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170 Cards in this Set
- Front
- Back
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What are the hallmarks of cancer?
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- Evasion of apoptosis
- Growth signal self-sufficiency - Anti-growth signal insensitivity - Sustained angiogenesis - Limitless replicative potential - Tissue invasion - Metastasis |
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What is the organization of normal epithelial cells in relation to the basement membrane?
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Normal cells with basal → apical differentiation
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What is the organization of epithelial cells in relation to the basement membrane undergoing hyperplasia?
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Cells ↑ in number
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What is the organization of epithelial cells in relation to the basement membrane undergoing dysplasia?
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Abnormal proliferation of cells with loss of size, shape, and orientation
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What is dysplasia?
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Abnormal proliferation of cells with loss of size, shape, and orientation
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What is the organization of epithelial cells in relation to the basement membrane undergoing carcinoma in situ?
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- Neoplastic cells have not invaded basement membrane
- High nuclear / cytoplasmic ratio and clumped chromatin - Neoplastic cells encompass entire thickness |
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What is the organization of epithelial cells in relation to the basement membrane undergoing invasive carcinoma?
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- Cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases)
- Can metastasize if they reach a blood or lymphatic vessel |
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What is the mechanism by which cells invade the basement membrane in invasive carcinoma?
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Collagenases and Hydrolases (Metalloproteinases)
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What is necessary for cancerous cells to metastasize?
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If they reach a blood or lymphatic vessel
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What is the organization of epithelial cells in relation to the basement membrane undergoing metastasis?
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Spread to distant organ
- Must survive immune attack - Seed and soil theory of metastasis |
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What is the "seed" in the seed and soil theory of metastasis?
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Tumor embolus
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What is the "soil" in the seed and soil theory of metastasis?
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Target organ: liver, lungs, bone, brain, etc
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What is the multidrug resistance protein 1 (MDR1)?
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P-glycoprotein
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What is P-glycoprotein also known as? What cells express this?
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AKA Multidrug Resistance Protein 1 (MDR1)
- Expressed by some cancer cells (eg, colon, liver) |
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What is the function of P-glycoprotein?
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Pumps out toxins, including chemotherapeutic agents (one mechanism of ↓ responsiveness or resistance to chemotherapy over time)
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What is the term for an ↑ in the number of cells?
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Hyperplasia
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What is the term for an adult cell type being replaced by another? Cause?
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Metaplasia
- Caused by irritation (eg, Barrett esophagus) and/or environmental exposure (eg, smoking-induced tracheal/bronchial squamous metaplasia) |
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What is the term for abnormal growth with loss of cellular orientation, shape, and size in comparison to normal tissue maturation?
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Dysplasia
- Commonly preneoplastic |
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What is the term for the loss of structural differentiation and function of cells, resembling primitive cells of the same tissue?
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Anaplasia
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What happens in Anaplasia? What is it associated with?
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- Loss of structural differentiation and function of cells, resembling primitive cells of same tissue
- Often equated with undifferentiated malignant neoplasms - May see giant cells with single large nucleus or several nuclei |
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What is the term for a clonal proliferation of cells that is uncontrolled and excessive?
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Neoplasia
- Benign of malignant |
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What is the term for fibrous tissue formation in response to neoplasm?
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Desmoplasia
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What is an example of Desmoplasia?
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Linitis plastica in diffuse stomach cancer
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What determines the tumor grade?
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Determined by degree of cellular differentiation and mitotic activity on histology
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What do the tumor grades mean?
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Graded 1-4:
- 1 = low grade, well differentiated - 4 = high grade, poorly differentiated, anaplastic |
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Which has more prognostic value: tumor grade or stage?
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Tumor stage has more prognostic value
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What determines the tumor stage?
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Stage = Spread
- Degree of localization / spread based on site and size of primary lesion, spread to regional lymph nodes, and presence of metastases - Based on clinical (c) or pathology (p) findings |
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What is the tumor staging system?
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- T = Tumor size
- N = Nodal involvement - M = Metastases TMN each has independent prognostic value |
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What is the difference between carcinoma and sarcoma?
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Both imply malignancy
- Carcinoma: epithelial origin, spreads lymphatically - Sarcoma: mesenchymal origin, spreads hematogenously |
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Which type of malignancy originates from epithelial tissue?
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Carcinoma
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Which type of malignancy originates from mesenchymal tissue?
