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Neoplasia

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    Neoplasia Neoplasia Presentation Transcript

    • My perceptions about cancer • Be in a group of 4. Prepare ½ crosswise paper. Select 1 (one) question and discuss your perception. Questions: • How does it develop? • How will it affect my patient? • How is it diagnosed? • How is it treated?
    • Neoplasia
    • Neoplasia • “new growth” • Neoplasm or tumor • Refer to abnormal masses of tissue, the growth of which is virtually autonomous and exceeds that of normal tissues • The growth persists after cessation of the initiating stimulus
    • According to clinical behavior • Benign - localized lesion without spread to other sites and amenable to surgical resection, the patient typically survives although there are exceptions • Malignant - aggressive behavior including invasion and destruction of adjacent tissues and spread to other sites
    • Components • Clonal expansion of neoplastic cells constituting the tumor parenchyma • Supporting stroma composed of nonneoplastic connective tissue and blood vessels, abundant collagenous stroma (desmoplasia) and such tumors are rock hard (scirrhous)
    • Benign tumors • • • • Adenomas Cystadenomas Papillomas Polyps
    • Malignant tumors • • • • Carcinomas Sarcomas Mixed tumors Teratomas
    • Characteristics • Differentiation – refers to how closely tumor cells histologically resemble their normal cell counterparts • Anaplasia – lack of differentiation • Benign – well differentiated • Malignant – well differentiated to undifferentiated
    • • Pleomorphism – variation in the shape and size of cells and/or nuclei • Abnormal nuclear morphology - hyperchromatism - irregularly clumped chromatin - prominent nucleoli - increased nuclear to cytoplasmic ratios • Abundant and/or atypical mitoses • Loss of polarity
    • • Tumor giant cells • Ischemic necrosis • Dysplasia - loss of cellular uniformity and architectural organization - can occur next to a frank malignancy and in many cases antedates the development of cancer - dysplasia do not equate to malignancy and dysplastic cells do not necessarily progress to cancer
    • - when dysplastic changes are marked and involve the entire thickness of an epithelium it is referred to as carcinomain-situ and this lesion can be a forerunner to invasive carcinoma
    • Rates of Growth • Fast growing tumors can have a high cell turnover, that is rates of proliferation and apoptosis are both high • The portion of tumor cells that is actively proliferating is called the growth fraction • In general but not always, the growth rate of tumors inversely correlates with the level of differentiation; better differentiated tumors grow more slowly
    • Cancer Stem Cells and Cancer Cell Lineages • A clinically detectable tumor is a heterogenous population of cells originating from the clonal expansion of a single cell • Tumor stem cells can be derived by mutation of normal stem cells or from differentiated precursors that acquire the symmetric division properties of stemness (the ability to sustain persistent growth of the larger tumor
    • Local Invasion • Most benign tumors grow as cohesive, expnsile masses that develop a surrounding rim of condensed connective tissue or capsule • Malignant neoplasms are typically invasive and infiltrative, destroying normal tissues
    • Metastasis • Invsion of lymphatics, blood vessels or body cavities by tumor followed by transport and growth of secondary tumor masses discontinuous from the primary tumor • This is the single most important feature distinguishing benign from malignant tumors
    • Pathways of Spread • Seeding of body cavities and surfaces • Lymphatic spread • Hematogenous spread
    • • • • • • • • • • • 10 Causes of Death in the Philippines (2009) -DOH Diseases of the heart Diseases of the vascular system Malignant neoplasms Pneumonia Accidents TB, all forms Diabetes mellitus Chronic lower respiratory disease Nephritis, nephrotic and neoplasia Certain conditions originating in the perinatal area
    • 10 Causes of Cancer Deaths in the Philippines (2010) - DOH • • • • • • • • • • Breast cancer Lung cancer Liver cancer Cervical cancer Colon cancer Thyroid cancer Rectal cancer Ovarian cancer Prostate cancer Non-Hodgkin’s Lymphoma
