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Colorectal adenocarcinoma (view source)

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#redirect [[Colorectal_tumours#Colorectal_adenocarcinoma]]
'''Colorectal adenocarcinoma''' is very common and a leading cause of death due to [[cancer]]. This article deals with ''colorectal adenocarcinoma not otherwise specified''.
 
''Colorectal carcinoma'', abbreviated ''CRC'', is typically considered a synonym.
 
==General==
*Very common.
*Rectum and sigmoid > proximal large bowel.
 
Presentation:
*Bright red blood per rectum (BRBPR).
*Constipation.
*Symptoms of bowel obstruction - nausea, vomiting.
 
Pathogenesis - see ''[[Colorectal_tumours#Pathogenesis_of_colorectal_carcinoma|pathogenesis of colorectal carcinoma]]''.
 
==Gross==
Often circumferential or near circumferential:
*These are referred to as "apple core lesion" ''or'' "napkin-ring" lesion.
 
Mucosa:
*Granular appearance.
*Raised (exophytic) ''or'' heaped edges with ulceration.
 
Note:
*''Total mesorectal excisions'' should be assessed for completeness.
*The (soft tissue) radial margins, as present in TMEs and right hemicolectomies, should be inked.<ref>URL: [http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=13954 http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=13954]. Accessed on: 6 February 2013. </ref><ref name=pmid15790712>{{Cite journal  | last1 = Bateman | first1 = AC. | last2 = Carr | first2 = NJ. | last3 = Warren | first3 = BF. | title = The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin? | journal = J Clin Pathol | volume = 58 | issue = 4 | pages = 426-8 | month = Apr | year = 2005 | doi = 10.1136/jcp.2004.019802 | PMID = 15790712 }}</ref>
 
===Images===
<gallery>
Image:Colon_cancer.jpg | CRC - gross. (WC)
Image:Colon_cancer_2.jpg | CRC - gross. (WC)
</gallery>
<gallery>
Image:Rectum - anterior view.jpg | Rectum - anterior view. (WC)
Image:Rectum - lateral_view.jpg | Rectum - lateral view. (WC)
Image:Rectum - anterior and lateral - inked.jpg| Rectum - inked. (WC)
Image:Rectum - opened.jpg | Rectum - opened (WC)
</gallery>
 
==Microscopic==
Features:
*Nuclear atypia:
**Nuclear pseudostratification.
**Nuclear hyperchromasia.
**Chromatin clearing or granularity.
*+/-Necrosis.
*Architecture - important for grading:
**Glands.
**Sheets.
 
===Images===
<gallery>
Image:Cecal adenocarcinoma.jpg | Cecal adenocarcinoma. (WC)
Image:Colonic_mucinous_adenocarcinoma_-_very_low_mag.jpg | [[Mucinous adenocarcinoma]] - very low mag. (WC/Nephron)
Image:Colonic_mucinous_adenocarcinoma_-_low_mag.jpg | Mucinous adenocarcinoma - low mag. (WC/Nephron)
Image:Adenocarcinoma_coli.jpg | Colorectal adenocarcinoma. (WC)
Image:Crc_met_to_node1.jpg | CRC [[lymph node metastasis]]. (WC/Nephron)
</gallery>
www:
*[http://www.flickr.com/photos/euthman/2480926690/in/set-72057594114099781 Colorectal adenocarcinoma (flickr.com/euthman)].
 
===Grading===
Based on component composed of glands:
*>=50% of tumour = low-grade (''well-differentiated'' and ''moderately differentiated'').
*<50% of tumour = high-grade (''poorly-differentiated'' and ''undifferentiated'').
 
