Gastrointestinal tract polyps

Gastrointestinal tract polyps, also gastrointestinal polyps or GI polyps, are the bread & butter of a GI pathologists workload. Some of 'em are benign... some pre-malignant... some malignant... some weird. Most GI polyps are from the intestine, i.e. intestinal polyps.

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?

A set of decision trees for GI polyps

Decision tree - GI polyps

GI polyp

Polypoid (Lollipop-like)

Sessile (flat)

Nuclear changes

No nuc. change

Serrated

Not serrated

Polypoid adenoma (below)

Serrated

Not serrated

SSA vs. HP

Normal vs. VA

HP

See misc. polyps (below)

Notes:

• Polypoid:
  • Stalk visible (lollipop handle visible) or epithelial surface on three sides (or more).
• Sessile (flat):
  • "Line of muscularis mucosa" visible +/- test tube-like intestinal crypts.
• Nuclear changes:
  • Nuclear enlargement (elongation), crowding/pseudostratification, hyperchromasia (more blue) - especially at the surface, i.e. adjacent to the lumen (as opposed to the base of the crypt).

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

Notes:

• Juvenile polyps may have marked inflammation.

Hamartomatous polyps - basic DDx:

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

Tabular comparison of colonic polyps

Overview in two tables

Common

Type	Key feature(s)	Details	Prevalence / prognosis	Other	DDx	Image
Normal mucosa / no pathology	test tubes in a rack-like morphology	small nuclei, abundant goblet cells	common / benign	moderate inflammation is normal	microscopic colitis, colonic spirochetes, microsporidiosis	Normal - low mag. (ohio-state.edu)
Hyperplastic polyp	serrated at the surface	abundant goblet cells, usu. left colon; no features of SSA	common / benign	may be syndromic, e.g. hyperplastic polyposis syndrome	sessile serrated adenoma	HP (WC)
Traditional adenoma	nuclear hyperchromasia & pseudostratification / crowding at the luminal aspect	decreased goblet cells, usu. polypoid - on a stalk, usu. left colon	common / premalignant	tubular adenoma, tubulovillous adenoma, villous adenoma	traditional serrated adenoma, reactive changes (inflammation)	TA - high mag. (WC), TA - low mag. (WC)

Less common

Type	Key feature(s)	Details	Prevalence / prognosis	Other	DDx	Image
Sessile serrated adenoma (SSA)	basal crypt dilation & serration	boot-shaped crypts, horizontal crypts, branching crypts	uncommon / pre-malignant	AKA sessile serrated polyp	hyperplastic polyp	SSA - low mag. (WC)
Traditional serrated adenoma (TSA)	nuclear hyperchromasia & pseudostratification / crowding at the surface, serrated, villous-like architecture	decreased goblet cells	very rare / premalignant	called "traditional" to differentiate from SSA	traditional serrated adenoma (esp. villous adenoma)	TSA - low mag. (WC), TSA - high mag. (WC)
Juvenile polyp (retention polyp)	dilated glands, increased lamina propria	eroded surface (due to trauma), stalk (polypoid), inflammation - common	uncommon / benign if in isolation	may be part of juvenile polyposis syndrome	inflammatory pseudopolyp	Gastric JP - low mag. (WC)
Inflammatory pseudopolyp	inflammation, erosion/ulceration adjacent to polyp	loss of mucosa adjacent to pseudopolyp	uncommon / seen in IBD, increased risk of malignancy	only seen in IBD; Dx implies IBD	juvenile polyp	Image
Peutz-Jeghers polyp (PJP)	branching smooth muscle	tree-like growth pattern	very rare / syndromic; assoc. with cancer	PJP not pre-malignant lesion in itself; see Peutz-Jeghers syndrome	normal, classically in the small bowel	PJP - low mag. (WC)

Common problems

Submucosal invasion

• This may be difficult to assess histomorphologically.

