Untitled Quiz

Tumor (Neoplasia)

• Definition: A new growth of tissue, usually forming a mass.
• Malignant neoplasm is Cancer.
• Tumor means swelling in Greek.
• Neoplasia: neo - new, plasia - formation.

Cancer

• Uncontrolled division of genetically abnormal cells.
• Cells spread into surrounding tissues and distant places.

Pathogenesis of Cancer

• Interaction between environmental factors and a genetically susceptible host.
• Normal cells divide as needed, stop dividing, attach to other cells, and die at the proper time.
• Cancer cells lose the ability to control division, attachment, staying in place, and apoptosis.

Differences Between Cancer and Normal Cells

• Cancer cells are less specialized than normal cells.
• Cancer cells can ignore apoptotic signals.
• Cancer cells can influence normal cells, molecules, and blood vessels surrounding the tumor (microenvironment).
• Cancer cells can hide from or use the immune system to survive and grow.

Causes of Cancer

• DNA damage (physical injury to DNA strands) from:
  • Environmental factors (tobacco, ionizing radiation, UV rays, viruses).
  • Endogenous causes (Reactive oxygen species (ROS) released during cellular metabolism).
  • Random injury during DNA replication.
• Protective events after DNA damage are:
  • Arrest of cell division.
  • Activation of DNA repair enzymes.
  • Induction of apoptosis.
• Unrepaired DNA damage leads to gene mutations.

DNA Damage

• Different types of DNA damage (single-strand break, mis-match, damaged base, double-strand break, intra-strand crosslink, inter-strand crosslink).
• Causes of DNA damage (Cellular metabolism, UV light exposure, ionizing radiation, chemical exposure, replication errors).
• DNA repair mechanisms (Direct reversal, base excision repair, nucleotide excision repair, mismatch repair, double-strand break repair (homologous recombination, non-homologous end joining), apoptosis).

Gene Mutation

• A permanent change in DNA that creates an abnormal protein or prevents specific protein formation.
• Acquired gene mutations: The most common cause of cancer; caused by damage to genes during a person's life.
• Cancer arising from acquired mutations is called sporadic cancer.
• Germline mutations: Less common; occur in sperm or ova cells; inherited from parents.
• Cancer arising from inherited mutations is called inherited cancer.

Genes Linked to Cancer

• Tumor suppressor genes:
  • Protectative genes that monitor cell division, repair DNA damage, and control apoptosis.
  • Recessive mutations that decrease the function of these genes induce cancer.
• Oncogenes:
  • Present normally as proto-oncogenes involved in growth (cell division).
  • Dominant mutations that increase these genes' function induce cancer.

Carcinogenic Agents: Viral, Chemical, and Physical

• Viruses:
  • 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, Cancer cervix.
• Chemicals:
  • Arsenic, benzene, cadmium, chromium, coal tar - Skin, lung, and liver cancer.
  • Aflatoxin (product of Aspergillus flavis fungus) - DNA breaks and hepatocellular carcinoma.
  • High-fat diet - Colon cancer ; Tobacco - Lung cancer ; Alcohol - Liver cancer ; Estrogen - Endometrial-Breast cancers; Androgen - Prostate Cancer.
• Physical:
  • 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

• By tumor behavior (benign, in situ, malignant, unknown behavior)
• By tissue of origin (epithelial, connective tissue)

Microscopic Criteria of Malignant Cells

• Undifferentiated cells (anaplastic or atypical).
• Non-uniform cells (pleomorphic).
• Dark-stained nucleus (hyperchromatic).
• Increased nucleus-cytoplasm ratio (N/C ratio).
• Prominent nucleoli.
• Loss of polarity.
• Frequent abnormal mitoses.

Benign vs. Malignant Tumors

• Differentiation (well vs. lack of differentiation).
• Growth (expansile vs. infiltrative).
• Capsules (present vs. absent).
• Metastasis (absent vs. present).
• Prognosis (good vs. bad).

Carcinoma vs. Sarcoma

• Carcinoma: Malignant tumor of epithelium; cells arranged in groups separated by fibrous stroma; firm; spreads early by lymphatic spread.
• Sarcoma: Malignant tumor of mesenchymal tissue; individual cells in sheets separated by delicate, vascular stroma; soft and fleshy; spreads early by blood.