===Peritumour lymphocytic response===
*[[AKA]] ''Crohn's-like lymphoid reaction''.
*[[AKA]] ''Crohn's like reaction''.<ref name=pmid19825961>{{Cite journal  | last1 = Ogino | first1 = S. | last2 = Nosho | first2 = K. | last3 = Irahara | first3 = N. | last4 = Meyerhardt | first4 = JA. | last5 = Baba | first5 = Y. | last6 = Shima | first6 = K. | last7 = Glickman | first7 = JN. | last8 = Ferrone | first8 = CR. | last9 = Mino-Kenudson | first9 = M. | title = Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. | journal = Clin Cancer Res | volume = 15 | issue = 20 | pages = 6412-20 | month = Oct | year = 2009 | doi = 10.1158/1078-0432.CCR-09-1438 | PMID = 19825961 }}</ref>
*[[AKA]] ''Crohn-like repsonse''.<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Colon_12protocol_3200.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Colon_12protocol_3200.pdf]. Accessed on: 14 September 2012.</ref>
 
====General====
*Finding associated with improved survival in CRC.<ref name=pmid7821914 >{{Cite journal  | last1 = Harrison | first1 = JC. | last2 = Dean | first2 = PJ. | last3 = el-Zeky | first3 = F. | last4 = Vander Zwaag | first4 = R. | title = Impact of the Crohn's-like lymphoid reaction on staging of right-sided colon cancer: results of multivariate analysis. | journal = Hum Pathol | volume = 26 | issue = 1 | pages = 31-8 | month = Jan | year = 1995 | doi =  | PMID = 7821914 }}</ref>
 
====Microscopic====
[[Onlinepathology]] advocates use of the Ueno criteria. They have a better inter-rater reproducibility than the older Graham criteria<ref name=pmid2362940/> and are less complicated.
 
=====Ueno criteria (2013)=====
Required criteria:<ref name=pmid23525613>{{Cite journal  | last1 = Ueno | first1 = H. | last2 = Hashiguchi | first2 = Y. | last3 = Shimazaki | first3 = H. | last4 = Shinto | first4 = E. | last5 = Kajiwara | first5 = Y. | last6 = Nakanishi | first6 = K. | last7 = Kato | first7 = K. | last8 = Maekawa | first8 = K. | last9 = Miyai | first9 = K. | title = Objective Criteria for Crohn-like Lymphoid Reaction in Colorectal Cancer. | journal = Am J Clin Pathol | volume = 139 | issue = 4 | pages = 434-41 | month = Apr | year = 2013 | doi = 10.1309/AJCPWHUEFTGBWKE4 | PMID = 23525613 }}</ref>
*Non-MALT lymphoid aggregates (peritumoural) >= 1 mm.
 
Ignore:
#Muscosa-associated lymphoid tissue (MALT) = mucosal lymphoid aggregates, submucosal lymphoid aggregates adjacent to the musuclaris mucosae.
#Lymph nodes - these have a (fibrous) capsule.
#Irregular shape (not round).
 
=====Graham criteria (1990)=====
Required criteria:<ref name=pmid2362940>{{Cite journal  | last1 = Graham | first1 = DM. | last2 = Appelman | first2 = HD. | title = Crohn's-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator. | journal = Mod Pathol | volume = 3 | issue = 3 | pages = 332-5 | month = May | year = 1990 | doi =  | PMID = 2362940 }}</ref>
*Peritumoral:
*#Lymphoid aggregates with germinal centres focally.
*#Stellate fibrosis.
*#No previous clinical and pathologic evidence of [[Crohn's disease]].
 
Note:
*Should '''not''' be confused with [[intratumoural lymphocytic response]].
**The intratumoural lymphocytic response is associated with MSI-H cancers.
 
=====Images=====
<gallery>
Image:Peritumour lymphocytic response - low mag.jpg | PLR - low mag. (WC)
Image:Peritumour lymphocytic response - intermed mag.jpg | PLR - intermed. mag. (WC)
</gallery>
www:
*[http://jcp.bmjjournals.com/content/62/8/679/F2.large.jpg Peritumour lymphocytic response in endometrial carcinoma (bmjjournals.com)].
*[http://ajcp.ascpjournals.org/content/134/3/478/F3.expansion.html Peritumour lymphocytic response in CRC (ascpjournals.org)].<ref name=pmid20716806>{{Cite journal  | last1 = Ross | first1 = JS. | last2 = Torres-Mora | first2 = J. | last3 = Wagle | first3 = N. | last4 = Jennings | first4 = TA. | last5 = Jones | first5 = DM. | title = Biomarker-based prediction of response to therapy for colorectal cancer: current perspective. | journal = Am J Clin Pathol | volume = 134 | issue = 3 | pages = 478-90 | month = Sep | year = 2010 | doi = 10.1309/AJCP2Y8KTDPOAORH | PMID = 20716806 | URL = http://ajcp.ascpjournals.org/content/134/3/478.full}}</ref>
 
