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Questions and Answers
What characterizes neoplasms in terms of their growth in relation to normal tissue?
What characterizes neoplasms in terms of their growth in relation to normal tissue?
Which of the following best describes the incidence of cancer?
Which of the following best describes the incidence of cancer?
How do balanced translocations contribute to cancer development?
How do balanced translocations contribute to cancer development?
Which of the following statements about hereditary cancers is true?
Which of the following statements about hereditary cancers is true?
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What is a key characteristic of tumor suppressor genes in the context of cellular proliferation?
What is a key characteristic of tumor suppressor genes in the context of cellular proliferation?
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What role do epigenetic changes play in cancer development?
What role do epigenetic changes play in cancer development?
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Which of the following factors does NOT influence the growth of neoplasms?
Which of the following factors does NOT influence the growth of neoplasms?
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What type of genetic alterations are often associated with tumor cells?
What type of genetic alterations are often associated with tumor cells?
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What is a key characteristic of malignant tumors compared to benign tumors?
What is a key characteristic of malignant tumors compared to benign tumors?
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Which of the following tumors is classified as benign?
Which of the following tumors is classified as benign?
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How are tumors graded?
How are tumors graded?
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What does the 'N' in the TNM staging system represent?
What does the 'N' in the TNM staging system represent?
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Which of the following is an example of a tumor marker?
Which of the following is an example of a tumor marker?
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What is a distinguishing feature of benign tumors during diagnosis?
What is a distinguishing feature of benign tumors during diagnosis?
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Which classification involves tumors derived from more than one germ cell layer?
Which classification involves tumors derived from more than one germ cell layer?
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Which method is NOT typically used for the diagnosis of tumors?
Which method is NOT typically used for the diagnosis of tumors?
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What is the primary purpose of molecular profiling in tumor analysis?
What is the primary purpose of molecular profiling in tumor analysis?
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Which of the following tumor types is classified as a carcinogenic tumor of epithelial origin?
Which of the following tumor types is classified as a carcinogenic tumor of epithelial origin?
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What is required for tumor development involving tumor suppressor genes?
What is required for tumor development involving tumor suppressor genes?
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Which of the following describes malignant tumors?
Which of the following describes malignant tumors?
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What suffix is typically used in the nomenclature of benign tumors?
What suffix is typically used in the nomenclature of benign tumors?
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Which of these conditions is considered an acquired preneoplastic disorder?
Which of these conditions is considered an acquired preneoplastic disorder?
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Which pathway is typical for the metastatic spread of carcinomas?
Which pathway is typical for the metastatic spread of carcinomas?
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What is a distinguishing characteristic of malignant cells?
What is a distinguishing characteristic of malignant cells?
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What triggers the process of angiogenesis in tumors?
What triggers the process of angiogenesis in tumors?
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Which of the following is not a feature of benign tumors?
Which of the following is not a feature of benign tumors?
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Which process is involved in tumor cell migration during metastasis?
Which process is involved in tumor cell migration during metastasis?
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What type of tumors are termed 'sarcomas'?
What type of tumors are termed 'sarcomas'?
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Which factor contributes to tumor vascularization?
Which factor contributes to tumor vascularization?
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What are polyp tumors characterized by?
What are polyp tumors characterized by?
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What typically occurs during the extravasation process of tumor cells?
What typically occurs during the extravasation process of tumor cells?
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Which term describes the tumor characteristic of variation in size and shape?
Which term describes the tumor characteristic of variation in size and shape?
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Study Notes
Neoplasia
- An abnormal growth of tissue that is uncoordinated with the normal tissue.
- Can persist even after the stimulus that caused it has ceased.
General Characteristics of Neoplasms
- Neoplasms are unresponsive to normal growth factors that regulate cell division.
- They compete with normal cells and tissues for their metabolic needs.
- They have a degree of autonomy and continue to grow regardless of their local environment or the host's nutritional status.
- They require endocrine stimulatory signals for growth.
Epidemiology of Cancer
- Cancer incidence is influenced by age, race, geographic factors, and genetics.
- Cancer is most common at the extremes of age.
- Geographic variations in cancer rates are often due to differences in environmental exposures.
- Most cancers are sporadic, but some are familial.
