Pathology Lecture 5 PDF

KAAF UNIVERSITY COLLEGE SCHOOL OF NURSING/MW/PHN PATHOLOGY Lecture 5 LECT. RICHMOND KWAKYE NEOPLASM  neoplasm Neoplasia means ―new growth, and a new growth is called a neoplasm. Tumour originally applied to the swelling caused by inflammation, bu...

KAAF UNIVERSITY COLLEGE SCHOOL OF NURSING/MW/PHN PATHOLOGY Lecture 5 LECT. RICHMOND KWAKYE NEOPLASM  neoplasm Neoplasia means ―new growth, and a new growth is called a neoplasm. Tumour originally applied to the swelling caused by inflammation, but the non-neoplastic usage of tumor has almost vanished; thus, the term is now equated with neoplasm. Oncology (Greek oncos = tumor) is the study of tumors or neoplasms. According to the eminent British oncologist, Rupert A. Willis, a neoplasm “is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change”.  James Ewing’s definition is that “a neoplasm is a relatively autonomous growth of tissue”.  The persistence of tumours, even after the inciting stimulus is gone, results from genetic alterations that are passed down to the progeny of the tumour cells. These genetic changes allow excessive and unregulated proliferation that becomes autonomous (independent of physiologic growth stimuli), although tumours generally remain dependent on the host for their nutrition and blood supply.  ONCOGENES Oncogenes are a group of genetic mutations that may cause cancer. They're a mutated form of genes that manage cell growth. When these genes change into oncogenes, they cause cells to grow and divide uncontrollably. Genes that promote autonomous cell growth in cancer cells are called oncogenes, and their unmutated cellular counterparts are called proto-oncogenes. Oncogenes are created by mutations in proto-oncogenes and are characterized by the ability to promote cell growth in the absence of normal growth-promoting signals.  PROTO-ONCOGENES Genes that regulate normal cell growth and division, but can mutate into oncogenes that cause cancer(RAS:lung, HER2: breast, Clyclin D)  Principles involved in the molecular basis of cancer. a. Nonlethal genetic damage lies at the heart of carcinogenesis. Such genetic damage (or mutation) may be acquired by the action of environmental agents, such as chemicals, radiation, or viruses/ bacteria, or it may be inherited in the germ line. The term environmental, used in this context, involves any acquired defect caused by exogenous agents or endogenous products of cell metabolism. b. A tumour is formed by the clonal expansion of a single precursor cell that has incurred genetic damage (i.e., tumors are monoclonal/multiclonal). c. Five classes of normal regulatory genes are the principal targets of genetic damage: i. the growth-promoting proto-oncogenes, ii. the growth-inhibiting tumour suppressor genes, iii. genes that regulate cell death (apoptosis), iv. genes involved in DNA repair. v. the metastatic genes. d. Carcinogenesis is a multistep process at both the phenotypic and the genetic levels, resulting from the accumulation of multiple mutations  A tumour is formed by the clonal expansion of a single precursor cell that has incurred genetic damage (i.e., tumors are monoclonal/multiclonal). A tumor is an abnormal mass of tissue that forms when cells grow and divide more than they should, or do not die when they should Tumors can grow in any part of the body, including organs, joints, and bones Flowchart depicting a simplified scheme of the molecular basis of cancer.  Neoplasm types Benign Malignant  A tumour is said to be benign when its microscopic and gross characteristics are considered relatively innocent, implying that it will remain localized, it cannot spread to other sites, and it is generally amenable to local surgical removal; the patient generally survives. Benign tumours can produce more than localized lumps, and sometimes they are responsible for serious disease.  Some examples of common benign neoplasms include fibroids, polyps, and sebaceous cysts. Fibroids are neoplasms that form in the female uterus, Polyps are neoplasms that form in the colon or large intestine, sebaceous cysts are neoplasms that form in the sebaceous glands of the skin.  Malignant tumours are collectively referred to as cancers, derived from the Latin word for crab, They adhere to any part that they seize on in an obstinate manner, similar to a crab. Malignant, as applied to a neoplasm, implies that the lesion can invade and destroy adjacent structures and spread to distant sites (metastasize) to cause death. Not all cancers pursue so deadly a course. Some are discovered early and are treated successfully, but the designation malignant always raises a red flag.  There are many common examples of malignant neoplasms. Lung cancer is a malignancy that occurs in the lungs. Leukemia is a form of malignant neoplasm that occurs in the blood. Lymphoma is when neoplasms form and flow through the lymph.  Nomenclature Neoplasms are named based upon two factors on the histologic types : mesenchymal and epithelial on behavioral patterns : benign and malignant neoplasms  The suffix -oma denotes a benign neoplasm. Benign mesenchymal neoplasms originating from muscle, bone, fat, blood vessel, nerve, fibrous tissue and cartilages are named as Rhabdomyoma( striated muscle fibres), osteoma, lipoma, hemangioma, neuroma, fibroma and chondroma respectively. Adenoma (benign neoplasm of glandular epithelium), fibroadenoma (benign neoplasm of the breast), and leiomyoma (benign neoplasm of smooth muscle). Some exceptions: Hepatoma (malignant neoplasm of liver), melanoma (malignant neoplasm of melanocytes), mesothelioma (malignant neoplasm of mesothelial cells), and seminoma (malignant germ cell neoplasm of testis).  