Neoplasia: Tumor and Cancer Overview PDF

Content: Tumor or neoplasia Target students: 301- FHB102-DENT 202 BY PROF. MAHMOUD TAG  Tumor (Neoplasia) Definition: It is a new growth of tissue which usually forms a mass. A malignant neoplasm is a Cancer. Tumor means swelling in Greek Neoplasia: neo: new & plasia: formation...

Content: Tumor or neoplasia Target students: 301- FHB102-DENT 202 BY PROF. MAHMOUD TAG  Tumor (Neoplasia) Definition: It is a new growth of tissue which usually forms a mass. A malignant neoplasm is a Cancer. Tumor means swelling in Greek Neoplasia: neo: new & plasia: formation.  Cancer Cancer is uncontrolled division of genetically abnormal cells and their spread into surrounding tissues and distant places.  Pathogenesis of cancer Cancer is due to an interaction between an environmental (external) factors and a genetically susceptible host. Normal cells divide as needed and stop. They attach to other cells and stay in place. Normal cells will commit suicide by apoptosis when they are no longer needed. Cancer cells lose their ability to stop dividing, to attach to other cells, to stay where they belong, and to die at the proper time. Differences between Cancer cells and Normal cells Cancer cells are: Less specialized than normal cells. Able to ignore apoptotic signals. Able to influence the normal cells, molecules and blood vessels surrounding the tumor: microenvironment. Able to hide from the immune system or use the immune system to stay alive and grow.  Causes of cancer - DNA damage: [physical injury to DNA strands] by: - Environmental factors: Tobacco, ionizing radiation, UV rays and viruses. - Endogenous causes such as Reactive oxygen species (ROS) released during cellular metabolism. - Random injury during DNA replication. - Protective events after DNA damage: arrest of cell division, activation of DNA repair enzymes or induction of apoptosis. Unrepaired DNA damage leads to gene Mutation. DNA Damage DNA Damage  Gene mutation A permanent change in DNA that creates an abnormal protein or prevents specific protein formation. Acquired gene mutations: These are the most common cause of cancer. They occur from damage to gene in a cell during a person’s life. Cancer that occurs because of acquired mutations is called sporadic cancer. Germline mutations: These are less common. They occur in a sperm cell or ova cell. They pass directly from parent to child at the time of conception. Cancer caused by germline mutations is called inherited cancer. It accounts for about 5- 20% of all cancers. Gene Mutation  Genes linked to cancer 1- Tumor suppressor genes: Protective genes by: - Monitoring the rate of cell division. - Repair DNA damage - Control apoptosis Recessive Mutations that decrease the function of these genes induce cancer 2- Oncogenes: Present normally as proto-oncogenes and involved in cell growth. Dominant Mutations that increase the function of these genes induce cancer  Carcinogenic agents Viral Carcinogenesis Virus Related cancer DNA (HPV) Cancer cervix HBV Hepatocellular carcinoma EBV Burkitt's lymphoma DNA Herpes virus 8 Kaposi sarcoma HCV Hepatocellular carcinoma AIDS related cancer Kaposi sarcoma, Non Hodgkin lymphoma and Cancer cervix  Chemical carcinogenesis Agent Related cancer Arsenic, benzene, Skin, lung and liver cadmium, chromium and coal tar Aflatoxin: a product of DNA breaks and aspergillus flavis fungus hepatocellular carcinoma that grows in crops stored in unhealthy conditions and humidity  Chemical carcinogenesis Agent Related Cancer High fat diet Colon cancer Tobacco Lung cancer Alcohol Liver cancer Estrogen Endometrial- Breast cancers Androgen Prostate Cancer  Physical carcinogenesis Agent Related cancer Ionizing radiation Bone, skin or blood cancers Ultraviolet rays Skin cancer Heat Cancer lip Inhalation of asbestos Mesothelioma of the pleura and Lung cancer  Classification of tumors 1- According to the behavior of the tumor into benign, in situ, malignant and tumors of unknown behavior. 2- According to the tissue of origin into epithelial tumors and connective tissue tumors. Microscopic criteria of malignant cells 1. Undifferentiated cells: anaplastic or atypical 2. Non uniform cells: pleomorphic. 3. Dark stained nucleus: hyperchromatic. 4. Increase nucleus-cytoplasmic (N/C) ratio. 5. Prominent nucleoli. 6. Loss of polarity. 7. Frequent abnormal mitoses.  