Chapter 7 Neoplasia

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

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

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

Characteristics of Benign and Malignant Neoplasms

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)

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

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

Cancer Incidence

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

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

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.

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

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

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.

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

Tumor Markers

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

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