Poor outcome predictors

Predictors of poor outcome with early submucosal invasion:

1. Lymphovascular invasion.
2. High-grade tumour budding.
   • Tumour bud = 1-4 cell(s); "high-grade budding" is >=10 tumour buds in a field of 0.385 mm².
     • If the microscope has a 22 mm eye piece and...
       • A 20x objective, the field is approximately 0.950 mm² -- to match the area/bud -- it would be 24.68 buds/0.950 mm².
       • A 40x objective, the field is approximately 0.238 mm² -- to match the area/bud -- it would be 6.17 buds/0.238 mm².
3. Extensive submucosal invasion.
   • >= 4 mm width or >= 2 mm depth.

If none of the above factors is present the risk of lymph node metastasis is < 1%. The presence of one risk factor increases the risk to ~20%. If multiple risk factors are present the chance of lymph node metastases is greater than 35%.

Adenomatous vs. hyperplastic

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

	Hyperplastic polyp (HP)	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 (luminal)
Image(s)	low mag.	low mag, low mag.	low mag, very high mag.	low mag., high mag.

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

General

• Most common type of polyp:
  • Approximately 90% of all colonic polyps.
  • Most common type of gastric polyp.
• May be part of hyperplastic polyposis syndrome.

Microscopic

Features:

• Irregular crypt architecture - tortuosity.
• Serrated epithelial cells (at the surface of the gland) - only colorectal polyps - key feature.
  • Serrated appearance = saw-tooth appearance, epithelium has jagged edge.

Notes:

• Significant negatives:
  • No nuclear atypia.
  • In the colon goblet cells should be present (as is usual).

DDx:

• Sessile serrated adenoma.

Images:

• HP - high mag. (WC).
• HP - lower mag. (WC).

Subclassification

• Usually not subclassified as there is no demonstrated prognostic significance; the subtyping is an academic exercise.

HPs may be subclassified into two groups:

1. Microvesicular serrated polyps (MVSPs).
2. Goblet cell serrated polyps (GCSPs).

Features of the HP subtypes:

Subtype	Histology	Mutations	Clinical relevance
Microvesicular	microvesicles at the surface, serration at the surface to the mid portion of glands	BRAF V600E, CIMP	possible sessile serrated adenoma precursor
Goblet cell	superficial goblet cells, serration at the surface	KRAS	unknown; probably benign

Notes:

• CIMP = CpG island methylation phenotype.

Inflammatory pseudopolyp

• AKA inflammatory polyp.

General

• Not a true polyp.
• The label inflammatory pseudopolyp = inflammatory bowel disease (IBD).
  • If there is no history of IBD... reconsider the diagnosis.

Microscopic

Features:

• Polypoid shape.
• Inflammation - key feature.

Negatives:

• No nuclear atypia.
• No dilated glands.

DDx:

• Juvenile polyp.
• Solitary rectal ulcer.

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.

Notes:

• They are all considered pre-malignant, i.e. if you leave 'em in place they often develop into cancer.
• If multiple... think about familial adenomatous polyposis (FAP).

Management of (adenomatous colonic) 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

General

• Most common group of adenomas in GI tract - includes tubular adenoma, tubulovillous adenoma, and villous adenoma.

Microscopic

1. Nuclear changes at the surface (of the mucosa) - key feature.
   • Cigar-shaped (elongated) nucleus (usu. length:width > 3:1) - key feature.
     • Normal nuclei are round.
   • Nuclear crowding/pseudostratification - key feature.
   • Nuclear hyperchromasia (more blue).
   • +/-Loss of nuclear polarity (nuclei no longer on basement membrane).
2. Loss/decrease of goblet cells (common).
3. Cytoplasmic hyperchromasia.

Notes:

• Nuclear changes deep to the surface are non-neoplastic if normal appearing mucosa (with small round nuclei) is superficial to it; mucosa that is more blue and atypical deep and less blue without nuclear atypia at the surface is said to be "maturing".
  • Classically, adenomatous polyps have "reverse maturation":
    • The surface is more hyperchromatic (more blue).
    • The base is more mature (more globlet cells, no nuclear changes -- less blue).

