DR.ROOPA Pathophysiology Premed 3 NEOPLASIA DR.ROOPA Pathophysiology Premed 3

Neoplasia Means new growth. Is the uncontrolled, disorderly proliferation of cells, resulting in a benign or malignant tumor or neoplasm.

A neoplasm , as defined by Willis , is “an abnormal mass of tissue the growth of which exceeds and is uncordinated with that of the normal tissues and persists in the same manner after the cessation of the stimuli which evoked the change”.

Dysplasia- is a reversible change. Often precedes malignancy. Morphologically manifests by disorderly maturation and spatial arrangement of cells, marked variability in nuclear size and shape and increased, often abnormal , mitosis .

nomenclature A neoplasm is often referred to as a tumor, and the study of tumors is called oncology. Oncos – tumor, logos –study of Types Benign tumor Malignant tumor( cancer)

Benign tumors: In general , benign tumors are designated by attaching the suffix –oma to the cell type from which the tumor arises. Eg.fibrous tissue tumor is a fibroma. Malignant tumors: Mesenchymal tissue or its derivatives are called sarcomas. Eg fibrosarcoma Epithelial tissue origuin are called carcinoma. Eg:adenocarcinoma

Malignant vs Benign (+) invasion: spread to nearby structures (+)metastasis: spread to distant structures (+)anaplasia : cells are very different from the normal cells (poorly differentiated) (-) invasion (+) capsule (-)metastasis Resemble the tissue of origin (well differentiated)

Tumor characteristics Differentiation and anaplasia Rate of growth Local invasion metastasis

Anaplasia A state of complete un differentiation Anaplastic cells show: Pleomorphism Hyperchromatism (dark nuclei) Increased nuclear-cytoplasm ratio Abnormal mitosis Prominent nucleoli

Basic underlying cause of cancer 4 kinds of genes are damaged: Genes that promote growth Genes that inhibit growth Genes that regulate apoptosis Genes involved in DNA repair Cancers develop in multiple steps.

“cancer genes “cause bad things in cells Autonomous growth Insensitivity to growth – inhibitory signals Evasion of apoptosis Limitless replication Sustained angiogenesis Invasion and metastasis

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 rhabdomyosarcoma leiomyosarcoma liposarcoma Teratoma: from all 3 germ layers skin, bone, cartilage, teeth, ovaries and testis: most common may also be benign

teratomas consist of bits of bone,INTESTINAL epithelium, muscle, fat, nerve, tooth, etc.

Osteosarcoma

Liposarcoma

Teratoma

Forms of Benign tumors Papilloma: Adenoma: glandular epithelium -ovary, breast Mesenchymal origin -leiomyoma, lipoma, fibroma, chondroma

epithelium of skin, larynx and tongue; fingerlike projections 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 .- Endocrine abnormalities prolactinoma ovarian tumors Paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells.they commomnly presented with cancers of the lung, breast, ovaries or lymphatic system. eg:ectopic production of hormones lung cancer : ACTH

summary :Risk factors 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

Cancer suppresor genes (anti oncogene) p53: “ guardian of the genome” ,gatekeeper gene 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( Wilms tumour of the kidney) BRCA -1: breast and ovarian CA *BRCA – 2: breast CA RB codes for pRB protein, master brake on cell cycle (retinoblastoma, bone, bladder, lung, and breast cancer)

Grading: degree of differentiation of the cells Staging: spread of the tumor or degree of localisation -uses the TNM system Tumor size Lymphonode involvement Metastasis

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