Neoplasia PDF

NEOPLASIA [Document subtitle] BY:BASANT Tumor (Neoplasia) Definition: A tumor is a new growth of tissue, usually forming a mass. A malignant neoplasm is cancer. The word "tumor" means swelling in Greek. Neoplasia: "neo" means new and "plasia" means formation. Cancer...

NEOPLASIA [Document subtitle] BY:BASANT Tumor (Neoplasia) Definition: A tumor is a new growth of tissue, usually forming a mass. A malignant neoplasm is cancer. The word "tumor" means swelling in Greek. Neoplasia: "neo" means new and "plasia" means formation. Cancer Cancer is the 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 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 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 in their proper location, and to die at the proper time. Differences Between Cancer Cells and Normal Cells Cancer cells are: o Less specialized than normal cells. o Able to ignore apoptotic signals. o Able to influence the normal cells, molecules, and blood vessels surrounding the tumor (microenvironment). o Able to hide from the immune system or use the immune system to stay alive and grow. Causes of Cancer - DNA Damage DNA damage can be caused by: o Environmental factors: Tobacco, ionizing radiation, UV rays, and viruses. o Endogenous causes: Reactive oxygen species (ROS) released during cellular metabolism. o Random injury during DNA replication. Protective events after DNA damage include: o Arrest of cell division, activation of DNA repair enzymes, or induction of apoptosis. Unrepaired DNA damage leads to gene mutations Gene Mutation A gene mutation is a permanent change in DNA that creates an abnormal protein or prevents specific protein formation. Types of Gene Mutations 1. Acquired Gene Mutations o These are the most common cause of cancer. o They occur due to damage to genes in a cell during a person's life. o Cancer caused by acquired mutations is called sporadic cancer. 2. Germline Mutations o These are less common. o They occur in a sperm cell or ova cell and are passed directly from parent to child Cancer caused by germline mutations is called inherited cancer and accounts for about 5-20% of all cancers. Genes Linked to Cancer 1. Tumor Suppressor Genes o These are protective genes that: ▪ Monitor the rate of cell division. ▪ Repair DNA damage. ▪ Control apoptosis. o Recessive mutations that decrease the function of these genes can induce cancer. 2. Oncogenes o These are present normally as proto-oncogenes and are involved in cell growth. o Dominant mutations that increase the function of these genes can induce cancer. ‫شرح‬ Classification of Tumors 1. According to the Behavior of the Tumor: o Benign: Non-cancerous tumors that grow slowly and do not spread. o In Situ: Tumors that are localized and have not invaded surrounding tissues. o Malignant: Cancerous tumors that grow uncontrollably and have the potential to spread (metastasize). o Tumors of Unknown Behavior: Tumors whose behavior cannot be determined based on available data. 2. According to the Tissue of Origin: o Epithelial Tumors: Tumors that arise from epithelial cells (cells that line organs, glands, and other structures). o Connective Tissue Tumors: Tumors that arise from connective tissue (such as bone, cartilage, and fat). Microscopic Criteria of Malignant Cells 1. Undifferentiated Cells: These cells are anaplastic or atypical, meaning they lack the normal characteristics of the tissue from which they originated. 2. Non-uniform Cells: Malignant cells are pleomorphic, meaning they vary in size and shape. 3. Dark Stained Nucleus: The nucleus of malignant cells is hyperchromatic, meaning it appears darker due to increased DNA content. 4. Increased Nucleus-Cytoplasm (N/C) Ratio: Malignant cells have a larger nucleus compared to the cytoplasm. 5. Prominent Nucleoli: The nucleolus within the cell nucleus is more pronounced. 6. Loss of Polarity: Malignant cells lose the normal orientation and structure, making them appear disorganized. 7. Frequent Abnormal Mitoses: There are abnormal or irregular cell divisions. ‫شرح الجداول‬ Methods of Spread of Malignant Tumors 1. Local Invasion: o Mechanism of Tumor Cell Invasion and Metastasis: A) Decrease in adherence of tumor cells to each other by inhibition of E-cadherin expression. B) Increased secretion of growth factors. C) Degradation of the extracellular matrix (ECM) through secretion of collagenase, cathepsin B, and gelatinase. D) Attachment of malignant cells to ECM components. E) Failure to synthesize the basement membrane. F) Migration of tumor cells via secretion of motility factors. 2. Locally Malignant Tumors (Tumors of Unknown Behavior): o A group of malignant tumors that spread locally without distant metastasis. Examples include: 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 the pituitary gland. 6. Giant cell tumor of bone (grade I and II). 3. Blood Spread: o Sarcoma is the most common tumor spread via blood. o Venous spread is more common than arterial spread and forms tumor emboli that stop first in the lungs or liver. o Carcinomas with early blood spread: ▪ Renal cell carcinoma. ▪ Hepatocellular carcinoma. ▪ Follicular carcinoma of the thyroid. ▪ Choriocarcinoma of the uterus. 