git 7-csbrp

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

E N D