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.

Diagnostic variability for colorectal polyps is substantial among community pathologists.

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 .

"Other" includes diagnoses which require history or tissue surround the polyp. These include the polyps seen in:

• Cowden syndrome.
• Cronkhite-Canada syndrome.

Tabular comparison of colonic polyps

Overview in two tables

Common colonic polyps

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	colonic spirochetes, cryptosporidiosis, microscopic colitis, CMV colitis	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 (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 (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 (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 (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 (WC)

Common problems

Submucosal invasion

• This may be difficult to assess histomorphologically; these one should show a friend.

Pseudoinvasion

See pseudoinvasion in colorectal adenomatous polyps.

Early invasion

See high risk features in (colorectal) adenomatous polyps with carcinoma.

Adenomatous vs. hyperplastic

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

Attribute	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)	HP (WC)	SSA (WC)	TSA (WC)	TA (WC)

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.

Normal

Normal colorectal mucosa

General

• Endoscopists go after anything that is polypoid... and that may be normal.

Microscopic

Features:

• Test tube like glands.
• Minimal palisading.
  • Nuclei <3:1 = height:width.
• No nuclear pseudostratification. †
• Deep part of crypt is more hyperchromatic than superficial component - important.
  • The surface should be lighter staining than the deeper aspect, i.e. the deeper glands are dark blue and the superficial gland are light blue.

Note:

• † May be seen in reactive changes.

DDx (colorectal mucosa with minimal changes):

• CMV colitis.
• Cryptosporidiosis.
• Intestinal spirochetosis.
• Lymphocytic colitis.
• Collagenous colitis.

Images

• 

  Normal colon adjacent to a tubular adenoma. (WC/Nephron)

www:

• Normal colorectal mucosa (uwa.edu.au).
• Colon (siumed.edu).
• Normal colorectal mucosa (maricopa.edu).

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Normal

SIGMOID COLON, BIOPSY:
- COLORECTAL-TYPE MUCOSA WITHIN NORMAL LIMITS.

COLON, 70 CM, BIOPSY:
- COLORECTAL-TYPE MUCOSA WITHIN NORMAL LIMITS.

Mucosa and submucosa

POLYP, SIGMOID COLON, BIOPSY:
- COLONIC MUCOSA AND SUBMUCOSA WITHIN NORMAL LIMITS.

Lymphoid nodule present

POLYP, ASCENDING COLON, BIOPSY:
- COLONIC MUCOSA AND SUBMUCOSA WITHIN NORMAL LIMITS WITH A MORPHOLOGICALLY BENIGN
LYMPHOID NODULE.

Note:

• Lymphoid nodules manifest endoscopically as a small polypoid protuberances. It is worthwhile to report the presence of lymphoid nodules as they reassure the endoscopist that they probably sampled the abnormality they saw.

Suspected missed lesion

RECTOSIGMOID, BIOPSY:
- COLORECTAL-TYPE MUCOSA WITH A LYMPHOID AGGREGATE.
- NEGATIVE FOR ACTIVE COLITIS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY -- SEE COMMENT.

COMMENT:
The clinical history is noted. This biopsy does not show neoplastic tissue; however, the
biopsy may not be representative of the lesion seen.

Levels were cut and these did not yield additional information. There are no changes to
suggest a chronic colitis.

Correlation with imaging may be useful. A re-biopsy is suggested.

Fecal material

Fecal matter redirects here.

General

• Common.
• Associated with poor bowel preparation.
• Endoscopists go after anything that is polypoid and that may be nothing more than poo.

Microscopic

Features:

• Plant material:
  • Yellow staining chicken wire-like material - may be linear.
    • Thick cell walls often without cytoplasm and usually without a nucleus.
• Meat:
  • Eosinophilic honeycomb-like material without nuclei and without inflammation.
    • Essentially ischemic skeletal muscle without inflammation.
• +/-Microorganisms.
• +/-Inflammatory cells.

DDx:

• Necrosis.
  • Colorectal adenocarcinoma.

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TRANSVERSE COLON, BIOPSY:
- FECAL MATERIAL.
- NO DEFINITE COLONIC MUCOSA IDENTIFIED.

