Colorectal adenocarcinoma

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
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:

• Bright red blood per rectum (BRBPR).
• Constipation.
• Symptoms of bowel obstruction - nausea, vomiting.

Pathogenesis - see pathogenesis of colorectal carcinoma.

Clinical - serum:

• CEA elevated.
• CA19-9 elevated.
• Colon cancer-specific antigen-2 (CCSA-2) elevated.
  • 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.

Images

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  CRC - gross. (WC)

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  CRC - gross. (WC)

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  Rectum - anterior view. (WC)

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  Rectum - lateral view. (WC)

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  Rectum - inked. (WC)

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  Rectum - opened (WC)

Microscopic

Features:

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

DDx:

• Other adenocarcinomas (e.g. anal gland adenocarcinoma, lung adenocarcinoma, ovarian adenocarcinoma, ductal adenocarcinoma of the prostate).
• Traditional adenoma esp. with high-grade dysplasia.
• Sessile serrated adenoma with dysplasia.

Images

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  CRC - low mag. (WC)

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  CRC - intermed. mag. (WC)

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  CRC - high mag. (WC)

• 

  CRC - low mag. (WC)

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  CRC - intermed. mag. (WC)

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  CRC - high mag. (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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  Cecal adenocarcinoma. (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 response.

General

• Finding associated with improved survival in CRC.

Microscopic

There are two sets of criteria (Ueno and Graham). The Ueno criteria 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

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  TILs - high mag. (WC)

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  TILS - very high mag. (WC)

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  TILs - high mag.

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  TILs - very high mag.

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  TILs - extremely high mag.

www:

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

Tumour deposits

• AKA discoutinuous extramural extension.
• AKA peritumoral deposits.

General

Definition - TNM/AJCC 7th edition:

• Microscopic or macroscopic nodule in the lymphatic drainage bed of the tumour.
  • No standardized distance (from tumour) criteria are defined.
• No findings suggestive of it being a lymph node replaced by tumour:
  1. No significant lymphoid tissue.
  2. 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.

Staging implications:

• Tumour deposits are not counted as (positive) lymph nodes 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.

Note:

• The definition of tumour deposit has changed significantly between the TMN/AJCC fifth, sixth and seventh editions.

Ueno criteria

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 plane of 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, 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.

See also

• Colon.
• Colorectal tumours.