Colorectal Cancer Staging and Histopathology

TNM Classification

• T1 stage: superficial tumor
• T2 stage: lamina propria
• T3 stage: beneath muscle, in fat tissue
• T4 stage: outside of colon, metastasis

Colon Epithelial Cells

• Normal cells: nuclei located at the bottom
• Tumor cells: nuclei not neatly located at the bottom
• Goblet cells: whitish, decrease in number with tumor formation

Polyps

• Polyp shape: varies
• Etiology:
  • Hyperplasia: most common, no danger for tumor formation
  • Neoplasia: dysplastic polyps
  • Inflammation
• Forms of polyps:
  • Pedunculated polyp: stalk polyp
  • Sessile polyp: often caused by hypermethylation, BRAF mutations

Hyperplastic Polyp

• Serrated lumina (up and down lumen)
• No dysplasia
• No hyperchromasia, enlarged nuclei, disturbed growth patterns, or mitosis
• Many Goblet cells present

Dysplastic Polyp

• Hyperchromasia
• Enlarged nuclei
• Disturbed growth patterns
• Mitoses
• Few or no Goblet cells

Adenocarcinoma Colon

• Submucosal proliferation of glands
• Epithelial cells also under the mucosal layer (invasive growth)

Development of Colon Carcinoma

• Stepwise process
• Accumulation of mutations
• Morphologic features increasing during progression

Genes Involved in Colon Carcinoma

• APC
• KRAS
• SMAD2/SMAD4
• TP53

Population Screening

• pT1 CRC: targeted screening

Risks and Follow-up

• Lymph node metastases: risk assessment based on differentiation grade
• High-risk patients: removal of lymph node

Differentiation Grade

• Well differentiated: tubules in >95% of the tumor
• Moderately differentiated: tubules in 50-95% of the tumor
• Poorly differentiated: tubules in <50% of the tumor

Familial Syndromes

• FAP: germline mutation of APC, part of the Wnt pathway
• Lynch syndrome: non-polyposis, high risk for endometrial carcinoma
• MAP: MUTYH-associated polyposis
• Other familial syndromes

Microsatellite Instability

• MSI-high: sporadic (15%) or Lynch syndrome (2-3%)
• Germline defects in one of the MMR-genes (MLH1, PMS2, MSH2, and MSH6)

Lynch Syndrome Cancers

• Colorectal cancers (80%)
• Endometrial cancers (50%)
• Other cancers (pancreatic, gastric, small bowel, sebaceous skin, ovarian, genitourinary, GBM)
• Screening: colonoscopy, endometrial sampling, transvaginal ultrasound, dermatological examination, urine testing

MSI-HIGH CRC (Sporadic)

• Mostly MLH-1 promoter methylation
• IHC MLH1 and PMS-2 negative
• BRAF V600E mutation

Pathology of MSI-H Colon-Carcinoma

• Right-sided
• Older age
• Genes frequently involved: known
• New possibilities for immunotherapies

This quiz covers the TNM classification system for colorectal cancer, including the different stages of tumor progression and the histopathological changes observed in the colon.