Difference between revisions of "Gastrointestinal tract polyps"

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[[Image:Polyp-2.jpeg|thumb|right|Endoscopic image of a gastrointestinal polyp.]]
'''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.
'''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.


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*Adenomatous - premalignant, several types (see below).
*Adenomatous - premalignant, several types (see below).
Mnemonic: ''HHI-A''.
Mnemonic: ''HHI-A''.
Diagnostic variability for colorectal polyps is substantial among community pathologists.<ref name=pmid10502165>{{Cite journal  | last1 = Rex | first1 = DK. | last2 = Alikhan | first2 = M. | last3 = Cummings | first3 = O. | last4 = Ulbright | first4 = TM. | title = Accuracy of pathologic interpretation of colorectal polyps by general pathologists in community practice. | journal = Gastrointest Endosc | volume = 50 | issue = 4 | pages = 468-74 | month = Oct | year = 1999 | doi =  | PMID = 10502165 }}</ref>


=Basic approach=
=Basic approach=
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{{familytree | D | | | | E | | | | F | | G |D=Nuclear changes|E=No nuc. change|F=Serrated|G=Not serrated}}
{{familytree | D | | | | E | | | | F | | G |D=Nuclear changes|E=No nuc. change|F=Serrated|G=Not serrated}}
{{familytree | |!| | | |,|-|^|-|.| | | |!| | | |!| |}}
{{familytree | |!| | | |,|-|^|-|.| | | |!| | | |!| |}}
{{familytree | H | | I | | J | | K | | L |H=Polypoid adenoma<br>(below)|I=Serrated|J=Not serrated|K=SSA vs. HP|L=Normal vs. VA}}
{{familytree | H | | I | | J | | K | | L |H=Polypoid adenoma<br>(below)|I=Serrated|J=Not serrated|K=[[sessile serrated adenoma|SSA]] versus HP|L=Normal versus VA}}
{{familytree | | | | | |!| | | |!| | | | | | | | | |}}
{{familytree | | | | | |!| | | |!| | | | | | | | | |}}
{{familytree | | | | | M | | N | | | | | | | | |M=HP|N=See misc.<br>polyps (below)}}
{{familytree | | | | | M | | N | | | | | | | | |M=[[Hyperplastic polyp|HP]]|N=See misc.<br>polyps (below)}}
{{familytree/end}}
{{familytree/end}}


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{{familytree | B | | | | | |C | | | | |B=Serrated|C=Non-serrated}}
{{familytree | B | | | | | |C | | | | |B=Serrated|C=Non-serrated}}
{{familytree | |!| | | |,|-|-|-|+|-|-|-|.| |}}
{{familytree | |!| | | |,|-|-|-|+|-|-|-|.| |}}
{{familytree | D | | E | | F | | G |D=TSA|E=Tubular arch.|F=Tubulovillous arch.|G=Villous arch.}}
{{familytree | D | | E | | F | | G |D=[[Traditional serrated adenoma|TSA]]|E=Tubular arch.|F=Tubulovillous arch.|G=Villous arch.}}
{{familytree | | | | | |!| | | |!| | | |!| |}}
{{familytree | | | | | |!| | | |!| | | |!| |}}
{{familytree | | | | | H | | I | | J |H=TA|I=TVA|J=VA}}
{{familytree | | | | | H | | I | | J |H=[[Tubular adenoma of the gastrointestinal tract|TA]]|I=[[Tubulovillous adenoma|TVA]]|J=[[Villous adenoma|VA]]}}
{{familytree/end}}
{{familytree/end}}
Notes:<ref>{{Ref PBoD|860}}</ref>  
Notes:<ref>{{Ref PBoD|860}}</ref>  
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{{familytree | D | | E | | F | | G |D=Benign|E=Inflam. p.|F=Hamart.|G=Benign}}
{{familytree | D | | E | | F | | G |D=Benign|E=Inflam. p.|F=Hamart.|G=Benign}}
{{familytree | | | | | |,|-|-|-|+|-|-|-|.| |}}
{{familytree | | | | | |,|-|-|-|+|-|-|-|.| |}}
{{familytree | | | | | H | | I | | J |H=PJP|I=Juvenile|J=Other}}
{{familytree | | | | | H | | I | | J |H=[[Peutz-Jeghers polyp|PJP]]|I=[[Juvenile polyp|Juvenile]]|J=Other}}
{{familytree/end}}
{{familytree/end}}
Notes:
Notes:
*Juvenile polyps may have marked inflammation.
*[[Juvenile polyp]]s may have marked inflammation.




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*Juvenile polyp/Retention polyp -- ''DIES'' (dilated glands, incr. LP, eroded surface, stalk).
*Juvenile polyp/Retention polyp -- ''DIES'' (dilated glands, incr. LP, eroded surface, stalk).
*Peutz-Jeghers polyp (PJP) - frond-like with all mucosa components .
*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=
=Tabular comparison of colonic polyps=
==Overview in two tables==
===Common colonic polyps===
{| class="wikitable sortable"
! Type
! Key feature(s)
! Details
! Prevalence / prognosis
! Other
! [[DDx]]
! Image
|-
| [[Normal colorectal mucosa|Normal mucosa]] / no pathology
| test tubes in a rack-like morphology
| small nuclei, abundant goblet cells
| common / benign
| moderate inflammation is normal
| missed lesion, [[colonic spirochetes]], [[cryptosporidiosis]], [[microscopic colitis]], [[CMV colitis]]
| [[Image:Rectum - intermed mag.jpg|thumb|center|150px| Normal rectum (WC)]]
|-
| [[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]]
| [[Image:Hyperplastic polyp -- intermed mag.jpg |thumb|center|150px| 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 of the gastrointestinal tract|tubular adenoma]], [[tubulovillous adenoma]], [[villous adenoma]]
| [[traditional serrated adenoma]], reactive changes (inflammation)
| [[Image:Tubular_adenoma_4_low_mag.jpg|thumb|center|150px| TA (WC)]]
|}


Adenomatous polyps & hyperplastic polyps - a comparison (adapted from Li and Burgart<ref>{{cite journal |author=Li SC, Burgart L |title=Histopathology of serrated adenoma, its variants, and differentiation from conventional adenomatous and hyperplastic polyps |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=3 |pages=440-5 |year=2007 |month=March |pmid=17516746 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=131&page=440}}</ref>):  
===Less common===
{| class="wikitable sortable"
! 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
| [[Image:Sessile_serrated_adenoma_2_low_mag.jpg|thumb|center|150px|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)
| [[Image:Traditional_serrated_adenoma_low_mag.jpg|thumb|center|150px|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
| [[Image:Gastric_juvenile_polyp_-_very_low_mag.jpg|thumb|center|150px|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:Inflammatory polyp -- low mag.jpg|thumb|center|120px|IP (WC)]]
|-
| [[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
| [[Image:Peutz-Jeghers_syndrome_polyp.jpg|thumb|center|120px|PJP (WC)]]
|}
 
==Common problems==
===Submucosal invasion===
*This may be difficult to assess histomorphologically; these one should show a friend.
 
===Pseudoinvasion===
:See ''[[Gastrointestinal_tract_polyps#Pseudoinvasion_in_colorectal_adenomatous_polyps|pseudoinvasion in colorectal adenomatous polyps]]''.
===Early invasion===
:See ''[[Gastrointestinal_tract_polyps#High-risk_features_in_.28colorectal.29_adenomatous_polyps_with_carcinoma|high risk features in (colorectal) adenomatous polyps with carcinoma]]''.
 
