Neoplasia PDF

NEOPLASIA Dr.Kidus.  LEARNING OBJECTIVES Difference between neoplastic &non-neoplastic lesions Contrast benign from malignant tumors Methods and mechanisms of metastasis Etiologic factors in carcinogenesis Understand clinical effects of neoplasms Cancer diagnosis...

NEOPLASIA Dr.Kidus.  LEARNING OBJECTIVES Difference between neoplastic &non-neoplastic lesions Contrast benign from malignant tumors Methods and mechanisms of metastasis Etiologic factors in carcinogenesis Understand clinical effects of neoplasms Cancer diagnosis modalities  What is Neoplasia?  DEFINITION Literally ( Neoplasia-‘new growth’) Technically (Willis)- abnormal mass of tissue the growth of which exceeds and persists in the same excessive manner even after cessation of the stimulus evoking the transformation. 4  In the modern era, a neoplasm can be defined as a disorder of cell growth that is triggered by a series of acquired mutations affecting a single cell and its clonal progeny The causative mutations give the neoplastic cells a survival and growth advantage, resulting in excessive proliferation that is independent of physiologic growth signals (autonomous) 5  Nomenclature  Neoplasms named based on two factors Histologic types-mesenchymal/epithelial Behavioral patterns -benign/malignant 6  Benign Tumors A tumor is said to be benign when its gross and microscopic appearances are considered relatively innocent, (localized, will not spread to other sites, local surgical removal; understandably, the patient generally survives). However, “benign” tumors may cause significant morbidity and are sometimes even fatal  In general, benign tumors are designated by attaching the suffix -oma to the name of the cell type from which the tumor originates. Tumors of mesenchymal cells generally follow this rule. For example, a benign tumor arising in fibrous tissue is called a fibroma, whereas a benign cartilaginous tumor is a chondroma. Benign epithelial tumors is more complex; some are classified based on their cells of origin, microscopic pattern, and macroscopic architecture.  Adenoma is applied to benign epithelial neoplasms derived from glands. Benign epithelial neoplasms with microscopically or macroscopically visible fingerlike or warty projections from epithelial surfaces are referred to as papillomas. Those that form large cystic masses, such as in the ovary, are referred to as cystadenomas. Some tumors produce papillary patterns that protrude into cystic spaces and are called papillary cystadenomas.  Malignant Tumors. Malignant tumors are collectively referred to as cancers, derived from the Latin word for crab, because they tend to adhere to any part that they seize on in an obstinate manner. Malignant tumors can invade and destroy adjacent structures and spread to distant sites (metastasize) to cause death. Not all cancers pursue so deadly a course.some excised surgically or are treated successfully with chemotherapy or radiation, but the designation malignant always raises a red flag.  The nomenclature of malignant tumors essentially follows the same schema used for benign neoplasms, with certain additions. Malignant tumors – Arising in solid mesenchymal tissues are usually called sarcomas (Greek sar = fleshy; e.g., fibrosarcoma, chondrosarcoma, leiomyosarcoma, and rhabdomyosarcoma), – Arising from blood-forming cells are designated leukemias (literally, white blood) or lymphomas (tumors of lymphocytes or their precursors).  Malignant neoplasms of epithelial cell origin, derived from any of the three germ layers, are called carcinomas. – Ectodermally derived epidermis, – Mesodermally derived renal tubules, – Endodermally derived lining of the gastrointestinal tract. Carcinomas may be further qualified. – Squamous cell carcinoma =stratified squamous epithelium – Adenocarcinoma =epithelial cells grow in a glandular pattern. Sometimes the tissue or organ of origin renal cell adenocarcinoma or bronchogenic squamous cell carcinoma. Not infrequently, a cancer is composed of cells of unknown tissue origin, and must be designated merely as an undifferentiated malignant tumor  Mixed Tumors. In most benign and malignant neoplasms, all of the parenchymal cells closely resemble one another. Infrequently, however, divergent differentiation of a single neoplastic clone creates a mixed tumor, such as the mixed tumor of salivary gland. These tumors contain epithelial components scattered within a myxoid stroma that may contain islands of cartilage or bone  Characteristics of Benign and Malignant Neoplasms Differences can be discussed Based on the following 1. Differentiation & anaplasia 2. Rate of growth 3. Local invasion 4. Metastasis 14  1. Differentiation &anaplasia Differentiation –extent to which neoplastic cells resemble comparable normal cells both morphologically & functionally. Well differentiated –resemble mature normal tissue Poorly or undifferentiated tumors-primitive appearing, unspecialized cells. 