Images:

• Small tubular adenoma - high mag. (WC).
• Tubular adenoma - intermed. mag. (WC).
• Tubulovillous adenoma (WC).

Typing

Subclassified as:

• Tubular adenoma (most common), tubular component >75%.
• Villous adenoma (least common ~= 1% of (traditional) adenomas), villous component >50%.
• Tubulovillous adenoma (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%.

Note 1:

• 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.
• Historically, there were different definitions for tubular adenoma, tubulovillous adenoma, and villous adenomas.
  • Health Organization (WHO) criteria: villous adenomas >80% villous architecture.

Note 2:

• There is no formal definition of "villous" architecture.
  • VL suggests: slender finger-like projections with length-to-width ratio greater than 4.

Note 3:

• The term tubular adenoma is used in different contexts; it should not be confused with Sertoli cell nodule (AKA testicular tubular adenoma).

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 discernible neck or stalk.

Note:

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

Traditional serrated adenoma

General

• Very rare.

Microscopic

Features:

• Serrated.
• Nuclear atypia (as in tubular adenoma).
• Villous architecture.

DDx:

• Villous adenoma.

Images:

• TSA - low mag. (WC).
• TSA - intermed. mag. (WC).
• TSA - very high mag. (WC).

Sessile serrated adenoma

• Often abbreviated SSA.
• AKA sessile serrated polyp.

General

• Colonic lesion.
• 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

Features:

• 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. (WC).
• SSA - intermed. mag. (WC).
• SSA - high mag. (WC).

Hamartomatous polyps

Overview

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

• AKA retension polyp in adults.

General

May be part of a syndrome:

• Juvenile polyposis syndrome (JPS) - see JPS article for criteria.
• Cronkhite-Canada syndrome.
• Cowden syndrome.

Microscopic

Features:

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

Mnemonic DIES = dilated glands, increased LP & inflammation of the LP, eroded/smooth surface, stalk.

Notes:

• May have nuclear changes like those seen in adenomatous polyps.

DDx:

• Inflammatory polyp.

Images:

• Juvenile polyp (nature.com).
• Juvenile polyp of the stomach - very low mag. (WC)
• Juvenile polyp of the stomach - very low mag. (WC).

IHC

• Usually none.

Notes:

• IHC can be used if it is suspected to have dysplasia (p53, Ki-67).
  • p53 mutations in dysplastic epithelium -- negative stain (normal).

Peutz-Jeghers polyp

General

Epidemiology

Features:

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

Clinical

Features:

• Melanocytic macules.
  • Lips, buccal mucosa, and digits.
  • Multiple Peutz-Jeghers polyps.

Increased risk of various neoplasms - primarily:

• Breast and gastrointestinal cancer.
• Others tumours:
  • Granulosa cell tumour.
  • Sertoli cell tumour - esp. with calcification.

Microscopic

Features:

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

Notes:

• Frond = leaflike expansion.
  • The key is "thick" smooth muscle bundles - if one is lucky one sees branching.
    • "Thick" ~= thickness of muscularis mucosae.

Images:

• Peutz-Jeghers polyp - intestine (WC).
• Peutz-Jeghers polyp - stomach (WC).
• Peutz-Jeghers polyp (nature.com).

Cowden disease

Main article: Cowden syndrome

• AKA Cowden syndrome.

General

Etiology:

• PTEN gene mutation.

Clinical features:

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

Note:

• Lame mnemonic PATH: Papilloma (oral), Acral keratosis, Trichilemmoma, Hamartomatous polyps.

Microscopic

Features:

• Hamartomatous polyp - features non-specific. (???)

Cronkhite-Canada syndrome

• Abbreviated CCS.

General

Clinical features:

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

Microscopic

Features:

• Polyps have same morphology as juvenile polyp/retension polyp.
• Crypt dilation and edema in non-polypoid mucosa - key feature.

See also

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

External links

• Serrated polyps quiz (unibas.ch) - nice quiz... though it is annoying that one has to click on the images to enlarge 'em.