Neoplasia(1).pdf

Neoplasia Karen Gil MD, MHSN Objectives 1. 2. 3. 4. Histogenesis of neoplasms Classification of neoplasms Causes of neoplasms Differences between benign and malignant tumors 5. Effects of tumor on host, oncogenes, agents 6. Genetics of neoplasia Definition of Neoplasia • Mass that developed due...

Neoplasia Karen Gil MD, MHSN Objectives 1. 2. 3. 4. Histogenesis of neoplasms Classification of neoplasms Causes of neoplasms Differences between benign and malignant tumors 5. Effects of tumor on host, oncogenes, agents 6. Genetics of neoplasia Definition of Neoplasia • Mass that developed due to abnormal cell or tissue growth • Term “neo”- new and “plasma”-formation • Abnormal mass of autonomous cells • Neoplasia refers to various types of growths including non-cancerous or benign tumors, precancerous growths, carcinoma in situ and malignant or cancerous tumors Neoplasia components Two basic components: • Neoplastic cells: • The proliferating neoplastic cells that make up the main tumor • Reactive Stroma • The supportive stroma that is made up of blood vessels and the connective tissue (“silent collaborator”) Schematic illustration of tumor microenvironment showing different cell phenotypes including different hematopoietic cells. Tumor Nomenclature Benign • suffix - “-oma” • eg. lipoma, hemangioma, adenoma, lymphangioma, myoma, etc. Malignant (CANCER - “crab”) • Dependent on embryonal origin of affected tissue • Mesenchymal origin – sarcomas • Epithelial origin – carcinoma • Lymphoproliferative – leukemia, lymphomas Classification of Neoplasms • Behavior • Benign • Malignant • Degree of differentiation • Well-differentiated • Poorly-differentiated • Embryological origin • Epithelial • Lymphoprolipherative • Mesenchymal • Gross appearance • Well-circumscribed • Infiltrative The Gleason Score Benign vs Malignant Tumors • Tumors are classified as benign or malignant based on multiple characteristics they display Benign Tumors • Grow slowly and have distinct borders • Do not invade surrounding tissue • Do not invade other parts of the body • May cause compression without tissue invasion • Treatment mainly consist in surgical removal Benign vs Malignant Malignant tumors (cancerous) • Can grow quickly and have irregular borders • Often invade surrounding tissue • Can spread toother parts of the body through a process called metastasis • Cancerous cells travel to other parts of the body through the blood and lymphatic system • Treatment can consist in surgery, radiotherapy, chemotherapy, immunotherapy or a combination of therapies to prevent cancer spread Comparison Between Benign and Malignat Tumors Characteristic Benign Malignant Differentiation/ Anaplasia Well differentiated; structure may be typical of tissue of origin Some lack of differentiation with anaplasia; structure is often atypical Rate of growth Progressive and slow; may come to an standstill or regress; mitotic figures are rare and normal Erratic and may be slow or rapid; mitotic figures may be numerous and abnormal Local Invasion Usually cohesive and expansile well - demarcated masses that do NOT invade or infiltrate surrounding normal tissue Locally invasive, infiltrating the surrounding normal tissues; sometimes may be seemingly cohesive and expansile Metastasis Absent Frequently present; the larger and more undifferentiated the primary, the more likely are metastasis Benign vs Malignant Tissue Organ Benign Malignant Mesenchymal tumors Fibroma Fibrosarcoma Connective tissue and derivates Lipoma Osteoma Liposarcoma Osteosarcoma Chondrosarcoma Chondroma Epithelial and related tissues Blood vessels Lymph vessels Synovium Mesothelium Brain coverage Hemangioma Lymphangioma Meningioma Leukemias Blood cells and related cells Lymphoid cells Muscle Smooth Striated Epithelial tumors Stratified squamous Basal cells of skin and adnexa Epithelial lining Glands or ducts Angiosarcoma Lymphangiosarcoma Synovial sarcoma Mesothelioma Invasive meningioma Malignant lymphomas Leiomyoma Leiomyosarcoma Rhabdomyoma Squamous cell papilloma Rhabdomyosarcoma Squamous carcinoma Adenoma Adenocarcinoma Basal cell carcinoma Tissue Organ Benign Respiratory passages Neuroectoderm Renal epithelium Liver cells Urinary tract epithelium Placental epithelium (trophoblast) Testicular epithelium (gerrm cells) Malignant Broncghogenic carcinoma Nevus Renal tubular adenoma Liver cell adenoma Transitional cell pa pilloma Hydatidiform mole Carcinoid tumor Malignant melanoma Renal cell carcinoma Hepatocellular carcinoma Transitional cell carcinoma Choriocarcinoma Seminoma Embryonal cell carcinoma Mixed tumors Salivary glands Pleomorphic adenoma Breast Fibroadenoma Malignant mixed tumor of salivary glands origin Malignant cystosarcoma phylloides Wilms tumor Mature teratoma Immature teratoma Renal More than one neoplastic cell type Dysplasia • Disorderly proliferation (non neoplastic), abnormal growth of epithelial cells • “dys”- abnormal • Loss of cellular uniformity and orientation • Pleomorphism - variation in size and shape • Hyperchromatic nuclei • Mitosis (more abundant than usual) • Only seen by microscope Dysplasia Grading Depend in the organ • Two levels • Low grade – earliest form of a pre-cancerous lesion • High grade – carcinoma in situ (CIN), transformation