Tumor Spread: Mechanisms

• Local invasion: Decrease in cell-cell adhesion with E-cadherin inhibition; Increase growth factor secretion; Degradation of extracellular matrix (ECM) through collagenase, cathepsin B, and gelatinase; Attachment of malignant cells to ECM components; Failure to synthesize basement membrane; Migration of tumor cells through secretion of mobility factor.
• Blood spread
  • Sarcoma is the most common tumor spread via blood.
  • Venous spread more common than arterial.
  • It forms tumor emboli first in the lung or liver.
  • Examples: Renal cell carcinoma, hepatocellular carcinoma, follicular carcinoma of thyroid, choriocarcinoma of uterus.
• Lymphatic spread (tumor emboli, lymphatic permeation).
  • Common in carcinomas
• Transcoelomic implantation (spread of malignant tumors in organs covered by serous membranes)
• e.g., cancer of stomach/colon spreads through peritoneum to ovaries forming Krukenberg tumor.

Locally Malignant Tumors

• Tumors with unknown behavior that spread locally but don't spread to distant sites (no metastasis)

Tumor Angiogenesis

• Definition: The formation of new blood vessels in tumors.
• Pathogenesis: Tumors develop blood vessels from VEGF & FGF to get nutrients and oxygen.
• Importance: Necessary for tumor survival, growth, waste removal, increasing tumor size, and spread/metastasis.

Cancer Stem Cells (CSCs)

• Definition: Stem cells within malignant tumors possessing characteristics of normal stem cells.
• Characters: Tumorigenic potential, self-renewal capacity, small population in tumor (escape therapy), resistance to drugs/radiation/cell stress, relapse & metastasis, and targets for specific therapies.

Tumors of Epithelium

• Benign: Papilloma, Adenoma
• Malignant: Carcinoma (squamous cell carcinoma, basal cell carcinoma, transitional cell carcinoma, carcinoma in situ, adenocarcinoma, mucoid carcinoma)

Papilloma

• Definition: Benign tumor of surface epithelium, often HPV-associated.
• Gross: Cauliflower-like, finger-like, or branched projections.
• Microscopically: Benign proliferated epithelial cells over fibrovascular core; intact basement membrane.
• Types: Squamous cell (skin, lip, tongue), Columnar cell (breast duct, adenomatous polyp, villous papilloma), Transitional cell (urinary bladder & ureter)

Adenoma

• Definition: Benign tumor arising from glandular epithelium.
• Site: Thyroid, ovary, breast, GIT, and pituitary.
• Types: Solid, Cystic (cystadenoma), Mixed, Adenomatous polyp (villous), Fibroadenoma.
• Microscopic: Capsulated, differentiated cells like the original gland.

Carcinoma

• Definition: Malignant tumor of epithelial origin.
• Gross Appearance: Fungating/polypoid (cauliflower mass), Infiltrating (thickening and narrowing), Ulcerative (malignant ulcer).
• Types (Microscopic): (squamous cell, basal cell, transitional cell, carcinoma in situ, adenocarcinoma, mucoid carcinoma, anaplastic, and large cell carcinoma)).
• Squamous cell carcinoma definition and gross/microscopic features, including sites.
• Basal cell carcinoma definition, gross/microscopic features, including sites, and Rodent ulcer characteristics.
• Carcinoma in situ definition and microscopic characteristics, including sites. Additional types, including microscopic features.

Fibroma, Lipoma, Chondroma, Osteoma, Leiomyoma, Rhabdomyoma, Hemangioma, Nevus, Melanoma & Sarcoma

• Specific benign tumors of fibrous tissue, fat tissue, cartilage, bone, smooth muscle, striated/cardiac muscle, blood vessels, pigmented cells, and malignant tumors of pigmented cells and mesenchymal tissue. Their general microscopic characteristics are also included.

Para-neoplastic Syndromes

• Definition: Disorders resulting from substances produced by a tumor affecting distant organs by hormones or cytokines which are triggered by an altered immune system response to a neoplasm, These occur remotely from the tumor itself, Examples include Cushing syndrome and hypercalcemia.

Disturbances of Growth (Hyperplasia, Hypertrophy, Atrophy, Metaplasia, Dysplasia)

• Descriptions of these common cellular growth changes.