Definition/General
Introduction:
Colorectal adenocarcinoma is the most common malignant tumor of the large intestine, representing 95% of colorectal cancers
It is the third most common cancer worldwide and a leading cause of cancer-related mortality.
Origin:
Arises from colonic epithelium through adenoma-carcinoma sequence
Most cases develop from preexisting adenomatous polyps over 5-10 years
Can also arise from sessile serrated adenomas.
Classification:
WHO Classification includes conventional adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, and adenosquamous carcinoma
Molecular classification includes MSI-H, MSS, and CIMP subtypes.
Epidemiology:
Peak incidence 60-70 years
Male predominance
Higher incidence in developed countries
Strong association with Lynch syndrome and familial adenomatous polyposis.
Clinical Features
Presentation:
Change in bowel habits
Rectal bleeding
Abdominal pain
Weight loss
Fatigue (anemia)
Bowel obstruction (advanced cases)
Mass effect symptoms.
Symptoms:
Altered bowel habits (diarrhea/constipation)
Blood in stool
Tenesmus
Abdominal cramping
Constitutional symptoms (weight loss, fatigue)
Palpable mass.
Risk Factors:
Age >50 years
Family history of colorectal cancer
Lynch syndrome
Familial adenomatous polyposis
Inflammatory bowel disease
Diet high in red meat.
Screening:
Fecal occult blood testing
Colonoscopy
CEA levels elevated
CT colonography
Sigmoidoscopy
Stool DNA testing.
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Gross Description
Appearance:
Ulcerating or polypoid mass
Gray-white to tan coloration
Firm consistency
May obstruct bowel lumen
Serosal involvement in advanced cases.
Characteristics:
Size typically 2-8 cm
Irregular margins
Central ulceration common
Desmoplastic reaction around tumor
May perforate bowel wall.
Size Location:
Left-sided tumors often smaller and obstructing
Right-sided tumors larger and polypoid
Rectal tumors may involve anal canal.
Multifocality:
Usually unifocal
Synchronous tumors in 5% of cases
Metachronous development possible
Associated with adenomatous polyps.
Microscopic Description
Histological Features:
Malignant glands infiltrating through bowel wall
Variable differentiation
Cribriform pattern common
Desmoplastic stroma
Lymphovascular invasion frequent.
Cellular Characteristics:
Enlarged hyperchromatic nuclei
Loss of polarity
Increased mitotic activity
Mucin production variable
Necrosis and apoptosis present.
Architectural Patterns:
Glandular (most common)
Cribriform
Solid areas (poorly differentiated)
Papillary (uncommon)
Mixed patterns frequent.
Grading Criteria:
Well differentiated (>95% glands)
Moderately differentiated (50-95% glands)
Poorly differentiated (<50% glands)
Based on worst area.
Immunohistochemistry
Positive Markers:
CK20 positive (95%)
CDX2 positive (90%)
CEA positive
CK7 negative (usually)
Villin positive
SATB2 positive.
Negative Markers:
CK7 negative (helps exclude upper GI primary)
TTF-1 negative
PAX8 negative
WT1 negative
PSA negative.
Diagnostic Utility:
CK20+/CK7- pattern supports colorectal origin
CDX2 confirms intestinal differentiation
SATB2 highly specific for lower GI tract.
Molecular Subtypes:
MSI-H (15%): MLH1/MSH2/MSH6/PMS2 loss
MSS (85%): Intact MMR proteins
BRAF mutations in sporadic MSI-H tumors.
Molecular/Genetic
Genetic Mutations:
APC mutations (80%)
KRAS mutations (40%)
PIK3CA mutations (20%)
TP53 mutations (50%)
BRAF mutations (10%)
SMAD4 mutations.
Molecular Markers:
Microsatellite instability (MSI) testing mandatory
MLH1 promoter methylation in sporadic cases
Chromosomal instability pathway most common.
Prognostic Significance:
MSI-H tumors better prognosis
BRAF mutations worse prognosis in MSS tumors
Stage most important prognostic factor.
Therapeutic Targets:
Anti-EGFR therapy (cetuximab) if KRAS/NRAS wild-type
Immune checkpoint inhibitors for MSI-H tumors
BRAF inhibitors for BRAF-mutated tumors.
Differential Diagnosis
Similar Entities:
Metastatic adenocarcinoma from other sites
Diverticular disease with dysplasia
Inflammatory bowel disease with dysplasia
Endometriosis
Adenoma with high-grade dysplasia.
Distinguishing Features:
Primary colorectal: CK20+/CK7-, CDX2+, SATB2+
Metastatic breast: ER+, GATA3+
Metastatic pancreatic: CK7+, DPC4 loss.
Diagnostic Challenges:
Distinction from metastatic adenocarcinoma
Recognition of Lynch syndrome cases
Differentiating from inflammatory conditions.
Rare Variants:
Mucinous adenocarcinoma (>50% mucin)
Signet-ring cell carcinoma
Adenosquamous carcinoma
Undifferentiated carcinoma
Medullary carcinoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Colectomy specimen, [location] measuring [size] cm
Tumor Location
Tumor located at [anatomic site], [distance] cm from [landmark]
Tumor Size
Tumor measures [X] x [Y] x [Z] cm
Histologic Type
Adenocarcinoma, [conventional/mucinous/other] type
Histologic Grade
[Well/Moderately/Poorly] differentiated
Depth of Invasion
Tumor invades [mucosa/submucosa/muscularis propria/subserosa/serosa] (pT[X])
Lymph Nodes
[X] of [Y] lymph nodes involved (pN[X])
Margins
Proximal margin: [negative/positive], Distal margin: [negative/positive], Radial margin: [negative/positive]
Lymphovascular Invasion
Lymphovascular invasion: [Present/Absent]
Perineural Invasion
Perineural invasion: [Present/Absent]
MMR Status
Mismatch repair proteins: MLH1 [retained/lost], MSH2 [retained/lost], MSH6 [retained/lost], PMS2 [retained/lost]
TNM Staging
pT[X]N[X]M[X], Stage [I/II/III/IV]
Final Diagnosis
Final diagnosis: Colorectal adenocarcinoma, [grade], pT[X]N[X]M[X], Stage [X]