- Familial cancers can be autosomal dominant or autosomal recessive.
- Autosomal dominant familial cancers are often linked to inherited mutations in tumor suppressor genes.
- Autosomal recessive familial cancers are linked to inherited defects in DNA repair.
- Familial cancers tend to be bilateral and appear earlier in life than their sporadic counterparts.
- Preneoplastic disorders increase the risk of cancer development.
Genetic Lesions in Cancer
- Tumor cells can acquire mutations through various mechanisms, including point mutations and chromosomal abnormalities.
- Balanced translocations contribute to cancer development by overexpressing oncogenes or generating fusion proteins with altered signaling capacity.
- Deletions commonly affect tumor suppressor genes, while gene amplification increases the expression of oncogenes.
- Overexpression of microRNAs (miRNAs) can contribute to cancer by reducing tumor suppressor expression.
- Deletion or loss of expression of miRNAs can lead to overexpression of proto-oncogenes.
- Tumor suppressor genes and DNA repair genes can be silenced by epigenetic changes, involving methylation of the promoter.
Insensitivity to Growth Inhibitory Signals
- Tumor suppressor genes encode proteins that inhibit cell proliferation by regulating the cell cycle.
- Both copies of a tumor suppressor gene need to be dysfunctional for cancer development.
- Individuals with a familial predisposition to cancer inherit one defective copy of a tumor suppressor gene and lose the second one through somatic mutation.
- Individuals with sporadic cancer lose both copies of the tumor suppressor gene through somatic mutation.
Benign and Malignant Tumors
- Neoplasm refers to a tumor or swelling.
- Benign tumors are considered innocent, remaining localized and not spreading to other sites.
- Malignant tumors, or cancers, can invade and destroy adjacent structures and spread to distant sites (metastasize).
- Benign tumors resemble normal cells in morphology and function. They are well-differentiated with few and normal mitotic figures. They grow slowly and remain localized.
- Malignant tumors display a range of characteristics including pleomorphism, hyperchromasia, high nuclear-to-cytoplasmic ratio, giant cell formation, nuclear pleomorphism, numerous and atypical mitotic figures, and loss of polarity.
Acquired Preneoplastic Disorders
- Persistent regenerative cell replication, such as a long-standing skin ulcer or hepatic cirrhosis.
- Hyperplastic and dysplastic proliferations, such as endometrial hyperplasia or dysplastic changes in the bronchus.
- Chronic atrophic gastritis.
- Chronic ulcerative colitis.
- Leukoplakia of the oral cavity.
- Villous adenomas of the colon.
Nomenclature of Benign Tumors
- The cell type of origin + suffix "-oma", e.g., fibroma, chondroma, leiomyoma.
- Adenoma: Glandular pattern.
- Papilloma: Epithelial surfaces, forming microscopic or macroscopic finger-like structures.
- Polyp: Mass projecting above the mucosal surface, forming a macroscopically visible structure.
- Cystadenoma: Hollow cystic masses, often found in the ovary.
- Fibroadenoma of the breast and benign mixed tumors of salivary glands (pleomorphic adenoma) are considered mixed types.
Malignant Tumors
- Pleomorphism: Variation in size and shape of cells.
- Hyperchromasia: Increased nuclear pigmentation.
- High nuclear/cytoplasmic (N/C) ratio.
- Giant cells with multiple nuclei.
- Nuclear pleomorphism with coarse and clumped chromatin.
- Numerous mitoses with atypical forms.
- Loss of polarity: Cells fail to form a recognizable pattern.
- Dysplasia: Loss of uniformity in individual cells and their architectural orientation, potentially affecting the entire epithelial thickness (carcinoma in situ).
Mechanisms of Local and Distant Spread
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Invasion of ECM:
- Tumor cells detach from each other due to loss of E-cadherin.
- They attach to matrix components.
- They degrade the ECM by producing proteases and inducing fibroblasts to produce proteases, including metalloproteinases like gelatinases, collagenases, and stromelysins.
- Tumor cell migration is driven by cytokines, cleavage products of matrix components, and growth factors.
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Vascular Dissemination:
- Intravasation: Degradation of blood vessels' basement membranes, forming tumor emboli that evade the immune system by aggregating with leukocytes and platelets.
