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What is the term for the study of tumors?
What is the primary difference between benign and malignant tumors?
What is the term for a tumor that results from a transformed epithelial cell that produces a gland-like structure?
What is the term for a disorganized tissue that resembles the tissue at the site of origin?
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What is the term for a tumor that is composed of parenchyma and stroma?
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What is the term for a tumor that grows into a finger-like projection?
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What is the term for a tumor that arises from cartilage?
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What is the term for a tumor that originates from a different location than the tissue of origin?
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What is the term for a hollow cystic mass that is common in the ovary?
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What is the term for a type of mixed tumor containing cells from all three germ layers?
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Which type of neoplasm affects the lymph nodes and extranodal sites?
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What is the most common salivary gland tumor?
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What is the term for a malignancy of melanocytes seen in the skin and oral cavity?
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What is the term for a malignancy of pleural tissue?
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What is the term for a type of tumor that arises from cells of mesenchymal origin?
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What is the term for a malignancy of testicular tissue?
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What is the term for a type of tumor that arises from epithelial cells?
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What is the primary characteristic that distinguishes malignant neoplasms from benign neoplasms?
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What is the term for the spread of a tumor to a distant site?
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What is the term for a change in the size and shape of cells and their nuclei?
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What is the term for the process by which cancer cells break away from the primary tumor and enter the bloodstream?
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What is the term for the first node that receives lymph from a primary tumor?
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What is the term for the loss of differentiation of cells, resulting in a more primitive appearance?
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What is the term for the process by which cancer cells spread to lymph nodes and other lymphatic tissues?
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What is the term for a change in the shape and size of the nucleus, resulting in a darkly staining nucleus?
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What is the term for a tumor that is confined to the entire epithelial layer and has not invaded into the underlying connective tissue?
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Which of the following chronic inflammatory disorders is associated with esophageal adenocarcinoma?
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What is the primary function of tumor suppressor genes?
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Which of the following genes is commonly affected in cancers and is a tumor suppressor gene?
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What is the result of a translocation between chromosomes 9 and 22 in chronic myeloid leukemia?
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Which of the following is a characteristic of oncogenes?
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What is the result of a deletion of a tumor suppressor gene on chromosome 13q14?
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Which of the following is a type of genetic mutation that can contribute to cancer development?
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What is the role of microRNAs in cancer formation?
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Which of the following is a characteristic of aneuploidy?
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What is the result of the fusion of the BCR gene on chromosome 22 with the ABL gene on chromosome 9?
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What is the role of p53 protein in the cell cycle?
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What is the Warburg effect in cancer cells?
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What is the role of transforming growth factor-β (TGF-β) in cancer?
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What is the function of E-cadherin in cell adhesion?
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What is the role of the RB gene in the cell cycle?
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What is the result of a mutation in the TP53 gene?
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What is the role of adenomatous polyposis coli (APC) gene in cancer?
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What is the characteristic of cancer cells that allows them to invade into connective tissue?
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What is the term for the process by which cancer cells stimulate new blood vessel growth?
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What is the primary mechanism by which tumor cells evade immune recognition?
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What is the primary function of PD-L1 in tumor cells?
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What is the consequence of defective DNA mismatch repair in inherited disorders?
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What is the role of BRCA1 and BRCA2 genes in cancer development?
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What is the primary consequence of genomic instability in cancer development?
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What is the primary mechanism of action of therapies targeting immune checkpoints?
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What is the primary consequence of EBV and HPV evasion of immune surveillance?
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What is the primary function of immune checkpoints in cancer development?
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What is the primary function of RAS in cellular growth?
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What is the result of a mutation in the RB gene?
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What is the role of ABL in signal transduction pathways?
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What is the primary function of MYC in cellular growth?
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What is the result of a mutation in the EGF receptor?
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What is the role of CDK inhibitors in the cell cycle?
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What is the primary characteristic of self-sufficiency in growth signals?
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What is the result of a mutation in the HER2 gene?
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What is the role of nuclear transcription factors in cellular growth?
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What is the result of a mutation in the signal transduction pathways involving RAS and ABL?
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What is the consequence of tumor production of hormones and procoagulants?
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What is the cause of cachexia?
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What is the primary treatment for cachexia?
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What is the term for symptoms not explained by local or distant spread of tumor?
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What is the most common association of paraneoplastic syndrome?
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What is the term for progressive loss of body fat and lean body mass?
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Which type of radiation is known to cause papillary thyroid cancer?
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What is the primary mechanism by which Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma?
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Which of the following genes is inactivated by the E6 protein of Human Papillomavirus (HPV)?