===Adenomatous vs. hyperplastic===
Adenomatous polyps & hyperplastic polyps - a comparison (adapted from Li and Burgart<ref name=pmid17516746>{{cite journal |author=Li SC, Burgart L |title=Histopathology of serrated adenoma, its variants, and differentiation from conventional adenomatous and hyperplastic polyps |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=3 |pages=440-5 |year=2007 |month=March |pmid=17516746 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=131&page=440}}</ref>):  
{| class="wikitable"
{| class="wikitable"
| ||'''Hyperplastic polyp (HPP)''' ||'''Sessile serrated adenoma (SSA)''' ||'''Traditional serrated adenoma (TSA)''' ||'''Traditional adenoma'''<br>-tubular adenoma<br>-tubulovillous adenoma<br>-villous adenoma
! Attribute
! Hyperplastic polyp (HP)
! Sessile serrated adenoma (SSA)
! Traditional serrated adenoma (TSA)
! Traditional adenoma'''<br>-tubular adenoma<br>-tubulovillous adenoma<br>-villous adenoma
|-
|-
|Classic location ||rectum/left colon ||right colon ||rectum/left colon ||rectum/left colon
|Classic location ||rectum/left colon ||right colon ||rectum/left colon ||rectum/left colon
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|-
|-
|Image(s)
|Image(s)
| [http://commons.wikimedia.org/wiki/File:Hyperplastic_polyp2.jpg low mag.]
| [[Image:Hyperplastic polyp -- intermed mag.jpg |thumb|center|150px|HP (WC)]]
| [http://commons.wikimedia.org/wiki/File:Sessile_serrated_adenoma_2_low_mag.jpg low mag], [http://commons.wikimedia.org/wiki/File:Sessile_serrated_adenoma.jpg low mag.]
| [[Image:Sessile_serrated_adenoma_2_low_mag.jpg|thumb|center|150px|SSA (WC)]]
| [http://commons.wikimedia.org/wiki/File:Traditional_serrated_adenoma_low_mag.jpg low mag], [http://commons.wikimedia.org/wiki/File:Traditional_serrated_adenoma_very_high_mag.jpg very high mag.]
| [[Image:Traditional_serrated_adenoma_low_mag.jpg|thumb|center|150px|TSA (WC)]]
|[http://commons.wikimedia.org/wiki/File:Tubular_adenoma_2_low_mag.jpg low mag.], [http://commons.wikimedia.org/wiki/File:Tubular_adenoma_2_high_mag.jpg high mag.]
|[[Image:Tubular_adenoma_2_low_mag.jpg|thumb|center|150px|TA (WC)]]
|}
|}
Normal colonic mucosa:  
Normal colonic mucosa:  
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*Abundant goblet cells.
*Abundant goblet cells.
*Moderate inflammation.
*Moderate inflammation.
*Paneth cells - present in right colon.
*[[Paneth cell]]s - present in right colon.
*Glands - straight, no branching; "test tube" shape.
*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.
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=
=Normal=
==Normal colorectal mucosa==
===General===
===General===
*Most common colonic polyp (90% of all colonic polyps<ref name=Ref_PBoD858/>).
*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====
<gallery>
Image:Rectum - low mag.jpg | Rectum - low mag. (WC)
Image:Rectum - intermed mag.jpg | Rectum - intermed. mag. (WC)
Image:Rectum - alt - intermed mag.jpg | Rectum - intermed. mag. (WC)
Image:Rectum - high mag.jpg | Rectum - high mag. (WC)
</gallery>
www:
*[http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/images/col10he.jpg Normal colorectal mucosa (uwa.edu.au)].<ref>URL: [http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm]. Accessed on: 18 October 2012.</ref>
*[http://www.siumed.edu/~dking2/erg/GI027b.htm Colon (siumed.edu)].
*[http://www.gwc.maricopa.edu/class/bio202/Digestive/DigestHisto/ColonA.htm Normal colorectal mucosa (maricopa.edu)].
 
===Sign out===
====Normal====
<pre>
Cecum, Biopsy:
- Colorectal-type mucosa within normal limits.
</pre>


===Microscopy===
<pre>
Features:<ref name=Ref_PBoD858/>
Right Colon, Biopsy:
*Irregular crypt architecture - tortuosity.
- Colonic mucosa within normal limits.
*Serrated epithelial cells (at the surface of the gland).
</pre>
**''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:
<pre>
*[http://commons.wikimedia.org/wiki/File:Hyperplastic_polyp1.jpg HP - high mag. (WC)].
Transverse Colon, Biopsy:
*[http://commons.wikimedia.org/wiki/File:Hyperplastic_polyp2.jpg HP - lower mag. (WC)].
- Colonic mucosa within normal limits.
</pre>


=Inflammatory pseudopolyp=
<pre>
*[[AKA]] ''inflammatory polyp''.
Left Colon, Biopsy:
===General===
- Colonic mucosa within normal limits.
*Not a true polyp.
</pre>
*The label ''inflammatory pseudopolyp'' = [[inflammatory bowel disease]] (IBD).
 
**If there is no history of IBD... reconsider the diagnosis.
<pre>
Rectum, Biopsy:
- Colorectal mucosa within normal limits.
</pre>
 
=====Block letters=====
<pre>
SIGMOID COLON, BIOPSY:
- COLORECTAL-TYPE MUCOSA WITHIN NORMAL LIMITS.
</pre>
 
<pre>
COLON, 70 CM, BIOPSY:
- COLORECTAL-TYPE MUCOSA WITHIN NORMAL LIMITS.
</pre>
 
=====Polypoid fragments=====
<pre>
POLYP, SIGMOID COLON, BIOPSY:
- POLYPOID FRAGMENT OF COLORECTAL-TYPE MUCOSA WITHIN NORMAL LIMITS.
</pre>
 
=====Mucosa and submucosa=====
<pre>
POLYP, SIGMOID COLON, BIOPSY:
- COLONIC MUCOSA AND SUBMUCOSA WITHIN NORMAL LIMITS.
</pre>
 
====Lymphoid nodule present====
*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.
 
<pre>
POLYP, RECTUM, BIOPSY:
- RECTAL MUCOSA WITHIN NORMAL LIMITS WITH A MORPHOLOGICALLY BENIGN LYMPHOID AGGREGATE.
</pre>
 
<pre>
COLON, RIGHT SIDE, BIOPSY:
- COLONIC MUCOSA WITH MORPHOLOGICALLY BENIGN LYMPHOID AGGREGATES,
  NO SIGNIFICANT PATHOLOGY.
</pre>
 
=====Submucosa present=====
<pre>
POLYP, ASCENDING COLON, BIOPSY:
- COLONIC MUCOSA AND SUBMUCOSA WITHIN NORMAL LIMITS WITH A MORPHOLOGICALLY BENIGN
LYMPHOID NODULE.
</pre>
 
====Suspected missed lesion====
<pre>
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.
</pre>
 
====Micro - suspected IBD====
The sections show colorectal-type mucosa. The glands show no significant architectural
abnormalities and mature normally to the surface. Rare apoptotic epithelial cells are seen. There is no cryptitis. Neutrophils are not apparent in the lamina propria.


