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Colorectal tumours (view source)

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'''Colorectal tumours''' 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.


An introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article.  The precursor lesion of colorectal carcinoma (CRC) is, typical, an adenomatous polyp.  Polyps are discussed in the ''[[intestinal polyps]]'' article.  
''Colonic tumours'' and ''rectal tumours'' redirect here.


==Classification==
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.
*Colon & rectum, most common --by far-- is [[adenocarcinoma]].<ref>{{Ref PBoD|864}}</ref>


Other tumours - many (incomplete list):<ref>{{Ref WMSP|198}}</ref>
=Classification=
*Mucinous carcinoma.
===Most common===
*Adenosquamous carcinoma.
*Colon & rectum - most common = [[colorectal adenocarcinoma|adenocarinoma]].<ref name=Ref_PBoD864>{{Ref PBoD|864}}</ref>
 
===Others===
Other tumours - many (incomplete list):<ref name=Ref_WMSP198>{{Ref WMSP|198}}</ref>
*[[Mucinous carcinoma]].
**Need > 50% mucinous component.<ref name=pmid17679024 >{{cite journal |author=Tozawa E, Ajioka Y, Watanabe H, ''et al.'' |title=Mucin expression, p53 overexpression, and peritumoral lymphocytic infiltration of advanced colorectal carcinoma with mucus component: is mucinous carcinoma a distinct histological entity? |journal=Pathol. Res. Pract. |volume=203 |issue=8 |pages=567–74 |year=2007 |pmid=17679024 |doi=10.1016/j.prp.2007.04.013 |url=}}</ref>
*[[Adenosquamous carcinoma]].
*Signet-ring carcinoma.
*Signet-ring carcinoma.
*Squamous carcinoma.
*Squamous carcinoma.
*Neuroendocrine neoplasms (carcinoid tumours).
*[[Neuroendocrine neoplasm]]s (carcinoid tumours).
*Lipoma.
*[[Lipoma]].
*Leiomyoma.
*[[Leiomyoma]].
*[[Gastrointestinal stromal tumour]] (GIST) - dealt with in a separate article.
*[[Gastrointestinal stromal tumour]] (GIST) - dealt with in a separate article.
*Angiosarcoma.
*[[Angiosarcoma]].
*Lymphoma (Non-Hodgkin's lymphoma).
*Lymphoma (Non-Hodgkin's lymphoma).


==Grading==
Notes:
*"Adenocarcinoma in situ" and "high-grade dysplasia" is used interchangeably by many in the colon and rectum.
*[[Mucinous carcinoma]] - percentage required to call varies by site:
**Splitting hairs - ''adenocarcinoma in situ'' is ''invasion into the lamina propria'', high-grade dysplasia does not have lamina propria invasion. Ergo, the difference (in my opinion) amounts to seeing a [[desmoplastic stroma]] (adenocarcinoma) or not seeing one (dysplasia).
 
Grading 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:
====Squamous carcinoma====
*N0 - no positive nodes.
{{Main|Squamous carcinoma}}
*N1 - 1-3 positive nodes.
*Rare.
*N2 - 4+ positive nodes.
**In the context of a rectal tumour, retrograde growth from the [[anus]] should be considered.


==Staging of colorectal cancer==
==Staging of colorectal cancer==
===Simple version===
{{Main|Colorectal cancer staging}}
Tumour/node grade for stage:<ref>TN 2006 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==
==Pathogenesis of colorectal carcinoma==
===Overview===
Colorectal carcinoma is thought to arise from one of two pathways:<ref name=pmid16483003>{{cite journal |author=Goldstein NS |title=Serrated pathway and APC (conventional)-type colorectal polyps: molecular-morphologic correlations, genetic pathways, and implications for classification |journal=Am. J. Clin. Pathol. |volume=125 |issue=1 |pages=146–53 |year=2006 |month=January |pmid=16483003 |doi= |url=}}</ref><ref name=pmid18314605>{{cite journal |author=Rüschoff J, Aust D, Hartmann A |title=[Colorectal serrated adenoma: diagnostic criteria and clinical implications] |language=German |journal=Verh Dtsch Ges Pathol |volume=91 |issue= |pages=119–25 |year=2007 |pmid=18314605 |doi= |url=}}</ref>
Colorectal carcinoma is thought to arise from one of two pathways:<ref name=pmid16483003>{{cite journal |author=Goldstein NS |title=Serrated pathway and APC (conventional)-type colorectal polyps: molecular-morphologic correlations, genetic pathways, and implications for classification |journal=Am. J. Clin. Pathol. |volume=125 |issue=1 |pages=146–53 |year=2006 |month=January |pmid=16483003 |doi= |url=}}</ref><ref name=pmid18314605>{{cite journal |author=Rüschoff J, Aust D, Hartmann A |title=[Colorectal serrated adenoma: diagnostic criteria and clinical implications] |language=German |journal=Verh Dtsch Ges Pathol |volume=91 |issue= |pages=119–25 |year=2007 |pmid=18314605 |doi= |url=}}</ref>
#APC (adenomatous polyposis coli) gene mutation pathway, [[AKA]] classic adenoma-carcinoma pathway.
#APC (adenomatous polyposis coli) gene mutation pathway, [[AKA]] classic adenoma-carcinoma pathway.
#Serrated pathway, AKA mutator pathway, mismatch repair pathway.
#Serrated pathway, AKA mutator pathway, mismatch repair pathway.
#*Associated with microsatellite instability (MSI).
#*Common associated gene mutations:
#*#MLH1.
#*#PMS2.
#*#MSH2.
#*#MSH6.
#*Less common gene mutations:
#*#PMS1.
#*#MLH3.
#*#MSH3.