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What is the primary mechanism by which Epstein-Barr virus (EBV) causes Burkitt lymphoma?
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What is the primary mechanism by which Helicobacter pylori causes gastric adenocarcinoma and gastric lymphoma?
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What is the primary mechanism by which Hepatitis B virus (HBV) causes hepatocellular carcinoma?
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What is the primary mechanism by which Human T-cell leukemia virus type 1 (HTLV-1) is transmitted?
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Which of the following is a characteristic of Epstein-Barr virus (EBV) encoded gene, LMP1?
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What is the primary mechanism by which Human Papillomavirus (HPV) causes oropharyngeal carcinoma?
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Which of the following factors is used to determine the grade of a cancer?
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What does the 'T' component of the TNM system represent?
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What is the clinical value of staging compared to grading?
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What does the 'N' component of the TNM system represent?
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What is the significance of 'M0' in the TNM system?
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What is the significance of 'T0' in the TNM system?
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Which of the following is a characteristic of poorly differentiated cancer cells?
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What is the primary purpose of fine-needle aspiration in laboratory diagnosis?
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What is the role of immunohistochemistry in laboratory diagnosis?
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What is the purpose of flow cytometry in laboratory diagnosis?
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What is the role of tumor markers in laboratory diagnosis?
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What is the purpose of molecular techniques in laboratory diagnosis?
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What is the role of cytologic smear in laboratory diagnosis?
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What is the role of molecular profiling in laboratory diagnosis?
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Study Notes
Types of Neoplasms
- A neoplasm is also known as a tumor, which can be benign or malignant
- Depends on the host for nutrients, blood supply, and endocrine support if hormone responsive
Benign Neoplasms
- Remain localized based on microscopic/gross characteristics
- Can be cured of disease
- Ending in "oma" (e.g., fibroma, chondroma, adenoma, papilloma)
- Determined by cell type (e.g., fibroma - tumor of fibroblasts, chondroma - derived from cartilage)
Malignant Neoplasms
- Locally aggressive and can spread to distant sites (metastasis)
- Known as cancer
- Ending in "carcinoma" or "sarcoma"
- Determined by type of tissue (e.g., carcinoma - epithelial derived, sarcoma - mesenchymal derived)
Tumor Composition
- Made of parenchyma (transformed/neoplastic cells) and stroma (connective tissue, inflammatory cells, blood vessels)
- Parenchyma determines biologic behavior, and stroma is needed for growth
Teratoma
- Type of mixed tumor containing cells from all three germ layers (ecto/meso/endoderm)
- Common in ovary and testis, can be found in oral cavity (dermoid cyst)
Pleomorphic Adenoma
- Most common salivary gland tumor (affects major and minor salivary glands)
- Exception to benign "oma" ending
Differentiation and Anaplasia
- Lack of differentiation (anaplasia) is a sign of malignancy, where cells have a backward formation
- Pleomorphism is characterized by cells and nuclei of different shapes and sizes, with prominent nucleoli
- Increased nuclear-cytoplasmic ratio, mitotic figures (may be atypical), and loss of polarity are indicative of anaplasia
- Hyperchromatism is a characteristic of anaplastic cells, where the nucleus stains dark
- Tumor giant cells are a feature of anaplasia
- Dysplasia is a disturbance of architecture and proliferative disorder that increases the risk of cancer
Benign vs Malignant Neoplasm
- Benign neoplasms will grow within and may be contained in a capsule, whereas malignant neoplasms will breakthrough the capsule and spread to other areas
- Infiltration and destruction of underlying structures are characteristic of malignant neoplasms
- Metastasis is the spread of tumor to a distant site, which can occur by blood vessels, lymphatics, or body cavities
Metastasis