===Intratumoural lymphocytic response===
*[[AKA]] '' tumour-infiltrating lymphocytes'', abbreviated ''TILs''.
 
====General====
*Finding is suggestive of microsatellite instabillity.<ref name=pmid21114775>{{Cite journal  | last1 = Iacopetta | first1 = B. | last2 = Grieu | first2 = F. | last3 = Amanuel | first3 = B. | title = Microsatellite instability in colorectal cancer. | journal = Asia Pac J Clin Oncol | volume = 6 | issue = 4 | pages = 260-9 | month = Dec | year = 2010 | doi = 10.1111/j.1743-7563.2010.01335.x | PMID = 21114775 }}</ref>
**May be seen in the context of [[Lynch syndrome]].
 
====Microscopic====
Features:
*Lymphocytes are between the tumour cells.<ref name=pmid19638537/> †
**Other lymphocytes do not count.
 
Note:
* † Definitions vary substantially - some authors consider lymphocytes adjacent to the tumour (in the stroma around the tumour cells) "intratumoural".<reF name=pmid9349235>{{Cite journal  | last1 = Ropponen | first1 = KM. | last2 = Eskelinen | first2 = MJ. | last3 = Lipponen | first3 = PK. | last4 = Alhava | first4 = E. | last5 = Kosma | first5 = VM. | title = Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer. | journal = J Pathol | volume = 182 | issue = 3 | pages = 318-24 | month = Jul | year = 1997 | doi = 10.1002/(SICI)1096-9896(199707)182:3318::AID-PATH8623.0.CO;2-6 | PMID = 9349235 |URL = http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291096-9896%28199707%29182:3%3C318::AID-PATH862%3E3.0.CO;2-6/pdf}}</ref>
 
=====Images=====
<gallery>
Image:Tumour_infiltrating_lymphocytes_in_colorectal_carcinoma_-_high_mag.jpg | TILs - high mag. (WC/Nephron)
Image:Tumour_infiltrating_lymphocytes_in_colorectal_carcinoma_-_very_high_mag.jpg | TILs - very high mag. (WC/Nephron)
</gallery>
www:
*[http://jcp.bmjjournals.com/content/62/8/679/F3.large.jpg TILs in endometrial carcinoma (bmjjournals.com)].<ref name=pmid19638537>{{Cite journal  | last1 = Garg | first1 = K. | last2 = Soslow | first2 = RA. | title = Lynch syndrome (hereditary non-polyposis colorectal cancer) and endometrial carcinoma. | journal = J Clin Pathol | volume = 62 | issue = 8 | pages = 679-84 | month = Aug | year = 2009 | doi = 10.1136/jcp.2009.064949 | PMID = 19638537 | URL = http://jcp.bmjjournals.com/content/62/8/679.full?related-urls=yes&legid=jclinpath;62/8/679 }}</ref>
*[http://ajcp.ascpjournals.org/content/134/3/478/F2.expansion.html TILs in CRC (ascpjournals.org)].<ref name=pmid20716806/>
 