===Microscopic===
====Rare PMNs - no cryptitis====
Features:
The sections show colorectal mucosa with rare lymphoid aggregates. The architecture is
*Polypoid shape.
within normal limits. The epithelium matures normally to the surface. Very rare neutrophils
*Inflammation - '''key feature'''.
are present within the lamina propria. A very small number of crypts have one or two
neutrophils. No definite cryptitis is present.


Negatives:
==Fecal material==
*No nuclear atypia.
{{Main|Fecal material}}
*No dilated glands.


DDx:
=Hyperplastic polyp=
*Juvenile polyp.
:''The [[stomach]] lesion is dealt with in [[hyperplastic polyp of the stomach]]''.
*[[Solitary rectal ulcer]].
{{Main|Hyperplastic polyp}}


=Adenomatous polys=
=Inflammatory pseudopolyp=
Several types of adenomatous polyps are recognized. 
{{Main|Inflammatory pseudopolyp}}


=Adenomatous polyps=
==Overview==
Several types of adenomatous polyps are recognized: 
*Traditional adenomas (have three subtypes):
*Traditional adenomas (have three subtypes):
*#Tubular adenoma - most common, lowest malignant potential.
*#Tubular adenoma - most common, lowest malignant potential.
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*#Villous adenoma - highest malignant potential.
*#Villous adenoma - highest malignant potential.
*Sessile serrated adenomas:  
*Sessile serrated adenomas:  
**New kid on the block, some people doubt their existance.
**New kid on the block.
*Traditional serrated adenomas - nuclear features of 'traditional adenoma' + serrated architecture.
*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.
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 (intestinal) polyps==
===Management of (adenomatous colonic) polyps===
Follow-up interval for polyps (colonoscopy interval):<ref name=pmid17167138>{{cite journal |author=Levine JS, Ahnen DJ |title=Clinical practice. Adenomatous polyps of the colon |journal=N. Engl. J. Med. |volume=355 |issue=24 |pages=2551–7 |year=2006 |month=December |pmid=17167138 |doi=10.1056/NEJMcp063038 |url=http://content.nejm.org/cgi/reprint/355/24/2551.pdf}}</ref>
Follow-up interval for polyps (colonoscopy interval):<ref name=pmid17167138>{{cite journal |author=Levine JS, Ahnen DJ |title=Clinical practice. Adenomatous polyps of the colon |journal=N. Engl. J. Med. |volume=355 |issue=24 |pages=2551–7 |year=2006 |month=December |pmid=17167138 |doi=10.1056/NEJMcp063038 |url=http://content.nejm.org/cgi/reprint/355/24/2551.pdf}}</ref>
*Normal follow-up (includes presence of ''hyperplastic polyps''): ~10 years.
*Normal follow-up (includes presence of ''hyperplastic polyps''): ~10 years.
Line 168: Line 384:
*Inadequately removed polyps: <6 months.
*Inadequately removed polyps: <6 months.


Classified as ''high risk'' (any of the following):<ref name=pmid17167138/>
Classified as ''high risk polyp'' (any of the following):<ref name=pmid17167138/>
*Tubulovillous.
*Tubulovillous.
*Villous.
*Villous.
Line 176: Line 392:
Mnemonic: ''GAS'' = grade (high), architecture (tubulovillous, villous), size (>1 cm).
Mnemonic: ''GAS'' = grade (high), architecture (tubulovillous, villous), size (>1 cm).


==Traditional adenoma==
Note:
===Microscopic===
*''High risk polyp'', as defined above, is also called '''advanced adenoma''';<ref name=pmid18347350>{{Cite journal  | last1 = Laiyemo | first1 = AO. | last2 = Murphy | first2 = G. | last3 = Albert | first3 = PS. | last4 = Sansbury | first4 = LB. | last5 = Wang | first5 = Z. | last6 = Cross | first6 = AJ. | last7 = Marcus | first7 = PM. | last8 = Caan | first8 = B. | last9 = Marshall | first9 = JR. | title = Postpolypectomy colonoscopy surveillance guidelines: predictive accuracy for advanced adenoma at 4 years. | journal = Ann Intern Med | volume = 148 | issue = 6 | pages = 419-26 | month = Mar | year = 2008 | doi =  | PMID = 18347350 | URL = http://www.annals.org/content/148/6/419.full.pdf }}</ref> however, it should be noted that there are different definitions for ''advanced adenoma'' (e.g. ''Winawer & Zauber''<ref name=pmid11916153>{{Cite journal  | last1 = Winawer | first1 = SJ. | last2 = Zauber | first2 = AG. | title = The advanced adenoma as the primary target of screening. | journal = Gastrointest Endosc Clin N Am | volume = 12 | issue = 1 | pages = 1-9, v | month = Jan | year = 2002 | doi =  | PMID = 11916153 }}</ref> include early invasive tumours). Thus, it is best to avoid the term.
#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).
#Loss/decrease of goblet cells (common).
#Cytoplasmic hyperchromasia.


Notes:
==Pseudoinvasion in colorectal adenomatous polyps==
*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".
*[[AKA]] ''pseudoinvasion''.
**Classically, adenomatous polyps have "reverse maturation":
*[[AKA]] ''epithelial misplacement''.
***The surface is more hyperchromatic (more blue).
{{Main|Pseudoinvasion in colorectal adenomatous polyps}}
***The base is more mature (more globlet cells, no nuclear changes -- less blue).


===Typing===
==High-risk features in (colorectal) adenomatous polyps with carcinoma==
Subclassified as:<ref name=pbod860>{{Ref PBoD|860}}</ref>
Predictors of poor outcome with early submucosal invasion:<ref name=pmid15300569>{{Cite journal  | last1 = Ueno | first1 = H. | last2 = Mochizuki | first2 = H. | last3 = Hashiguchi | first3 = Y. | last4 = Shimazaki | first4 = H. | last5 = Aida | first5 = S. | last6 = Hase | first6 = K. | last7 = Matsukuma | first7 = S. | last8 = Kanai | first8 = T. | last9 = Kurihara | first9 = H. | title = Risk factors for an adverse outcome in early invasive colorectal carcinoma. | journal = Gastroenterology | volume = 127 | issue = 2 | pages = 385-94 | month = Aug | year = 2004 | doi =  | PMID = 15300569 }}</ref>
*Tubular (most common), tubular component >75%.
#High tumour grade.
*Villous (least common ~= 1% of (traditional) adenomas), villous component >50%.
#[[Lymphovascular invasion]].
*Tubulovillous (uncommon ~5-10% of (traditional) adenomas), villous component >=25% & <=50%.
#High-grade [[tumour budding]].
#*Tumour bud = 1-4 cell(s); "high-grade budding" is >=10 tumour buds in a field of 0.385 mm<sup>2</sup>.<ref name=pmid11952856>{{Cite journal  | last1 = Ueno | first1 = H. | last2 = Murphy | first2 = J. | last3 = Jass | first3 = JR. | last4 = Mochizuki | first4 = H. | last5 = Talbot | first5 = IC. | title = Tumour 'budding' as an index to estimate the potential of aggressiveness in rectal cancer. | journal = Histopathology | volume = 40 | issue = 2 | pages = 127-32 | month = Feb | year = 2002 | doi =  | PMID = 11952856 }}</ref>‡
#**If the microscope has a 22 mm eye piece and...
#***A 20x objective, the field is approximately 0.950 mm<sup>2</sup> -- to match the buds/area -- it would be 24.68 buds/0.950 mm<sup>2</sup>.
#***A 40x objective, the field is approximately 0.238 mm<sup>2</sup> -- to match the buds/area -- it would be 6.17 buds/0.238 mm<sup>2</sup>.
#Extensive submucosal invasion.
#*>= 4 mm width ''or'' >= 2 mm depth.


