Colorectal adenocarcinoma

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.

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

• 

  Cecal adenocarcinoma. (WC)

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  Mucinous adenocarcinoma - very low mag. (WC/Nephron)

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  Mucinous adenocarcinoma - low mag. (WC/Nephron)

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  Colorectal adenocarcinoma. (WC)

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  CRC lymph node metastasis. (WC/Nephron)

www:

• 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.
• AKA Crohn-like repsonse.

General

• Finding associated with improved survival in CRC.

Microscopic

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

Ueno criteria (2013)

Required criteria:

• 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:

• Peritumoral:
  1. Lymphoid aggregates with germinal centres focally.
  2. Stellate fibrosis.
  3. 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

• 

  PLR - low mag. (WC)

• 

  PLR - intermed. mag. (WC)

www:

• Peritumour lymphocytic response in endometrial carcinoma (bmjjournals.com).
• Peritumour lymphocytic response in CRC (ascpjournals.org).

Intratumoural lymphocytic response

• AKA tumour-infiltrating lymphocytes, abbreviated TILs.

General

• Finding is suggestive of microsatellite instabillity.
  • May be seen in the context of Lynch syndrome.

Microscopic

Features:

• Lymphocytes are between the tumour cells. †
  • 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".

Images

• 

  TILs - high mag. (WC/Nephron)

• 

  TILs - very high mag. (WC/Nephron)

www:

• TILs in endometrial carcinoma (bmjjournals.com).
• TILs in CRC (ascpjournals.org).

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.
• No standardized criteria for tumour deposits.

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

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:

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).
• BRAF mutation analysis.
  • V600E missense mutation found in ~10% CRC.

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

• Colon.
• Colorectal tumours.