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Questions and Answers
What is a defining characteristic of neoplasms?
What is a defining characteristic of neoplasms?
How does age influence the incidence of cancer?
How does age influence the incidence of cancer?
Which type of genetic mutation often contributes to malignancy through the overexpression of oncogenes?
Which type of genetic mutation often contributes to malignancy through the overexpression of oncogenes?
What type of gene alterations are frequently associated with familial cancers?
What type of gene alterations are frequently associated with familial cancers?
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What role do tumor suppressor genes play in cancer development?
What role do tumor suppressor genes play in cancer development?
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What best describes sporadic cancers?
What best describes sporadic cancers?
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Which statement about miRNAs in cancer is correct?
Which statement about miRNAs in cancer is correct?
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What is a common characteristic of preneoplastic disorders?
What is a common characteristic of preneoplastic disorders?
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What characterizes benign tumors in contrast to malignant tumors?
What characterizes benign tumors in contrast to malignant tumors?
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Which of the following tumor markers is specifically associated with hepatocellular carcinoma?
Which of the following tumor markers is specifically associated with hepatocellular carcinoma?
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What is the purpose of molecular profiling in tumor analysis?
What is the purpose of molecular profiling in tumor analysis?
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Which of the following is NOT a method used for the diagnosis of tumors?
Which of the following is NOT a method used for the diagnosis of tumors?
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In the TNM staging system, what does the 'N' represent?
In the TNM staging system, what does the 'N' represent?
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How are tumors graded?
How are tumors graded?
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Which of the following tumor antigens is considered a tumor-specific antigen?
Which of the following tumor antigens is considered a tumor-specific antigen?
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What is a key characteristic of malignant tumors in terms of growth?
What is a key characteristic of malignant tumors in terms of growth?
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What is the primary difference between benign and malignant tumors regarding their growth behavior?
What is the primary difference between benign and malignant tumors regarding their growth behavior?
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Which characteristic is not typical of malignant tumors?
Which characteristic is not typical of malignant tumors?
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What is the mechanism through which angiogenesis is triggered in tumors?
What is the mechanism through which angiogenesis is triggered in tumors?
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What describes the term 'neoplasm'?
What describes the term 'neoplasm'?
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In which scenario is a tumor suppressor gene most likely to be dysfunctional?
In which scenario is a tumor suppressor gene most likely to be dysfunctional?
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What is the metabolic process through which tumor cells evade the immune system during vascular dissemination?
What is the metabolic process through which tumor cells evade the immune system during vascular dissemination?
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Which statement about dysplasia is accurate?
Which statement about dysplasia is accurate?
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Which of the following correctly identifies a common pathway for tumor metastasis?
Which of the following correctly identifies a common pathway for tumor metastasis?
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What role do matrix metalloproteinases (MMPs) play in tumor invasion?
What role do matrix metalloproteinases (MMPs) play in tumor invasion?
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What type of tumor is characterized by the suffix '-oma' in its nomenclature?
What type of tumor is characterized by the suffix '-oma' in its nomenclature?
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Which of the following preneoplastic disorders is associated with a persistent regenerative cell replication?
Which of the following preneoplastic disorders is associated with a persistent regenerative cell replication?
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Which of the following is an example of a malignant tumor?
Which of the following is an example of a malignant tumor?
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What defines organ tropism in tumor metastasis?
What defines organ tropism in tumor metastasis?
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How do tumor cells migrate after degrading the extracellular matrix?
How do tumor cells migrate after degrading the extracellular matrix?
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Study Notes
Neoplasia
- Neoplasia is an abnormal growth of tissue that is uncoordinated with the normal tissue.
- Neoplasms may persist even after the stimulus that initiated the growth is removed.
General Characteristics of Neoplasms
- Neoplasms are unresponsive to the normal growth factors that control cell division.
- Neoplasms compete with normal cells and tissues for nutrients.
- Neoplasms are autonomous and increase in size regardless of their local environment or the nutritional status of the host.
- Neoplasms require endocrine signals for their growth.
Epidemiology of Cancer
- Cancer incidence varies with age, race, geographic factors, and genetic backgrounds.
- Cancer is most common at the two extremes of age.
- Geographic variation in cancer rates is often due to different environmental exposures.
- Most cancers are sporadic, but some are familial.
- Hereditary cancers can be autosomal dominant or autosomal recessive. Autosomal dominant cancers often involve mutations in tumor suppressor genes, while autosomal recessive cancers are often associated with defects in DNA repair.