In other words:
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%.<ref name=pmid15300569/>
*Tubular T/V >75% / <25%; Tubulovillous T/V <=75%-50% / 25%-<50%; Villous T/V <=50% / >50%.


Notes:<ref name=pbod860/>
Note:
*Most villous adenomas are sessile, i.e. flat.<ref name=emed_va>[http://emedicine.medscape.com/article/170283-overview http://emedicine.medscape.com/article/170283-overview]</ref>
*‡Tumour budding as per international consensus is now assessed in field area of 0.785 mm<sup>2</sup>.<ref name=pmid28548122>{{Cite journal  | last1 = Lugli | first1 = A. | last2 = Kirsch | first2 = R. | last3 = Ajioka | first3 = Y. | last4 = Bosman | first4 = F. | last5 = Cathomas | first5 = G. | last6 = Dawson | first6 = H. | last7 = El Zimaity | first7 = H. | last8 = Fléjou | first8 = JF. | last9 = Hansen | first9 = TP. | title = Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. | journal = Mod Pathol | volume = 30 | issue = 9 | pages = 1299-1311 | month = Sep | year = 2017 | doi = 10.1038/modpathol.2017.46 | PMID = 28548122 }}</ref>
*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.<ref name=emed_va/>
**Health Organization (WHO) criteria: villous adenomas >80% villous architecture.


===Grading===
==Traditional adenoma==
Most institutions grade adenomas into:<ref>[http://www.pathologyoutlines.com/colontumor.html#adenoma http://www.pathologyoutlines.com/colontumor.html#adenoma]</ref>
:''Includes '''tubular adenoma''', '''tubulovillous adenoma''', and '''villous adenoma'''.''
*Low grade.
{{Main|Traditional adenoma}}
**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.
==Traditional serrated adenoma==
{{Main|Traditional serrated adenoma}}


Micrograph:
==Sessile serrated adenoma==
*[http://commons.wikimedia.org/wiki/File:Tubular_adenoma_high_mag.jpg Tubular adenoma negative for high grade dysplasia - high mag.] - wikimedia.org.
{{Main|Sessile serrated adenoma}}


===Margins===
=Malignant polyps=
*Some pathologists believe it is impossible to determine margins in polypectomies.
==Colorectal adenocarcinoma==
*Others comment on what they see and then disclaim based on limitations with something like "... margin clear in plane of section."
{{Main|Colorectal adenocarcinoma}}


The ''Haggitt classification'' is margin call taken to the extreme.
===General===
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.
*Diagnosis may be a challenging on a small biopsy.
In short:<ref>[http://www.ganfyd.org/index.php?title=Haggitt_classification http://www.ganfyd.org/index.php?title=Haggitt_classification]</ref><ref name=pmid4007423>{{Cite journal  | last1 = Haggitt | first1 = RC. | last2 = Glotzbach | first2 = RE. | last3 = Soffer | first3 = EE. | last4 = Wruble | first4 = LD. | title = Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. | journal = Gastroenterology | volume = 89 | issue = 2 | pages = 328-36 | month = Aug | year = 1985 | doi = | PMID = 4007423 }}</ref>
*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:  
====Clinical====
*Dr. Haggitt is know for his tragic demise. He was shot by a resident that was about to be fired.<ref>Two die in UW medical school shooting. seattlepi.com. URL: [http://www.seattlepi.com/local/pathweb.shtml http://www.seattlepi.com/local/pathweb.shtml]. Accessed on: April 23, 2009.</ref>
Invasion can be predicted based on endoscopic findings:
 
*[[Kudo pit pattern]].<ref name=pmid18458845>{{Cite journal  | last1 = Onishi | first1 = T. | last2 = Tamura | first2 = S. | last3 = Kuratani | first3 = Y. | last4 = Onishi | first4 = S. | last5 = Yasuda | first5 = N. | title = Evaluation of the depth score of type V pit patterns in crypt orifices of colorectal neoplastic lesions. | journal = J Gastroenterol | volume = 43 | issue = 4 | pages = 291-7 | month =  | year = 2008 | doi = 10.1007/s00535-008-2161-1 | PMID = 18458845 }}</ref>
==Traditional serrated adenoma==
*Non-lifting sign.<ref name=pmid7926542>{{Cite journal  | last1 = Uno | first1 = Y. | last2 = Munakata | first2 = A. | title = The non-lifting sign of invasive colon cancer. | journal = Gastrointest Endosc | volume = 40 | issue = 4 | pages = 485-9 | month =  | year =  | doi =  | PMID = 7926542 }}</ref>
===General===
**Presence predicts deeper invasion.<ref name=pmid10462651>{{Cite journal  | last1 = Ishiguro | first1 = A. | last2 = Uno | first2 = Y. | last3 = Ishiguro | first3 = Y. | last4 = Munakata | first4 = A. | last5 = Morita | first5 = T. | title = Correlation of lifting versus non-lifting and microscopic depth of invasion in early colorectal cancer. | journal = Gastrointest Endosc | volume = 50 | issue = 3 | pages = 329-33 | month = Sep | year = 1999 | doi = 10.1053/ge.1999.v50.98591 | PMID = 10462651 }}</ref>
*Very rare.


===Microscopic===
===Microscopic===
Features:
One of the two following:
*Serrated.
#Dysplasia and evidence of invasion - features:<ref name=pmid22827760>{{Cite journal  | last1 = Kimura | first1 = R. | last2 = Fujimori | first2 = T. | last3 = Ichikawa | first3 = K. | last4 = Ajioka | first4 = Y. | last5 = Ueno | first5 = H. | last6 = Ohkura | first6 = Y. | last7 = Kashida | first7 = H. | last8 = Togashi | first8 = K. | last9 = Yao | first9 = T. | title = Desmoplastic reaction in biopsy specimens of early colorectal cancer: a Japanese prospective multicenter study. | journal = Pathol Int | volume = 62 | issue = 8 | pages = 525-31 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1827.2012.02840.x | PMID = 22827760 }}</ref>
*Nuclear atypia (as in tubular adenoma).
#*Nuclear changes seen in adenomatous polyps - malignant-appearing cells.
*Villous architecture.
#**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''':
#*#Malignant-appearing cells in the submucosa.
#*#*Pseudoinvasion must be excluded.
#*#[[Desmoplastic stromal response]].
#*#*Spindle cells with:
#*#**Large nuclei (nucleus ~ size of a plasma cell).
#*#**Eosinophilic cytoplasm.
#[[Signet ring cell carcinoma|Signet ring cells]].  


DDx:
DDx:
*Villous adenoma.
*[[Pseudoinvasion]] - surrounded by lamina propria, desmoplasia lacking, hemosiderin-laden macrophages.
 
*[[Reactive changes]].
Images:
*[http://commons.wikimedia.org/wiki/File:Traditional_serrated_adenoma_low_mag.jpg TSA - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Traditional_serrated_adenoma_intermed_mag.jpg TSA - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Traditional_serrated_adenoma_very_high_mag.jpg TSA - very high mag. (WC)].


