Difference between revisions of "Colorectal tumours"

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'''Colorectal tumours''', especially '''colorectal carcinomas''', are very common.  They are the bread and butter of GI pathology.  Non-tumour colon is dealt with in the ''[[colon]]'' article.
'''Colorectal tumours''', especially '''colorectal carcinomas''', are very common.  They are the bread and butter of GI pathology.  Non-tumour colon is dealt with in the ''[[colon]]'' article.
''Colonic tumours'' and ''rectal tumours'' redirect here.


An introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article.  The precursor lesion of colorectal carcinoma (CRC) is, typically, an [[adenomatous polyps|adenomatous polyp]].  Polyps are discussed in the ''[[intestinal polyps]]'' article.  
An introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article.  The precursor lesion of colorectal carcinoma (CRC) is, typically, an [[adenomatous polyps|adenomatous polyp]].  Polyps are discussed in the ''[[intestinal polyps]]'' article.  
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==Microsatellite instability cancers==
==Microsatellite instability cancers==
*Abbreviated ''MSI cancers''.
*Abbreviated ''MSI cancers''.
===General===
{{Main|Microsatellite instability in colorectal cancer}}
*Can be sporadic, i.e. non-syndromic.<ref name=pmid24199172>{{Cite journal  | last1 = Heinimann | first1 = K. | title = Toward a Molecular Classification of Colorectal Cancer: The Role of Microsatellite Instability Status. | journal = Front Oncol | volume = 3 | issue =  | pages = 272 | month =  | year = 2013 | doi = 10.3389/fonc.2013.00272 | PMID = 24199172 }}</ref>
*Strong association with [[Lynch syndrome]].<ref>{{Cite journal  | last1 = Mensenkamp | first1 = AR. | last2 = Vogelaar | first2 = IP. | last3 = van Zelst-Stams | first3 = WA. | last4 = Goossens | first4 = M. | last5 = Ouchene | first5 = H. | last6 = Hendriks-Cornelissen | first6 = SJ. | last7 = Kwint | first7 = MP. | last8 = Hoogerbrugge | first8 = N. | last9 = Nagtegaal | first9 = ID. | title = Somatic mutations in MLH1 and MSH2 are a Frequent Cause of Mismatch-repair Deficiency in Lynch Syndrome-like Tumors. | journal = Gastroenterology | volume =  | issue =  | pages =  | month = Dec | year = 2013 | doi = 10.1053/j.gastro.2013.12.002 | PMID = 24333619 }}</ref><ref name=pmid24199172/>


Features:<ref name=pmid20420947>{{cite journal |author=Boland CR, Goel A |title=Microsatellite instability in colorectal cancer |journal=Gastroenterology |volume=138 |issue=6 |pages=2073–2087.e3 |year=2010 |month=June |pmid=20420947 |doi=10.1053/j.gastro.2009.12.064 |url=}}</ref>
=Specific entities=
*Prognosis: slightly better than other [[CRC]] without MSI.
==Colorectal adenocarcinoma==
*Treatment implication: different response to chemotherapy.
*[[AKA]] ''colorectal adenocarcinoma not otherwise specified''.
*[[AKA]] ''colorectal carcinoma'', abbreviated ''CRC''.
{{Main|Colorectal adenocarcinoma}}


====When to test====
==Secondary colorectal cancer==
*National Comprehensive Cancer Network (NCCN) in the USA recommends testing all individual with colorectal cancer that are under the age of 70 years.<ref>URL: [http://www.medscape.com/viewarticle/821981 http://www.medscape.com/viewarticle/821981]. Accessed on: 12 January 2016.</ref> 
===General===
*A draft document (2015) from CAP, ASCO suggests testing all colorectal cancer cases for MSI.<ref>URL: [http://www.amp.org/committees/clinical_practice/documents/20150327CRCMMDraftRecommendationsforOCP-UPDATEDfinaldraft_001.pdf http://www.amp.org/committees/clinical_practice/documents/20150327CRCMMDraftRecommendationsforOCP-UPDATEDfinaldraft_001.pdf]. Accessed on: 12 January 2016.</ref>
*Uncommon.
*In Canada the guidelines vary by the province.<ref>URL: [http://www.ncbi.nlm.nih.gov/books/NBK321468/ http://www.ncbi.nlm.nih.gov/books/NBK321468/]. Accessed on: 12 January 2016.</ref>
*May be suspected.
 
