Difference between revisions of "Colorectal adenocarcinoma"

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*Constipation.  
*Constipation.  
*Symptoms of bowel obstruction - nausea, vomiting.
*Symptoms of bowel obstruction - nausea, vomiting.
*Weight loss.


Pathogenesis - see ''[[Colorectal_tumours#Pathogenesis_of_colorectal_carcinoma|pathogenesis of colorectal carcinoma]]''.
Pathogenesis - see ''[[Colorectal_tumours#Pathogenesis_of_colorectal_carcinoma|pathogenesis of colorectal carcinoma]]''.
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Image:Crc_met_to_node1.jpg | CRC [[lymph node metastasis]]. (WC/Nephron)
Image:Crc_met_to_node1.jpg | CRC [[lymph node metastasis]]. (WC/Nephron)
</gallery>
</gallery>
<gallery>
File:3 13657755265018 sl 1.png|Medullary carcinoma of cecum.
File:3 13657755265018 sl 2.png|Medullary carcinoma of cecum.
File:3 13657755265018 sl 3.png|Medullary carcinoma of cecum.
File:3 13657755265018 sl 4.png|Medullary carcinoma of cecum.
</gallery>
Medullary carcinoma of cecum of elderly woman. A. Tumor extends from the luminal surface at upper left into the muscularis propria at lower right. Note variable longitudinal spaces in the tumor. B. Tumor extends into pericolic fat. Note relative circumscription, with pushing borders. C. Tumor cells, often in seeming syncitiums, strew lymphocytes. D. In other areas, there appears to be a pattern suggesting nests and stromal trabeculums. Chromogranin/synaptophysin were negative.
www:
www:
*[http://www.flickr.com/photos/euthman/2480926690/in/set-72057594114099781 Colorectal adenocarcinoma (flickr.com/euthman)].
*[http://www.flickr.com/photos/euthman/2480926690/in/set-72057594114099781 Colorectal adenocarcinoma (flickr.com/euthman)].


===Grading===
===Grading===
8th edition of AJCC - based on component composed of glands:
*Grade 1: >95% of tumour = ''well-differentiated''.
*Grade 2: >=50-95% of tumour = ''moderately differentiated''.
*Grade 3: <50% of tumour = ''poorly-differentiated''.
*Grade 4: 0% glandular, no mucin, no squamous differentiation = ''undifferentiated''.
====Old system====
Based on component composed of glands:
Based on component composed of glands:
*>=50% of tumour = low-grade (''well-differentiated'' and ''moderately differentiated'').
*>=50% of tumour = low-grade (''well-differentiated'' and ''moderately differentiated'').
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*[[AKA]] ''discoutinuous extramural extension''.
*[[AKA]] ''discoutinuous extramural extension''.
*[[AKA]] ''peritumoral deposits''.
*[[AKA]] ''peritumoral deposits''.
====General====
{{Main|Tumour deposit}}
Definition - TNM/AJCC 7th edition:<ref name=pmid21555695/>
*Microscopic or macroscopic nodule in the lymphatic drainage bed of the tumour.
**No standardized distance (from tumour) criteria are defined.<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>
*No findings suggestive of it being a lymph node replaced by tumour:
*#No significant lymphoid tissue.
*#Irregular contour.
*#*Round nodules of tumour are considered lymph nodes that are replaced by tumour.
 
Significance:
*Poor prognosticator.
**Can be understood as a type of invasive front/border, e.g. ''well-circumscribed border'' versus ''infiltrative border''.<ref name=pmid24112678/>
 