4. Lymphatic Spread: o Tumor Emboli: Small groups of tumor cells spread to regional lymph nodes. o Lymphatic Permeation: Solid cords of tumor block the lymph vessels and lead to retrograde spread. Example: Edema of the skin around the nipple (Peau d’orange). o Perineurial Lymphatic Spread: Spread via lymphatic vessels near large nerves. o Carcinoma is the most common tumor spread via lymphatics. Transcoelomic Implantation Spread of malignant tumors in organs covered by serous membranes. For example, carcinoma of the stomach or colon can spread through the peritoneum to the ovaries, forming a Krukenberg tumor. Definition: Tumors induce the formation of new blood vessels. Pathogenesis: New blood vessels supply oxygen and nutrients to the tumor. Tumor cells secrete vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), promoting capillary growth. Cancer cells stop producing PKG, which inhibits angiogenesis, allowing tumors to make their own blood vessels through cancer stem cells. Importance of Tumor Angiogenesis Tumor survival and growth. Waste removal. Increased tumor size. Spread and metastasis. New blood vessels may be lined by endothelium and cancer cells, aiding blood spread. Cancer Stem Cells (CSCs) Definition: Stem cells found within malignant tumors. Characteristics: 1. Give rise to all cell types found in the tumor (tumorigenic). 2. Self-renewing with unlimited proliferative capacity. 3. A minor population in tumor cells, enabling them to escape therapy. 4. Resistance to drugs, radiation, and cell stress. 5. Cause relapse and metastasis. 6. CSCs are targets for specific therapies. Tumors of Epithelium Benign Tumors: o Papilloma o Adenoma Malignant Tumors: o Carcinoma Papilloma Definition: A benign tumor arising from surface epithelium, strongly associated with HPV. Gross Appearance: 1. Cauliflower-like outward projection. 2. Slightly elevated or finger-like growth.  3. Simple or branched. Microscopically: Benign proliferated epithelial cells cover a fibro-vascular core. The basement membrane remains intact. Types of Papilloma 1. Squamous Cell Papilloma: Skin, lip, and tongue. 2. Columnar Cell Papilloma: o Duct papilloma of the breast: Arises from the epithelium of the main duct near the nipple. o Adenomatous polyp: Mixed adenoma/papilloma tumor arising from the mucosa of the GIT and gall bladder, some types considered precancerous. 3. Transitional Cell Papilloma: Arises mainly from the urothelium of the urinary bladder and ureter. Adenoma Definition: A benign tumor arising from secretory or glandular epithelium. Site: Thyroid, ovary, breast, GIT, and pituitary. Types and Gross Appearance: 1. Solid: Pituitary adenoma. 2. Cystic (Cystadenoma): Ovary and thyroid adenomas. 3. Mixed with fibrous tissue: Breast fibroadenoma. 4. Adenomatous polyp: GIT. Microscopically: Capsulated and formed of differentiated cells similar to the original gland. Carcinoma Definition: A malignant tumor of epithelium. Gross Appearance: o Fungating or polypoid: Outward, complex branching cauliflower mass. o Infiltrating: Transmural growth causing thickening and narrowing. o Ulcerative: Malignant ulcer. Microscopic Types of Carcinoma 1. Carcinoma Arising from Surface Epithelium: o Squamous cell carcinoma o Basal cell carcinoma o Transitional cell carcinoma o Carcinoma in situ (intraepithelial carcinoma) 2. Carcinoma Arising from Glandular Epithelium: o Adenocarcinoma o Mucoid carcinoma  3. Adenosquamous carcinoma 4. Anaplastic carcinoma 5. Large cell carcinoma 6. Small cell carcinoma Carcinoma - Gross Appearance of Malignant Ulcer Large Raised, everted edges Fixed, hard, infiltrating base Necrotic floor Carcinoma - Microscopic Features 1. Squamous Cell Carcinoma: o Definition: Malignant tumor arising from stratified squamous epithelium. o Gross Appearance: Fungating, infiltrating, ulcerative. o Microscopic: Dermal infiltration by masses of large pleomorphic squamous cells. Central cells replaced by keratin, forming epithelial pearls or cell nests. o Sites: Skin, lip, tongue, larynx, esophagus, cervix, vagina, vulva, and anal canal. 2. Basal Cell Carcinoma: o Definition: Malignant tumor arising from the basal cell layer of the skin, locally malignant. o Gross Appearance: Small nodule that increases in size and ulcerates. o Microscopic: Dermal infiltration by masses of hyperchromatic basal cells, arranged in a palisade manner. o Sites: Sun-exposed areas of the face. 3. Carcinoma in Situ (Pre-invasive Carcinoma): o Definition: Intraepithelial malignant cells with intact basement membrane. o Microscopic: Malignant changes in the epithelial cells before the basement membrane is infiltrated (no stromal invasion). o Sites: Cervix, breast, and bronchi. o Will not usually form a mass. Teratoma Definition: A benign tumor of the ovary or testis composed of mature tissue representing at least two embryonic layers (ectoderm, mesoderm, or endoderm). Types of Teratoma: 1. Ectodermal (most common): Squamous epithelium, sebaceous glands, hair follicles, brain tissue. 2. Mesodermal (second most common): Bone, cartilage, smooth muscle, fibroadipose tissue. 3. Endodermal: Intestinal or respiratory epithelium, thyroid, salivary glands.  Origin: Teratomas arise from pluripotent stem cells as germ cells and embryonal cells. Hamartoma Definition: A focal malformation consisting of the same tissue elements normally found at that site, but growing in a disorganized manner. Para-neoplastic Syndrome Definition: Disorders caused by substances produced by the tumor (hormones or cytokines) or triggered by an altered immune system response to a neoplasm. These effects occur remotely from the tumor itself. Examples: o Cushing syndrome (increased cortisone levels): Associated with small cell carcinoma of the lung. o Hypercalcemia: Associated with squamous carcinoma of the lung. Disturbance of Growth 1. Hyperplasia: o Definition: Proliferation of cells, resulting in an increase in the number of normal-looking cells in a given tissue. 2. Hypertrophy: o Definition: Increase in the size of cells. 3. Atrophy: o Definition: Decrease in the size of the organ due to the reduction in size and number of its cells. 4. Metaplasia: o Definition: The conversion of one type of tissue into another type. 5. Dysplasia: o Definition: Atypical hyperplasia or the appearance of abnormal hyperplastic cells within the epithelium.