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.