15  Benign- well differentiated (generally) Malignant- range from well –moderately-to poorly differentiated. Malignant tumors with undifferentiated cells anaplastic (anaplasia-form back ward-literally) 16 Morphology: anaplastic cells include Large polymorphic, hyper chromatic nucleus High nuclear to cytoplasmic ratio 1:1 Large nucleoli with high &often abnormal mitosis Tumor giant cells &loss of polarity of epithelial arrangements 17 Rhabdomyosarcoma (anaplastic) 18  Functionally- well differentiated well function e.g-  Endocrine tumors  hormones (thyroid, adrenal)  Epithelial keratin,  Hepatocellular carcinoma bile 19 2. Rate of growth Benign (most)- have slow rate of growth Most malignant-grow fast Some benign tumors e.g –uterine leiomyoma grow during pregnancy regress in menopause because of estrogen stimulation (variable growth) Rate of growth correlate with differentiation 20  Occasionally –cancers decrease in size &disappear e.g renal cell carcinoma,malignant melanoma, choriocarcinoma 3. Local invasion Benign tumors –remain localized to their site of origin, don’t invade or metastasize to distant sites. Malignant tumors- invade &metastasize 21  Most benign –encapsulated by fibrous rim Hemangiomas and neurofibromas are exceptionals Encapsulation keep benign tumors as discrete ,rapidly palpable &easily movable therefore easy to enucleate surgically 22  Fibroadenoma of the breast. The tan-colored, encapsulated small tumor is sharply demarcated from the whiter breast tissue. 23  Malignant neoplasms –grow progressive infiltration, invasion and destruction of surrounding tissues. So, poorly demarcated (well-defined cleavage plane is lacking ) Connective tissues are favored invasive path for most malignant neoplasms due to elaboration of matrix degrading enzymes e.g- collagenases Arteries are resistant to invasion than veins & lymphatics Cartilage –most resistant for invasion 24  Cut section of an invasive ductal carcinoma of the breast. The lesion is retracted, infiltrating the surrounding breast substance, and would be stony hard on palpation. 25  4.Metastasis- Transfer of malignant cells from one site to another not directly connected with 26  Mechanisms of invasion &Metastasis Invasion & metastasis –hall marks of malignancy Are major causes of mortality & morbidity 28  Most malignant neoplasm metastasize but few – basal cell carcinoma, – glioma, – dermatofibroma, in soft tissues. Pattern of metastasize is unpredictable Approximately 30% of newly diagnosed solid tumors (excluding skin cancers other than melanomas) present with metastases.. 29 Metastatic cascade has two phases: 1. Invasion of the extracellular matrix 2. Vascular dissemination &homing of tumor cells. 1. Invasion of the extracellular matrix Histologically tissues separated by two types of ECM: Interstitial connective tissue &basement membrane 30 Invasion of the ECM is an active process that can be resolved in to several steps : 1. Detachment of tumor cells from each other 2. Attachment to matrix components 3. Degradation of the ECM 4. Migration of tumor cells 31  1.Detachment – Normal cells are glued to each other by adhesion molecules e.g –E-cadherin – In epithelial cancers there is down regulation of E- cadherin 32  2. Attachment Receptor mediated attachment of tumor cells to laminin & fibronectin is important for invasion & metastasis In addition to laminin receptors, tumor cells express integrins that can serve as receptors for fibronectin, laminin and collagen 34 3. Degradation Tumor cells create passage ways for invasion by active enzymatic degradation of the ECM components Is done by producing protiolytic enzymes or inducing host cells (e.g-fibroblasts& infiltrating macrophages) to elaborate proteases e.g type iv collagenase The action of proteases is regulated by antiproteases 35 4. Locomotion (migration) Propelling tumor cells through the degraded BMs &zones of matrix proteolysis Migration mediated by 2 molecules: a. Tumor cell derived motility factors b. cleavage products of matrix components (e.g- collagen ,laminin) 37  SPREED PATHWAYS Malignant tumor cells disseminate through one of 3 ways: 1. Direct seeding of body cavities or surfaces 2. Lymphatic spread & 3. Hematogenous spread 39 1. Seeding of body cavities &surfaces (transcoelomic spread) May occur whenever a malignant neoplasm penetrates into a natural “open field” Most involved- peritoneal cavity, pleura, subarachnoid spaces& joint spaces Ovarian & appendicial carcinomas 40  2. Lymphatic spread Most common pathway for initial dissemination of carcinomas, but sarcoma may also use this route. The pattern of LN involvement follows the natural routes of drainage. E.g –Breast Ca in UOQ Axillary LNs 41  Local LNs may be bypassed “skip metastasis” – because of venous-lymphatic anstomosis or obstruction of lymphatics. E.g –Gastric Ca – metastasize to supraclavicular LNs (sentinel node) Enlargement of LNs may be caused by: -spread &growth of cancer cells or -reactive hyperplasia 42 3. Hematogenous spread Typical for all sarcomas &certain carcinomas can Liver &lung –frequently involved –because systemic &venous blood supply (out flow) Others include Brain & Bones – E.g- Para vertebral plexus-involvement in thyroid & prostatic Cas. Renal cell Ca-involve renal veins inferior vena cava RH 43 A liver studded with metastatic cancer 44  Comparison between a benign tumor of the myometrium (leiomyoma) 45 and a malignant tumor of similar origin (leiomyosarcoma).  