Neoplasia I L 9 PDF

NEOPLASIA I Session 9 L9 WHAT IS A TUMOR? HOW DO TUMORS DEVELOP? Ass. Prof. Dr. Hadeel Abdulelah Karbel Histopathologist F. I. C. M. path. 1 References Robbins basic pathology. Muir's Textbook of pathology. 2  OBJECT...

NEOPLASIA I Session 9 L9 WHAT IS A TUMOR? HOW DO TUMORS DEVELOP? Ass. Prof. Dr. Hadeel Abdulelah Karbel Histopathologist F. I. C. M. path. 1 References Robbins basic pathology. Muir's Textbook of pathology. 2  OBJECTIVES Definitions of tumour and neoplasia Definitions of benign versus malignant How tumors develop Clonality Neoplastic versus normal cells Features of neoplasms Dysplasia Types of neoplasms 3  WHAT IS A TUMOUR? Tumor – Swelling of any nature Inflammatory..abscess. Traumatic …trauma. Neoplasm…abnormal cellular growth. 4  WHAT IS NEOPLASM? Abnormal growth of cells which persists after initiating stimulus has been removed. Cell growth escaped from normal regulatory mechanism. Benign Malignant 5  OBJECTIVES Definitions of tumour and neoplasia Definitions of benign versus malignant How tumors develop Clonality Neoplastic versus normal cells Features of neoplasms Dysplasia Types of neoplasms 6  BENIGN NEOPLASM Cells grow as a compact mass and remain at their site of origin 7  COLONIC ADENOMA 8  MALIGNANT NEOPLASM Growth of cells is uncontrolled Cells can spread into surrounding tissue and spread to distant sites Cancer = a malignant neoplasm 9  Colonic adenomas ('polyps') Colorectal adenocarcinoma 10  OBJECTIVES Definitions of tumour and neoplasia Definitions of benign versus malignant Features of the cancers Clonality Neoplastic versus normal cells Features of neoplasms Dysplasia Types of neoplasms 11  Features of the cancer Cancer is a genetic disorder caused by DNA mutations that are (for the most part) acquired spontaneously or induced by environmental insults. These genetic alterations are heritable ,being passed to daughter cells upon cell division. As a result, cells harboring these alterations are subject to darwinian selection 12  The change must cause an alteration in cell growth and behavior Oncogenes & tumor suppressor genes. Alteration is to more than one gene Sequence of gene alterations from normal to benign to malignant Intrinsic (e.g. inherited) and extrinsic (environmental) factors  Immunological Theory of Cancer The elimination step consists of the immune system surveying for all cancerous cells and destroying them. However, there are times when tumorous cells remain undetected while remaining dormant. This period is defined as equilibrium because there are cancerous cells in the body, but they are not doing any harm. The final step is escape in which the tumor gains dominance over the immune system and starts spreading Somatic Mutation Theory of Cancer The somatic mutation theory analyzes the development of cancer by looking at genetic factors. Specific genetic mutations are directly linked to specific cancers Stem Cell Theory of Cancer This theory assumes that cancer is a result of a stem cell that is unregulated and grows uncontrollably. Cancer viewed as a reprogrammed cell with the Egg Cell’s Genetic Program (ECGP)  Tumor Progression Multiple mutations lead to colon cancer Genetic changes --> tumor changes 13  OBJECTIVES Definitions of tumour and neoplasia Definitions of benign versus malignant How tumors develop Clonality Neoplastic versus normal cells Features of neoplasms Dysplasia Types of neoplasms 14  CLONALITY The change must be non-lethal and be passed onto “daughter” cells therefore the genetic alterations are seen in every cell– monoclonal population Initially demonstrated using the enzyme G6PD encoded on the X chromosome. 15  Clonality In heterozygous women, cells are a mix, containing either G6PD A or G6PD B - mosaicism If neoplasms develop in those people they consist of cells that all have the same enzyme ----- loss of heterozygosity or 16 Normal Cancer  OBJECTIVES Definitions of tumour and neoplasia Definitions of benign versus malignant How tumors develop Clonality Neoplastic versus normal cells Features of neoplasms Dysplasia Types of neoplasms 17  HOW DO NEOPLASTIC CELLS DIFFER FROM NORMAL CELLS? Alterations in growth control – Proliferation stimulated – Cell death suppressed – Factors regulating growth receptors Alterations in cellular interactions – Cell-cell – Cell-stroma 18  GROWTH CONTROL Increased cell proliferation – More cells enter cell cycle – Cell cycle “speeded up” doubling time Cells have changed life span – Decreased apoptosis Modification of cell metabolism Angiogenesis 19  GROWTH CONTROL In normal tissues, the rates of new cell growth and old cell death are kept in balance In cancer, this balance is disrupted This disruption can result from 1) uncontrolled cell growth or 2)loss of a cell's ability to undergo apoptosis 20  GROWTH CONTROL Altered synthesis of growth factors – Autocrine or paracrine effect Altered receptors – Increased – Decreased – Mutated Excess/modified growth control proteins 21 22  CELLULAR INTERACTIONS Cell-cell interactions Cell-stromal interactions – e.g. with basement membrane Important in normal cells and tissues for differentiation, embryogenesis, growth regulation 23  CELLULAR INTERACTIONS Normal Malignant invasion 24  DIFFERENCES BETWEEN BENIGN AND MALIGNANT NEOPLASMS Size Growth characteristics Vascularity/necrosis Function Invasion/metastasis. 