Tumors Benign cells Malignant cells  Tumor Pleomorphism Loss of polarity  Tumor Hyperchromatic Increase nucleo- nucleus cytoplasmic ratio  Tumor Mitosis Prominent nucleoli  Difference between benign and malignant tumors Characters Benign Malignant Differentiation Well lack of differentiated differentiation Growth Expansile Infiltrative Invasion Capsulated No Capsule Metastasis No Metastatic spread Prognosis Good Bad Difference between carcinoma and sarcoma Character Carcinoma Sarcoma Definition Malignant tumor of Malignant tumor of epithelium mesenchymal tissue Structure The cells are Individual cells in arranged in sheets separated by groups separated delicate, vascular by fibrous stroma stroma Consistency Firm Soft and fleshy Spread Early by Early by blood lymphatic  Tumor Carcinoma Sarcoma  Methods of spread of malignant tumors 1- Local invasion: Mechanism of tumor cell invasion and metastasis: A) Decrease adherence of tumor cells to each other by inhibition of E-cadherin expression B) Increase growth factor secretion. C) Degradation of ECM through secretion of collagenase, cathepsin B and gelatinase. D) Attachment of malignant cells to ECM component. E) Failure to synthesize basement membrane. F) Migration of tumor cells by secretion of motility factor.  Locally malignant tumors Tumor of unknown behavior- borderline- locally aggressive Definition: Group of malignant tumors which spread locally only i.e. there is no distant spread or metastasis. Examples: 1- Basal cell carcinoma of the skin (rodent ulcer). 2- Adamantinoma of the jaw. 3- Carcinoid tumor of the appendix. 4- Astrocytoma of the brain. 5- Craniopharyngioma of pituitary gland. 6- Giant cell tumor of bone (grade I and II).  Blood spread Sarcoma is the commonest tumor spread via blood Venous spread more common than arterial. It forms tumor emboli which stop first in the lung or liver Carcinomas with early blood spread: - Renal cell carcinoma. - Hepatocellular carcinoma. - Follicular carcinoma of thyroid. - Choriocarcinoma of uterus. Blood spread  Lymphatic spread Tumor emboli: [ Small group of tumor cell spread to regional lymph node] Lymphatic permeation: [ Solid cord of tumor blocks the lymph vessel and leads to retrograde spread]: ex Edema of the skin around the nipple (Peau d’orange) Perineurial lymphatic spread: spread via lymphatic vessels near big nerves Carcinoma is the commonest tumor spread via lymphatics Lymphatic spread  Retrograde Lymphatic spread Peau d’orange Peau d’orange Perineural lymphatic spread  Transcoelomic implantation Spread of malignant tumors in organs covered by serous membranes. E.g. carcinoma of stomach or colon spreads through the peritoneum to the ovaries forming Krukenberg tumor Transcelomic spread/krukenberg  Tumor angiogenesis Definition: Tumors induced new blood vessels formation Pathogenesis: A source of blood supply to provide the oxygen and other nutrients Tumor cells secret vascular endothelial growth factor ( VEGF) and fibroblast growth factor (FGF) that induce capillary growth. Cancer cells stop producing PKG which inhibits angiogenesis. The tumors are able to make their own blood vessels through cancer stem cells. Tumor angiogenesis Importance of tumor angiogenesis Tumor survival and growth Waste pathway Increase size of the tumor Spread and metastasis New blood vessels may be lined by endothelium and cancer cells helping blood spread  Cancer stem cells (CSCs) Stem cells found within the malignant tumor They have the original characters of normal stem cell Characters: 1- Give rise to all cell types found in tumor: Tumorigenic 2- Self-renewal so they have unlimited proliferative capacity 3- Minor population in tumor cells so they escape therapy 4- Resistance to drugs, radiation and cell stress. 5- Relapse and metastasis 6- CSCs are targets for specific therapies Cancer stem cells  Tumors of Epithelium Benign tumors - Papilloma - Adenoma Malignant tumors - Carcinoma  Papilloma Definition: A benign tumor arises from surface epithelium. It is strongly associated with HPV. Gross: 1- Cauliflower like outward projection. 2- Slightly elevated or finger like growth. 3- Simple or branched. Microscopically: 1- Benign proliferated epithelial cells cover a fibro-vascular core. 2- The basement membrane is intact. Papilloma  Papilloma Types of papilloma: 1- Squamous cell papilloma. Skin, lip and tongue. 2- Columnar cell papilloma. a) Duct papilloma of the breast: It arises from the epithelium of the main duct near the nipple. b) Adenomatous polyp: Mixed adenoma/papilloma tumor. It arises from the mucosa of the GIT and gall bladder. A type of adenomatous polyp called villous papilloma is considered precancerous. 3- Transitional cell papilloma. It arises mainly from the urothelium of the urinary bladder and ureter.  Adenoma Definition: A benign tumor arises from the secretory or glandular epithelium. Site: thyroid, ovary, breast, GIT and pituitary. Types and gross picture: 1- Solid: pituitary adenoma. 2- Cystic (cystadenoma): ovary and thyroid adenomas. 3- Mixed with fibrous tissue: breast fibroadenoma. 