Malignant neoplasm nomenclature essentially follows the same scheme used for benign neoplasm with certain additions. Malignant neoplasms arising from mesenchymal tissues are called sarcomas (Greed sar =fleshy). Thus, it is a fleshy tumour. These neoplasms are named as fibrosarcoma, liposarcoma, osteosarcoma, hemangiosarcoma etc. Malignant neoplasms of epithelial cell origin derived from any of the three germ layers are called carcinomas.  CHARACTERISTICS/PROPERTIES OF MALIGNANT CELLS Increased nucleo-cytoplasmic ratio Nuclear hyperchromasia Increase in the amount of the nuclear chromatin Irregularity in chromatin distribution such that they appear in clumps or appear unevenly granular. There is loss of the normal reticular appearance that is seen in benign cells. Anisokaryosis (refers to the variation in the size and shape of nuclei from cell to cell. It's a key characteristic of cancer cells ) Anisocytosis (Anisocytosis describes red blood cells that are of different sizes.) Increased size and prominence of the nucleoli  Multinucleation Abnormal mitotic figures Anaplasia dedifferentiation (or loss of the structural and functional differentiation) of normal cells during tumorigenesis. Abnormal or irregular staining patterns of the nuclei such as having hyperchromasia and hypochromasia Nuclear membrane may demonstrate irregular outline such as crenation, lobulation, elongation and spindle shape. Nuclei may appear vesicular Metastases  Metastasis It is defined as a transfer of malignant cells from one site to another not directly connected with it Metastasis is the most reliable sign of malignancy. The invasiveness of cancers permits them to penetrate in to the blood vessel, lymphatic and body cavities providing the opportunity for spread. Most malignant neoplasm metastasies except few such as gliomas in the central nervous system, basal cell carcinoma (Rodent ulcer) in the skin and dermatofibrosarcoma in soft tissues.  Characteristics of Benign and Malignant Neoplasms The difference in characteristics of these neoplasms can be conveniently discussed under the following headings: 1. Differentiation & anaplasia 2. Rate of growth 3. Local invasion 4. Metastasis  1. Differentiation & anaplasia well-differentiated tumours cells resemble mature normal cells of tissue of origin In general, benign neoplasms are well differentiated. Malignant neoplasms in contrast, range from well differentiated, moderately differentiated to poorly differentiate types. Malignant neoplasm composed of undifferentiated cells are said to be anaplastic  2.Rate of growth Most benign tumours grow slowly whereas; most malignant tumours grow rapidly sometimes, at erratic pace. Some benign tumours for example uterine leiomyoma increase in size during pregnancy due to probably steroidal effects (estrogen) and regress in menopause. In general, the growth rate of neoplasms correlate with their level of differentiation and thus, most malignant neoplasms grow more rapidly than do benign neoplasms.  3. Local invasion Nearly all benign neoplasms grow as cohesive expansile masses that remains localized to their site of origin and do not have the capacity to invade or metastasize to distant sites, as malignant neoplasms. The growth of malignant neoplasms is accompanied by progressive infiltration, invasion and destruction of the surrounding tissue.  Sequential steps in mechanisms of tumor invasion & metastasis: A.Carcinoma in-situ(a group of abnormal cells that are found only in the place where they first formed in the body) b. Malignant cell surface receptors bind to basement membrane components (ex.laminin). c. Malignant cell disrupt and invade basement membrane by releasing collagenase type IV and other protease. d. Invasion of the extracellular matrix e. Detachment f. Embolization g. Survival in the circulation h. Arrest i. Extravasation (the leakage of a fluid from its intended space into the surrounding area) j. Evasion of host defense k. Progressive growth l. Metastasis summary of sequential steps  Pathways of spread: Dissemination of malignant neoplasm may occur through one of the following pathways. 1. Seeding of body cavities and surfaces (transcoelomic spread) This seeding may occur wherever a malignant neoplasm penetrates into a natural “open field”. Most often involved is the peritoneal cavity, but any other cavities such as pleural, pericardial, sub- arachnoid and joint spaces-may be affected.  2.Lymphatic spread Lymphatic route is the most common pathway for the initial dissemination of carcinomas The pattern of lymph node involvement follows the natural routes of drainage. Lymph nodes involvement in cancers is in direct proportion to the number of tumour cell reaching the nodes.  3. Hematogenous spread Typical for all sarcomas and certain carcinomas. Lung & liver are common sites of metastasis because they receive the systemic and venous out flow respectively. Other major sites of hematogenous spread include brain and bones. In the circulation, tumour cells form emboli by aggregation and by adhering to circulating leukocytes particularly platelets. 