Neoplasia
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Questions and Answers

What is the term for the study of tumors?

  • Oncogenesis
  • Tumorigenesis
  • Oncology (correct)
  • Neoplasia

    • What is the primary difference between benign and malignant tumors?

  • Size of the tumor
  • Type of cells involved
  • Ability to spread to distant sites (correct)
  • Location of the tumor

    • What is the term for a tumor that results from a transformed epithelial cell that produces a gland-like structure?

  • Chondroma
  • Papilloma
  • Fibroma
  • Adenoma (correct)

    • What is the term for a disorganized tissue that resembles the tissue at the site of origin?

    <p>Hamartoma</p> Signup and view all the answers

    What is the term for a tumor that is composed of parenchyma and stroma?

    <p>All of the above</p> Signup and view all the answers

    What is the term for a tumor that grows into a finger-like projection?

    <p>Papilloma</p> Signup and view all the answers

    What is the term for a tumor that arises from cartilage?

    <p>Chondroma</p> Signup and view all the answers

    What is the term for a tumor that originates from a different location than the tissue of origin?

    <p>Choristoma</p> Signup and view all the answers

    What is the term for a hollow cystic mass that is common in the ovary?

    <p>Cystadenoma</p> Signup and view all the answers

    What is the term for a type of mixed tumor containing cells from all three germ layers?

    <p>Teratoma</p> Signup and view all the answers

    Which type of neoplasm affects the lymph nodes and extranodal sites?

    <p>Lymphoma</p> Signup and view all the answers

    What is the most common salivary gland tumor?

    <p>Pleomorphic adenoma</p> Signup and view all the answers

    What is the term for a malignancy of melanocytes seen in the skin and oral cavity?

    <p>Melanoma</p> Signup and view all the answers

    What is the term for a malignancy of pleural tissue?

    <p>Mesothelioma</p> Signup and view all the answers

    What is the term for a type of tumor that arises from cells of mesenchymal origin?

    <p>Sarcoma</p> Signup and view all the answers

    What is the term for a malignancy of testicular tissue?

    <p>Seminoma</p> Signup and view all the answers

    What is the term for a type of tumor that arises from epithelial cells?

    <p>Carcinoma</p> Signup and view all the answers

    What is the primary characteristic that distinguishes malignant neoplasms from benign neoplasms?

    <p>Infiltration and destruction of underlying structures</p> Signup and view all the answers

    What is the term for the spread of a tumor to a distant site?

    <p>Metastasis</p> Signup and view all the answers

    What is the term for a change in the size and shape of cells and their nuclei?

    <p>Pleomorphism</p> Signup and view all the answers

    What is the term for the process by which cancer cells break away from the primary tumor and enter the bloodstream?

    <p>Hematogenous spread</p> Signup and view all the answers

    What is the term for the first node that receives lymph from a primary tumor?

    <p>Sentinel lymph node</p> Signup and view all the answers

    What is the term for the loss of differentiation of cells, resulting in a more primitive appearance?

    <p>Anaplasia</p> Signup and view all the answers

    What is the term for the process by which cancer cells spread to lymph nodes and other lymphatic tissues?

    <p>Lymphatic spread</p> Signup and view all the answers

    What is the term for a change in the shape and size of the nucleus, resulting in a darkly staining nucleus?

    <p>Hyperchromatism</p> Signup and view all the answers

    What is the term for a tumor that is confined to the entire epithelial layer and has not invaded into the underlying connective tissue?

    <p>Carcinoma in situ</p> Signup and view all the answers

    Which of the following chronic inflammatory disorders is associated with esophageal adenocarcinoma?

    <p>Barrett esophagus</p> Signup and view all the answers

    What is the primary function of tumor suppressor genes?

    <p>To prevent uncontrolled growth and induce apoptosis</p> Signup and view all the answers

    Which of the following genes is commonly affected in cancers and is a tumor suppressor gene?

    <p>TP53</p> Signup and view all the answers

    What is the result of a translocation between chromosomes 9 and 22 in chronic myeloid leukemia?

    <p>Fusion of the ABL gene with the BCR gene</p> Signup and view all the answers

    Which of the following is a characteristic of oncogenes?

    <p>They promote cell growth and proliferation</p> Signup and view all the answers

    What is the result of a deletion of a tumor suppressor gene on chromosome 13q14?

    <p>Retinoblastoma</p> Signup and view all the answers

    Which of the following is a type of genetic mutation that can contribute to cancer development?