Staging implications:
*Tumour deposits are '''not''' counted as (positive) lymph nodes<ref name=pmid21555695>{{Cite journal  | last1 = Nagtegaal | first1 = ID. | last2 = Tot | first2 = T. | last3 = Jayne | first3 = DG. | last4 = McShane | first4 = P. | last5 = Nihlberg | first5 = A. | last6 = Marshall | first6 = HC. | last7 = Påhlman | first7 = L. | last8 = Brown | first8 = JM. | last9 = Guillou | first9 = PJ. | title = Lymph nodes, tumor deposits, and TNM: are we getting better? | journal = J Clin Oncol | volume = 29 | issue = 18 | pages = 2487-92 | month = Jun | year = 2011 | doi = 10.1200/JCO.2011.34.6429 | PMID = 21555695 }}</ref> and in the context of positive lymph nodes do not change the N stage.
**If no positive lymph nodes are present, the N stage is pN1c.
*The T stage is ''not'' affected by tumour deposits.<ref name=pmid21555695/>
 
Notes:
*The definition of ''tumour deposit'' has changed significantly between the TMN/AJCC fifth, sixth and seventh editions.<ref name=pmid21555695/>
*Conceptually the same as the ''[[in-transit metastasis]]'' of [[malignant melanoma]]<ref name=pmid19136930>{{Cite journal  | last1 = Puppa | first1 = G. | last2 = Ueno | first2 = H. | last3 = Kayahara | first3 = M. | last4 = Capelli | first4 = P. | last5 = Canzonieri | first5 = V. | last6 = Colombari | first6 = R. | last7 = Maisonneuve | first7 = P. | last8 = Pelosi | first8 = G. | title = Tumor deposits are encountered in advanced colorectal cancer and other adenocarcinomas: an expanded classification with implications for colorectal cancer staging system including a unifying concept of in-transit metastases. | journal = Mod Pathol | volume = 22 | issue = 3 | pages = 410-5 | month = Mar | year = 2009 | doi = 10.1038/modpathol.2008.198 | PMID = 19136930 }}</ref> and [[dermatopathology]].
 
=====Ueno criteria=====
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 plane of section.


===Tumour regression===
===Tumour regression===
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*BRAF mutation analysis.
*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>
**''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>
*Microsatellite instability - see ''[[microsatellite instability in colorectal cancer]]''.


Note:
Note:
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-- TWELVE LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 12 ).
-- TWELVE LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 12 ).
-- PLEASE SEE TUMOUR SUMMARY.
-- PLEASE SEE TUMOUR SUMMARY.
</pre>
===Biomarker and molecular testing===
<pre>
The Colorectal Cancer Panel (BRAF, KRAS, NRAS, PIK3CA, PTEN) was ordered on block {}. MMR testing was ordered on block {}.
</pre>
</pre>


Latest revision as of 14:43, 19 December 2023

Colorectal adenocarcinoma
Diagnosis in short

Colorectal adenocarcinoma. H&E stain.
LM DDx other adenocarcinomas (e.g. anal gland adenocarcinoma, lung adenocarcinoma, ovarian adenocarcinoma), traditional adenoma esp. with high-grade dysplasia, sessile serrated adenoma with dysplasia
IHC CK20 +ve, CDX2 +ve, CK7 -ve, beta-catenin (nuclear) +ve
Grossing notes lower anterior resection for cancer grossing, other protocols
Staging colorectal cancer staging
Site rectum, colon, cecum, appendix
Associated Dx long standing IBD (Crohn's disease, ulcerative colitis), traditional adenoma esp. with high-grade dysplasia, sessile serrated adenoma esp. with dysplasia
Syndromes familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, Juvenile polyposis syndrome, serrated polyposis syndrome, MUTYH polyposis syndrome, Cowden syndrome
Signs +/-blood in stools, +/-abdominal mass, +/-rectal mass, +/-signs of bowel obstruction (nausea, vomiting), +/-narrow caliber stools
Symptoms +/-constipation
Prevalence common
Blood work +/-anemia (microcytic), +/-CEA elevated
Radiology +/-"apple core" lesion (classic), +/-findings of bowel obstruction (air-fluid levels esp. with transition point)
Endoscopy +/-suspicious mass (exophytic or ulcerated), presence of non-lifting sign, Kudo pit pattern Type VI or Type VN
Prognosis good to poor
Other fecal occult blood test (FOBT) +ve
Clin. DDx colorectal tumours, other causes - DDx dependent on presentation
Treatment usually surgical resection +/-chemotherapy +/-radiation

Colorectal adenocarcinoma is very common, a leading cause of death due to cancer, and the most common form of colon cancer.