==Sessile serrated adenoma==
Note:
*Often abbreviated ''SSA''.
*Desmoplastic response is ''not'' predictive of submucosal invasion in pedunculated polyps.<ref name=pmid20665053>{{Cite journal  | last1 = Hirose | first1 = M. | last2 = Fukui | first2 = H. | last3 = Igarashi | first3 = Y. | last4 = Fujimori | first4 = Y. | last5 = Katake | first5 = Y. | last6 = Sekikawa | first6 = A. | last7 = Ichikawa | first7 = K. | last8 = Tomita | first8 = S. | last9 = Imura | first9 = J. | title = Detection of desmoplastic reaction in biopsy specimens is useful for predicting the depth of invasion of early colorectal cancer: a Japanese collaborative study. | journal = J Gastroenterol | volume = 45 | issue = 12 | pages = 1212-8 | month = Dec | year = 2010 | doi = 10.1007/s00535-010-0288-3 | PMID = 20665053 }}
*[[AKA]] sessile serrated polyp.
</ref>
===General===
*Colonic lesion.
*More common in the right colon, i.e. ascending colon.


Epidemiology:
====Image====
*Thought to lead to colorectal cancer through a different pathway that most tumours in the left colon/rectum.
<gallery>
Image:Cecal_adenocarcinoma.jpg | Colorectal carcinoma. (WC/Nephron)
</gallery>


===Microscopic===
===Sign out===
Features:
<pre>
*Serrated.
RECTOSIGMOID TUMOUR, BIOPSY:
*Crypt dilation at base - a '''key feature''' - very common.  
- INVASIVE ADENOCARCINOMA, MODERATELY DIFFERENTIATED.
**"Boot"-shape or "L"-shaped glands.
</pre>
*Crypt branching.
*Horizontal crypts (crypts that run along the muscular mucosae).


Notes:
<pre>
*Typically do not have nuclear atypia, i.e. no nuclear crowding, no nuclear hyperchromasia, no cigar-shaped nuclei.
RECTUM, BIOPSY:
- INVASIVE ADENOCARCINOMA, MODERATELY DIFFERENTIATED.
</pre>


Micrographs:
<pre>
*[http://commons.wikimedia.org/wiki/File:Sessile_serrated_adenoma.jpg SSA - low mag. (WC)].
RECTUM, BIOPSY:
*[http://commons.wikimedia.org/wiki/File:Sessile_serrated_adenoma2.jpg SSA - intermed. mag. (WC)].
- HIGHLY SUSPICIOUS FOR INVASIVE ADENOCARCINOMA, SEE MICROSCOPIC.
*[http://commons.wikimedia.org/wiki/File:Sessile_serrated_adenoma3.jpg SSA - high mag. (WC)].
- TUBULOVILLOUS ADENOMA WITH HIGH-GRADE DYSPLASIA.
</pre>


=Hamartomatous polyps (overview)=
====Micro====
Numerous types of hamartomatous polyps exist: 
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).
*Peutz-Jeghers syndrome.
*Juvenile polyposis syndrome.
*Cowden's disease.


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


Further reading: ''Gastrointestinal & Liver Pathology''.<ref name=Ref_GLP345>{{Ref GLP|345}}</ref>
=====Suspicious=====
The sections shows multiple fragments of 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).


==Juvenile polyp==
Cribriforming of glands is identified at multiple foci. Goblet cells are rare in the
===General===
dysplastic epithelium.
*Referred to ''retension polyps'' in non-juveniles.


===Microscopic===
One fragment of tissue, measuring approximately 2 millimetres, has increased numbers of plump stromal cells (desmoplastic response); this is suspicious for invasive adenocarcinoma.
Features:<ref name=Ref_PBoD859>{{Ref PBoD|859}}</ref><ref name=pmid12692201>{{Cite journal  | last1 = Bronner | first1 = MP. | title = Gastrointestinal inherited polyposis syndromes. | journal = Mod Pathol | volume = 16 | issue = 4 | pages = 359-65 | month = Apr | year = 2003 | doi = 10.1097/01.MP.0000062992.54036.E4 | PMID = 12692201 | url = http://www.nature.com/modpathol/journal/v16/n4/full/3880773a.html }}</ref>
*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.
=Hamartomatous polyps=
==Overview==
There are three well known hamartomatous polyp syndromes:<ref name=Ref_GLP345>{{Ref GLP|345}}</ref> 
*[[Peutz-Jeghers syndrome]].
*[[Juvenile polyposis syndrome]].
*[[Cowden's disease]].


Notes:  
There are two obscure hamartomatous polyp syndromes:<ref name=Ref_GLP345>{{Ref GLP|345}}</ref>
*Nuclear changes may be like those seen in adenomatous polyps.
*Bannayan-Riley-Ruvalcaba syndrome (BRBS).
*IHC can be used as an adjunct (p53, Ki-67).
*Devon polyposis syndrome (DPS).
**p53 mutations in dysplastic epithelium -- negative stain (normal).


Images:  
Notes:
*[http://www.nature.com/modpathol/journal/v16/n4/fig_tab/3880773f4.html Juvenile polyp (nature.com)].
*BRBS is due to a PTEN mutation<ref name=omim153480>{{OMIM|153480}}</ref> (the same gene associated with Cowden's disease).
*[http://commons.wikimedia.org/wiki/File:Gastric_juvenile_polyp_-_very_low_mag.jpg Juvenile polyp of the stomach - very low mag. (WC)]
*DPS is reported in only one family that lives in Devon, UK.<ref name=pmid1644320>{{Cite journal  | last1 = Allibone | first1 = RO. | last2 = Nanson | first2 = JK. | last3 = Anthony | first3 = PP. | title = Multiple and recurrent inflammatory fibroid polyps in a Devon family ('Devon polyposis syndrome'): an update. | journal = Gut | volume = 33 | issue = 7 | pages = 1004-5 | month = Jul | year = 1992 | doi =  | PMID = 1644320 }}</ref>
*[http://commons.wikimedia.org/wiki/File:Gastric_juvenile_polyp_-_2_-_very_low_mag.jpg Juvenile polyp of the stomach - very low mag. (WC)].


DDx:
==Juvenile polyp==
*Inflammatory polyp.
{{Main|Juvenile polyp}}


==Peutz-Jeghers polyp==
==Peutz-Jeghers polyp==
===General===
{{Main|Peutz-Jeghers polyp}}
====Epidemiology====
Features:<ref name=Ref_PBoD859/><ref name=pmid12692201>{{Cite journal  | last1 = Bronner | first1 = MP. | title = Gastrointestinal inherited polyposis syndromes. | journal = Mod Pathol | volume = 16 | issue = 4 | pages = 359-65 | month = Apr | year = 2003 | doi = 10.1097/01.MP.0000062992.54036.E4 | PMID = 12692201 | url = http://www.nature.com/modpathol/journal/v16/n4/full/3880773a.html }}</ref>
*[[Peutz-Jeghers syndrome]] is autosomal dominant.
*Altered gene: STK11.
 