3. Hematogenous spread  Premalignant disorders a) Heredity premalignant disorders, Familial cancers: Evidence of familial clustering of cancer are documented E.g. Breast, ovarian, colonic, and brain cancers Autosmal recessive syndromes of defective DNA repair B) Acquired preneoplastic disorders  Types of carcinogenesis: A large number of agents cause genetic damages and induce neoplastic transformation of cells. They fall into the following three categories: a) Chemical carcinogenesis b) Radiation carcinogenesis c) Viral carcinogenesis , bacteria(H. pylori)  Effects of tumour on the host: Local and Hormonal Effects Cancers arising within or metastatic to an endocrine gland may cause an endocrine insufficiency by destroying the gland. Neoplasms in the gut, both benign and malignant, may cause obstruction as they enlarge  Cancer Cachexia Individuals with cancer commonly suffer progressive loss of body fat and lean body mass accompanied by profound weakness, anorexia, and anemia. Unlike starvation, the weight loss seen in cachexia results equally from loss of fat and lean muscle. There is some correlation between the tumor burden and the severity of the cachexia.  IMMUNOLOGY Immunology is defined as the study of the molecules, cells, organs, and systems responsible for the recognition and disposal of foreign material Immunity can be defined as the way in which the body can protect itself from invasion by pathogenic microorganism and provide a defense against their harmful effect. Immunity is classified in to two major groups - Non specific immunity - Specific immunity  The Immune System The immune system is a complex and sophisticated defense mechanism that protects the human body from harmful pathogens, such as bacteria, viruses, and other foreign substances It is composed of various cells, tissues, and organs. These components work in harmony to identify, neutralize, and eliminate foreign invaders by distinguishing between self and non-self and recognizing specific patterns found on the surface of a pathogen.  THE IMMUNE SYSTEM TYPES They are : the innate/natural/non-specific immune system and the adaptive immune system. The innate immune system provides the first line of defense and is always “on.” It acts rapidly upon encountering pathogens It includes physical barriers like the skin, hair, and mucous membranes, acidic content of GIT, Vagina Certain white blood cells, such as basophils, mast cells, monocytes, neutrophils, and macrophages, that respond quickly to infections.  IN:INSIDE NATE: born Already present before birth The immediate, first line defense mechanisms This form of immunity is always present, even before infection , ready to provide defense against microbes It protect individual against infection. Eliminate damaged cells  When a pathogen breaches the innate defenses, the adaptive immune system (also known as the acquired immune system) comes into play to control infection. It is more specific to pathogens, has memory, and develops over time, through either encountering a pathogen or receiving a vaccination  The adaptive immune system relies on white blood cells called T and B lymphocytes. T cells produce a cell-mediated immune response, and B cells produce the humoral immune response IgG from mother to fetus  Host Defense against Tumours— Tumour Immunity The idea that tumours are not entirely self and may be recognized by the immune system was conceived by Paul Ehrlich, who proposed that immune recognition of autologous tumour cells may be capable of eliminating tumours. Subsequently, Lewis Thomas and Macfarlane Burnet formalized this concept by coining the term immune surveillance, which implies that a normal function of the immune system is to survey the body for emerging malignant cells and destroy them.  Anti-tumour Effector Mechanisms. Cell-mediated immunity is the dominant anti-tumour mechanism in vivo. Although antibodies can be made against tumours, there is no evidence that they play a protective role under physiologic conditions. 1) Cytotoxic T lymphocytes: CD8+ CTLs play a protective role against virus- associated neoplasms (e.g., EBV- and HPV-induced tumors) and have been demonstrated in the blood and tumour infiltrates of cancer patients. 2) Natural killer cells: NK cells are lymphocytes that are capable of destroying tumour cells without prior sensitization and thus may provide the first line of defense against tumour cells. After activation with IL-2 and IL-15, NK cells can lyse a wide range of human tumours.  3) Macrophages: Activated macrophages exhibit cytotoxicity against tumour cells in vitro. T cells, NK cells, and macrophages may collaborate in antitumour reactivity, because interferon-γ, a cytokine secreted by T cells and NK cells, is a potent activator of macrophages. 4) Antibodies: Although there is no evidence for the protective effects of antitumor antibodies against spontaneous tumors, administration of monoclonal antibodies against tumor cells can be therapeutically effective. A monoclonal antibody against CD20, a B-cell surface antigen, is widely used for treatment of lymphomas  Immune Surveillance and Escape Most cancers occur in persons who do not suffer from any overt immunodeficiency. It is evident, then, that tumor cells must develop mechanisms to escape or evade the immune system in immunocompetent hosts. Immune Surveillance and Escape