into cancer is high, still treatment is effective • Three levels • Mild • Moderate • Severe Dysplasia Grading Dysplasia Grading • Higher grades (high and severe) more likely to turn into cancer • Invasive carcinoma • Penetrates the epithelial basement membrane to invade the tissue Tumor Progression Hyperplasia is increased cell production in a normal tissue or organ abnormal cells within a tissue or organ uncontrolled growth of a group of cells disregarding the normal rule of cell division Anaplasia “to form backward”lack of differentiation • is a qualitative alteration of differentiation • Anaplastic cells are typically poorly differentiated or undifferentiated, and exhibit advanced cellular pleomorphism • Pleomorphism – variation in size and shape of cells • There is increased mitotic activity, loss of cell orientation, and lack of normal organization in the anaplastic tissue • In nonneoplastic tissue, anaplasia may represent the borderline between dysplasia and neoplasia • malignant neoplasms, are frequently composed of cells that are pleomorphic and anaplastic Etiology of Neoplasms • Genetic disease caused by DNA mutations • Monoclonal in essence • All cells are similar Inherited • Retinoblastoma (Rb gene mutation) • Multiple poliposis coli (familial) Acquired • Environmental • Exposure to physical - chemical agents • Age Hereditable tumors Tumor Gene Inheritance Retinoblastoma Rb AD Adenomatous poliposis colon / adenocarcinoma APC AD Neurofibroma Nf1 / Nf2 AD Breast adenocarcinoma BRC1 / BRC 2 AD Xerodema pigmentosum Defect in DNA repair AR Bloom Syndrome Defect in DNA repair AR Fanconi Anemia Defect in DNA repair AR Carcinogenesis • There are some factors which are responsible for change of normal cell into cancer cell. Those factors or agents are known as carcinogens • It is believed that all cells carry certain cancer producing oncogenes • Oncogenes are the genes that are responsible for induction of tumors • Under certain conditions these genes are triggered to multiply rapidly into malignant neoplasm Etiological agents that induce Cancer 1. Environmental factors: • tobacco, smokes, diets, environmental pollutants etc • Lung cancer • Heavy smoking • lung, oral cavity and esophagus cancer • Excessive intake of alcohol • liver cancer Etiological agents that induce Cancer 2. Chemical carcinogen: • Nickel compounds, cadmium, arsenic, nitrosamines, trichloroethylene, arylamines, benzopyrene, aflatoxins, reactive oxygen radicals etc 3. Physical carcinogen: UV rays (ultraviolet), ionizing radiation (x-rays and gamma rays) Etiological agents that induce Cancer 4. Biological carcinogen: • Virus: • Virus has also been associated with various types of cancers • These viruses are called oncoviruses • Rous sarcoma virus (RSV) is the first discovered retro-virus causing cancer • Oncovirus- Human papilloma virus (HPV), Epstein-BarrVirus, (EBV), Hepatitis B virus, Herpes virus • Hepatitis B and C virus is casually related with hepato-cellular carcinoma • Cytomegalovirus (CMV) is associated with Kaposi’s sarcoma. • Human papilloma virus (HPV) is a chief suspect of cervix cancer • Bacteria • Helicobacter pylori • Stomach cancer Etiological agents that induce Cancer 5. Endogenous factors: • • • • • • Mutations change in DNA replication metabolic reactions generating reactive oxygen radicals Immune system defects Ageing Etiology and Pathogenesis • The commonly accepted basis of the pathogenesis of cancer is the damage to the genetic cells • Mutation • disturbance of gene expression • activation of tumor promoter gene • inactivation of tumor suppressor genes, etc. Oncogene • is a mutated gene that has the potential to cause cancer • Before an oncogene becomes mutated, it is called a proto-oncogene, and it plays a role in regulating normal cell division • Cancer can arise when a proto-oncogene is mutated • causing the cell to divide and multiply uncontrollably Tumor Suppressor Gene • A tumor suppressor gene encodes a protein that acts to regulate cell division • Promotes apoptosis • Prevent DNA damage • When a tumor suppressor gene is inactivated by a mutation, the protein it encodes is not produced or does not function properly, and as a result, uncontrolled cell division may occur • Such mutations may contribute to the development of a cancer Tumor Suppressor Gene Tumor Markers • A tumor marker is anything present in or produced by cancer cells or other cells of the body in response to cancer or certain benign (noncancerous) tumors • proteins or other substances that are made at higher amounts by cancer cells than normal cells • Two main types • Circulating markers • Tumor tissue markers Tumor Markers • Circulating tumor markers can be found in the blood, urine, stool, or other bodily fluids • Used to • estimate prognosis • determine the stage of cancer • detect cancer that remains after treatment (residual disease) or that has returned after treatment • assess how well a treatment is working • monitor whether the treatment has stopped working Tumor Markers • Tumor tissue markers are found in the actual tumors themselves (biopsy) • Tumor tissue markers are used to: • diagnose, stage, and/or classify cancer • estimate prognosis • select an appropriate treatment (e.g., treatment with a targeted therapy)