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 - 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; 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)	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.

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 colorectal mucosa (uwa.edu.au).
• Colon (siumed.edu).
• Normal colon adjacent to a tubular adenoma (WC).
• Normal colorectal mucosa (maricopa.edu).

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Normal

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.

• Abbreviated HP.

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.

Gross

Features:

• Flat lesion, usually <= 5mm.
• Typically in the distal large bowel (rectum, sigmoid colon).

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; glands darker staining deep... lighter staining luminal.
  • In the colon goblet cells should be present (as is usual).
• Inflammation -- cryptitis or even crypt abscesses -- is considered to arise due to trauma.^{[citation needed]}
  • It is usually not reported.

DDx:

• Sessile serrated adenoma.
• Normal colon.

Images:

• WC:
  • HP - high mag. (WC).
  • HP - lower mag. (WC).
• www:
  • Microvesicular HP (flickr.com/jhetzel).
  • HP of colon (flickr.com/jian-hua_qiao_md).

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.

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COLONIC POLYP, 35 CM, BIOPSY: 
- HYPERPLASTIC POLYP.

COLONIC POLYP, SIGMOID COLON, BIOPSY: 
- HYPERPLASTIC POLYP.

POLYP, RECTUM, BIOPSY: 
- HYPERPLASTIC POLYP.

Numerous hyperplastic polyps

COLONIC POLYP(S), BIOPSY: 
- HYPERPLASTIC POLYP, SEE COMMENT.  

COMMENT: 
Eight pieces of tissue were received.  On microscopy eight pieces of tissue 
are identified and all eight (individually) have the diagnostic features of a
hyperplastic polyp.  If these fragments all represent individual polyps and more
polyps of this type are present in the individual, it raises the possibility of 
a serrated polyposis syndrome.

Micro

Goblet cell type

The sections show colonic-type mucosa with superficial serrations rich in goblet cells. There are no serrations in the crypt base and there is no crypt base dilation. No dysplasia is present.

Generic

The sections show colonic-type mucosa with superficial serrations. There are no serrations in the crypt base and there is no crypt base dilation. No dysplasia is present.

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.

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.

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.

General

• Most common group of adenomas in gastrointestinal tract.
• Usually arise in the context of an APC mutation.
• Many are seen in the context of familial adenomatous polyposis.

Microscopic

1. Nuclear changes at the surface of the mucosa - key feature.
   • Size and shape or size change:
     • Cigar-shaped (elongated) nucleus (usu. length:width > 3:1) with nuclear hyperchromasia (more blue).
     • Large round nuclei +/- vesicular appearance (clearing) -- nuclei have white space.
   • Nuclear crowding/pseudostratification - important.
   • +/-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).
• Ampullary adenomas often have less prominent pseudostratification and fine chromatin.

Images

• 

  Small tubular adenoma - high mag. (WC/Nephron).

• 

  Tubular adenoma - intermed. mag. (WC/Nephron).

• 

  Tubulovillous adenoma (WC/Nephron).

www:

• TA (flickr.com).
• TA with HGD (flickr.com).
• TA with HGD (daveproject.org).

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.
  • Onlinepathology 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

Adenomas are usually graded with a two-tier system:

Feature	Low grade dysplasia (LGD)	High grade dysplasia (HGD)	Importance
Architecture	tubular, minimal focal gland fusion acceptable	any of the following: (gland) cribriforming, glandular budding, intraluminal papillary tufting, sheeting (of epithelium), lamina propria invasion †	key feature
Cytology	usu. no features of HGD	any of the following: loss of nuclear stratification, enlarged nuclei, loss of cell polarity, prominent nucleoli, open (clear) chromatin	supportive feature, not sufficient alone for HGD

Low power colour can be suggestive of HGD:

Feature	Low grade	High grade
Colour	light blue	dark blue

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.

Image:

• Tubular adenoma, negative for high-grade dysplasia - high mag. (WC).

Margins

Main article: Surgical 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."

Haggitt classification

The Haggitt classification is a staging scheme. 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 mostly useless; most polyps do not have a discernible neck or stalk.

Note:

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

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Tubular adenoma - negative for high-grade

COLONIC POLYP, SIGMOID COLON, BIOPSY: 
- TUBULAR ADENOMA.
- NEGATIVE FOR HIGH-GRADE DYSPLASIA.

Tubulovillous adenoma - negative for high-grade

COLONIC POLYP, SIGMOID COLON, BIOPSY: 
- TUBULOVILLOUS ADENOMA.
- NEGATIVE FOR HIGH-GRADE DYSPLASIA.

Villous adenoma - negative for high-grade

COLONIC POLYP, DESCENDING COLON, BIOPSY: 
- VILLOUS ADENOMA.
- NEGATIVE FOR HIGH-GRADE DYSPLASIA.

Tubular adenoma with focal high-grade dysplasia

COLONIC POLYP, TRANSVERSE COLON, BIOPSY:
- TUBULAR ADENOMA WITH FOCAL HIGH-GRADE DYSPLASIA.

Tubular adenoma with high-grade dysplasia

COLONIC POLYP, SIGMOID COLON, BIOPSY: 
- TUBULAR ADENOMA WITH HIGH-GRADE DYSPLASIA.

