1. Chapter 7 Neoplasia

2. Neoplasia
Proliferation the process of cell division is the mechanism for cell replacement
Differentiation process of specialization whereby new cells acquire all the characteristics of the cells they replace
Apoptosis programmed cell death (to keep the number of total cells constant) eliminates damaged or unwanted cells
In malignant neoplasms, accumulation of cells results from excessive and uncontrolled proliferation and evasion of apoptosis

3. Benign Tumors Contain cells that look like normal tissue cells
May perform the normal function of the tissue, i.e., secrete hormones, but may lead to oversecretion
Grow slowly
Surrounded by a fibrous capsule
Do not infiltrate, invade, or metastasize
Can damage nearby organs by compressing them

4. Malignant Tumors
Contain cells that do not look like normal adult cells
Do not perform normal functions of the tissue
Grow rapidly
Lack capsules—sends “legs” into surrounding tissue (the word cancer means “crab” based on these legs)
Infiltrate, invade, and metastasize (to distant sites)
Can compress and/or destroy the surrounding tissues

5. Characteristics of Benign and Malignant Neoplasms

6. Cell Cycle
Normally, the number of cells produced = the number of cells that die.
The total number of cells in the body remains constant.
In cancer, growth fraction (dividing:resting cells) increases and doubling time decreases
Malignant cells in a primary tumor develop the ability to escape, travel, and survive in the blood, exit the blood, and develop a secondary tumor (metastasis)

7. Cancer: Cells Gone Haywire
Anaplasia loss of cell differentiation in cancerous tissues
Pleomorphism multiple morphologic changes in cancer cells
Genetic instability
Growth factor independence
Loss of cell density
Loss of cohesiveness
Faulty cell to cell communication
Immortality
Abnormal production of hormones and other substances

8. How Cancer Spreads Direct invasion and extension
Seeding of cancer cells in body cavities
Metastatic spread through lymphatic or vascular pathways
To metastasize, a cancer cells needs to
Break loose from the primary tumor
Invade the surrounding extracellular matrix
Gain access to a blood vessel
Survive its passage in the bloodstream
Emerge at a favorable location
Invade surrounding tissue

9. Cancer Incidence

10. Molecular Pathogenesis of Cancer
Genetic damage or a mutation that changes the cell’s physiology
Susceptibility to cancer involves defects in:
DNA repair mechanisms
Growth factor signaling pathways
Evasion of apoptosis
Development of sustained angiogenesis, invasion and metastasis
Genes involved in cancer
proto-oncogenes control cell growth and replication
Growth factors, growth factor receptors, transcription factors, cell cycle proteins, apoptosis inhibitors
tumor suppressor genes growth inhibiting regulatory genes

11. Etiology of Cancer Highly complex
Encompasses both molecular and cellular origins
Influenced by external and contextual factors such as heredity and environmental factors

12. Stages of Carcinogenesis
Initiation: Initial mutation occurs.
Promotion: Mutated cells are stimulated to divide.
Progression: Tumor cells compete with one another and develop more mutations, which make them more aggressive.

13. Host and Environmental Factors
Mendelian inheritance of genes (BRCA-1, BRCA-2, RB)
Reproductive hormones
Obesity
Immune surveillance and tumor antigens
Chemical carcinogens (cigarettes, alcohol, diet)
Radiation
Viruses, bacteria

14. Systemic Manifestations of Cancer
Anemia
Anorexia and cachexia
Fatigue and sleep disturbances
Ectopic hormones or factors secreted by tumor cells (paraneoplastic disorders)

15. Paraneoplastic Syndromes
Cancer cells produce hormones or hormone-like proteins.
ADH
ACTH
PTH-related protein
Cancer cells produce proteins that affect clotting.
Paraneoplastic neurologic disorders.

16. Cancer Diagnosis Tumor markers (prostate-specific antigen)
Cytologic studies (Pap smear)
Tissue biopsy (fine needle aspiration)
Immunohistochemistry (estrogen receptor)
Microarray technology (gene chips)

17. Tumor Markers

18. Grading Versus Staging
Grading: Microscopic examination of differentiation and number of mitoses
I = well differentiated; IV = poorly differentiated
Staging: Clinical, radiographic, surgical examination of extent and spread  treatment, prognosis
TNM: T1–4 = tumor size, N0–3 = lymph node involvement, M0–1 = metastasis
AJC: stages 0–IV = size of primary lesion and presence of nodal spread and metastasis

19. Cancer Treatment Surgery Radiation therapy Chemotherapy
Hormone and antihormone therapy
Biotherapy
Targeted therapy