The colon and rectum are lumped together as the mucosa in the large bowel is very similar. Thus, colonic adenocarcinoma and rectal adenocarcinoma redirect to this article.

The larger generally topic of colorectal tumours and the pathogenesis of colorectal adenocarcinoma is dealt with in the colorectal tumours article.

Colorectal carcinoma, abbreviated CRC, is typically considered a synonym. Cecal adenocarcinoma is also lumped into CRC.

General

  • Very common.
  • Rectum and sigmoid > proximal large bowel.

Presentation:

Pathogenesis - see pathogenesis of colorectal carcinoma.

Clinical - serum:

  • CEA elevated.[1]
  • CA19-9 elevated.
  • Colon cancer-specific antigen-2 (CCSA-2) elevated.[2]
    • Relatively new; preliminary in 2014.

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.[3][4]

Images

  • CRC - gross. (WC)

  • CRC - gross. (WC)

  • Rectum - anterior view. (WC)

  • Rectum - lateral view. (WC)

  • Rectum - inked. (WC)

  • Rectum - opened (WC)

Microscopic

Features:

  • Nuclear atypia:
    • Nuclear pseudostratification.
    • Nuclear hyperchromasia.
    • Chromatin clearing or granularity.
  • +/-Necrosis.
  • Architecture - important for grading:
    • Glands.
    • Sheets.

DDx:

Images

  • CRC - low mag. (WC)

  • CRC - intermed. mag. (WC)

  • CRC - high mag. (WC)

  • CRC - low mag. (WC)

  • CRC - intermed. mag. (WC)

  • CRC - high mag. (WC)

  • Cecal adenocarcinoma. (WC/Nephron)

  • Colorectal adenocarcinoma. (WC)

  • CRC lymph node metastasis. (WC/Nephron)

  • Medullary carcinoma of cecum.

  • Medullary carcinoma of cecum.

  • Medullary carcinoma of cecum.

  • Medullary carcinoma of cecum.

Medullary carcinoma of cecum of elderly woman. A. Tumor extends from the luminal surface at upper left into the muscularis propria at lower right. Note variable longitudinal spaces in the tumor. B. Tumor extends into pericolic fat. Note relative circumscription, with pushing borders. C. Tumor cells, often in seeming syncitiums, strew lymphocytes. D. In other areas, there appears to be a pattern suggesting nests and stromal trabeculums. Chromogranin/synaptophysin were negative.

www:

Grading

8th edition of AJCC - based on component composed of glands:

  • Grade 1: >95% of tumour = well-differentiated.
  • Grade 2: >=50-95% of tumour = moderately differentiated.
  • Grade 3: <50% of tumour = poorly-differentiated.
  • Grade 4: 0% glandular, no mucin, no squamous differentiation = undifferentiated.

Old system

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).

Peritumoural lymphocytic response

  • AKA Crohn's-like lymphoid reaction.
  • AKA Crohn's like reaction.[5]
  • AKA Crohn-like response.[6]
Main article: Peritumoural lymphocytic response

Intratumoural lymphocytic response

  • AKA tumour-infiltrating lymphocytes, abbreviated TILs.
Main article: Intratumoural lymphocytic response in colorectal carcinoma

Tumour deposits

  • AKA discoutinuous extramural extension.
  • AKA peritumoral deposits.
Main article: Tumour deposit

Tumour regression

There is a three tiered regression grading system by Ryan et al. for colorectal cancer that has essentially been adopted by CAP:[7]

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.

Note:

  • ‡ High stage colorectal cancer (CRC) may be CK7 +ve/CK20 +ve; in one series, 13% of stage 3 and 17% of stage 4 colorectal cancers were CK7 +ve/CK20 +ve.[8]

Molecular

Note:

  • KRAS mutations and BRAF mutations are considered mutually exclusive as they occur in the same pathway.