    <p>All of the above</p> Signup and view all the answers

    What is the role of microRNAs in cancer formation?

    <p>To reduce the activity of protein and inhibit gene expression</p> Signup and view all the answers

    Which of the following is a characteristic of aneuploidy?

    <p>A chromosome number that is not a multiple of 23</p> Signup and view all the answers

    What is the result of the fusion of the BCR gene on chromosome 22 with the ABL gene on chromosome 9?

    <p>The development of chronic myeloid leukemia</p> Signup and view all the answers

    What is the role of p53 protein in the cell cycle?

    <p>To induce cell quiescence and apoptosis in response to DNA damage</p> Signup and view all the answers

    What is the Warburg effect in cancer cells?

    <p>The increased fermentation of glucose to lactate even in the presence of oxygen</p> Signup and view all the answers

    What is the role of transforming growth factor-β (TGF-β) in cancer?

    <p>To inhibit cell proliferation and induce apoptosis</p> Signup and view all the answers

    What is the function of E-cadherin in cell adhesion?

    <p>To regulate cell-cell adhesion and maintain tissue architecture</p> Signup and view all the answers

    What is the role of the RB gene in the cell cycle?

    <p>To regulate the G1-S checkpoint and induce quiescence</p> Signup and view all the answers

    What is the result of a mutation in the TP53 gene?

    <p>Inactivation of the p53 protein, leading to uncontrolled cell growth</p> Signup and view all the answers

    What is the role of adenomatous polyposis coli (APC) gene in cancer?

    <p>To regulate Wnt/β-catenin signaling and prevent colon cancer</p> Signup and view all the answers

    What is the characteristic of cancer cells that allows them to invade into connective tissue?

    <p>Penetration of the basement membrane</p> Signup and view all the answers

    What is the term for the process by which cancer cells stimulate new blood vessel growth?

    <p>Angiogenesis</p> Signup and view all the answers

    What is the primary mechanism by which tumor cells evade immune recognition?

    <p>Expressing factors that suppress or 'trick' immune system</p> Signup and view all the answers

    What is the primary function of PD-L1 in tumor cells?

    <p>To inhibit immune response against tumor cells</p> Signup and view all the answers

    What is the consequence of defective DNA mismatch repair in inherited disorders?

    <p>Increased risk of colon cancer</p> Signup and view all the answers

    What is the role of BRCA1 and BRCA2 genes in cancer development?

    <p>To promote homologous recombination in DNA repair</p> Signup and view all the answers

    What is the primary consequence of genomic instability in cancer development?

    <p>Increased risk of cancer due to inability to repair DNA</p> Signup and view all the answers

    What is the primary mechanism of action of therapies targeting immune checkpoints?

    <p>Blocking PD-1 receptors on cytotoxic T cells</p> Signup and view all the answers

    What is the primary consequence of EBV and HPV evasion of immune surveillance?

    <p>All of the above</p> Signup and view all the answers

    What is the primary function of immune checkpoints in cancer development?

    <p>To inhibit immune response against tumor cells</p> Signup and view all the answers

    What is the primary function of RAS in cellular growth?

    <p>To stimulate proliferation regulators by altering genes that regulate growth</p> Signup and view all the answers

    What is the result of a mutation in the RB gene?

    <p>The checkpoint at G1-S is disabled, allowing cells to proliferate unchecked</p> Signup and view all the answers

    What is the role of ABL in signal transduction pathways?

    <p>To function as a signal transducer molecule of tyrosine kinase</p> Signup and view all the answers

    What is the primary function of MYC in cellular growth?

    <p>To activate transcription of genes that regulate growth-promoting genes</p> Signup and view all the answers

    What is the result of a mutation in the EGF receptor?

    <p>The cell becomes a constitutively active oncoprotein</p> Signup and view all the answers

    What is the role of CDK inhibitors in the cell cycle?

    <p>To enforce checkpoints to ensure defects do not move forward</p> Signup and view all the answers

    What is the primary characteristic of self-sufficiency in growth signals?

    <p>The ability to produce own growth factors or cause stromal cells to produce growth factors</p> Signup and view all the answers

    What is the result of a mutation in the HER2 gene?

    <p>The cell becomes a constitutively active oncoprotein</p> Signup and view all the answers

    What is the role of nuclear transcription factors in cellular growth?

    <p>To activate transcription of genes that regulate growth-promoting genes</p> Signup and view all the answers

    What is the result of a mutation in the signal transduction pathways involving RAS and ABL?