Rectum

RECTUM, BIOPSY:
- FECAL MATERIAL.
- NO DEFINITE RECTAL MUCOSA IDENTIFIED.

Hyperplastic polyp

The stomach lesion is dealt with in hyperplastic polyp of the stomach.

Main article: Hyperplastic polyp

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 - esp. neutrophils - key feature.

Negatives:

• No nuclear atypia.
  • May have focal nuclear hyperchromasia and nuclear enlargement.
• No dilated glands.

DDx:

• Juvenile polyp.
• Solitary rectal ulcer.

Images:

• Pseudopolyp (humpath.com).
• Pseudopolyp (ucsf.edu).

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SIGMOID COLON POLYP, PERI-DIVERTICULAR, BIOPSY:
- INFLAMMATORY PSEUDOPOLYP.

POLYP, DESCENDING COLON, BIOPSY:
- INFLAMED POLYPOID FRAGMENT OF COLORECTAL-TYPE MUCOSA.
-- NEGATIVE FOR DYSPLASIA.

Micro

The sections show a fragment of colorectal mucosa with focal ulceration, acute inflammation and a well-vascularized stroma with plump stromal cells. Occasional stromal cells have nuclear hyperchromasia.

Adenomatous polyps

Overview

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.
• 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), attenuated FAP, MUTYH polyposis syndrome, serrated polyposis syndrome.

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 polyp (any of the following):

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

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

Note:

• High risk polyp, as defined above, is also called advanced adenoma; however, it should be noted that there are different definitions for advanced adenoma (e.g. Winawer & Zauber include early invasive tumours). Thus, it is best to avoid the term.

Pseudoinvasion in colorectal adenomatous polyps

• AKA pseudoinvasion.

General

• Mimic of invasion.
• Pedunculated polyps.
• Left-sided lesions, esp. sigmoid colon.

Microscopic

Features - classic:

1. Dysplastic glands surrounded by lamina propria.
2. Hemosiderin.
3. Lack of desmoplastic reaction.

• +/-Cystic spaces with rounded contours without cells floating in them.

Memory device (classic features) LDH:

• Lamina propria.
• Desmoplasia lacking.
• Hemosiderin.

DDx:

• Colorectal adenocarcinoma.

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COLON POLYP, SIGMOID COLON AT 45 CM, EXCISION:
- TUBULAR ADENOMA.
-- NEGATIVE FOR HIGH-GRADE DYSPLASIA.
- SUBMUCOSA PRESENT, NO EVIDENCE OF INVASION.
- ABUNDANT HEMOSIDERIN-LADEN MACROPHAGES.

High-risk features in (colorectal) adenomatous polyps with carcinoma

Predictors of poor outcome with early submucosal invasion:

1. High tumour grade.
2. Lymphovascular invasion.
3. 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.
4. 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%.

Traditional adenoma

Includes tubular adenoma, tubulovillous adenoma, and villous adenoma.

Main article: Traditional adenoma

Traditional serrated adenoma

Main article: Traditional serrated adenoma

Sessile serrated adenoma

Main article: Sessile serrated adenoma

Malignant polyps

Colorectal adenocarcinoma

Main article: Colorectal adenocarcinoma

General

• Diagnosis may be a challenging on a small biopsy.

Clinical

Invasion can be predicted based on endoscopic findings:

• Kudo pit pattern.
• Non-lifting sign.
  • Presence predicts deeper invasion.

Microscopic

One of the two following:

1. Dysplasia and evidence of invasion - features:
   • Nuclear changes seen in adenomatous polyps - malignant-appearing cells.
     • Enlarged nuclei.
     • Chromatin hyperchromatic or vesicular.
     • Round-shape or cigar-shaped and pseudostratified.
   • Architectural changes - usually those of high-grade dysplasia:
     • Cribriforming - most common.
     • Papillary tufting.
     • Budding.
     • Sheeting.
   • Deep involvement - one of the two following - key feature:
     1. Malignant-appearing cells in the submucosa.
        • Pseudoinvasion must be excluded.
     2. Desmoplastic stromal response.
        • Spindle cells with:
          • Large nuclei (nucleus ~ size of a plasma cell).
          • Eosinophilic cytoplasm.
2. Signet ring cells.