Sign out

Right hemicolectomy

TERMINAL ILEUM, CECUM, ASCENDING COLON AND APPENDIX, RIGHT HEMICOLECTOMY:
- INVASIVE ADENOCARCINOMA, LOW-GRADE, pT2, pN0.
-- MARGINS NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
-- PLEASE SEE TUMOUR SUMMARY.
- SMALL BOWEL WALL WITHIN NORMAL LIMITS.
- APPENDIX WITHOUT SIGNIFICANT PATHOLOGY.
- TWELVE LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 12 ).

Mucinous component present

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 ).

Left hemicolectomy

LEFT COLON, LEFT HEMICOLECTOMY:
- INVASIVE ADENOCARCINOMA, LOW-GRADE, pT1, pN0.
-- MARGINS NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
-- TWELVE LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 12 ).
-- PLEASE SEE TUMOUR SUMMARY.

Biomarker and molecular testing

The Colorectal Cancer Panel (BRAF, KRAS, NRAS, PIK3CA, PTEN) was ordered on block {}. MMR testing was ordered on block {}.

See also

References

  1. ↑ Bagaria, B.; Sood, S.; Sharma, R.; Lalwani, S. (Sep 2013). "Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis).". Cancer Biol Med 10 (3): 148-57. doi:10.7497/j.issn.2095-3941.2013.03.005. PMID 24379990.
  2. ↑ Xue, G.; Wang, X.; Yang, Y.; Liu, D.; Cheng, Y.; Zhou, J.; Cao, Y. (2014). "Colon cancer-specific antigen-2 may be used as a detecting and prognostic marker in colorectal cancer: a preliminary observation.". PLoS One 9 (4): e94252. doi:10.1371/journal.pone.0094252. PMID 24710115.
  3. ↑ URL: http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=13954. Accessed on: 6 February 2013.
  4. ↑ Bateman, AC.; Carr, NJ.; Warren, BF. (Apr 2005). "The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin?". J Clin Pathol 58 (4): 426-8. doi:10.1136/jcp.2004.019802. PMID 15790712.
  5. ↑ Ogino, S.; Nosho, K.; Irahara, N.; Meyerhardt, JA.; Baba, Y.; Shima, K.; Glickman, JN.; Ferrone, CR. et al. (Oct 2009). "Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype.". Clin Cancer Res 15 (20): 6412-20. doi:10.1158/1078-0432.CCR-09-1438. PMID 19825961.
  6. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Colon_12protocol_3200.pdf. Accessed on: 14 September 2012.
  7. ↑ Ryan, R.; Gibbons, D.; Hyland, JM.; Treanor, D.; White, A.; Mulcahy, HE.; O'Donoghue, DP.; Moriarty, M. et al. (Aug 2005). "Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer.". Histopathology 47 (2): 141-6. doi:10.1111/j.1365-2559.2005.02176.x. PMID 16045774.
  8. ↑ Hernandez, BY.; Frierson, HF.; Moskaluk, CA.; Li, YJ.; Clegg, L.; Cote, TR.; McCusker, ME.; Hankey, BF. et al. (Mar 2005). "CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue microarray.". Hum Pathol 36 (3): 275-81. doi:10.1016/j.humpath.2005.01.013. PMID 15791572.
  9. ↑ Monzon, FA.; Ogino, S.; Hammond, ME.; Halling, KC.; Bloom, KJ.; Nikiforova, MN. (Oct 2009). "The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer.". Arch Pathol Lab Med 133 (10): 1600-6. doi:10.1043/1543-2165-133.10.1600. PMID 19792050.
  10. ↑ Tie J, Gibbs P, Lipton L, et al. (July 2010). "Optimizing targeted therapeutic development: Analysis of a colorectal cancer patient population with the BRAF(V600E) mutation". Int J Cancer. doi:10.1002/ijc.25555. PMID 20635392.
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