Gastrointestinal tract polyps

Intestinal polyps are often the bread & butter of a GI pathologists workload. Some of 'em are benign... some pre-malignant... some malignant... some weird.

Overview - there are four basic types:

• Hyperplastic - harmless, most common - 90% of all colonic polyps.
• Hamartomatous - weriod stuff, syndromic things.
• Inflammatory - think inflammatory bowel disease, aka pseudopolyps.
• Adenomatous - premalignant, several types (see below).

Mnemonic: HHI-A.

Basic approach

1. Sessile (flat) or polypoid (spherical, possibly has a stalk)?
2. Nuclear features of adenoma & loss of goblets (hyperchromatic nuclei, nuclei round vs. flat, loss of nuclear stratification)?
3. Inflammation?
4. Serrated architecture?

Decision tree for colorectal polyps

Decision tree - colorectal polyps

colorectal p.

polypoid

sessile

nuclear features

no nuc. change

serrated

not serrated

polypoid a.

serrated

not serrated

SSA

normal

HP

misc.

Decision tree - polypoid adenoma

polypoid adenoma

serrated

non-serrated

TSA

tubular arch.

tubulovillous arch.

villous arch.

TA

TVA

VA

Notes:

• TA, tubular component >75%.
• VA, villous component >50%.

Decision tree - miscellaneous polyps

misc. polyps

inflam.

no inflam.

benign

inflam. p.

hamart.

benign

PJP

juvenile

other

Hamartomatous polyps - basic DDx:

• Juvenile polyp/Retention polyp -- DIES (dilated glands, incr. LP, eroded surface, stalk).
• Peutz-Jeghers polyp - frond-like with all mucosa components .

Tabular comparison

Adenomatous polyps & hyperplastic polyps - a comparison (adapted from Li and Burgart):

	Hyperplastic polyp (HPP)	Sessile serrated adenoma (SSA)	Traditional serrated adenoma (TSA)	Traditional adenoma -tubular adenoma -tubulovillous adenoma -villous adenoma
Classic location	rectum/left colon	right colon	rectum/left colon	rectum/left colon
Morphology	polypoid	flat (sessile)	polypoid	polypoid
Cytologic atypia -cigar nuclei -hyperchromasia -nuclear crowding	absent	absent	present	present
Location of worst atypia	-	-	basal	luminal
Cytoplasm	eosinophilic	prominent eosinophilia	eosinophilic	basophilic
Goblet cells	abundant	common	less common	less common
Luminal Serration	present	common	present	absent
SSA architecture -Basal crypt serration -Basal crypt dilation -Horizonatal crypts -Branched crypts	absent	present	absent	absent
Key feature(s)	serrated luminal surf. & goblets	abnorm. crypt arch. & sessile	nuclear atypia & serrated	nuclear atypia

Normal colonic mucosa:

• Nuclei - round and basally located.
• Abundant goblet cells.
• Moderate inflammation.
• Paneth cells - present in right colon.
• Glands - straight, no branching; "test tube" shape.

Notes: Left colon refers to the sigmoid colon, descending colon and the distal half of the transverse colon; right colon refers to the cecum, ascending colon and proximal half of the transverse colon.

Hyperplastic polyp

• Most common colonic polyp (90% of all colonic polyps).

Microscopy

Features:

• Irregular crypt architecture - tortuosity.
• Serrated epithelial cells (at the surface of the gland).
  • Serrated appearance = saw-tooth appearance, epithelium has jagged edge.
• Significant negatives:
  • No nuclear atypia.
  • Goblet cells should be present (as is usual in the colon).

Images:

• HP - high mag. - wikimedia.org.
• HP - lower mag. - wikimedia.org.

Adenomatous polys

Several types of adenomatous polyps are recognized.

• Traditional adenomas (have three subtypes):
  1. Tubular adenoma - most common, lowest malignant potential.
  2. Tubulovillous adenoma.
  3. Villous adenoma - highest malignant potential.
• Sessile serrated adenomas:
  • New kid on the block, some people doubt their existance.
• Traditional serrated adenomas - nuclear features of 'traditional adenoma' + serrated architecture.

They are all considered pre-malignant, i.e. if you leave 'em in place they often develop into cancer.

Management of polyps

Follow-up interval for polyps (colonoscopy interval):

• Normal follow-up (includes presence of hyperplastic polyps): ~10 years.
• 1-2 low risk (adenomatous) polyps: 5-10 years.
• 3-10 low risk polyps or a high risk polyp: 3 years.
• >10 low risk polyps: <3 years.
• Inadequately removed polyps: <6 months.

Classified as high risk (any of the following):

• Tubulovillous.
• Villous.
• High grade dysplasia.
• Size >= 1 cm.

Mnemonic: GAS = grade (high), architecture (tubulovillous, villous), size (>1 cm).