====Clinical====
Features:<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/175200 http://www.ncbi.nlm.nih.gov/omim/175200]. Accessed on: 13 July 2010.</ref>
*Melanocytic macules.
**Lips, buccal mucosa, and digits.
**Multiple Peutz-Jeghers polyps
 
Increased risk of various neoplasms - primarily:
*Breast and gastrointestinal cancer.<ref name=pmid20581245>{{cite journal |author=Beggs AD, Latchford AR, Vasen HF, ''et al.'' |title=Peutz-Jeghers syndrome: a systematic review and recommendations for management |journal=Gut |volume=59 |issue=7 |pages=975–86 |year=2010 |month=July |pmid=20581245 |doi=10.1136/gut.2009.198499 |url=}}</ref>
*Others tumours:<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/175200 http://www.ncbi.nlm.nih.gov/omim/175200]. Accessed on: 22 December 2010.</ref>
**[[Granulosa cell tumour]].
**[[Sertoli cell tumour]] - esp. with calcification.
 
===Microscopy===
Features:<ref name=Ref_PBoD859/><ref name=pmid12692201>{{Cite journal  | last1 = Bronner | first1 = MP. | title = Gastrointestinal inherited polyposis syndromes. | journal = Mod Pathol | volume = 16 | issue = 4 | pages = 359-65 | month = Apr | year = 2003 | doi = 10.1097/01.MP.0000062992.54036.E4 | PMID = 12692201 | url = http://www.nature.com/modpathol/journal/v16/n4/full/3880773a.html }}</ref>
*Frond-like polyp with all three components of mucosa:
*# Muscosal epithelium (melanotic mucosa, goblet cells).
*# Lamina propria.
*# M. mucosae.
 
Image:
*[http://commons.wikimedia.org/wiki/File:Peutz-Jeghers_syndrome_polyp.jpg Peutz-Jeghers syndrome polyp (WC)].
*[http://www.nature.com/modpathol/journal/v16/n4/fig_tab/3880773f3.html Peutz-Jeghers polyp (nature.com)].


==Cowden disease==
==Cowden disease==
===Etiology===
{{Main|Cowden syndrome}}
*[[AKA]] Cowden syndrome.
===General===
Etiology:
*PTEN gene mutation.
*PTEN gene mutation.


Clinical features:<ref>{{Ref PBoD|858-9}}</ref>
Clinical features:<ref name=Ref_PBoD858-9>{{Ref PBoD|858-9}}</ref>
*Hamartomatous polyps.  
*Hamartomatous polyps.  
*Facial trichilemmomas (hair follicle root sheath epithelium tumour).  
*Facial [[trichilemmoma]]s (hair follicle root sheath epithelium tumour).  
*Oral papillomas.  
*Oral papillomas.  
*Acral keratoses (peripheral keratoses).
*Acral keratoses (peripheral keratoses).


Note:
*Lame mnemonic ''PATH'':<ref>URL: [http://www.pathologyexpert.com/boards/onlinefiles/syndromes.htm http://www.pathologyexpert.com/boards/onlinefiles/syndromes.htm]. Accessed on: 6 December 2011.</ref> ''P''apilloma (oral), ''A''cral keratosis, ''T''richilemmoma, ''H''amartomatous polyps.
===Microscopic===
Features:
*Hamartomatous polyp - features non-specific. (???)
=Weird stuff=
==Cronkhite-Canada syndrome==
==Cronkhite-Canada syndrome==
*Abbreviated ''CCS''.
*Abbreviated ''CCS''.
{{Main|Cronkhite-Canada syndrome}}
==Ganglioneuroma==
{{Main|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.
DDx:
*[[Hyperplastic polyp with perineuromatous stroma]].


====Images====
<gallery>
Image:Ganglioneuroma_-_intermed_mag.jpg | Ganglioneuroma - intermed. mag. (WC/Nephron)
Image:Ganglioneuroma_-_high_mag.jpg | Ganglioneuroma - high mag. (WC/Nephron)
Image:Ganglioneuroma_-_very_high_mag.jpg | Ganglioneuroma - very high mag. (WC/Nephron)
</gallery>
==Inflammatory myoglandular polyp==
===General===
===General===
Clinical features:<ref>{{Ref PBoD|858-9}}</ref>
*Controversial - probably '''not''' a distinct pathologic entity.<ref name=pmid8338196>{{Cite journal  | last1 = Bhathal | first1 = PS. | last2 = Chetty | first2 = R. | last3 = Slavin | first3 = JL. | title = Myoglandular polyps. | journal = Am J Surg Pathol | volume = 17 | issue = 8 | pages = 852-3 | month = Aug | year = 1993 | doi =  | PMID = 8338196 }}</ref>
*Hamartomatous polyps.  
*Rare, benign, non-neoplastic.<ref name=pmid20102635>{{Cite journal  | last1 = Meniconi | first1 = RL. | last2 = Caronna | first2 = R. | last3 = Benedetti | first3 = M. | last4 = Fanello | first4 = G. | last5 = Ciardi | first5 = A. | last6 = Schiratti | first6 = M. | last7 = Papini | first7 = F. | last8 = Farelli | first8 = F. | last9 = Dinatale | first9 = G. | title = Inflammatory myoglandular polyp of the cecum: case report and review of literature. | journal = BMC Gastroenterol | volume = 10 | issue =  | pages = 10 | month =  | year = 2010 | doi = 10.1186/1471-230X-10-10 | PMID = 20102635 | PMC = 2828397 | URL = http://www.biomedcentral.com/1471-230X/10/10 }}</ref>
*Ectodermal abnormalities (nail atrophy, skin pigment, alopecia).
*Large bowel, usually rectosigmoid.
 
===Microscopic===
Features:<ref name=pmid1309176>{{Cite journal  | last1 = Nakamura | first1 = S. | last2 = Kino | first2 = I. | last3 = Akagi | first3 = T. | title = Inflammatory myoglandular polyps of the colon and rectum. A clinicopathological study of 32 pedunculated polyps, distinct from other types of polyps. | journal = Am J Surg Pathol | volume = 16 | issue = 8 | pages = 772-9 | month = Aug | year = 1992 | doi =  | PMID = 1309176 }}</ref>
#[[Granulation tissue]] within the lamina propria.
#Lamina propria smooth muscle.
#Irregular gland architecture:
#*Cystic dilatation.
#*Tortuosity.
 
DDx:<ref name=pmid8338196/>
*[[Mucosal prolapse syndrome]].
*Polypoid prolaping mucosal fold in [[diverticular disease]].
*[[Inflammatory cloacogenic polyp]].
*[[Inflammatory cap polyp]].
 
Image:
*[http://www.biomedcentral.com/1471-230X/10/10/figure/F3 IMP (biomedcentral.com)].<ref name=pmid20102635/>
 
==Leiomyoma==
{{Main|Colonic leiomyoma}}
{{Main|Leiomyoma}}
*May present as a polyp in the colon.<ref name=pmid21915840>{{Cite journal  | last1 = Kemp | first1 = CD. | last2 = Arnold | first2 = CA. | last3 = Torbenson | first3 = MS. | last4 = Stein | first4 = EM. | title = An unusual polyp: a pedunculated leiomyoma of the sigmoid colon. | journal = Endoscopy | volume = 43 Suppl 2 UCTN | issue =  | pages = E306-7 | month =  | year = 2011 | doi = 10.1055/s-0030-1256640 | PMID = 21915840 }}</ref>


==Colonic polyp with reactive subepithelial cells==
===Microscopic===
===Microscopic===
Features:
Features:
*Polyps have same morphology as juvenile polyp/retension polyp.
*Surface epithelium with a reduced quantity of cytoplasm and less goblets (regenerative appearance).
*Mildly atypical subepithelial cells with pale moderate-to-abundant cytoplasm and nuclear enlargement +/-nuclear hyperchromasia.
 