    • Genetic Predisposition • Inherited Cancer Syndromes (Autosomal Dominant) - Retinoblastoma, Li-Fraumeni syndrome, Melanoma, Familial adenomatous polyposis (colon cancer), Neurofibromatosis 1 and 2, Breast and ovarian cancer, Multiple endocrine neoplasia 1 and 2, Hereditary nonpolyposis colon cancer, Nevoid basal cell carcinoma syndrome, Cowden syndrome, Peutz-Jegher syndrome, Renal cell carcinoma
    • • Inherited Autosomal Recessive Syndrome of Defective DNA Repair - Xeroderma pigmentosum, Ataxiatelangiectasia, Bloom syndrome, Fanconi anemia • Familial cancers - Breast cancer, Ovarian cancer, Pancreatic cancer
    • Nonhereditary Predisposing Conditions • Proliferation – regenerative, metaplastic, hyperplastic or dysplastic – all increase the risk of developing malignancy, since it is proliferating cells that accumulate the genetic lesions necessary for carcinogenesis
    • • Chronic Inflammation: - increases the pool of stem cells that can be subject to the effects of mutagens - produces cytokines and growth factors to drive cell survival and proliferation - promotes genomic instability by the production of reactive oxygen species • Precancerous conditions
    • Molecular Basis of Cancer • Non-lethal genetic damage underlies carcinogenesis • Tumors develop as clonal progeny of a single genetically damaged progenitor cell • Carcinogenesis is a multistep process • Although tumors begin as monoclonal proliferations by the time they are clinically evident, they are extremely heterogenous
    • • Four classes of normal regulatory genes are the targets of genetic damage: - growth promoting proto-oncogenes - growth inhibiting tumor suppressor genes - genes that regulate apoptosis - genes that regulate DNA repair
    • Essential Alterations for Malignant Transformation • • • • • • Self sufficiency in growth signals Insensitivity to growth-inhibitory signals Evasion of apoptosis Defects in DNA repair Limitless replicative potential Sustained angiogenesis (nutrition and waste removal)
    • • Ability to invade and metastasize • Ability to escape immune recognition and regulation • Oncogenes – are genes that promote autonomous cell growth in cancer • Proto-oncogenes – unmutated normal counterparts • Oncoproteins – products of oncogenes
    • Proto-oncogenes, Oncogenes and Oncoproteins • Mutations convert proto-oncogenes into constitutively active oncogenes that endow the cell with growth self-sufficiently • Growth factors • Growth factor receptors • Signal-transducing proteins
    • Oncogenes • Growth factors - PDGF-β-chain (astrocytoma, osteosarcoma) - Fibroblast growth factors (Stomach, bladder, breast cancers and melanoma) - TGF-α (astrocytoma, hepatocellular cancer) - HGF (thyroid)
    • • Growth factor receptors - EGF-receptor family (squamous cell carcinoma of the lungs, gliomas, breast and ovarian cancers) - CSF-1 receptor (Leukemia) - receptor for neurotrophic factors (Multiple endocrine neoplasia 2A and 2B), familial meduallry thyroid cancer) - PDGF receptor (Gliomas) - Receptor for stem cell factor (GI and soft tissue tumors)
    • • Proteins involved in signal transduction - GTP-binding (RAS) (Colon, Lung, Pancreatic, bladder and kidney tumors, melanomas, hematologic) - nonreceptor tyrosine kinase (chronic myeloid and acute lymphoblastic leukemia) - RAS signal transduction (melanomas) - WNT signal transduction (hepatoblastomas and hepatocellular carcinoma)
    • • Nuclear Regulatory Proteins - Transcriptional activators (MYC) (Burkitt lymphoma, neuroblastoma, small cell carcinoma of lungs) • Cell Cycle Regulators - Cyclins (Mantle cell lymphoma, Breast and esophageal cancers, Breast cancer - Cyclin-dependent kinase (glioblastoma, melanoma, sarcoma)
    • Carcinogenic Agents • Chemical - initiation (direct acting and indirect acting agents) - promotion • Radiation (UV and ionizing) • Oncogenic viruses and microbes (Heliobacter pylori, HPV, EBV, Hepatitis B and C)
    • Host Defense Against Tumors • Tumor antigens • Antitumor Effector Mechanisms • Immune Surveillance and Escape
    • Clinical Aspects of Neoplasia • Location and impingement on adjacent structures • Functional activity (hormone production) • Bleeding and infection • Symptoms from tumor rupture or infarction • Cachexia (wasting)
    • Grading and Staging • Grading – based primarily on the degree of differentiation (how well the tumor resembles its normal counterpart), architectural features or number of mitoses • Staging – based on size of the primary tumor and the extent of local and distant spread
    • Laboratory Diagnosis • • • • Histologic and cytologic method Immunohistochemistry Flow cytometry Molecular diagnosis