4- Adenomatous polyp: glands take polypoid shape: GIT Microscopically: Capsulated and formed of differentiated cells as the original gland.  Adenoma Fibroadenoma Adenoma of breast thyroid gland Carcinoma Definition: it is a malignant tumor of epithelium. Gross (Naked eye appearance): Fungating or polypoid: outward complex branching cauliflower mass. Infiltrating: transmural growth causing thickening and narrowing. Ulcerative: Malignant ulcer. Carcinoma: Gross  Characters of malignant ulcer Large. Raised everted edges. Fixed hard infiltrating base. Necrotic floor.  Carcinoma Microscopic types (classification) of carcinoma: 1- Carcinoma arising from surface epithelium: - Squamous cell carcinoma. - Basal cell carcinoma. - Transitional cell carcinoma. - Carcinoma in situ (intra epithelial carcinoma) 2- Carcinoma arising from glandular epithelium: - Adenocarcinoma - Mucoid carcinoma 3-Adenosquamous carcinoma 4- Anaplastic carcinoma 5- Large cell carcinoma 6- Small cell carcinoma  Carcinoma: Microscopic Squamous cell Basal cell carcinoma carcinoma  Carcinoma Microscopic Transitional cell carcinoma Carcinoma in situ  Carcinoma Microscopic Adenocarcinoma Mucoid carcinoma  Squamous cell carcinoma Definition: Malignant tumor arises from the stratified squamous epithelium. Gross: Fungating- Infiltrating-Ulcerative. Microscopically: Dermal infiltration by masses of large pleomorphic polygonal squamous cells. The cells in the central area are replaced by keratin. These masses are called Epithelial pearl or Cell nest. Sites: skin, lip, tongue, larynx, esophagus, cervix, vagina, vulva, and anal canal. Squamous cell carcinoma Squamous cell carcinoma  Basal cell carcinoma Definition: malignant tumor arises from basal cell layer of skin. It is a locally malignant tumor that destroys surrounding tissue but does not give metastasis. Gross: 1- Small nodule increases in size and then ulcerate. 2- The ulcer has eroded edge Rodent ulcer. 3- Enlargement of cervical lymph nodes with rodent ulcer is usually due to secondary bacterial infection. Basal cell carcinoma  Basal cell carcinoma Microscopically: Dermal infiltration by masses of hyperchromatic malignant Basal cells. The peripheral cell layers are arranged near each other in a Palisade manner. Sites: sun exposed areas face.  Carcinoma in situ Pre-invasive carcinoma. Definition: intraepithelial malignant cells with intact basement membrane. Microscopically: malignant changes appear in the epithelial cells before the basement membrane is infiltrated (no stromal invasion). Sites: cervix, breast and bronchi. Carcinoma in situ will not usually form a mass Fibroma: Benign tumor of fibrous tissue Lipoma: Benign tumor of fatty tissue Chondroma: Benign tumor of cartilage Osteoma: Benign tumor of bone Leiomyoma: Benign tumor of smooth muscle Rhabdomyoma: Benign tumor of striated or cardiac muscles. Hemangioma: Benign tumor of blood vessels Nevus: Benign tumor of pigmented cells Melanoma: Malignant tumor of pigmented cells  Sarcoma: Malignant tumor of mesenchymal tissue Liposarcoma Osteosarcoma  Teratoma Benign tumor of the ovary or testis composed of mature tissue representing at least 2 embryonic layers (ectoderm, mesoderm or endoderm) Ectodermal (most common): squamous epithelium, sebaceous glands, hair follicles, brain tissue Mesodermal (second most common): bone, cartilage, smooth muscle, fibroadipose tissue Endodermal: intestinal or respiratory epithelium, thyroid, salivary gland Origin of teratoma: It arises from pluripotent stem cells as germ cells and embryonal cells. Teratoma DSL  Hamartoma Definition: - It is focal malformation consists of the same tissue elements normally found at that site but they are growing in a disorganized manner. Hamartoma DSL  Para-neoplastic syndrome Definition: - They are disorders result from substances produced by the tumor (hormones or cytokines), that are triggered by an altered immune system response to a neoplasm. They occur remotely from the tumor itself. Examples: - Cushing syndrome (increase cortisone level) associated with small cell carcinoma of the lung. - Hypercalcemia associated with squamous carcinoma of the lung.  Disturbance of Growth 1- Hyperplasia: proliferation of cells Definition: it is increase in the number of normal looking cells in a given tissue. 2- Hypertrophy: (increase in the volume of cells) Definition: it is increase in the size of cells.  3- Atrophy: Definition: It is the decrease in size of the organ due to decrease in the size and number of its cells. 4- Metaplasia: (conversion of cell type) Definition: change of one type of tissue into another type. 5- Dysplasia: (disordered proliferation) Definition: it is atypical hyperplasia or the appearance of abnormal hyperplastic cells within the epithelium.