    <p>The cell becomes a constitutively active oncoprotein</p> Signup and view all the answers

    What is the consequence of tumor production of hormones and procoagulants?

    <p>Systemic effects and immune function alteration</p> Signup and view all the answers

    What is the cause of cachexia?

    <p>Cytokines or other soluble factors produced by the tumor and host</p> Signup and view all the answers

    What is the primary treatment for cachexia?

    <p>Remove the underlying cause (tumor)</p> Signup and view all the answers

    What is the term for symptoms not explained by local or distant spread of tumor?

    <p>Paraneoplastic syndrome</p> Signup and view all the answers

    What is the most common association of paraneoplastic syndrome?

    <p>Lung and breast cancers and hematologic malignancies</p> Signup and view all the answers

    What is the term for progressive loss of body fat and lean body mass?

    <p>Cachexia</p> Signup and view all the answers

    Which type of radiation is known to cause papillary thyroid cancer?

    <p>Therapeutic radiation to the head and neck</p> Signup and view all the answers

    What is the primary mechanism by which Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma?

    <p>By targeting CD4+ T cells</p> Signup and view all the answers

    Which of the following genes is inactivated by the E6 protein of Human Papillomavirus (HPV)?

    <p>p53</p> Signup and view all the answers

    What is the primary mechanism by which Epstein-Barr virus (EBV) causes Burkitt lymphoma?

    <p>By stimulating proliferation of B cells through CD40</p> Signup and view all the answers

    What is the primary mechanism by which Helicobacter pylori causes gastric adenocarcinoma and gastric lymphoma?

    <p>By stimulating chronic inflammation</p> Signup and view all the answers

    What is the primary mechanism by which Hepatitis B virus (HBV) causes hepatocellular carcinoma?

    <p>By stimulating chronic inflammation and hepatocyte death</p> Signup and view all the answers

    What is the primary mechanism by which Human T-cell leukemia virus type 1 (HTLV-1) is transmitted?

    <p>Through sexual intercourse, blood products, and breastfeeding</p> Signup and view all the answers

    Which of the following is a characteristic of Epstein-Barr virus (EBV) encoded gene, LMP1?

    <p>It promotes B-cell proliferation through CD40</p> Signup and view all the answers

    What is the primary mechanism by which Human Papillomavirus (HPV) causes oropharyngeal carcinoma?

    <p>By inactivating p53 and RB genes</p> Signup and view all the answers

    Which of the following factors is used to determine the grade of a cancer?

    <p>Number of mitotic figures</p> Signup and view all the answers

    What does the 'T' component of the TNM system represent?

    <p>Size of the primary lesion and invasion of adjacent structures</p> Signup and view all the answers

    What is the clinical value of staging compared to grading?

    <p>Staging has greater clinical value than grading</p> Signup and view all the answers

    What does the 'N' component of the TNM system represent?

    <p>Extent of lymph node involvement</p> Signup and view all the answers

    What is the significance of 'M0' in the TNM system?

    <p>Absence of metastasis</p> Signup and view all the answers

    What is the significance of 'T0' in the TNM system?

    <p>Carcinoma in situ</p> Signup and view all the answers

    Which of the following is a characteristic of poorly differentiated cancer cells?

    <p>Loss of differentiation and a more primitive appearance</p> Signup and view all the answers

    What is the primary purpose of fine-needle aspiration in laboratory diagnosis?

    <p>To collect cells from palpable tissue masses for analysis</p> Signup and view all the answers

    What is the role of immunohistochemistry in laboratory diagnosis?

    <p>To provide a definitive diagnosis of a specific tissue type</p> Signup and view all the answers

    What is the purpose of flow cytometry in laboratory diagnosis?

    <p>To diagnose lymphomas and leukemias</p> Signup and view all the answers

    What is the role of tumor markers in laboratory diagnosis?

    <p>To screen for disease, detect recurrence, and monitor response to therapy</p> Signup and view all the answers

    What is the purpose of molecular techniques in laboratory diagnosis?

    <p>To diagnose malignancy using fluorescence in situ hybridization (FISH) or PCR analysis</p> Signup and view all the answers

    What is the role of cytologic smear in laboratory diagnosis?

    <p>To detect cervical cancer and fungal infections</p> Signup and view all the answers

    What is the role of molecular profiling in laboratory diagnosis?

    <p>To sequence entire genomes and assess modifications genome-wide</p> Signup and view all the answers

    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.

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