===Tumour deposits===
*[[AKA]] ''discoutinuous extramural extension''.
*[[AKA]] ''peritumoral deposits''.
====General====
*Poor prognosticator.
**Can be understood as a type of invasive front/border, e.g. ''well-circumscribed border'' versus ''infiltrative border''.<ref name=pmid24112678/>
*No standardized criteria for tumour deposits.<ref name=pmid24112678>{{Cite journal  | last1 = Ueno | first1 = H. | last2 = Hashiguchi | first2 = Y. | last3 = Shimazaki | first3 = H. | last4 = Shinto | first4 = E. | last5 = Kajiwara | first5 = Y. | last6 = Nakanishi | first6 = K. | last7 = Kato | first7 = K. | last8 = Maekawa | first8 = K. | last9 = Nakamura | first9 = T. | title = Peritumoral deposits as an adverse prognostic indicator of colorectal cancer. | journal = Am J Surg | volume =  | issue =  | pages =  | month = Oct | year = 2013 | doi = 10.1016/j.amjsurg.2013.04.009 | PMID = 24112678 }}</ref>
 
Ueno ''et al.'' propose that a tumour deposit is either:<ref name=pmid24112678/>
#>=2 mm from the tumour front
#>=2 mm (radially) from the deepest aspect of the muscularis propria, if the tumour is not present in the section.
 
===Tumour regression===
There is a three tiered regression grading system by Ryan ''et al''. for colorectal cancer that has essentially been adopted by [[CAP]]:<ref name=pmid16045774>{{Cite journal  | last1 = Ryan | first1 = R. | last2 = Gibbons | first2 = D. | last3 = Hyland | first3 = JM. | last4 = Treanor | first4 = D. | last5 = White | first5 = A. | last6 = Mulcahy | first6 = HE. | last7 = O'Donoghue | first7 = DP. | last8 = Moriarty | first8 = M. | last9 = Fennelly | first9 = D. | title = Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. | journal = Histopathology | volume = 47 | issue = 2 | pages = 141-6 | month = Aug | year = 2005 | doi = 10.1111/j.1365-2559.2005.02176.x | PMID = 16045774 }}</ref>
{| class="wikitable sortable"
! Grade
! Features
|-
| Grade 1
| small groups of tumour cells or single tumour cells
|-
| Grade 2
| definite tumour but more fibrosis ("cancer outgrown by fibrosis")
|-
| Grade 3
| definite tumour with no fibrosis ''or'' tumour with a lesser amount of fibrosis ("fibrosis outgrown by cancer")
|}
 
==IHC==
*CK7 -ve.
*CK20 +ve.
*CEA +ve.
*CDX2 +ve.
 
==Molecular==
*KRAS mutation analysis.
**Mutation present ~ 40% of [[CRC]].
**Mutations in codons 12 or 13 associated with failure of anti-EGFR therapy (e.g. ''cetuximab'', ''panitumumab'').<ref name=pmid19792050>{{Cite journal  | last1 = Monzon | first1 = FA. | last2 = Ogino | first2 = S. | last3 = Hammond | first3 = ME. | last4 = Halling | first4 = KC. | last5 = Bloom | first5 = KJ. | last6 = Nikiforova | first6 = MN. | title = The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. | journal = Arch Pathol Lab Med | volume = 133 | issue = 10 | pages = 1600-6 | month = Oct | year = 2009 | doi = 10.1043/1543-2165-133.10.1600 | PMID = 19792050 }}</ref>
*BRAF mutation analysis.
**''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>
 
Note:
*KRAS mutations and BRAF mutations are considered mutually exclusive as they occur in the same pathway.
 
==Sign out==
===Right hemicolectomy===
<pre>
TERMINAL ILEUM, CECUM, ASCENDING COLON AND APPENDIX, RIGHT HEMICOLECTOMY:
- INVASIVE ADENOCARCINOMA WITH A MUCINOUS COMPONENT, LOW-GRADE, pT1, pN0.
-- MARGINS NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
-- PLEASE SEE TUMOUR SUMMARY.
- SMALL BOWEL WALL WITHIN NORMAL LIMITS.
- APPENDIX WITHOUT SIGNIFICANT PATHOLOGY.
- FOURTEEN LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 14 ).
</pre>
 
==See also==
*[[Colon]].
 
==References==
{{Reflist|2}}


[[Category:Diagnosis]]
[[Category:Diagnosis]]
[[Category:Colorectal tumours]]
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