- Familial cancers tend to be bilateral and appear earlier in life than sporadic cancers.
- Acquired preneoplastic disorders increase the risk of developing cancer.
Genetic Lesions in Cancer
- Tumor cells can acquire mutations through various mechanisms, including point mutations and chromosomal abnormalities.
- Balanced translocations contribute to carcinogenesis by overexpressing oncogenes or generating fusion proteins with altered signaling.
- Deletions often impact tumor suppressor genes, while gene amplification increases oncogene expression.
- Overexpression of microRNAs (miRNAs) can lead to carcinogenesis by suppressing tumor suppressors, while deletion or loss of miRNA expression can result in overexpression of proto-oncogenes.
- Tumor suppressor genes and DNA repair genes can be silenced through epigenetic changes, such as methylation of the promoter.
Insensitivity to Growth Inhibitory Signals
- Tumor suppressor genes produce proteins that inhibit cellular proliferation by regulating the cell cycle.
- Both copies of a tumor suppressor gene must be dysfunctional for tumor development.
- In familial tumor predisposition, one defective tumor suppressor gene copy is inherited, and the other is lost through somatic mutation.
- In sporadic cases, both copies of the tumor suppressor gene are inactivated through somatic mutations.
Tumor Classification: Benign and Malignant
- A neoplasm is a tumor or swelling.
- Tumors can be benign or malignant.
- Benign tumors are considered innocent as they remain localized and do not spread to other sites, although they may produce local effects.
- Malignant tumors, also known as cancers, can invade and destroy adjacent structures and spread to distant sites (metastasize).
Benign Tumors
- Benign tumors closely resemble their normal cells of origin in morphology and function.
- Cells in benign tumors are well-differentiated.
- Mitoses are very rare and normal in configuration in benign tumors.
- Benign tumors grow slowly and are localized, without infiltration.
Acquired Preneoplastic Disorders
- Persistent regenerative cell replication, such as in long-standing skin ulcers and hepatic cirrhosis.
- Hyperplastic and dysplastic proliferations, such as endometrial hyperplasia and dysplastic bronchial changes.
- Chronic atrophic gastritis.
- Chronic ulcerative colitis.
- Leukoplakia of the oral cavity.
- Villous adenomas of the colon.
Nomenclature of Benign Tumors
- Benign tumor names are formed using the cell type of origin followed by the suffix "-oma" (e.g., fibroma, chondroma, leiomyoma).
- Specific names based on cell type:
- Adenoma: Glandular pattern.
- Papilloma: Epithelial surfaces, producing microscopic or macroscopic finger-like structures.
- Polyp: Mass projecting above the mucosal surface, forming a macroscopically visible structure.
- Cystadenomas: Hollow cystic masses (often found in the ovary).
- Fibroadenoma of the breast and benign mixed tumor of salivary glands (pleomorphic adenoma): Mixed type.
Malignant Tumors
- Malignant tumors have distinct characteristics:
- Pleomorphism: Variation in size and shape of cells.
- Hyperchromasia: Increased nuclear pigmentation.
- High nuclear-to-cytoplasmic ratio.
- Giant cells with multiple nuclei.
- Nuclear pleomorphism, with coarse and clumped chromatin.
- Numerous atypical mitoses.
- Loss of polarity: Cells fail to form a recognizable pattern of orientation.
- Dysplasia: Loss of uniformity in individual cells and their architectural orientation (partial or full thickness of the epithelium, called carcinoma in situ).
- Malignant tumors grow rapidly, infiltrating, invading, and destroying surrounding tissues.
- Metastasis: Secondary implants discontinuous with the primary tumor.
- Pathways of Metastasis:
- Seeding within body cavities.
- Lymphatic spread (typical of carcinomas).
- Hematogenous spread (common in sarcomas, but also used by carcinomas).
- The liver and lungs are common sites for secondary tumors.
Mechanisms of Local and Distant Spread
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Invasion of the Extracellular Matrix (ECM) - Tumor cells invade the ECM in four distinct stages:
- Detachment of tumor cells from each other through loss of surface E-cadherins.
- Attachment of tumor cells to ECM components.
- Degradation of ECM via proteases produced by tumor cells and induced fibroblasts, including metalloproteinases like gelatinases, collagenases, and stromelysins.
- Migration of tumor cells driven by cell-derived cytokines, cleavage products of matrix components, and certain growth factors.
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Vascular Dissemination:
- Intravasation: Degradation of blood vessels' basement membranes, leading to formation of tumor emboli by aggregation with leukocytes and platelets, effectively hiding tumor cells from the immune system.
