Colorectal adenocarcinoma

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Colorectal adenocarcinoma
Diagnosis in short
LM DDx other adenocarcinomas
IHC CK20 +ve, CDX2 +ve, CK7 -ve, beta-catenin (nuclear) +ve
Site rectum, colon, cecum, appendix
Syndromes familial adenomatous polyposis, Lynch syndrome
Signs +/-blood in stools, +/-abdominal mass, +/-rectal mass, +/-signs of bowel obstruction (nausea, vomiting)
Symptoms constipation
Prevalence common
Blood work +/-anemia (microcytic)
Radiology +/-"apple core" lesion
Endoscopy +/-suspicious mass (exophytic or ulcerated)
Prognosis good to poor

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.

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

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 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.[1][2]

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.

Images

www:

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.[3]
  • AKA Crohn-like repsonse.[4]

General

  • Finding associated with improved survival in CRC.[5]

Microscopic

Onlinepathology advocates use of the Ueno criteria. They have a better inter-rater reproducibility than the older Graham criteria[6] and are less complicated.

Ueno criteria (2013)

Required criteria:[7]

  • Non-MALT lymphoid aggregates (peritumoural) >= 1 mm.

Ignore:

  1. Muscosa-associated lymphoid tissue (MALT) = mucosal lymphoid aggregates, submucosal lymphoid aggregates adjacent to the musuclaris mucosae.
  2. Lymph nodes - these have a (fibrous) capsule.
  3. Irregular shape (not round).
Graham criteria (1990)

Required criteria:[6]

  • Peritumoral:
    1. Lymphoid aggregates with germinal centres focally.
    2. Stellate fibrosis.
    3. No previous clinical and pathologic evidence of Crohn's disease.

Note:

Images

  • PLR - low mag. (WC)

  • PLR - intermed. mag. (WC)

www:

Intratumoural lymphocytic response

  • AKA tumour-infiltrating lymphocytes, abbreviated TILs.

General

  • Finding is suggestive of microsatellite instabillity.[9]

Microscopic

Features:

  • Lymphocytes are between the tumour cells.[10] †
    • 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".[11]
Images

  • TILs - high mag. (WC/Nephron)

  • TILs - very high mag. (WC/Nephron)

www:

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.[12]
  • No standardized criteria for tumour deposits.[12]

Ueno et al. propose that a tumour deposit is either:[12]

  1. >=2 mm from the tumour front
  2. >=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:[13]

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).[14]
  • BRAF mutation analysis.
    • V600E missense mutation found in ~10% CRC.[15]

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 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 ).

See also

References

  1. ↑ URL: http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=13954. Accessed on: 6 February 2013.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Colon_12protocol_3200.pdf. Accessed on: 14 September 2012.
  5. ↑ Harrison, JC.; Dean, PJ.; el-Zeky, F.; Vander Zwaag, R. (Jan 1995). "Impact of the Crohn's-like lymphoid reaction on staging of right-sided colon cancer: results of multivariate analysis.". Hum Pathol 26 (1): 31-8. PMID 7821914.
  6. ↑ 6.0 6.1 Graham, DM.; Appelman, HD. (May 1990). "Crohn's-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator.". Mod Pathol 3 (3): 332-5. PMID 2362940.
  7. ↑ Ueno, H.; Hashiguchi, Y.; Shimazaki, H.; Shinto, E.; Kajiwara, Y.; Nakanishi, K.; Kato, K.; Maekawa, K. et al. (Apr 2013). "Objective Criteria for Crohn-like Lymphoid Reaction in Colorectal Cancer.". Am J Clin Pathol 139 (4): 434-41. doi:10.1309/AJCPWHUEFTGBWKE4. PMID 23525613.
  8. ↑ 8.0 8.1 Ross, JS.; Torres-Mora, J.; Wagle, N.; Jennings, TA.; Jones, DM. (Sep 2010). "Biomarker-based prediction of response to therapy for colorectal cancer: current perspective.". Am J Clin Pathol 134 (3): 478-90. doi:10.1309/AJCP2Y8KTDPOAORH. PMID 20716806.
  9. ↑ Iacopetta, B.; Grieu, F.; Amanuel, B. (Dec 2010). "Microsatellite instability in colorectal cancer.". Asia Pac J Clin Oncol 6 (4): 260-9. doi:10.1111/j.1743-7563.2010.01335.x. PMID 21114775.
  10. ↑ 10.0 10.1 Garg, K.; Soslow, RA. (Aug 2009). "Lynch syndrome (hereditary non-polyposis colorectal cancer) and endometrial carcinoma.". J Clin Pathol 62 (8): 679-84. doi:10.1136/jcp.2009.064949. PMID 19638537.
  11. ↑ Ropponen, KM.; Eskelinen, MJ.; Lipponen, PK.; Alhava, E.; Kosma, VM. (Jul 1997). "Prognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer.". J Pathol 182 (3): 318-24. doi:10.1002/(SICI)1096-9896(199707)182:3318::AID-PATH8623.0.CO;2-6. PMID 9349235.
  12. ↑ 12.0 12.1 12.2 Ueno, H.; Hashiguchi, Y.; Shimazaki, H.; Shinto, E.; Kajiwara, Y.; Nakanishi, K.; Kato, K.; Maekawa, K. et al. (Oct 2013). "Peritumoral deposits as an adverse prognostic indicator of colorectal cancer.". Am J Surg. doi:10.1016/j.amjsurg.2013.04.009. PMID 24112678.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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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