- Hematogenous spread usually occurs by veins (thin-walled)
- The most frequent site of metastasis is the lungs
- Carcinomas spread by lymphatics, while sarcomas spread by hematogenous (blood) route
- Sentinel lymph node is the first node that receives lymph from the primary tumor and can be detected by injecting dye
Environmental Factors for Malignancy
- Occupational exposure, sunlight (ultraviolet light), and urban location (exposure to asbestos) are environmental factors that contribute to malignancy
- Important exposures include diet, smoking, alcohol consumption, and reproductive history
- Infectious agents, such as viral (Human papillomavirus-HPV) and bacterial (H.pylori), can contribute to malignancy
Cancer Frequency and Death Rate
- Cancer frequency increases with age
- Death rate is common between 55-75 and declines after 75
- Children are susceptible to cancer, including lymphomas, leukemias, CNS tumors, and sarcomas
Predisposing Conditions for Malignancy
- Chronic inflammatory disorders, such as inflammatory bowel disease and Barrett esophagus, can increase the risk of malignancy
- Immunodeficiency, including virus-induced malignancies, can increase the risk of malignancy
- Precursor lesions, such as squamous metaplasia/dysplasia of bronchial mucosa and endometrial hyperplasia/dysplasia, are susceptible to progressing to malignancy
Genetic Abnormalities and Cancer
- Genes affected by genetic abnormalities can contribute to malignant behavior of cancer cells
- Oncogenes promote cell growth and encode transcription factors, while tumor suppressor genes prevent uncontrolled growth
- Genes regulate apoptosis, interactions between tumor and host cells, and can be inherited or occur spontaneously
- Driver mutations can activate or inactivate protein products, leading to cancer progression
Hallmarks of Cancer
- Eight fundamental changes in cell physiology demonstrated by all cancers:
- Self-sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Altered cellular metabolism
- Evasion of apoptosis
- Immortality (Limitless replicative potential)
- Sustained angiogenesis
- Invasion & Metastasis
- Evasion of immune surveillance
Self-Sufficiency in Growth Signals
- Oncogenes can produce own growth factors or cause stromal cells to produce growth factors
- Cell proliferation process:
- Growth factor binds to specific receptor on membrane
- Activation of growth receptor, activates signal-transducing proteins
- Transmit signal across cytosol to nucleus or by cascade of signal transduction molecules
- Activate nuclear factors that initiate & regulate DNA transcription & biosynthesis of other cellular components for cell division
- Cell enters cell cycle for cell division
- Growth factor receptors:
- If mutated or overexpressed, can become oncoprotein (encoded by oncogenes)
- Examples include epidermal growth factor receptor family (EGF)-ERBB1 and ERBB2, HER2 (ERBB2) associated with breast cancers
Downstream Signal Transducing Proteins
- Cancer growth can happen with mutations to signal pathways
- Most common signal pathways involve RAS and ABL
- RAS:
- One of the common mutated oncogenes
- Role: stimulates proliferation regulators by altering genes that regulate growth
- Bind GDP (guanosine diphosphate) and GTP (guanosine triphosphate)
- RAS is inactive with GDP, becomes activated with GTP by growth factors (EGF & PDGF)
- Becomes inactivated by losing phosphate group (reverts to GDP)
- If stays in activated state by point mutation, will continue to send pro-growth signals
- ABL:
- Functions as signal transducer molecule of tyrosine kinase
Nuclear Transcription Factors
- Regulate expression of growth-promoting genes
- Examples include MYC gene:
- Activates transcription of genes including growth-promoting genes to drive cell cycle (especially cyclin-dependent kinases (CDK))
- If altered, keep sending cells through cell cycle and enhance changes in metabolism needed for cell growth
Cell Cycle
- Four phases: Gap1-G1, Synthesis-S, Gap2-G2, and Mitosis-M
- Purpose: Cells undergo DNA replication and cell division
- Starts with G1 phase
- Enter G1 from G0 (non-active state) or after round of mitosis
- Controlled by activators and inhibitors (cyclins and cyclin-dependent kinases (CDK); checkpoints to ensure defects do not move forward (CDK inhibitors enforce checkpoints)
Checkpoints
- Checkpoint 1-G1-S: monitors health of cell and DNA integrity
- Checkpoint 2-G2-M: DNA is properly replicated before cell division takes place
- If detect irregularities, cell can repair itself, enter senescence (can’t replicate), or apoptosis
- CDK inhibitors (e.g. p16) can become defective, allow cells with damaged DNA to divide and cells at risk for malignancy
Insensitivity to Growth-Inhibitory Signals
- Tumor suppressor genes:
- Slow down cell proliferation