- Extravasation: Free tumor cells adhere to endothelium and then transmigrate through the basement membrane using a mechanism similar to intravasation.
Development of Sustained Angiogenesis
- Vascularization of tumors is crucial for their growth and is controlled by the balance between angiogenic and antiangiogenic factors produced by tumor and stromal cells.
- Hypoxia triggers angiogenesis through the actions of HIF-1α on the transcription of the pro-angiogenic factor VEGF.
- Numerous factors regulate angiogenesis, including p53, which induces synthesis of the angiogenesis inhibitor.
Invasion of Tissues
- Invasion of tissues, a hallmark of malignancy, occurs in four steps:
- Loosening of cell-cell contacts.
- Degradation of the extracellular matrix (ECM).
- Attachment to new ECM components.
- Migration of tumor cells.
- Cell-cell contacts are weakened by inactivation of E-cadherin through various pathways.
- Basement membrane and interstitial matrix degradation is mediated by proteolytic enzymes secreted by tumor and stromal cells, including matrix metalloproteinases (MMPs).
- Proteolytic enzymes also release growth factors from the ECM and create chemotactic and angiogenic fragments.
- The location of the primary tumor can predict the metastatic site for many tumors.
- Many tumors are arrested in the first capillary bed they encounter, most commonly the lungs and liver.
- Some tumors exhibit organ tropism, possibly due to activation of adhesion or chemokine receptors whose ligands are expressed by endothelial cells at the metastatic site.
Nomenclature of Malignant Tumors
- Malignant tumors originating from mesenchymal tissue are called sarcomas (e.g., fibrosarcoma, chondrosarcoma, leiomyosarcoma).
- Malignant tumors originating from epithelial tissue (endoderm, mesoderm, and ectoderm) are called carcinomas (e.g., squamous cell carcinoma, adenocarcinoma).
- Malignant tumors with both mesenchymal and epithelial components (e.g., Teratomas) show divergent differentiation into all embryonic layers, commonly found in ovaries and testicles, and can be benign or malignant.
Characteristics of Benign and Malignant Tumors
- Benign and malignant tumors are distinguishable based on the degree of differentiation, growth rate, local invasiveness, and distant spread.
- Benign tumors resemble the tissue of origin and are well differentiated; malignant tumors are poorly or completely undifferentiated (anaplastic).
- Benign tumors grow slowly, while malignant tumors typically grow faster.
- Benign tumors are well circumscribed and have a capsule; malignant tumors are poorly circumscribed and invade surrounding tissues.
- Benign tumors remain localized, while malignant tumors are locally invasive and metastasize to distant sites.
Laboratory Diagnosis of Cancer
- Several methods exist for tumor diagnosis:
- Excision.
- Biopsy.
- Fine-needle aspiration.
- Cytologic smears.
- Immunohistochemistry and flow cytometry help diagnose and classify tumors by identifying distinct protein expression patterns.
- Tumor markers, proteins released by tumors into the serum, such as PSA, can screen populations for cancer and monitor recurrence after treatment.
- Molecular analyses are used for diagnosis, prognosis, detection of minimal residual disease, and diagnosis of hereditary cancer predisposition.
- Molecular profiling of tumors through cDNA arrays and sequencing can determine gene expression and identify mutations in the tumor genome, aiding in molecular stratification of tumors for treatment and prognostication.
Tumor Antigens (Tumor Markers)
- Tumor-Specific Antigens: Unique antigens specific for tumors, such as melanoma-associated antigen-1 (MAGE-1) and certain pancreatic and breast carcinoma antigens (CA-125, CA-119).
- Tumor-Associated Antigens: Shared by normal untransformed cells, such as prostate-specific antigens (PSA), alfa-fœtoprotein (AFP) in hepatocellular carcinoma, and carcinoembryonic (CEA) antigen in colorectal carcinomas.
Grading and Staging
- Grading: Based on cytological differentiation of tumor cells and mitotic activity within the tumor. Tumors are graded I, II, III, or IV, with increasing anaplasia.
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Staging Based on:
- The size of the primary lesion.
- Extent of spread to regional lymph nodes.
- Presence or absence of metastases.
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TNM staging system:
- T: Tumor size.
- N: Lymph node metastases.
- M: Distant metastases.
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Description
Explore the complexities of neoplasia, including its abnormal tissue growth characteristics and the unique factors influencing cancer incidence. This quiz delves into the biological and epidemiological aspects of cancer, shedding light on environmental and genetic influences.