===Bethesda criteria of 2004 for MSI testing===
MSI testing should be done if any of the following apply:<ref>{{Cite journal  | last1 = Umar | first1 = A. | last2 = Boland | first2 = CR. | last3 = Terdiman | first3 = JP. | last4 = Syngal | first4 = S. | last5 = de la Chapelle | first5 = A. | last6 = Rüschoff | first6 = J. | last7 = Fishel | first7 = R. | last8 = Lindor | first8 = NM. | last9 = Burgart | first9 = LJ. | title = Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. | journal = J Natl Cancer Inst | volume = 96 | issue = 4 | pages = 261-8 | month = Feb | year = 2004 | doi = | PMID = 14970275 }}</ref>
*Colorectal cancer in patient <50 years old.
*Colorectal cancer with MSI-H histology <60 years old.
*Regardless of age - any of the following:
**HNPCC-associated tumours.
**Synchronous colorectal cancer.
**Metachronous colorectal cancer.
*Colorectal cancer in an individual with:
**One or more first degree relatives with a HNPCC-related tumour diagnosed when <50 years old.
**Two or more first- or second degree relatives with HNPCC-related tumours (diagnosed at any age).
 
Note:
*Formally known as ''Revised Bethesda Guidelines for Hereditary Nonpolyposis
Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability''.
 
====MSI classification====
MSI associated cancers can be classified into:<ref name=pmid16106253>{{cite journal |author=Lawes DA, Pearson T, Sengupta S, Boulos PB |title=The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers |journal=Br. J. Cancer |volume=93 |issue=4 |pages=472–7 |year=2005 |month=August |pmid=16106253 |pmc=2361590 |doi=10.1038/sj.bjc.6602708 |url=}}</ref><ref name=pmid11438476>{{cite journal |author=Guidoboni M, Gafà R, Viel A, ''et al.'' |title=Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis |journal=Am. J. Pathol. |volume=159 |issue=1 |pages=297–304 |year=2001 |month=July |pmid=11438476 |pmc=1850401 |doi= |url=}}</ref>
*MSI-H >= 30% of loci have abnormality.
*MSI-L <30% of loci have abnormality.
 
Note:
*In the context of '''''no''''' chemotherapy, individuals with MSI-H tumours have a superior outcome to those with MSI-L tumours.<ref name=pmid12867608>{{Cite journal  | last1 = Ribic | first1 = CM. | last2 = Sargent | first2 = DJ. | last3 = Moore | first3 = MJ. | last4 = Thibodeau | first4 = SN. | last5 = French | first5 = AJ. | last6 = Goldberg | first6 = RM. | last7 = Hamilton | first7 = SR. | last8 = Laurent-Puig | first8 = P. | last9 = Gryfe | first9 = R. | title = Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. | journal = N Engl J Med | volume = 349 | issue = 3 | pages = 247-57 | month = Jul | year = 2003 | doi = 10.1056/NEJMoa022289 | PMID = 12867608 }}</ref>
**With chemotherapy the outcomes are similar.
 
===Gross===
Features:<ref name=pmid20420947>{{cite journal |author=Boland CR, Goel A |title=Microsatellite instability in colorectal cancer |journal=Gastroenterology |volume=138 |issue=6 |pages=2073–2087.e3 |year=2010 |month=June |pmid=20420947 |doi=10.1053/j.gastro.2009.12.064 |url=}}</ref>
*Location: proximal colon, i.e. right-sided, predominance.


===Microscopic===
===Microscopic===
Features:<ref name=pmid20420947>{{cite journal |author=Boland CR, Goel A |title=Microsatellite instability in colorectal cancer |journal=Gastroenterology |volume=138 |issue=6 |pages=2073–2087.e3 |year=2010 |month=June |pmid=20420947 |doi=10.1053/j.gastro.2009.12.064 |url=}}</ref>
Features:
*Lymphocytic infiltrate - see ''[[intratumoural lymphocytic response]]''.
*Normal colorectal mucosa.
*Large peritumoural collections of lymphocytes - see ''[[peritumoural lymphocytic response]]''.
*Atypical cells in the lamina propria or submucosa.
*Pushing border.<ref>Pollet, A. 18 October 2010.</ref>
*Histomorphology:
**Poorly differentiated.
**Mucinous.
**[[Signet ring cell carcinoma|Signet ring]].
**Medullary.<ref name=pmid18283560>{{cite journal |author=Truta B, Chen YY, Blanco AM, ''et al.'' |title=Tumor histology helps to identify Lynch syndrome among colorectal cancer patients |journal=Fam. Cancer |volume=7 |issue=3 |pages=267–74 |year=2008 |pmid=18283560 |doi=10.1007/s10689-008-9186-8 |url=}}</ref>
 
===Molecular===
Commonly associated abnormalities in the genes:
#MLH1.
#PMS2.
#MSH2.
#MSH6.
Less common abnormalities:
#PMS1.
#MLH3.
#MSH3.
 
