Neoplasia
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Rapid summary for last-minute revision before your exam.
Neoplasia — Key Facts for FMGE Core concept: Neoplasia is autonomous, uncontrolled cell proliferation with loss of normal growth control High-yield point: Benign tumors are encapsulated and don’t metastasize; malignant tumors are invasive and can metastasize via blood or lymph ⚡ Exam tip: Grading vs staging and tumor markers are high-yield topics in FMGE
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Standard content for students with a few days to months.
Neoplasia — FMGE Study Guide
Definitions
Neoplasia: New, uncontrolled growth of cells that exceeds normal tissue architecture and persists after the stimulus is removed
Tumor: Any swelling or mass; technically different from neoplasia but often used interchangeably
Benign tumor: Slow-growing, encapsulated, does not invade or metastasize (suffix: -oma) Malignant tumor: Rapid-growing, invasive, can metastasize (suffix: -carcinoma for epithelial, -sarcoma for mesenchymal)
Nomenclature
Benign Tumors
- Connective tissue: Lipoma, chondroma, osteoma, fibroma
- Smooth muscle: Leiomyoma
- Blood vessels: Hemangioma
- Glands: Adenoma (benign glandular tumor)
Malignant Tumors
- Carcinoma: Malignant tumor of epithelial origin (squamous cell carcinoma, adenocarcinoma)
- Sarcoma: Malignant tumor of mesenchymal origin (osteosarcoma, leiomyosarcoma, fibrosarcoma)
- Mixed tumors: Contain multiple cell types (e.g., pleomorphic adenoma of salivary gland)
- Teratoma: Germ cell tumor with multiple tissue types from all three embryologic layers
Special Nomenclature
- Leukemia: Malignant proliferation of WBCs in blood/bone marrow
- Lymphoma: Malignant lymphoid tumors
- Myeloma: Plasma cell neoplasm
- Seminoma/dysgerminoma: Testicular/ovarian germ cell tumors
Differences Between Benign and Malignant Tumors
| Feature | Benign | Malignant |
|---|---|---|
| Growth rate | Slow | Rapid |
| Capsulation | Encapsulated | Not encapsulated |
| Borders | Well-defined | Infiltrative/irregular |
| Metastasis | Absent | Present |
| Differentiation | Well-differentiated | Poorly differentiated |
| Mitosis | Rare, normal | Frequent, abnormal |
| Necrosis | Rare | Common |
| Recurrence | Rare after removal | Common |
Local Invasion and Metastasis
Mechanisms of Spread
Local invasion:
- Malignant cells lose adhesion molecules (E-cadherin)
- Secrete proteolytic enzymes (collagenase, MMPs) to degrade basement membrane
- Direct invasion into surrounding tissue
Lymphatic spread:
- Carcinomas spread via lymphatics more than sarcomas
- Sentinel lymph node: First node draining a tumor (important for staging)
- Can cause lymphangitic carcinomatosis
Hematogenous spread:
- Invasion of blood vessels (angioinvasion)
- Sarcomas commonly spread via blood
- Portal circulation → liver metastases (GI cancers)
- IVC → lung metastases (renal, testicular cancers)
Patterns of Metastasis
- Carcinoma: Lungs, liver, brain, bones
- Sarcoma: Lungs (most common)
- Prostate cancer: Bones (osteoblastic metastases)
- Breast cancer: Bones, brain, liver, lungs
- Colon cancer: Liver (portal drainage)
Seed and soil hypothesis: Certain tumors metastasize to specific organs due to microenvironment compatibility
Grading and Staging
Grading (Tumor Characteristics)
Based on degree of differentiation and mitotic activity:
- Grade I (G1): Well-differentiated, low mitotic rate
- Grade II (G2): Moderately differentiated
- Grade III (G3): Poorly differentiated
- Grade IV (G4): Anaplastic/undifferentiated
TNM Staging System
- T: Tumor size and local extent (T1-T4)
- N: Lymph node involvement (N0-N3)