Traditional adenoma

Microscopic

• Nuclear changes (key feature)
  • Loss of nuclear polarity (nuclei no longer on basement membrane)
  • Nuclear crowding/pseudostratification (key feature)
  • hyperchromasia
  • Cigar-shaped (elongated) nucleus - length:width > 3:1 (key feature)
    • Normal nuclei are round
• Loss/decrease of goblet cells
• Cytoplasmic hyperchromasia

Typing

Subclassified as:

• Tubular (most common), tubular component >75%.
• Villous (least common ~= 1% of (traditional) adenomas), villous component >50%.
• Tubulovillous (uncommon ~5-10% of (traditional) adenomas), villous component >=25% & <=50%.

In other words:

• Tubular T/V >75% / <25%; Tubulovillous T/V <=75%-50% / 25%-<50%; Villous T/V <=50% / >50%.

Notes:

• Most villous adenomas are sessile, i.e. flat.
• Tubular adenomas tend to be pedunculated, i.e. have a stalk.
• Villous adenomas have a worse prognosis and warrant closer follow-up.
• One needs only to remember the criteria for tubular adenomas and villous adenomas, as tubulovillous adenomas are what is left over.
  • Tubular adenomas >75% tubular, Villous adenoma >=50% villous.
• There are different definitions for tubular adenoma, tubulovillous adenoma, and villous adenomas.
  • Health Organization (WHO) criteria: villous adenomas >80% villous architecture.

Grading

Most institutions grade adenomas into:

• Low grade.
  • Near normal glandular architecture.
  • Goblet cells present.
• High grade.
  • Have "architectural complexity", i.e. cribriform glands, branching glands.
  • Lamina propria invasion.
  • Sheets of cells -- no longer resemble glands.

NOTE: In the colon, unlike other areas of the GI tract, invasive carcinoma is defined by neoplastic cells through the muscularis mucosae. In all other places, e.g. small bowel, invasive carcinoma is defined by neoplastic cells through the basement membrane.

Micrograph:

• Tubular adenoma negative for high grade dysplasia - high mag. - wikimedia.org.

Margins

• Some pathologists believe it is impossible to determine margins in polypectomies.
• Others comment on what they see and then disclaim based on limitations with something like "... margin clear in plane of section."

The Haggitt classification is margin call taken to the extreme. Surgeons may ask about it 'cause a guy (who probably didn't do a lot of pathology) put it in a widely read surgery textbook. In short:

• 0 - intramucosal carcinoma
• 1 - in submucosa but in head of polyp
• 2 - neck of polyp
• 3 - stalk of polyp
• 4 - submucosa of the bowel wall but above muscularis propria

It is a little scheme that is mostly useless. In the real world surgical pathology most polyps do not have a discernable neck or stalk.

Note:

• Dr. Haggitt is know for his tragic demise. He was shot by a resident that was about to be fired.

Sessile serrated adenomas

General

• More common in the right colon, i.e. ascending colon.

Epidemiology

• Thought to lead to colorectal cancer through a different pathway that most tumours in the left colon/rectum.

Microscopic

• Serrated.
• Crypt dilation at base - a key feature - very common.
  • "Boot"-shape or "L"-shaped glands.
• Crypt branching.
• Horizontal crypts (crypts that run along the muscular mucosae).

Notes:

• Typically do not have nuclear atypia, i.e. no nuclear crowding, no nuclear hyperchromasia, no cigar-shaped nuclei.

Micrographs:

• SSA - low mag. (wikimedia.org).
• SSA - intermed. mag. (wikimedia.org).
• SSA - high mag. (wikimedia.org).

Hamartomatous polyps

Numerous types of hamartomatous polyps exist:

• Peutz-Jeghers syndrome.
• Juvenile polyposis syndrome.
• Cowden's disease.

There are several obscure/very rare types not listed above.

Further reading: Gastrointestinal & Liver Pathology

Juvenile polyp

General

• Referred to retension polyps in non-juveniles.

Microscopic

Features:

• Eroded, smooth or lobulated surface.
• Pedunculated.
• Increased lamina propria (LP) +/- edema.
• Cystically dilated gland.
• Often inflammed.

Mnemonic DIES = dilated glands, increased LP, eroded/smooth surface, stalk.

Notes:

• Nuclear changes may be like those seen in adenomatous polyps.
• IHC can be used as an adjunct (p53, Ki67).
  • p53 mutations in dysplastic epithelium -- negative stain (normal).

Peutz-Jeghers polyp

Clinical/Epidemiology

Features:

• Peutz-Jeghers syndrome is autosomal dominant.
• Altered gene: STK11.

Microscopy

Features:

• Frond-like polyp with all three components of mucosa:
  1. Muscosal epithelium (melanotic mucosa, goblet cells).
  2. Lamina propria.
  3. M. mucosae.

Image:

• Peutz-Jeghers syndrome polyp (WC).

Cowden disease

Features:

• Hamartomatous polyps
• Facial trichilemmomas (hair follicle root sheath epithelium tumour),
• Oral papillomas,
• Acral keratoses (peripheral keratoses).

Etiology

• PTEN gene mutation.

Cronkhite-Canada syndrome

Features:

• Hamartomatous polyps,
• Ectodermal abnormalities (nail atrophy, skin pigment, alopecia).

See also

• Gastrointestinal pathology.
• Stomach.
• Small bowel.
• Colon.