===Sign out===
<pre>
POLYP, ASCENDING COLON, POLYPECTOMY:
- POLYPOID FRAGMENT OF COLONIC-TYPE MUCOSA WITH REACTIVE SUBEPITHELIAL
  CELLS, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.
 
COMMENT:
A pankeratin and CK7 immunostains are non-concerning. A CD68 immunostain
highlights lamina propria macrophages.
</pre>


=See also=
=See also=
Line 381: Line 621:
*[[Small bowel]].
*[[Small bowel]].
*[[Colon]].
*[[Colon]].
*[[Polypectomy]].


=References=
=References=
{{reflist|2}}
{{reflist|2}}
=External links=
*[http://kathrin.unibas.ch/polyp/index.html Serrated polyps quiz (unibas.ch)] - nice quiz... though it is annoying that one has to click on the images to enlarge 'em.


[[Category:Gastrointestinal pathology]]
[[Category:Gastrointestinal pathology]]

Latest revision as of 23:51, 18 March 2018

Endoscopic image of a gastrointestinal polyp.

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:[1]

  • Hyperplastic - harmless, most common - 90% of all colonic polyps.[2]
  • 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.[3]

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 versus HP
 
Normal versus 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:[4]

  • 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:


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:

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 missed lesion, colonic spirochetes, cryptosporidiosis, microscopic colitis, CMV colitis
Normal rectum (WC)
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
IP (WC)
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[5]):

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:

DDx (colorectal mucosa with minimal changes):

Images

www:

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Normal

Cecum, Biopsy:
- Colorectal-type mucosa within normal limits.
Right Colon, Biopsy:
- Colonic mucosa within normal limits.
Transverse Colon, Biopsy:
- Colonic mucosa within normal limits.
Left Colon, Biopsy:
- Colonic mucosa within normal limits.
Rectum, Biopsy:
- Colorectal mucosa within normal limits.
Block letters
SIGMOID COLON, BIOPSY:
- COLORECTAL-TYPE MUCOSA WITHIN NORMAL LIMITS.
COLON, 70 CM, BIOPSY:
- COLORECTAL-TYPE MUCOSA WITHIN NORMAL LIMITS.
Polypoid fragments
POLYP, SIGMOID COLON, BIOPSY:
- POLYPOID FRAGMENT OF COLORECTAL-TYPE MUCOSA WITHIN NORMAL LIMITS.
Mucosa and submucosa
POLYP, SIGMOID COLON, BIOPSY:
- COLONIC MUCOSA AND SUBMUCOSA WITHIN NORMAL LIMITS.

Lymphoid nodule present

  • 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.
POLYP, RECTUM, BIOPSY:
- RECTAL MUCOSA WITHIN NORMAL LIMITS WITH A MORPHOLOGICALLY BENIGN LYMPHOID AGGREGATE.
COLON, RIGHT SIDE, BIOPSY:
- COLONIC MUCOSA WITH MORPHOLOGICALLY BENIGN LYMPHOID AGGREGATES,
  NO SIGNIFICANT PATHOLOGY.
Submucosa present
POLYP, ASCENDING COLON, BIOPSY:
- COLONIC MUCOSA AND SUBMUCOSA WITHIN NORMAL LIMITS WITH A MORPHOLOGICALLY BENIGN
LYMPHOID NODULE.

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.

Micro - suspected IBD

The sections show colorectal-type mucosa. The glands show no significant architectural abnormalities and mature normally to the surface. Rare apoptotic epithelial cells are seen. There is no cryptitis. Neutrophils are not apparent in the lamina propria.

Rare PMNs - no cryptitis

The sections show colorectal mucosa with rare lymphoid aggregates. The architecture is within normal limits. The epithelium matures normally to the surface. Very rare neutrophils are present within the lamina propria. A very small number of crypts have one or two neutrophils. No definite cryptitis is present.

Fecal material

Hyperplastic polyp

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

Inflammatory pseudopolyp

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:

Management of (adenomatous colonic) polyps

Follow-up interval for polyps (colonoscopy interval):[7]

  • 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):[7]

  • 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;[8] however, it should be noted that there are different definitions for advanced adenoma (e.g. Winawer & Zauber[9] include early invasive tumours). Thus, it is best to avoid the term.

Pseudoinvasion in colorectal adenomatous polyps

  • AKA pseudoinvasion.
  • AKA epithelial misplacement.

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

Predictors of poor outcome with early submucosal invasion:[10]

  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.[11]
      • If the microscope has a 22 mm eye piece and...
        • A 20x objective, the field is approximately 0.950 mm2 -- to match the buds/area -- it would be 24.68 buds/0.950 mm2.
        • A 40x objective, the field is approximately 0.238 mm2 -- to match the buds/area -- 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%.[10]

Note:

  • ‡Tumour budding as per international consensus is now assessed in field area of 0.785 mm2.[12]

Traditional adenoma

Includes tubular adenoma, tubulovillous adenoma, and villous adenoma.

Traditional serrated adenoma

Sessile serrated adenoma

Malignant polyps

Colorectal adenocarcinoma

General

  • Diagnosis may be a challenging on a small biopsy.

Clinical

Invasion can be predicted based on endoscopic findings:

Microscopic

One of the two following:

  1. Dysplasia and evidence of invasion - features:[16]
    • 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:

Note:

  • Desmoplastic response is not predictive of submucosal invasion in pedunculated polyps.[17]

Image

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RECTOSIGMOID TUMOUR, BIOPSY:
- INVASIVE ADENOCARCINOMA, MODERATELY DIFFERENTIATED.
RECTUM, BIOPSY:
- INVASIVE ADENOCARCINOMA, MODERATELY DIFFERENTIATED.
RECTUM, BIOPSY:
- HIGHLY SUSPICIOUS FOR INVASIVE ADENOCARCINOMA, SEE MICROSCOPIC.
- TUBULOVILLOUS ADENOMA WITH HIGH-GRADE DYSPLASIA.

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.

Suspicious

The sections shows multiple fragments of 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).

Cribriforming of glands is identified at multiple foci. Goblet cells are rare in the dysplastic epithelium.

One fragment of tissue, measuring approximately 2 millimetres, has increased numbers of plump stromal cells (desmoplastic response); this is suspicious for invasive adenocarcinoma.

Hamartomatous polyps

Overview

There are three well known hamartomatous polyp syndromes:[18]

There are two obscure hamartomatous polyp syndromes:[18]

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

Notes:

  • BRBS is due to a PTEN mutation[19] (the same gene associated with Cowden's disease).
  • DPS is reported in only one family that lives in Devon, UK.[20]

Juvenile polyp

Peutz-Jeghers polyp

Cowden disease

  • AKA Cowden syndrome.

General

Etiology:

  • PTEN gene mutation.

Clinical features:[21]

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

Note:

  • Lame mnemonic PATH:[22] Papilloma (oral), Acral keratosis, Trichilemmoma, Hamartomatous polyps.

Microscopic

Features:

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

Weird stuff

Cronkhite-Canada syndrome

  • Abbreviated CCS.

Ganglioneuroma

General

Microscopic

Features - see ganglioneuroma:

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

DDx:

Images

Inflammatory myoglandular polyp

General

  • Controversial - probably not a distinct pathologic entity.[23]
  • Rare, benign, non-neoplastic.[24]
  • Large bowel, usually rectosigmoid.

