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NEOPLASIA DR.ROOPA Pathophysiology Premed 2 Neoplasia Neoplasm is an abnormal mass of tissue as a result of neoplasia. Uncontrollable or abnormal proliferation of cells. Types A neoplasm can be benign, potentially malignant (pre-cancer), or malignant (cancer). Benign neoplasms include uterine fibroids and melanocytic nevi (skin moles). They do not transform into cancer. Potentially malignant neoplasms include carcinoma in situ. They do not invade and destroy but, given enough time, will transform into a cancer. Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and eventually kill the host. Metastasis sometimes abbreviated mets, is the spread of a disease from one organ or part to another non-adjacent organ or part. cancer cells can break away, leak, or spill from a primary tumor, enter lymphatic and blood vessels, circulate through the bloodstream, and be deposited within normal tissue elsewhere in the body. Malignant (+) invasion: spread to nearby structures (+)metastasis: spread to distant structures (+)anaplasia : cells are very different from the normal cells (poorly differentiated) vs Benign (-) invasion (+) capsule (-)metastasis Resemble the tissue of origin (well differentiated) Anaplasia Pleomorphism Hyperchromatism (dark nuclei) Increased nuclear-cytoplasm ratio Abnormal mitosis Prominent nucleoli The more anaplastic, the more aggressive the cancer The more anaplastic, the more responsive to chemo and radiotherapy Forms of Malignant tumors Carcinoma: malignant tumor of epithelial origin 1. squamous cell carcinoma cancer of the skin cancer of the esophagus 2. adenocarcinoma: glands cancer of the breast cancer of the pancreas 3. transitional cell carcinoma cancer of the bladder Forms of Malignant tumors Sarcoma: of mesenchymal origin osteosarcoma rhabdosarcoma leiomyosarcoma liposarcoma Teratoma: from all 3 germ layers skin, bone, cartilage, teeth, intestinal ovaries and testis: most common may also be benign Osteosarcoma Liposarcoma Teratoma Forms of Benign tumors Papilloma: Adenoma: glandular epithelium -ovary, breast Mesenchymal origin -leiomyoma, lipoma, fibroma, chondroma Papilloma epithelium of skin, larynx and tongue; fingerlike projections Properties of Neoplasms Monoclonality the neoplasm comes from a single precursor cell Invasion enters the blood vessels and lymphatics Metastases blood vessels: sarcomas lymphatic: carcinoma Properties of Neoplasms Common sites of metastases liver, lung, brain, adrenal glands, lymph nodes bone marrow. Clinical signs of malignancy Cachexia wasting, weakness, weight loss, anemia, infection cause: CACHECTIN Endocrine abnormalities prolactinoma ovarian tumors Paraneoplastic syndromes ectopic production of hormones lung cancer : ACTH Carcinogenesis and carcinogens Chemical agents Physical agents Viruses Activation of cancer-promoting genes Inhibition of cancer-suppressing genes Carcinogenesis and carcinogens Cigarette smoking : lung CA, laryngeal CA Excessive sun: Skin CA Asbestos: Mesothelioma Nitrosamines: Gastric CA Alcohol: Esophageal CA Low-fiber diet: Colon CA Carcinogenesis and carcinogens High-fat diet: Breast CA Aniline dyes: bladder Ca Aflatoxin: liver CA PVC: Angiosarcoma of the liver DES: Clear cell adenocarcinoma of the vagina Nickle, chromium, uranium: lung CA Carcinogenesis and carcinogens HTLV – 1: Adult T cell leukemia HPV: cervical CA EBV: Nasopharyngeal CA, Burkitts lymphoma HBV: Hepatocellular CA HHV-8: Kaposi sarcoma Helicobacter pylori: Gastric CA An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a tumor cell. Oncogenes bcl-2: inhibits apoptosis Follicular lymphoma c-myc : Burkitts lymphoma Cancer suppresor genes (anti oncogene) A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. p53: “ guardian of the genome” mutated in 50% of all malignant tumors causes cell cycle arrest in G1, time for DNA repair unsuccessful repair: apoptosis LI-FRAUMENI SYNDROME familial cancers of the breast, soft tissue sarcomas, brain tumors, leukemias. Cancer suppresor genes (anti oncogene) WT-1 and WT-2: Wilms tumor BRCA -1: breast and ovarian CA BRCA – 2: breast CA The stage of a cancer is a descriptor (usually numbers I to IV) of how much the cancer has spread. Grading: degree of differentiation of the cells Staging: spread of the tumor -uses the TNM system TNM staging system Cancer staging can be divided into a clinical stage and a pathologic stage. In the TNM (Tumor, Node, Metastasis) system, clinical stage and pathologic stage are denoted by a small "c" or "p" before the stage. CANCER TREATMENT CHEMOTHERAPY CYTOTOXIC DRUGS+BODY DEFENSES SINGLE AGENT COMBINATION CHEMOTHERAPY _AVOIDS SINGLE AGENT RESISTANCE CAN USE LOWER DOSE BETTER REMISSION AND CURE RATE RADIATION TARGETS DNA KILL TUMOR WITHOUT DAMAGE TO SURROUNDING TISSUES TUMOR MUST BE ACCESSIBLE SURGERY METHOD OF CHOICE,CAN REMOVE ENTIRE TUMOR,DEBULKING ADJUVANT CHEMOTHERAPY OR RADIATION IMMUNOTHERAPY .ELIMINATES CANCER CELLS ONLY .PROVIDES PROTECTION AGAINST RECURRENCE .T_CELL BASED OR ANTIBODY RESPONSES .CONJUGATED ANTIBODIES .NONSPECIFIC ENHANCEMENT OF THE IMMUNE SYSTEM