Serdar Balcı

Tumors of Lower GI Tract

Serdar BALCI, MD


Those without stalks are referred to as sessile

As sessile polyps enlarge, proliferation of cells adjacent to the polyp and the effects of traction on the luminal protrusion, may combine to create a stalk

Polyps with stalks are termed pedunculated

Inflammatory Polyps

Robbins and Cotran Pathologic Basis of Disease

Hamartomatous Polyps

Occur sporadically

Components of various genetically determined or acquired syndromes

Robbins Basic Pathology

Juvenile Polyps

Pedunculated, smooth-surfaced, reddish lesions

<3 cm

Cystic spaces on cut sections

Dilated glands filled with mucin and inflammatory debris

Robbins Basic Pathology

Peutz-Jeghers Syndrome

Rare autosomal dominant disorder

Presence of multiple gastrointestinal hamartomatous polyps and mucocutaneous hyperpigmentation

Increased risk of several malignancies, colon, pancreas, breast, lung, ovaries, uterus, and testes

Germ line heterozygous loss-of-function mutations in the gene LKB1/STK11 are present in approximately half of the patients with the familial and subset of sporadic form

Intestinal polyps are most common in the small intestine, may also occur in the stomach and colon, rarely, in the bladder and lungs

Large and pedunculated

Lobulated contour

Arborizing network of connective tissue, smooth muscle, lamina propria, and glands lined by normal-appearing intestinal epithelium

Peutz-Jeghers polyp. Complex glandular architecture and bundles of smooth muscle help to distinguish Peutz-Jeghers polyps from juvenile polyps.

Robbins Basic Pathology

Hyperplastic Polyps

Common epithelial proliferations

Sixth and seventh decades of life

Decreased epithelial cell turnover and delayed shedding of surface epithelial cells, leading to a “pileup” of goblet cells

No malignant potential, must be distinguished from sessile serrated adenomas

Most commonly found in the left colon

Less than 5 mm in diameter

Smooth, nodular protrusions of the mucosa

Frequently multiple, in the sigmoid colon and rectum

Robbins Basic Pathology

Polyp surface with irregular tufting of epithelial cells

Robbins Basic Pathology

Robbins Basic Pathology

Tufting results from epithelial overcrowding

Epithelial crowding produces a serrated architecture when glands are cut in cross-section

Robbins Basic Pathology


Neoplastic mass lesion in the GI tract

Produce a mucosal protrusion, or polyp

Robbins Basic Pathology

Epithelial dysplasia

Small, often pedunculated polyps to large sessile lesions

No gender predilection

50% of adults living in the Western world beginning age 50

Precursors to colorectal cancer

Surveillance colonoscopy

fibromuscular stalk

Robbins and Cotran Pathologic Basis of Disease

Tubular adenoma with a smooth surface and rounded glands

Robbins Basic Pathology

Villous adenoma with long, slender projections that are reminiscent of small intestinal villi

Robbins Basic Pathology

The cytologic hallmark of epithelial dysplasia is nuclear hyperchromasia, elongation, and stratification

Changes are most easily appreciated at the surface of the adenoma, because the epithelium fails to mature as cells migrate out of the crypt

Robbins Basic Pathology

Sessile serrated adenoma

Lined by goblet cells without typical cytologic features of dysplasia. This lesion is distinguished from a hyperplastic polyp by involvement of the crypts

Most common in the right colon

Have a malignant potential similar to that of traditional adenomas

Robbins Basic Pathology

Robbins Basic Pathology

Robbins Basic Pathology

Robbins Basic Pathology

Familial Adenomatous Polyps

Autosomal dominant disorder

Numerous colorectal adenomas by the teenage years

Mutations of the adenomatous polyposis coli gene ( APC )

>100 polyps is necessary for a diagnosis of classic FAP, and as many as several thousand may be present

Robbins Basic Pathology

Robbins Basic Pathology

Except for their remarkable numbers, these growths are morphologically indistinguishable from sporadic adenomas

Colorectal adenocarcinoma develops in 100% of patients with untreated FAP, often before age 30

Prophylactic colectomy

Neoplasia at other sites

Hereditary Nonpolyposis Colorectal Cancer

Adenocarcinoma of Colon

The APC/β-catenin pathway

The classic adenoma-carcinoma sequence

80% of sporadic colon tumors

Involves mutation of the APC tumor suppressor early in the neoplastic process

Both copies of the APC gene must be functionally inactivated, either by mutation or epigenetic events, for adenomas to develop

No APC is present

β-Catenin is active independent of WNT status

WNT signal inhibits APC

β-Catenin enters nucleus

APC is active

β-Catenin is dectructed

Robbins Basic Pathology

β-Catenin is active in the nucleus

cyclin D1 and MYC transcribed for proliferation

TWIST and SLUG are expressed

They repress E-cadherin expression

Reduce contact inhibition

Robbins Basic Pathology

TP53 ?? 70% to 80% of colon cancers but is uncommonly affected in adenomas


10% in <1cm

50% >1cm

50% in adenocarcinoma

**SMAD2 and SMAD4, which are effectors of TGF-β signaling, normally inhibits cell cycle **

Loss of function TP53 and others caused by chromosomal deletions, chromosomal instability in this pathway


Robbins Basic Pathology

The microsatellite instability pathway

DNA mismatch repair deficiency

Due to loss of mismatch repair genes

Mutations in the oncogene BRAF and silencing of distinct groups of genes due to CpG island hypermethylation also are common in cancers that develop through DNA mismatch repair defects.

KRAS and TP53 typically are not mutated.

Robbins Basic Pathology

Adenocarcinoma distribution

Robbins Basic Pathology

Robbins Basic Pathology

A: Well-differentiated adenocarcinoma. Note the elongated, hyperchromatic nuclei. Necrotic debris, present in the gland lumen, is typical.

Robbins Basic Pathology

Poorly differentiated adenocarcinoma forms a few glands but is largely composed of infiltrating nests of tumor cells.

Robbins Basic Pathology

Mucinous adenocarcinoma with signet ring cells and extracellular mucin pools

Poor prognosis

Robbins Basic Pathology

Lymph node metastasis

Glandular structures within the subcapsular sinus.

Robbins Basic Pathology

B: Solitary subpleural nodule of colorectal carcinoma metastatic to the lung.

Robbins Basic Pathology

C: Liver containing two large and many smaller metastases. Note the central necrosis within metastases.

Robbins Basic Pathology

Robbins Basic Pathology

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Tumors of the Appendix