Microscopic

Features:[25]

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

DDx:[23]

Image:

Leiomyoma

  • May present as a polyp in the colon.[26]

Colonic polyp with reactive subepithelial cells

Microscopic

Features:

  • Surface epithelium with a reduced quantity of cytoplasm and less goblets (regenerative appearance).
  • Mildly atypical subepithelial cells with pale moderate-to-abundant cytoplasm and nuclear enlargement +/-nuclear hyperchromasia.

Sign out

POLYP, ASCENDING COLON, POLYPECTOMY:
- POLYPOID FRAGMENT OF COLONIC-TYPE MUCOSA WITH REACTIVE SUBEPITHELIAL 
  CELLS, SEE COMMENT.
- NEGATIVE FOR DYSPLASIA.

COMMENT:
A pankeratin and CK7 immunostains are non-concerning. A CD68 immunostain 
highlights lamina propria macrophages.

See also

References

  1. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 856. ISBN 0-7216-0187-1.
  2. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 858. ISBN 0-7216-0187-1.
  3. Rex, DK.; Alikhan, M.; Cummings, O.; Ulbright, TM. (Oct 1999). "Accuracy of pathologic interpretation of colorectal polyps by general pathologists in community practice.". Gastrointest Endosc 50 (4): 468-74. PMID 10502165.
  4. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 860. ISBN 0-7216-0187-1.
  5. Li SC, Burgart L (March 2007). "Histopathology of serrated adenoma, its variants, and differentiation from conventional adenomatous and hyperplastic polyps". Arch. Pathol. Lab. Med. 131 (3): 440-5. PMID 17516746. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=131&page=440.
  6. URL: http://www.lab.anhb.uwa.edu.au/mb140/CorePages/GIT/git.htm. Accessed on: 18 October 2012.
  7. 7.0 7.1 Levine JS, Ahnen DJ (December 2006). "Clinical practice. Adenomatous polyps of the colon". N. Engl. J. Med. 355 (24): 2551–7. doi:10.1056/NEJMcp063038. PMID 17167138. http://content.nejm.org/cgi/reprint/355/24/2551.pdf.
  8. Laiyemo, AO.; Murphy, G.; Albert, PS.; Sansbury, LB.; Wang, Z.; Cross, AJ.; Marcus, PM.; Caan, B. et al. (Mar 2008). "Postpolypectomy colonoscopy surveillance guidelines: predictive accuracy for advanced adenoma at 4 years.". Ann Intern Med 148 (6): 419-26. PMID 18347350.
  9. Winawer, SJ.; Zauber, AG. (Jan 2002). "The advanced adenoma as the primary target of screening.". Gastrointest Endosc Clin N Am 12 (1): 1-9, v. PMID 11916153.
  10. 10.0 10.1 Ueno, H.; Mochizuki, H.; Hashiguchi, Y.; Shimazaki, H.; Aida, S.; Hase, K.; Matsukuma, S.; Kanai, T. et al. (Aug 2004). "Risk factors for an adverse outcome in early invasive colorectal carcinoma.". Gastroenterology 127 (2): 385-94. PMID 15300569.
  11. Ueno, H.; Murphy, J.; Jass, JR.; Mochizuki, H.; Talbot, IC. (Feb 2002). "Tumour 'budding' as an index to estimate the potential of aggressiveness in rectal cancer.". Histopathology 40 (2): 127-32. PMID 11952856.
  12. Lugli, A.; Kirsch, R.; Ajioka, Y.; Bosman, F.; Cathomas, G.; Dawson, H.; El Zimaity, H.; Fléjou, JF. et al. (Sep 2017). "Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016.". Mod Pathol 30 (9): 1299-1311. doi:10.1038/modpathol.2017.46. PMID 28548122.
  13. Onishi, T.; Tamura, S.; Kuratani, Y.; Onishi, S.; Yasuda, N. (2008). "Evaluation of the depth score of type V pit patterns in crypt orifices of colorectal neoplastic lesions.". J Gastroenterol 43 (4): 291-7. doi:10.1007/s00535-008-2161-1. PMID 18458845.
  14. Uno, Y.; Munakata, A.. "The non-lifting sign of invasive colon cancer.". Gastrointest Endosc 40 (4): 485-9. PMID 7926542.
  15. Ishiguro, A.; Uno, Y.; Ishiguro, Y.; Munakata, A.; Morita, T. (Sep 1999). "Correlation of lifting versus non-lifting and microscopic depth of invasion in early colorectal cancer.". Gastrointest Endosc 50 (3): 329-33. doi:10.1053/ge.1999.v50.98591. PMID 10462651.
  16. Kimura, R.; Fujimori, T.; Ichikawa, K.; Ajioka, Y.; Ueno, H.; Ohkura, Y.; Kashida, H.; Togashi, K. et al. (Aug 2012). "Desmoplastic reaction in biopsy specimens of early colorectal cancer: a Japanese prospective multicenter study.". Pathol Int 62 (8): 525-31. doi:10.1111/j.1440-1827.2012.02840.x. PMID 22827760.
  17. Hirose, M.; Fukui, H.; Igarashi, Y.; Fujimori, Y.; Katake, Y.; Sekikawa, A.; Ichikawa, K.; Tomita, S. et al. (Dec 2010). "Detection of desmoplastic reaction in biopsy specimens is useful for predicting the depth of invasion of early colorectal cancer: a Japanese collaborative study.". J Gastroenterol 45 (12): 1212-8. doi:10.1007/s00535-010-0288-3. PMID 20665053.
  18. 18.0 18.1 Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 345. ISBN 978-0443066573.
  19. Online 'Mendelian Inheritance in Man' (OMIM) 153480
  20. Allibone, RO.; Nanson, JK.; Anthony, PP. (Jul 1992). "Multiple and recurrent inflammatory fibroid polyps in a Devon family ('Devon polyposis syndrome'): an update.". Gut 33 (7): 1004-5. PMID 1644320.
  21. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 858-9. ISBN 0-7216-0187-1.
  22. URL: http://www.pathologyexpert.com/boards/onlinefiles/syndromes.htm. Accessed on: 6 December 2011.
  23. 23.0 23.1 Bhathal, PS.; Chetty, R.; Slavin, JL. (Aug 1993). "Myoglandular polyps.". Am J Surg Pathol 17 (8): 852-3. PMID 8338196.
  24. 24.0 24.1 Meniconi, RL.; Caronna, R.; Benedetti, M.; Fanello, G.; Ciardi, A.; Schiratti, M.; Papini, F.; Farelli, F. et al. (2010). "Inflammatory myoglandular polyp of the cecum: case report and review of literature.". BMC Gastroenterol 10: 10. doi:10.1186/1471-230X-10-10. PMC 2828397. PMID 20102635. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828397/.
  25. Nakamura, S.; Kino, I.; Akagi, T. (Aug 1992). "Inflammatory myoglandular polyps of the colon and rectum. A clinicopathological study of 32 pedunculated polyps, distinct from other types of polyps.". Am J Surg Pathol 16 (8): 772-9. PMID 1309176.
  26. Kemp, CD.; Arnold, CA.; Torbenson, MS.; Stein, EM. (2011). "An unusual polyp: a pedunculated leiomyoma of the sigmoid colon.". Endoscopy 43 Suppl 2 UCTN: E306-7. doi:10.1055/s-0030-1256640. PMID 21915840.

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