===IHC===
Immunostains are commonly done for:
*MLH1.
*PMS2.
*MSH2.
*MSH6.
 
IHC interpretation:
*'''Loss of nuclear staining''' in nuclei of the tumour ''implies'' a mutation.
**Nuclear staining = normal.
* Patchy MSH6 is considered normal.{{fact}}<!-- possibly PMID 21297438 -->
 
MSI staining loss patterns:<ref name=pmid20632815/>
*MLH1 and PMS2 are often lost together, as MLH1 loss results in PMS2 loss.
*MSH2 and MSH6 are often lost together, as MSH2 loss results in MSH6 loss.
 
Implication of MSI staining loss patterns:
*PMS2 & MSH6 can be used as a screen.<ref name=pmid20632815>{{Cite journal  | last1 = Hall | first1 = G. | last2 = Clarkson | first2 = A. | last3 = Shi | first3 = A. | last4 = Langford | first4 = E. | last5 = Leung | first5 = H. | last6 = Eckstein | first6 = RP. | last7 = Gill | first7 = AJ. | title = Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair deficiency screening in colorectal adenocarcinoma. | journal = Pathology | volume = 42 | issue = 5 | pages = 409-13 | month =  | year = 2010 | doi = 10.3109/00313025.2010.493871 | PMID = 20632815 }}</ref>
 
====Etiology/significance loss of staining====
*MSH2 mutations (IHC stain -ve) - often associated with a germline mutation,<ref name=pmid16216036>{{cite journal |author=Mangold E, Pagenstecher C, Friedl W, ''et al.'' |title=Tumours from MSH2 mutation carriers show loss of MSH2 expression but many tumours from MLH1 mutation carriers exhibit weak positive MLH1 staining |journal=J. Pathol. |volume=207 |issue=4 |pages=385–95 |year=2005 |month=December |pmid=16216036 |doi=10.1002/path.1858 |url=}}</ref> while mutations in MLH1 are usually sporatic.<ref>A. Pollett. 2010.</ref>
*PMS2 mutations (IHC stain -ve) - often associated with a germline mutation.<ref name=pmid20205264>{{cite journal |author=Vaughn CP, Robles J, Swensen JJ, ''et al.'' |title=Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes |journal=Hum. Mutat. |volume=31 |issue=5 |pages=588–93 |year=2010 |month=May |pmid=20205264 |doi=10.1002/humu.21230 |url=}}</ref>


How to remember the more important MSI stuff:
DDx:
*The ''MSHs'' are paired together.
*Colorectal neuroendocrine tumour.
**''MSH'' (Mount Sinai Hospital) is where they started it in the city.
**''PMS'' sucks... it's with the other one (MLH).
*The higher numbers in the pairings ('''P'''MS2, '''M'''SH6) are the screening tests ('''''H'''igh Screen '''P'''ass'').
*The ''2''s (MSH2, PMS2) are associated with germline mutations (''Four legs good two legs bad!'').


=Specific entities=
===Images===
==Colorectal adenocarcinoma==
<gallery>
*[[AKA]] ''colorectal adenocarcinoma not otherwise specified''.
Image:Prostate carcinoma in rectum -- very low mag.jpg | Pca in rectum - very low mag. (WC)
*[[AKA]] ''colorectal carcinoma'', abbreviated ''CRC''.
Image:Prostate carcinoma in rectum -- low mag.jpg | Pca in rectum - low mag. (WC)
{{Main|Colorectal adenocarcinoma}}
Image:Prostate carcinoma in rectum -- intermed mag.jpg | Pca in rectum - intermed. mag. (WC)
Image:Prostate carcinoma in rectum -- high mag.jpg | Pca in rectum - high mag. (WC)
</gallery>
<gallery>
Image:Prostate carcinoma in rectum - PSAP -- intermed mag.jpg | Pca in rectum - PSAP - intermed. mag. (WC)
Image:Prostate carcinoma in rectum - PSA -- intermed mag.jpg | Pca in rectum - PSA - intermed. mag. (WC)
Image:Prostate carcinoma in rectum - CK20 -- intermed mag.jpg | Pca in rectum - CK20 - intermed. mag. (WC)
</gallery>


=See also=
=See also=
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*[[Gastrointestinal pathology]].
*[[Gastrointestinal pathology]].
*[[Tumour budding]].
*[[Tumour budding]].
*[[Tumour perforation in colorectal cancer]].
*[[Transanal minimally invasive surgery]].


=References=
=References=
Michael
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