Notes on Neoplasia

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Benign tumors:
• Mixed tumors, teratomas.

Malignant tumors:
• Carcinomas derived from epithelial tissue.
• Squamous cell carcinoma (upper respiratory, lungs, oropharynx, larynx).
• Adenocarcinoma (lung, pancreas, liver, breast, kidneys, prostate).
• Transitional cell carcinoma (urinary region).
• Sarcomas derived from connective tissue.

Tumor-like conditions:
• Hamartoma (indigenous location).
• Choristoma (forgien location).

Benign and Malignant tumors:
Benign tumors: resemble parent tissue; slow growth rate; single precursor cell; normal telomerase activity; non-invasive; non-metastatic.

Malignant tumors: are well-differentiated or low grade; variable growth rate; single precursor cell; increased telomerase activity; invasive; metastatic.

Non-neoplastic proliferations: polyclonal.
G6DP isoenzymes used to study mono- or polyclonality.
Steps in cell invasion:
• Cell receptor attachment to laminin.
• Cells release type IV collagenase.
• Cell receptor attachment to fibronectin in extracellular matrix.
• Cytokine and protease production.
• Angiogenesis.

Metastasis:
• Hepatic portal vein: liver.
• Vena cava: lungs.

Some carcinomas have lymphatic and hematogenous spread.

Seeding:
• Malignant cells exfoliate and implant and invade.
• Eg., ovarian cancers, lung cancers.

Bone metastasis:
• Most common site: vertebral column due to Batson paravertebral venous plexus and its connections with the inferior vena cava.
• Increased serum alkaline phosphatase.
• Increased PGE-2, IL-1 - substances that activate osteoclasts.
• Increased hormone production by some tumors.
• Bone pain.

Metastasis:
• Breast/lung cancers spread to lymph nodes.
• Breast cancers spread to lungs.
• Lung cancers spread to liver.
• Breast cancers spread to bone.
• Lung cancers spread to brain.

Genes involved in cancer:
• Proto-oncogenes: control normal growth and repair.
• Suppressor genes: control G1 to S phase entry, and nuclear transcription.
• Antiapoptosis genes; BCL2 family: control gene activity; BCL2 over-expressed by translocation t(14;18).
• Apoptosis genes: regulate programmed cell-death; TP53, BAX.
• DNA repair genes; mutations create abnormal protein products.

Carcinogenic agents:
• Polycyclic hydrocarbons in tobacco smoke; grab electrons from DNA.
• Direct-acting carcinogens; indirect-acting carcinogens activated by P-450.

Microbes:
• H. Pylori: stomach cancer.
• Schistosoma hematobium: squamous cell carcinoma of bladder.
• Clonorchis sinensis and opisthorchis viverrini: cholangiocarcinoma of bile ducts.

Radiation:
• Ionizing radiation: hydroxyl free radicals.
• AML and CML; papillary thyroid carcinoma; liver angiosarcoma; lung, breast and bone cancers.
• UV induced cancers: pyrimidine dimers distort DNA.
• Basal cell carcinoma; squamous cell carcinoma; malignant melanoma.

Physical injury:
• 3rd degree burns cause squamous cell carcinoma.
• Draining sinuses cause squamous cell carcinoma.

Defense against cancer:
• Humoral immunity.
• Type IV cellular immunity.
• NK cells.
• Macrophages.

Effects of cancer:
• Cachexia.
• Anemia.
• Hemostasis abnormalities like DIC, etc.
• Fever.
• Paraneoplastic syndromes.

Tumor markers:
• Used to identity tumors.
• Eg. CA 15-3: breast; CA 19-9: pancreatic; CA 125: ovarian.

Additional Reading:

Basic Pathology

1. Cell Injury
2. Inflammation and Repair
3. Immunopathology
4. Water, Electrolyte, Acid-Base, Hemodynamic Disorders
5. Genetic and Developmental Disorders
6. Environmental Pathology
7. Nutritional Disorders
8. Neoplasia
9. Vascular Disorders
10. Heart Disorders
11. Red Blood Cell Disorders
12. White Blood Cell Disorders
13. Lymphoid Tissue Disorders
14. Hemostasis Disorders
15. Blood Banking and Transfusion Disorders
16. Upper and Lower Respiratory Disorders
17. Gastrointestinal Disorders
18. Hepatobiliary and Pancreatic Disorders
19. Kidney Disorders
20. Lower Urinary Tract and Male Reproductive Disorders
21. Female Reproductive and Breast Disorders
22. Endocrine Disorders
23. Musculoskeletal Disorders
24. Skin Disorders
25. Nervous System Disorders
26. Notes on Tissue Regeneration

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