Invasion cannot be assessed

SIGMOID LESION, 25 CM, BIOPSY: 
- TUBULAR ADENOMA.
- NEGATIVE FOR HIGH-GRADE DYSPLASIA, SEE COMMENT.  

COMMENT: 
No stromal desmoplasia is identified. No definite submucosa is present; thus, the presence or absence of definite invasion cannot be assessed.

Fragment counting

COLONIC POLYP, TRANSVERSE COLON, BIOPSY:
- TUBULAR ADENOMA (IN 1/3 TISSUE FRAGMENTS).
- NEGATIVE FOR HIGH-GRADE DYSPLASIA. 

Notes

1. "Negative for high-grade dysplasia and malignancy" is recommended in the Canadian consensus. The reasoning for the first part is: "with low-grade dysplasia" may lead to over treatment by physicians that are not aware that all (traditional) adenomas have low-grade dysplasia.
2. The phrase "negative for [...] malignancy" is also recommended in the Canadian consensus. This is not endorsed by onlinepathology, as one very frequently does not get submucosa. It is like reporting "negative for muscularis propria invasion" on a urinary bladder biopsy without muscularis propria. Further, the guidelines are inconsistent in that they do not advise "negative for dysplasia and malignancy" for SSAs. If there is clinical suspicion of an invasive malignancy, it is useful to comment that no submucosa is present.

Micro

Tubular-tubulovillous interface

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).

No cribriforming of glands, epithelial budding or intraluminal papillary tufting is identified. Goblet cells are present in the dysplastic epithelium. Dysplastic nuclei have an ellipsoid-shape and basally stratified.

A small number of rare finger-like epithelial projections (villi) are noted; however these appear to comprise less than 20% of the sampled tissue. It is possible that the villous component is higher, due to sampling error; thus, this could represent a tubulovillous adenoma.

Tubulovillous adenoma

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

No cribriforming of glands, epithelial budding or intraluminal papillary tufting is identified. Goblet cells are rare in the dysplastic epithelium. Dysplastic nuclei have an ellipsoid-shape and basally stratified.

The villous component is over 25% of the lesion but less than 50% of the lesion.

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, abbreviated SSP.
• AKA sessile serrated lesion.
• AKA sessile serrated adenoma/polyp, abbreviated SSA/P.

General

• Colonic lesion.
• May be seen in the context of serrated polyposis syndrome.

Epidemiology:

• Thought to lead to colorectal cancer through a different pathway that most tumours in the left colon/rectum.
• Microvesicular hyperplastic polyps are hypothesized to be the the precursor of SSAs.

Gross

Features:

• Flat lesions, usually > 5 mm.
• Typically have a "mucous cap" - present ~65% of the time; useful for identification.
• Border not well-demarcated.
• More common in the proximal colon.

Note:

• Sessile lesions over 1 cm are usually SSAs.

Image:

• SSA - endoscopy (nature.com).

Microscopic

Features:

• Serrated epithelium at the surface and deep in the crypts.
  • Saw-tooth appearance, epithelium has jagged appearing edge.
• Crypt dilation at base with serrations - key feature.
  • Very common -- anecdotally the most sensitive feature.
• "Boot"-shape or "L"-shaped glands.
  • Shape may be similar to a hockey stick.
• Horizontal crypts = crypt long axis parallel to the muscularis mucosae.
• Crypt branching.

Minimal extent criteria - number of abnormal crypts with the above features:

• German Society of Pathology proposal: at least two abnormal crypts -- crypts do not have to be adjacent.
  • Onlinepathology prefers this definition.
• An expert panel lead by Rex states that one unequivocally altered crypt should prompt calling SSA.
• The WHO requires - depending on what you read:
  • Three adjacent crypts to be abnormal.
  • Two or three adjacent crypts to be abnormal.

Notes:

• Typically do not have nuclear atypia, i.e. no nuclear crowding, no nuclear hyperchromasia, no cigar-shaped nuclei.
  • SSAs with nuclear atypia may be referred to as advanced sessile serrated adenomas.

DDx:

• Hyperplastic polyp.
• Tubular adenoma - for SSA with dysplasia, TAs often less than 1 cm (uncommon for SSAs).

Images:

• SSA - low mag. (WC/Nephron).
• SSA - intermed. mag. (WC/Nephron).
• SSA - high mag. (WC/Nephron).
• SSA - low mag. (WC/Nephron).

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COLONIC POLYP, ASCENDING COLON, BIOPSY: 
- SESSILE SERRATED ADENOMA.
- NEGATIVE FOR DYSPLASIA.

COLONIC POLYP, ASCENDING COLON, BIOPSY: 
- SESSILE SERRATED ADENOMA WITH DYSPLASIA.

Note:

• The above exactly mirrors the Canadian consensus.

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. Usual morphology - 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.
     • 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 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).

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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:

• 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).

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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).
• Peutz-Jeghers polyp - stomach (WC).
• 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).
• Ganglioneuroma - high mag. (WC).
• Ganglioneuroma - very high mag. (WC).

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.