- M: Distant metastasis (M0-M1)
Stage grouping:
- Stage 0: Carcinoma in situ
- Stage I: Small, localized tumor
- Stage II: Larger or with minimal spread
- Stage III: Extensive local/regional spread
- Stage IV: Distant metastasis
Oncogenes and Tumor Suppressor Genes
Oncogenes (Growth-promoting genes)
- ras: GTPase signal transducer; mutated in many cancers (30% of all human tumors)
- myc: Transcription factor; overexpressed in Burkitt lymphoma (t(8;14))
- bcl-2: Prevents apoptosis; overexpressed in follicular lymphoma t(14;18)
- Her2/neu (ERBB2): Receptor tyrosine kinase; amplified in breast cancer
- bcr-abl: Tyrosine kinase; fusion in CML t(9;22) - targeted by imatinib
- EGFR: Growth factor receptor; mutated in lung adenocarcinoma
Tumor Suppressor Genes (Growth-inhibiting genes)
- p53: “Guardian of genome” - most frequently mutated gene in human cancers; prevents DNA-damaged cells from replicating
- Rb (Retinoblastoma): Blocks cell cycle at G1/S checkpoint; both alleles must be lost
- APC: Adenomatous polyposis coli; loss → familial adenomatous polyposis (FAP) → colon cancer
- BRCA1/BRCA2: DNA repair; mutations → breast and ovarian cancer
- WT1: Wilms tumor suppressor
- NF1/NF2: Neurofibromatosis (nerve sheath tumors)
Carcinogenic Agents
Chemical Carcinogenesis
Initiators (irreversible):
- Polycyclic aromatic hydrocarbons: Benzopyrene (smoke, charcoal-grilled meat) → lung, skin cancer
- Aromatic amines: 2-naphthylamine → bladder cancer
- Nitrosamines: Gastric cancer
- Alkylating agents: Chemotherapy agents (cyclophosphamide)
Promoters (reversible, require initiator):
- Phenobarbital (promotes liver tumors)
- Hormones (estrogen)
Carcinogenesis stages: Initiation (mutations) → Promotion (clonal expansion) → Progression (malignant phenotype)
Viral Oncogenesis
- HPV (Human Papillomavirus): E6 protein inactivates p53, E7 inactivates Rb → cervical carcinoma
- HBV, HCV: Chronic hepatitis → hepatocellular carcinoma
- EBV: Burkitt lymphoma, nasopharyngeal carcinoma, post-transplant lymphoproliferative disorder
- HTLV-1: Adult T-cell leukemia/lymphoma
- HHV-8 (Kaposi sarcoma-associated herpesvirus): Kaposi sarcoma
Radiation Carcinogenesis
- UV radiation: Basal cell carcinoma, squamous cell carcinoma, melanoma (DNA damage, pyrimidine dimers)
- Ionizing radiation: Leukemia (atomic bomb survivors), thyroid cancer (radioiodine)
Tumor Markers
| Marker | Associated Tumor |
|---|---|
| AFP | Hepatocellular carcinoma, non-seminomatous germ cell tumors |
| CEA | Colorectal cancer (also raised in pancreatitis, smoking) |
| CA-125 | Ovarian cancer |
| CA-19-9 | Pancreatic cancer |
| PSA | Prostate cancer |
| β-hCG | Choriocarcinoma, testicular germ cell tumors |
| Calcitonin | Medullary thyroid carcinoma |
| S-100 | Melanoma |
| Alkaline phosphatase | Bone metastases (osteoblastic), liver metastases |
Paraneoplastic Syndromes
Symptoms produced by tumors at sites distant from the tumor itself:
- PTHrP (Parathyroid hormone-related peptide): Hypercalcemia (squamous cell lung cancer, breast cancer)
- ACTH: Cushing syndrome (small cell lung cancer)
- ADH: SIADH (small cell lung cancer)
- EPO: Polycythemia (renal cell carcinoma, cerebellar hemangioma)
- 5-HT (Serotonin): Carcinoid syndrome (bronchial adenoma, GI carcinoid)
- Calcitonin: Diarrhea (medullary thyroid carcinoma)
Hallmarks of Cancer (Hanahan and Weinberg)
- Self-sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis
- Limitless replicative potential (telomerase activation)
- Sustained angiogenesis
- Ability to invade and metastasize
- Reprogramming energy metabolism (Warburg effect)
- Evasion of immune destruction
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