Definition/General
Introduction:
Colonic adenocarcinoma is the most common colorectal malignancy accounting for >95% of cases
It arises through the adenoma-carcinoma sequence
Cytological diagnosis is highly accurate with proper sampling.
Origin:
Develops through adenoma-carcinoma sequence
Sequential genetic alterations: APC → KRAS → p53
Microsatellite instability pathway
Serrated pathway.
Classification:
WHO classification: Adenocarcinoma NOS, mucinous, signet ring, medullary
Grade: Well, moderately, poorly differentiated
TNM staging.
Epidemiology:
Third most common cancer
Peak age 60-70 years
Equal gender distribution
Geographic variations
Diet and lifestyle factors.
Clinical Features
Presentation:
Change in bowel habits
Rectal bleeding
Abdominal pain
Weight loss
Iron deficiency anemia
Intestinal obstruction.
Symptoms:
Alternating diarrhea-constipation
Blood in stool
Tenesmus
Abdominal cramping
Fatigue.
Risk Factors:
Age >50 years
Adenomatous polyps
IBD
Family history
High-fat diet
Smoking.
Screening:
Colonoscopy
FOBT
FIT
CT colonography
Stool DNA tests.
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Gross Description
Appearance:
Polypoid masses
Ulcerative lesions
Annular constricting
Infiltrative
Mixed patterns.
Characteristics:
Firm consistency
Gray-white surface
Central ulceration
Raised edges
Hemorrhage and necrosis.
Size Location:
Left-sided (60%): Rectosigmoid
Right-sided (40%): Cecum, ascending
Variable sizes
Synchronous lesions (3-5%).
Multifocality:
Adenomatous background
Skip lesions
Lymph node involvement
Distant metastases.
Microscopic Description
Histological Features:
Malignant glandular epithelium
Nuclear atypia
Loss of polarity
Increased N/C ratio
Mitotic activity
Stromal invasion.
Cellular Characteristics:
Enlarged hyperchromatic nuclei
Irregular nuclear contours
Prominent nucleoli
Loss of goblet cells
Mucin depletion.
Architectural Patterns:
Irregular glands
Back-to-back glands
Cribriform pattern
Solid nests
Single cell infiltration.
Grading Criteria:
Well-differentiated: >95% glands
Moderately differentiated: 50-95% glands
Poorly differentiated: <50% glands.
Immunohistochemistry
Positive Markers:
CK20
CDX2
Villin
CEA
EMA
SATB2.
Negative Markers:
CK7 (usually)
TTF-1
p63
Chromogranin.
Diagnostic Utility:
Confirms colonic origin
Primary vs metastatic
Prognostic markers.
Molecular Subtypes:
MSI-high
MSS
CIN
Hypermutated.
Molecular/Genetic
Genetic Mutations:
APC (80%)
TP53 (60%)
KRAS (40%)
PIK3CA (20%)
BRAF (10%).
Molecular Markers:
MSI status
KRAS/BRAF mutations
HER2 amplification
PD-L1 expression.
Prognostic Significance:
Stage most important
Grade
MSI status
Lymphovascular invasion.
Therapeutic Targets:
EGFR inhibitors
VEGF inhibitors
PD-1 inhibitors (MSI-H)
MEK inhibitors.
Differential Diagnosis
Similar Entities:
High-grade adenoma
Inflammatory changes
Hyperplastic polyp
Metastatic adenocarcinoma.
Distinguishing Features:
Carcinoma: Stromal invasion
Adenoma: Intact basement membrane
Inflammatory: Uniform atypia.
Diagnostic Challenges:
Well-differentiated tumors
Mucinous variants
Crush artifacts
Inflammatory background.
Rare Variants:
Mucinous adenocarcinoma
Signet ring cell
Medullary carcinoma
Micropapillary.
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
Colonic cytology, adequate for evaluation
Diagnosis
Malignant - Adenocarcinoma
Malignant Features
Malignant glandular cells with [nuclear atypia] and [architectural abnormalities]
Differentiation
Grade: [Well/Moderately/Poorly] differentiated
Special Studies
Colonic markers: [CK20+, CDX2+]
MSI testing: [recommended]
Final Diagnosis
Colonic cytology: Adenocarcinoma