- Extravasation: Adhesion of free tumor cells to the endothelium, followed by transgression through the basement membrane by a similar mechanism to intravasation.
Development of Sustained Angiogenesis
- Vascularization is crucial for tumor growth and is regulated by the balance of angiogenic and antiangiogenic factors produced by tumor and stromal cells.
- Hypoxia triggers angiogenesis through the action of hypoxia-inducible factor 1-alpha (HIF-1α) on the transcription of vascular endothelial growth factor (VEGF).
- p53 can induce the synthesis of angiogenesis inhibitors.
Invasion of Tissues
- Occurs in four steps: loosening of cell-cell contacts, degradation of ECM, attachment to novel ECM components, and migration of tumor cells
- Cell-cell contacts are lost through inactivation of E-cadherin.
- Basement membrane and interstitial matrix degradation is mediated by proteolytic enzymes secreted by tumor cells and stromal cells, such as matrix metalloproteinases (MMPs).
- Proteolytic enzymes can release growth factors sequestered in the ECM and generate chemotactic and angiogenic fragments from ECM glycoproteins.
Metastatic Site Prediction
- The location of the primary tumor can help predict the metastatic site.
- Many tumors arrest in the first capillary bed they encounter, commonly in the lung and liver.
- Some tumors have organ tropism, potentially due to activation of adhesion or chemokine receptors that interact with ligands expressed by endothelial cells at the metastatic site.
Nomenclature of Malignant Tumors
- Mesenchymal origin: Sarcomas, e.g., fibrosarcoma, chondrosarcoma, leiomyosarcoma.
- Epithelial origin: Carcinomas, e.g., squamous cell carcinoma, adenocarcinoma.
- Two components (mesenchymal and epithelial): Teratomas, exhibiting divergent differentiation into all embryonic layers, commonly found in the ovaries and testicles, can be either benign or malignant.
Characteristics of Benign and Malignant Tumors
- Benign and malignant tumors differ in their degree of differentiation, rate of growth, local invasiveness, and distant spread.
- Benign tumors are well-differentiated, resembling the tissue of origin. 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 the surrounding normal tissues.
- Benign tumors remain localized. Malignant tumors are locally invasive and metastasize to distant sites.
Tumor Antigens (Tumor Markers)
- Tumor-specific antigens: Unique antigens found in tumors, e.g., melanoma-associated antigen-1 (MAGE-1), some pancreatic and breast carcinoma antigens (CA-125, CA-119).
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Tumor-associated antigens: Shared by normal and transformed cells.
- Examples include prostate-specific antigen (PSA), alfa-fetoprotein (AFP) in hepatocellular carcinoma, and carcinoembryonic (CEA) antigen in colorectal carcinomas.
Grading and Staging
- Grading: Based on cytological differentiation of tumor cells and the number of mitotic figures. Classified as grades I, II, III, or IV in order of increasing anaplasia.
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Staging: Based on:
- The size of the primary tumor.
- Extent of spread to regional lymph nodes.
- Presence of metastases.
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TNM staging system:
- T: Tumor size.
- N: Lymph node metastases.
- M: Distant metastases.
Laboratory Diagnosis of Cancer
- Tumor diagnosis uses various sampling methods, including excision, biopsy, fine-needle aspiration, and cytologic smears.
- Immunohistochemistry and flow cytometry are helpful in diagnosis and classification, as distinct protein expression patterns define different entities.
- Tumor markers, proteins released by tumors into the serum, can be used for screening and monitoring for recurrence after treatment. Examples include PSA.
- Molecular analyses are used for diagnosis, prognosis, detection of minimal residual disease, and diagnosis of hereditary predisposition to cancer.
- Molecular profiling using cDNA arrays and sequencing can determine the expression of large segments of the genome and catalog all mutations in the tumor genome, aiding in molecular stratification for treatment and prognostication.
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Description
This quiz explores the characteristics of neoplasia, including the uncoordinated growth of tissues and their autonomy from normal growth factors. Additionally, it delves into the epidemiology of cancer, discussing factors like age, race, and genetic influences on cancer incidence. Test your knowledge on these critical topics in pathology.
