Difference between revisions of "Colorectal tumours"

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Colorectal tumours (view source)

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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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==Staging of colorectal cancer==
==Staging of colorectal cancer==
*"Adenocarcinoma in situ" and "high-grade dysplasia" is used interchangeably by many in the colon and rectum.
{{Main|Colorectal cancer staging}}
**Splitting hairs - ''adenocarcinoma in situ'' is ''invasion into the lamina propria'', high-grade dysplasia does not have lamina propria invasion. Ergo, the difference amounts to seeing a [[desmoplastic stroma]] (adenocarcinoma) or not seeing one (dysplasia).
 
Staging of tumours:
*Tis - in situ (intramucosal).
*T1 - into submucosa (through mucularis mucosae).
**This is '''different than elsewhere''', e.g. in the ''small bowel'' tumour cells in the ''lamina propria'' is defined as T1.  The rationale for the ''T1'' definition in CRC is that no lymphatics are present in the mucosa, ergo no risk of distant spread.
*T2 - into muscularis propria.
*T3 - into fat beyond musclaris propria.
*T4 - into something else.
 
Nodes:
*N0 - no positive nodes.
*N1 - 1-3 positive nodes.
*N2 - 4+ positive nodes.
 
Notes:
*Memory device for N2 = 4+ +ve LNs: the number ''four'' in chinese sounds like ''death''.<ref>URL: [http://en.wikipedia.org/wiki/Numbers_in_Chinese_culture#Four http://en.wikipedia.org/wiki/Numbers_in_Chinese_culture#Four]. Accessed on: 28 June 2011.</ref>
 
==Overall stage==
===Simple version===
Tumour/node grade for stage:<ref>{{Ref TN2006| GS27}}</ref>
*Stage I - '''T1 or T2''' N0 M0.
*Stage II - '''T3 or T4''' N0 M0.
*Stage III - Tx '''N1 or N2''' M0.
*Stage IV - Tx Nx '''M1'''.
 
===Complex version===
Detailed tumour/node grade for stage:<ref>[http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_rectum_cancer_staged.asp http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_rectum_cancer_staged.asp]</ref>
*Stage I - T1 or T2.
*Stage IIA - T3.
*Stage IIB - T4.
*Stage IIIA - T1 N1 or T2 N1.
*Stage IIIB - T3 N1 or T4 N1.
*Stage IIIC - Tx N2.
*Stage IV - Tx Nx M1.


==Pathogenesis of colorectal carcinoma==
==Pathogenesis of colorectal carcinoma==
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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}}


====MSI classification====
==Secondary colorectal cancer==
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>
===General===
*MSI-H >= 30% of loci have abnormality.
*Uncommon.
*MSI-L <30% of loci have abnormality.
*May be suspected.
 
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===
DDx:
Immunostains are commonly done for:
*Colorectal neuroendocrine tumour.
*MLH1.
*PMS2.
*MSH2.
*MSH6.


IHC interpretation:
===Images===
*'''Loss of nuclear staining''' in nuclei of the tumour ''implies'' a mutation.
<gallery>
**Nuclear staining = normal.
Image:Prostate carcinoma in rectum -- very low mag.jpg | Pca in rectum - very low mag. (WC)
* Patchy MSH6 is considered normal.{{fact}}<!-- possibly PMID 21297438 -->
Image:Prostate carcinoma in rectum -- low mag.jpg | Pca in rectum - low mag. (WC)
 
Image:Prostate carcinoma in rectum -- intermed mag.jpg | Pca in rectum - intermed. mag. (WC)
MSI staining loss patterns:<ref name=pmid20632815/>
Image:Prostate carcinoma in rectum -- high mag.jpg | Pca in rectum - high mag. (WC)
*MLH1 and PMS2 are often lost together, as MLH1 loss results in PMS2 loss.
</gallery>
*MSH2 and MSH6 are often lost together, as MSH2 loss results in MSH6 loss.
<gallery>
 
Image:Prostate carcinoma in rectum - PSAP -- intermed mag.jpg | Pca in rectum - PSAP - intermed. mag. (WC)
Implication of MSI staining loss patterns:  
Image:Prostate carcinoma in rectum - PSA -- intermed mag.jpg | Pca in rectum - PSA - intermed. mag. (WC)
*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>
Image:Prostate carcinoma in rectum - CK20 -- intermed mag.jpg | Pca in rectum - CK20 - intermed. mag. (WC)
 
</gallery>
====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:
*The ''MSHs'' are paired together.
**''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=
==Colorectal adenocarcinoma==
*[[AKA]] ''colorectal adenocarcinoma not otherwise specified''.
*[[AKA]] ''colorectal carcinoma'', abbreviated ''CRC''.
{{Main|Colorectal adenocarcinoma}}


=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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