DDx:

• Pseudoinvasion - surrounded by lamina propria, desmoplasia lacking, hemosiderin-laden macrophages.
• Reactive changes.

Note:

• Desmoplastic response is not predictive of submucosal invasion in pedunculated polyps.

Image

• 

  Colorectal carcinoma. (WC/Nephron)

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RECTOSIGMOID TUMOUR, BIOPSY:
- INVASIVE ADENOCARCINOMA, MODERATELY DIFFERENTIATED.

Micro

The sections shows colorectal-type mucosa with a tubule-forming epithelium that has cellular pseudostratification and enlarged hyperchromatic nuclei, from the crypt base to the luminal aspect (dysplasia).

There is cribriforming of glands and epithelial budding. Plump spindle cells with eosinophilic cytoplasm surround the abnormal epithelium (desmoplastic stroma). No definite submucosa is identified; the diagnosis is based on the stromal desmoplasia.

Hamartomatous polyps

Overview

There are three well known hamartomatous polyp syndromes:

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

There are two obscure hamartomatous polyp syndromes:

• Bannayan-Riley-Ruvalcaba syndrome (BRBS).
• Devon polyposis syndrome (DPS).

Notes:

• BRBS is due to a PTEN mutation (the same gene associated with Cowden's disease).
• DPS is reported in only one family that lives in Devon, UK.

Juvenile polyp

• AKA retention polyp in adults.

General

May be part of a syndrome:

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

Gross

• Mushroom-like shape.

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.
• Hyperplastic polyp of the stomach - less lamina propria, foveolar hyperplasia (long tortuous glands).
• Cronkhite-Canada syndrome - have changes in the surrounding mucosa, clinical findings (nail atrophy, skin pigment, alopecia).

Images

www:

• Juvenile polyp (nature.com).

• 

  Juvenile polyp of the stomach - very low mag. (WC/Nephron)

• 

  Juvenile polyp of the stomach - very low mag. (WC/Nephron)

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).

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RECTOSIGMOID POLYP, BIOPSY: 
- RETENTION POLYP. 

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/Nephron)

• 

  Peutz-Jeghers polyp - stomach (WC/Nephron)

www:

• Peutz-Jeghers polyp (nature.com).

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Duodenum

POLYPS, DUODENUM, EXCISION:
- PEUTZ-JEGHERS POLYPS (x2) WITH BRUNNER'S GLANDS.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Colon

 POLYP, COLON (40 CM), EXCISION:
- PEUTZ-JEGHERS POLYP.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

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. (???)

Weird stuff

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 polyps/retension polyps.
• Crypt dilation and edema in non-polypoid mucosa - key feature.

DDx:

• Juvenile polyp.

Images:

• CCS (surgicalpathologyatlas.com).

Ganglioneuroma

Main article: Ganglioneuroma

General

• May be part of MEN 2B.

Microscopic

Features - see ganglioneuroma:

• Ganglion cells - key feature.
  • Large cells with a round nucleus and a prominent nucleolus.

Images

• 

  Ganglioneuroma - intermed. mag. (WC/Nephron)

• 

  Ganglioneuroma - high mag. (WC/Nephron)

• 

  Ganglioneuroma - very high mag. (WC/Nephron)

Inflammatory myoglandular polyp

General

• Controversial - probably not a distinct pathologic entity.
• Rare, benign, non-neoplastic.
• Large bowel, usually rectosigmoid.

Microscopic

Features:

1. Granulation tissue within the lamina propria.
2. Lamina propria smooth muscle.
3. Irregular gland architecture:
   • Cystic dilatation.
   • Tortuosity.

DDx:

• Mucosal prolapse syndrome.
• Polypoid prolaping mucosal fold in diverticular disease.
• Inflammatory cloacogenic polyp.
• Inflammatory cap polyp.

Image:

• IMP (biomedcentral.com).

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.