25  OBJECTIVES Definitions of tumour and neoplasia Definitions of benign versus malignant How tumors develop Clonality Neoplastic versus normal cells Features of neoplasms Dysplasia Types of neoplasms 26  Benign malignant Nuclear variation in size and Nuclear variation in size and shape minimal. shape minimal to marked, often variable (pleomorphism) Diploid Range of ploidy. Low mitotic count, normal Low to high mitotic count, mitosis. abnormal mitosis Retention of specialization Loss of specialization. 33  Benign malignant Structural differentiation Structural differentiation retained. showed wide range of changes. Organized. Not organized Functional differentiation Functional differentiation usually. often lost. 34  Benign vs Malignant Most important clinical question for neoplasms Determines appropriate therapy – Conservative vs wide excision – Evaluation of lymph nodes (staging) – Need for chemotherapy or radiation therapy 11  Benign vs Malignant Degree of differentiation – How closely do the parenchymal cells resemble normal cells of this type – The more differentiated the tumor cell, the more completely it retains the functional capabilities of its normal counterparts. – Benign neoplasms are usually “well- differentiated” – Anaplasia = lack of differentiation (bizarre nuclei, atypical mitoses, loss of cell polarity) – the more rapidly growing and the more anaplastic a tumor, the less likely it is to have specialized functional activity. Here are three abnormal mitoses. Mitoses by themselves are not indicators of malignancy. However, abnormal mitoses are highly indicative of malignancy. The marked pleomorphism and hyperchromatism of surrounding cells also favors 3m2alignancy.  OBJECTIVES Definitions of tumour and neoplasia Definitions of benign versus malignant How tumors develop Clonality Neoplastic versus normal cells Features of neoplasms Dysplasia Types of neoplasms 33  DYSPLASIA Dysplasia – referring to disorderly but non-neoplastic proliferation. Pre neoplastic change usually in epithelia Premalignant condition Increased cell growth Cellular atypia Altered differentiation Can range from mild to severe (in-situ) Sites –cervix –bladder –breast –others May not progress to cancer 15 normal epithelium 16 dysplasia  IN-SITU MALIGNANCY Epithelial neoplasm with features of malignancy Altered cell growth Cytological atypia Altered differentiation BUT - no invasion through basement membrane 37  In situ malignancy 38  POSSIBLE EVENTS Benign -------------------------------- Benign Benign ----------------------------- Dysplasia Benign ----- Dysplasia -------------In-situ Benign --Dysplasia --In-situ -- Invasive Dysplasia ------In-situ ------------Invasive In-situ ------------------------------- Invasive Invasive ---------------------------- Invasive 39  OBJECTIVES Definitions of tumour and neoplasia Definitions of benign versus malignant How tumors develop Clonality Neoplastic versus normal cells Features of neoplasms Dysplasia Types of neoplasms 40  Nomenclature Tumors are composed of – stroma (supporting connective tissue, blood supply) – parenchyma (the neoplastic cells which determines biologic behavior) 21  Nomenclature of Neoplasia Tumor is named according to: 1.. Parenchyma, Organ or Cell Hepatoma- liver Osteoma- bone Myoma- muscle 2. Pattern and Structure, either GROSS or MICROSCOPIC Fluid-filledà CYST Glandularà ADENO Finger-likeà PAPILLO Stalkà POLYP 22  TYPES OF NEOPLASMS Benign malignant Epithelial Connective tissue Lymphoid /haemopoietic Germ cell 43  BENIGN TUMORS Suffix- “OMA” is used Adipose tissue- LipOMA Bone- osteOMA Muscle- myOMA Blood vessels- angiOMA Fibrous tissue- fibrOMA OMA” but Malignant – HepatOMA, lymphOMA, gliOMA, melanOMA 23 Benign epithelial neoplasms Papilloma Squamous Transitional Adenoma Glandular 45  MALIGNANT EPITHELIAL NEOPLASMS CARCINOMAS Squamous: skin Transitional: bladder Adenoma: stomach, colon Basal cell: skin 46  Basal cell carcinoma Squamous cell carcinoma 47  Benign connective tissue neoplasms Smooth muscle:--------- Leiomyoma Fibrous tissue:------------Fibroma Bone: ----------------------Osteoma Cartilage: -----------------Chondroma Fat: - - - Lipoma Nerve: ---------------------Neurofibroma Nerve sheath: -----------Neurilemmoma Glial cells: -----------------Glioma 48  Leiomyoma 49  Malignant connective tissue neoplasms Smooth muscle: -------Leiomyosarcoma Bone: ---------------------Osteosarcoma Fibrous tissue: ----------Fibrosarcoma Cartilage:---------------- Chondrosarcoma Fat:------------------------ Liposarcoma Nerve: --------------------Neurofibrosarcoma Nerve sheath: ----------Neurilemmosarcoma Glial cells: ----------------Malignant glioma 50  LYMPHOID Malignant lymphoma (B and T) Hodgkins Disease BONE MARROW Leukaemia Myeloid or Lymphocytic Acute or Chronic 51  Hodgkin’s lymphoma 52  Germ cells Testis Teratoma malignant Seminoma Ovary Mature cystic teratoma (Dermoid cyst) benign 53 54