- Cause dividing cell to enter G0 phase (quiescence)
- Can enter senescence
- Can enter apoptosis
- Examples include:
- RB gene
- TP53 gene
- Other tumor suppressors: Transforming growth factor- β (TGF-β), E-cadherin, Adenomatous polyposis coli (APC) gene
RB Gene
- Known as retinoblastoma gene, “governor” of the cell cycle
- First tumor suppressor gene to be discovered
- Regulates the G1-S checkpoint
- Inactivated for cancers to occur
TP53 Gene
- Known as “guardian of the genome”
- Most common mutated gene in cancer
- Encodes for p53 protein (transcription factor-maintains integrity of genome)
- p53:
- Most important tumor suppressor
- Activated when DNA damaged and promotes DNA repair (during G1 phase)
- Role includes:
- Place cell in quiescence
- Induce senescence
- Activate apoptosis
- Mutations in DNA affect dividing cells, can lead to malignant transformation if p53 lost
Altered Cellular Metabolism
- Cancer cells utilize glycolytic pathway
- Use high levels of glucose and glutamine and increase fermentation (glucose to lactate)
- Warburg effect (aerobic glycolysis)
- Glycolytic pathway used in presence of ample oxygen
- Provides cancer cells with metabolic intermediates (rapidly dividing) for growth; mitochondrial oxidative phosphorylation does not
Autophagy
- Tumor cells can avoid process of autophagy and survive under minimum conditions
Evasion of Cell Death (Apoptosis)
- Cancer cells resistant to apoptosis by mutating genes to regulate apoptosis
- Loss of p53 and overexpression of BCL-2 family prevents apoptosis
Tumor Cell Immortality & Angiogenesis
- Can replicate endlessly (normal cells can replicate 70 times)
- Cancer cells continue with telomere maintenance
- Cells cannot enlarge beyond 1-2 mm in diameter (blood supply is needed)
- Cancer cells stimulate new blood vessel growth (neoangiogenesis)
- Provide nutrients, oxygen, endothelial cells help secrete growth factors to help stimulate growth of adjacent tumor cells
Tumor Cell Invasion
- Cancer cells invade into connective tissue by penetrating basement membrane (basal cell layer)
- Travel into connective tissue and go into vascular system by penetrating vascular basement membrane (way to metastasize to other locations)
- Circulate as single cells, can form embolus by aggregating and adhering to platelets or other blood cells
- Can be destroyed by host immune cells
Cancer Metastasis
- For metastasis to occur, need two factors:
- Anatomic location
- Vascular drainage of primary tumor & affinity of tumor for certain tissues
- Frequent sites of metastasis:
- Liver
- Lung
- Can occur in oral cavity (soft tissue and bone)
Evasion of Immune Surveillance
- Immune surveillance-function of immune system to scan & destroy malignant cells
- Cancer antigens-expressed by cancer cells and recognized as foreign by the immune system
- Stimulate immune system and tries to prevent cancer from emerging
- Tumor cells killed by cytotoxic T cells (lymphocytes) for specific antigens
- Three broad categories of antigens:
- Neoantigens
- Unmutated proteins
- Viral proteins
- Evasion of immune surveillance:
- Tumor cells invisible to immune system
- Tumor cells express factors that suppress or “trick” immune system
- Tumor cells change, making it difficult for cytotoxic T cells to defend properly
- Prevent immune checkpoints from working properly
- Immune checkpoint:
- Main one involves PD-L1 (programmed cell death ligand 1)
- PD-L1 expressed on surface of tumor cells
- PD-1 receptor causes cytotoxic cells to be unresponsive and cannot kill tumor cells
- Therapies that target these checkpoints (especially in melanoma, lung/bladder cancer)
Genomic Instability-Enabler of Malignancy
- If DNA cannot be repaired, increased risk for cancer
- Inherited disorders result of defect in DNA
- Examples include:
- Hereditary nonpolyposis colorectal syndrome (Lynch syndrome)
- Defect in DNA mismatch repair-cancer of cecum and proximal colon
- Xeroderma pigmentosum
- Autosomal recessive, defect in DNA repair (UV rays prevent normal replication)
- Increased risk for skin cancers (squamous cell and basal cell carcinoma)
- BRCA1 & BRCA2 genes-mutation to repair DNA by homologous recombination (develop chromosomal rearrangements and aneuploidy) susceptible to breast, ovarian, prostate cancer
Carcinogenic Agents
- Three classes of carcinogenic agents: chemicals, radiant energy (radiation), and microbes
- Chemicals: direct-acting agents (e.g. chemotherapy drugs), indirect-acting agents (e.g. polycyclic hydrocarbons, insecticides, arsenic, fungicides, nitrites)
- Radiation: ultraviolet light from sun, radiographs, radioactive elements; therapeutic radiation to head and neck can cause papillary thyroid cancer
Etiology of Cancer
- Microbes: DNA viruses (e.g. HPV, EBV, HBV), RNA viruses (e.g. HTLV-1), bacteria (e.g. H. pylori)
- Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL), targets CD4+ T cells, and has a latency period of 40-60 years
- Human Papillomavirus (HPV): low-risk types (1, 2, 4, 6, 7, 11) cause squamous papilloma and verruca vulgaris, high-risk types (16, 18, 31, 33) cause cervical, anogenital, and oropharyngeal cancer
- HPV genes E6 and E7 bind and degrade p53, stimulate expression of telomerase, and inhibit CDK inhibitor p21, leading to cell proliferation and immortality
Oropharyngeal Carcinoma
- Diagnosed with HPV-related cancer
- Vaccines can be used to prevent HPV-related cancer (e.g. Gardasil 9, Cervarix)
Effect of E6 and E7 Proteins
- Inactivate RB, p53, and p21, leading to cell proliferation and immortality
Epstein-Barr Virus
- Can cause infectious mononucleosis, oral hairy leukoplakia, Burkitt lymphoma, nasopharyngeal carcinoma, and Hodgkin lymphoma
- Virus attaches to CD21 receptor, infects B cells, and promotes B-cell proliferation through latent membrane protein 1 (LMP1)
Nasopharyngeal Carcinoma
- LMP1 expressed through NF- K B pathway
- Genetic and/or environmental factors contribute to development
Burkitt Lymphoma
- LMP1 acts as an oncogene, promoting B-cell proliferation through normal B-cell activation pathway
- Genetic and/or environmental factors contribute to development
Hepatitis B
- Causes hepatocellular carcinoma (liver cancer) through chronic inflammation, hepatocyte death, and NF- K B pathway activation
Helicobacter pylori
- Causes gastric adenocarcinoma and gastric lymphoma through chronic inflammation
- Classified as a carcinogen
- Can stimulate B-cell proliferation and promote inflammatory cytokines
Clinical Aspects of Neoplasia
- Effect on host: injury from benign/malignant tumors, damage to healthy tissues, release of hormones and procoagulants, and alteration of immune function
- Cachexia: progressive loss of body fat and lean body mass, profound weakness, anorexia, and anemia, caused by cytokines or other soluble factors produced by tumor and host
Paraneoplastic Syndrome
- Symptoms not explained by local or distant spread of tumor
- May represent earliest manifestation of occult neoplasm
- Can produce clinical illness and be lethal
- May mimic metastatic disease, commonly associated with lung, breast, and hematologic malignancies
Grading and Staging of Cancer
- Grading is based on the differentiation of tumor cells, number of mitotic figures, tumor necrosis, and presence of architectural features.
- Can be described as well, moderate, or poorly differentiated, or as low or high grade.
TNM Staging System
- T: Size of primary lesion and invasion of adjacent structures (T1-T4, T0: carcinoma in situ).
- N: Extent and spread to lymph nodes/involvement (N1-N3, N0: no nodal involvement).
- M: Presence or absence of metastasis (M0: no metastasis, M1: presence of metastasis).
- Staging has greater clinical value than grade and determines the type of treatment.
Laboratory Diagnosis
Frozen Section
- Performed during surgery, using fresh tissue.
- Evaluates margins, metastasis, and nodal involvement.
- Can be accurate but other methods are used to arrive at a final diagnosis.
Fine-needle Aspiration
- Collection of cells from a palpable tissue mass analyzed within minutes.
- Used to evaluate lymph nodes, thyroid gland, breast, and parotid.
Cytologic Smear
- Used to detect cervical cancer, fungal and viral infections (e.g., candidiasis, herpes).
- Superficial cells are collected and analyzed for abnormalities.
Excisional/Incisional Biopsy
- Used for lesions that are greater than 1 cm or suspected malignancy.
- A small piece is removed for definitive diagnosis.
Immunohistochemistry
- Used with routine H&E to accurately diagnose a specific tissue type.
- Helps with tumors that are poorly differentiated (e.g., cytokeratin markers to diagnose carcinoma).
Flow Cytometry
- Helps diagnose lymphomas and leukemias.
Tumor Markers
- Can be used as a screening tool, detect recurrence of disease, and response to therapy.
- Utilize a blood sample (e.g., prostate specific antigen (PSA) for prostate cancer).
Molecular Techniques
- Diagnose malignancy using fluorescence in situ hybridization (FISH) or PCR analysis.
- Detect minimal residual disease, help with prognosis and behavior, and determine type of therapy to use.
- Detect hereditary risk for cancer and provide genetic counseling.
Molecular Profiling
- Involves the analysis of individual genes or entire genome.
- Helps with identifying recurrent mutations in different cancers, patient care, and treatment.
- Measures all RNA expressed in cell population, proteins, and metabolites.
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Description
This quiz covers the basics of oncology, including the characteristics of benign and malignant tumors, their growth patterns, and differences between the two.