====Syndromes====
Both of the above described pathways are associated with syndromes:
#''[[Familial adenomatous polyposis]]'' (FAP) or ''familial polyposis coli'' (FPC).
#''Lynch syndrome'' ([[AKA]] ''[[hereditary non-polyposis colorectal cancer syndrome]]'' (HNPCC)).
===Pathways===
====APC gene mutation pathway====
Microscopic:
*[[Adenomatous polyps]].
====Mismatch repair pathway====
*Associated with [[microsatellite instability]] (MSI).
===Other ancillary studies===
*BRAF ''V600E'' missense mutation found in ~10% CRC.<ref name=pmid20635392>{{cite journal |author=Tie J, Gibbs P, Lipton L, ''et al.'' |title=Optimizing targeted therapeutic development: Analysis of a colorectal cancer patient population with the BRAF(V600E) mutation |journal=Int J Cancer |volume= |issue= |pages= |year=2010 |month=July |pmid=20635392 |doi=10.1002/ijc.25555 |url=}}</ref>
*[[KRAS mutation]] status.


Notes:
====BRAF V600E mutation====
*IHC interpretation:
{{Main|BRAF V600E mutation}}
**MLH1 and PMS2 are lost together.
Features:<ref name=pmid20635392/>
**MSH2 and MSH6 are lost together.
*Independently associated with BRAF V600E:
**Lost in nuclei of tumour.
**Usually older (>70 years old).
*Mutations in hMSH2 more often associated with a germline mutation, while mutation in MLH1 are usually sporatic.
**Female gender.  
**Right-sided tumour location.
*Worse prognosis - in the context of metastatic disease.
 
====KRAS mutation====
{{Main|KRAS mutation}}
Features:<ref name=pmid20956938>{{cite journal |author=Dunn EF, Iida M, Myers RA, ''et al.'' |title=Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab |journal=Oncogene |volume= |issue= |pages= |year=2010 |month=October |pmid=20956938 |doi=10.1038/onc.2010.430 |url=}}</ref><ref name=pmid19001320>{{cite journal |author=Di Nicolantonio F, Martini M, Molinari F, ''et al.'' |title=Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer |journal=J. Clin. Oncol. |volume=26 |issue=35 |pages=5705–12 |year=2008 |month=December |pmid=19001320 |doi=10.1200/JCO.2008.18.0786 |url=}}</ref>
*Patient must have ''wild type'' KRAS to get drugs; KRAS mutation predicts resistance to [[cetuximab]] (Erbitux) and [[panitumumab]] (Vectibix).
**Cetuximab and panitumumab are [[EGFR inhibitors]].


==MSI cancers==
==Microsatellite instability cancers==
===General===
*Abbreviated ''MSI cancers''.
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>
{{Main|Microsatellite instability in colorectal cancer}}
*Prognosis: slightly better than other CRC without MSI.
*Treatment implication: different response to chemotherapy.


====MSI classification====
=Specific entities=
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>
==Colorectal adenocarcinoma==
*MSI-H >= 30% of loci have abnormality.
*[[AKA]] ''colorectal adenocarcinoma not otherwise specified''.
*MSI-L <30% of loci have abnormality.
*[[AKA]] ''colorectal carcinoma'', abbreviated ''CRC''.
{{Main|Colorectal adenocarcinoma}}


===Gross===
==Secondary colorectal cancer==
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>
===General===
*Location: left-sided predominance.
*Uncommon.
*May be suspected.


===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.
*Normal colorectal mucosa.
*Pushing border.<ref>AP. 18 October 2010.</ref>
*Atypical cells in the lamina propria or submucosa.
*Histomorphology:
 
**Poorly differentiated.
DDx:
**Mucinous.
*Colorectal neuroendocrine tumour.
**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>


===Syndromes===
===Images===
*''Lynch syndrome'' AKA ''hereditary non-polyposis colorectal cancer syndrome'' (HNPCC).
<gallery>
*''Familial polyposis coli'' (FPC).
Image:Prostate carcinoma in rectum -- very low mag.jpg | Pca in rectum - very low mag. (WC)
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)
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=
*[[Anus]] - covers anal cancer and anal intraepithelial neoplasia.
*[[Colon]].
*[[Colon]].
*[[Gastrointestinal pathology]].
*[[Gastrointestinal pathology]].
*[[Tumour budding]].
*[[Tumour perforation in colorectal cancer]].
*[[Transanal minimally invasive surgery]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


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