaneous hyperpigmentation
Peutz-Jeghers Syndrome
Pathogenesis:• LOH of tumor suppressor gene
LKB1/STK11 – LKB1/STK11 is a kinase that regulates cell
polarization, growth, and metabolism • Polyps in PJ syndrome:
– Are not premalignant – Adenocarcinomas arise independently
Peutz-Jeghers Syndrome
• Barium enema radiograph showing multiple polyps (mostly pedunculated) and at least one large mass at the hepatic flexure coated with contrast in a patient with Peutz–Jeghers syndrome.
Polyps are large and pedunculated with a lobulated
contour
Morphology
• Hamartomatous polyp• Arborizing network of
connective tissue, smooth muscle, lamina propria
• Glands lined by normal-appearing intestinal epithelium
DD - Polyps of PJ syndrome from Juvenile polyps
• The arborization and presence of smooth muscle intermixed with lamina propria are helpful in distinguishing polyps of Peutz-Jeghers syndrome from juvenile polyps
Peutz-Jeghers Syndrome
Diagnosis:– Multiple polyps in the small intestine– Mucocutaneous hyperpigmentation &– Positive family history– Detection of LKB1/STK11 mutations
Surveillance: – There is increased risk of cancer– Routine surveillance of the GI tract, pelvis, and
gonads is recommended
Peutz-Jeghers Syndrome
Because of the increased risk of cancer, routine surveillance of the GI tract, pelvis,
and gonads is typically recommended
Cowden Syndrome • AD• Hamartomatous polyps• Loss-of-function mutations in PTEN • Characterized by:
– Macrocephaly– Intestinal hamartomatous polyps– Benign skin tumors
• Increased risk of GI malignancy• Other cancers:
– Breast carcinoma– Follicular carcinoma of the thyroid and – Endometrial carcinoma
Cowden Syndrome
HYPERPLASTIC POLYPS
• Sixth and seventh decades • Result from decreased epithelial cell
turnover and delayed shedding of surface epithelial cells
• No malignant potential • Importance: they must be distinguished
from sessile serrated adenomas, histologically similar lesions that have malignant potential
HYPERPLASTIC POLYPS
Morphology:•Commonly found in the left colon •< 5 mm in diameter •Smooth, nodular protrusions of the mucosa •Multiple (more frequently)•Serrated surface architecture
Hyperplastic polyp • A: Polyp surface with
irregular tufting of epithelial cells
• B: Tufting results from epithelial overcrowding
• C: Epithelial crowding produces a serrated architecture when glands are cut in cross-section
NEOPLASTIC POLYPS
NEOPLASTIC POLYPSColonic adenomas:• Characterized by the presence of epithelial dysplasia• Importance: precursors to colorectal adenocarcinomas• Small, pedunculated polyps / large sessile lesions
• Clinical Features: – Most adenomas are clinically silent– Large polyps may produce occult bleeding and anemia – Villous adenomas that cause hypoproteinemic
hypokalemia
Adenoma - Morphology
Gross:•Size: 0.3 to 10 cm in diameter •Pedunculated or Sessile •Velvetty surfaceHistology:•Dysplasia (Hyperchromatic nuclei, stratification, large nucleoli, reduced number of goblet cells)
• Adenomas can be classified as: (Architectural) – Tubular– Villous or– Tubulovillous
Tubular adenomas• Small• Pedunculated polyps • Histology: composed of small rounded,
or tubular, glands
Tubular adenomas
Pedunculated adenoma
Tubular adenoma
Tubular adenoma
Villous adenomas• Often larger• Sessile• Covered by slender villi
Villous adenomas
Surface of villous adenomaSurface of villous adenoma
Villous adenomas
Villous adenomas
Adenoma with intramucosal carcinoma
Tubulovillous adenomas
• They have a mixture of tubular and villous elements
Tubulovillous polyp
Tubulovillous polyp
Villous adenomas with adenocarcinomaNote: Villous architecture alone does not increase cancer
risk when polyp size is considered
Sessile serrated adenomas
• Overlap histologically with hyperplastic polyps• More commonly found in the right colon• High malignant potential• They lack features of dysplasia• Histology:
– Serrated architecture throughout the full length of the glands
– Lateral growth and crypt dilation – DD: Hyperplastic polyp: Serrated architecture is
typically confined to the surface
Sessile serrated adenomas
Sessile serrated adenomas
Tubular, Villous & Serrated adenomas
Adenomas - Risk of malignancy
• Most colorectal adenomas are benign• Risk factors for malignancy:
– Number of adenomas– Size is the most important characteristic that
correlates with risk of malignancy• Adenomas <1 cm in diameter – BENIGN• Adenomas > 4 cm in diameter – May contain Malignancy
– High-grade dysplasia increases the risk in that polyp
Familial Polyposis SyndromesFamilial Polyposis Syndromes
Familial Syndromes
Several syndromes characterized by the presence of colonic polyps and increased rates of colon cancer
Familial SyndromesThe genetic basis of these disorders has been established
FAMILIAL ADENOMATOUS POLYPOSISFAMILIAL ADENOMATOUS POLYPOSIS
• AD• Manifests in teenage• Numerous colonic polyps
– At least 100 polyps are necessary for a diagnosis of classic FAP
• Polyps are morphologically similar to sporadic adenomas
Familial adenomatous polyposis
Importance: if untreated– Colorectal adenocarcinoma - 100% – Often before age 30yrs
Note: Prophylactic colectomy is the standard therapy for individuals carrying APC mutations
Colectomy and Malignancy
• Colectomy prevents colorectal cancer• Risk for neoplasia at other sites remains
unchanged– Eg: Adenomas may develop elsewhere in the
GI tract, particularly adjacent to the ampulla of Vater and in the stomach
Variants of FAP
• Specific APC mutations have been associated with the development of other manifestations of FAP – Gardner syndrome – Turcot syndrome
Gardner’s syndrome
Turcot’s syndrome
HEREDITARY NON-POLYPOSIS COLORECTAL CANCER - HNPCC
• Synonym: Lynch syndrome• Familial clustering of cancers at several sites:
– Colorectum (at younger ages)– Stomach– Small bowel– Hepatobiliary tract– Endometrium– Ovary– Ureters – Brain and – Skin
HEREDITARY NON-POLYPOSIS COLORECTAL CANCER - HNPCC
Genetic defect:•Defective DNA mismatch repair genes•There are five such mismatch repair genes
– Majority of HNPCC cases involve MSH2 and MLH1
Causes for Lower GI bleedingCauses for Lower GI bleeding
Approach to hematochezia
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