Cancer Epidemiology The only certain way to avoid cancer is not to be born, to live is to incur the risk Occur in M>F –because of implementation of screening methods Bronchogenic Ca-common in males, Breast Ca- is common in females 46  Most cancers occur in ages >55years 50 years 50  Familial cancers e.g –Breast Ca, ovarian Ca, colonic Ca & some Brain Cancers Pattern of inheritance is not clear 51  Acquired preneoplastic disorders Fertile soil for growth of neoplasia-regeneration, hyperplasia& dysplastic proliferations e,g- endometrial hyperplasia, cervical dysplasia, hepatic regeneration  carcinomas 52  Non- neoplastic conditions predisposing to cancers Chronic atrophic gastritis gastric Ca, Ulcerative colitis colonic Ca Benign neoplasms may constitute premalignant conditions e.g- villous colonic adenoma villous adenocarcinoma 53  Carcinogenic agents and their cellular interactions Carcinogenic agents: 1. Chemical carcinogens 2. Radiant energy 3. oncogenic microbes,(viruses) 54  A. Chemical carcinogenesis Incomplete combustion products ( e.g-hydrocarbons), plant products, medical drugs have been involved in the causation of cancers in humans. Cancer induction steps: -initiation -promotion 55  Initiation-causes permanent DNA damage (mutations) Promoters-induce tumors in initiated cells, but they are non tumorogenic by themselves The effects of promoters are reversible Initiation alone, however, is not sufficient for tumor formation. 56  Initiators – – Direct acting-no transformation needed – Indirect acting (procarcinogens) metabolic conversion ultimate carcinogens DNA is their primary target 57 B.RADIATION CARCINOGENESIS Ultraviolate rays,ionizing radiation (X-RAY, gamma- RAYS ) Can transform &induce neoplasm E.g-UV light squamous cell Ca, malignant melanoma, basal cell Ca Ionizing radiation skin Cas, lung Cas, leukemias, breast &thyroid cancers 59  C. Viral & Bacterial Carcinogenesis DNA &RNA viruses- oncogenic ability Helicobacter pylori gastric lymphoma (MALToma) 1. DNA oncogenic viruses e.g –HPV, EBV (Epstein Barr virus), HBV HPV- integration of the viral DNA neoplastic transformation-  Causes- benign squamous papilloma(warts)- (type1,2,4,&7)  Squamous cell Ca of the cervix & anogenital region (types 16, 18  least commonly 31, 33, 35, &51 found in 85% of SCC) - oral &laryngeal Cas 60 EBV- Herpes virus implicated in pathogenesis of African form of Burkitt’s lymphoma The association is strong B-cell lymphoma-in immunocompromized patients Hodgkin’s lymphoma Nasopharyngeal carcinoma 61 CLINICAL FEATURS OF TUMORS Neoplasms are parasites Effects on hosts Pressure effects (impingement on adjacent structures) Hormonal effects Bleeding & secondary infections when ulcerate through adjacent normal tissue Initiation of acute symptoms following rupture or infarction Other 20 effects-DIC-following tissue factor release 62 Examples Pituitary adenoma endocrinopathies Metastasis to glands hormonal insufficiency Neoplasm in the GI obstruction Beta-cell adenoma of pancreas insulin hypoglycemia Cancer cachexia 63  Progressive weight loss accompanied by profound weakness, anorexia, anemia Cause Some explanations - food intake due to abnormal testing & central control of appetite High metabolic activity (BMR) Due to TNF-,IL-1,INF--BY tumor or host response against tumors 64  Grading &Staging of Cancers Grading –denotes level of differentiation Staging –extent of tumor spread &prognosis of cancers Grading is based on degree of differentiation of tumor cells & number of mitosis with in the tumor Cancers classified in to I-IV grades with increasing anaplasia Criteria for individual grades vary with each form of neoplasia 65  Staging –based on -size of primary lesion -extent of spread to regional LNs -presence or absence of metastasis Two staging systems – TNM &AJC (American Joint Committee) T- primary tumor, N-regional lymphnode, M-metastasis 66 General principles T1-T4 with increasing number N0-no nodal involvement,N1,N2,N3-involvment of an increasing number & range of nodes M0- no distant metastasis,M1 & some times M2- presence of blood born metastasis Staging is -important in selection of therapy -has greater clinical value than grading 67  DIAGNOSTIC TECHNIQUES OF Methods- NEOPLASMS 1. Excisional &incisional biopsy 2. Cytologic smears-FNAC, Pap smear-for cervical Ca, fluid cytology 3. Advanced techniques -immunocytochemistry, tumor marker studies 68 Tumor markers Biochemical indicators of a tumor Include surface antigens, cytoplasmic proteins, enzymes, & hormones Act as supportive lab tests e.g –HCG (human chorionic gonadotropic hormone) in association of GTDs -CEA ( chorioembrionic antigen)-colonic Ca -CA -125- ovarian Ca -Catecholamine- medullary thyroid Ca 69 THANK YOU  Short answer 1. What is the difference Between benign and malignancy 2. List the disseminated pathways of Malignant tumor cells 3. What is the commonest cause of death for female 4. What is the commonest ca in Ethiopia 5. List at least three environmental factors predisposiing for cancer