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
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:

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

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

• 

  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:

• 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

• 

  CRC - low mag. (WC)

• 

  CRC - intermed. mag. (WC)

• 

  CRC - high mag. (WC)

• 

  CRC - low mag. (WC)

• 

  CRC - intermed. mag. (WC)

• 

  CRC - high mag. (WC)

• 

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

• 

  Mucinous adenocarcinoma - low mag. (WC/Nephron)

• 

  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:

• Colorectal adenocarcinoma (flickr.com/euthman).

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.
• AKA Crohn-like response.

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:

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.

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.
• Microsatellite instability - see microsatellite instability in colorectal cancer.

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

• Colon.
• Colorectal tumours.