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Sarcoma
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Which type of malignancy spreads hematogenously?
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- Sarcomas
- Renal cell carcinoma (renal vein invasion), hepatocellular carcinoma (hepatic vein invasion), follicular carcinoma of the thyroid, and choriocarcinoma |
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Which type of malignancy spreads lymphatically?
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Carcinomas (exception: renal cell carcinoma, hepatocellular carcinoma, follicular carcinoma of thyroid, and choriocarcinoma spread hematogenously)
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What are the types of benign epithelial tumors?
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Adenoma and Papilloma
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What are the types of malignant epithelial tumors?
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Adenocarcinoma and Papillary Carcinoma
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What are the types of malignant blood cell tumors?
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Leukemia and Lymphoma
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What are the types of benign blood vessel tumors?
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Hemangioma
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What are the types of malignant blood vessel tumors?
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Angiosarcoma
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What are the types of benign smooth muscle tumors?
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Leiomyoma
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What are the types of malignant smooth muscle tumors?
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Leiomyosarcoma
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What are the types of benign striated muscle tumors?
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Rhabdomyoma
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What are the types of malignant striated muscle tumors?
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Rhabdomyosarcoma
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What are the types of benign connective tissue tumors?
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Fibroma
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What are the types of malignant connective tissue tumors?
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Fibrosarcoma
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What are the types of benign bone tumors?
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Osteoma
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What are the types of malignant bone tumors?
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Osteosarcoma
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What are the types of benign fat tumors?
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Lipoma
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What are the types of malignant fat tumors?
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Liposarcoma
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What are the typical characteristics of benign tumors?
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- Usually well differentiated
- Low mitotic activity - Well demarcated - No metastasis - No necrosis |
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What are the typical characteristics of malignant tumors?
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- May be poorly differentiated
- Erratic growth - Locally invasive / diffuse - May metastasize - ↓ Apoptosis (upregulation of telomerase prevents chromosome shortening and cell death) |
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What is the term for weakness and wasting of the body due to severe chronic illness?
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Cachexia
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What are the signs of cachexia?
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- Weight loss
- Muscle atrophy - Fatigue |
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What causes cachexia?
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Chronic diseases: cancer, AIDS, heart failure, TB
- Mediated by TNF-α (nicknamed cachectin), IFN-γ, and IL-6 |
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What inflammatory markers mediate cachexia?
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- TNF-α (cachechtin)
- IFN-γ - IL-6 |
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What neoplasm is associated with acanthosis nigricans (hyperpigmentation and epidermal thickening)?
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Visceral malignancies (especially stomach)
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What neoplasm is associated with actinic keratosis?
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Squamous cell carcinoma of skin
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What neoplasms are associated with AIDS?
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- Aggressive malignant lymphomas (non-Hodgkin)
- Kaposi sarcoma |
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What neoplasm is associated with auto-immune diseases (eg, Hashimoto thyroiditis, SLE)?
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Lymphoma
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What neoplasm is associated with Barrett esophagus (chronic GI reflux)?
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Esophageal adenocarcinoma
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What neoplasm is associated with chronic atrophic gastritis?
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Gastric Adenocarcinoma
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What neoplasm is associated with pernicious anemia?
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Gastric Adenocarcinoma
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What neoplasm is associated with post-surgical gastric remnants?
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Gastric Adenocarcinoma
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What neoplasm is associated with cirrhosis?
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Hepatocellular Carcinoma
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What neoplasm is associated with Cushing syndrome?
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Small cell lung cancer
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What neoplasm is associated with dermatomyositis?
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Lung cancer
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What neoplasms are associated with Down Syndrome?
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- ALL ("we ALL fall DOWN"
- AML |
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What neoplasm is associated with a Dysplastic Nevus?
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Malignant Melanoma
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What neoplasm is associated with hypercalcemia?
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Squamous cell lung cancer
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What neoplasm is associated with immunodeficiency states?
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Malignant lymphomas
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What neoplasm is associated with Lambert-Eaton myasthenic syndrome?
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Small cell lung cancer
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What neoplasm is associated with myasthenia gravis?
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Thymoma
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What neoplasm is associated with a pure RBC aplasia?
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Thymoma
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What neoplasms are associated with Paget disease of bone?
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- Secondary osteosarcoma
- Fibrosarcoma |
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What neoplasm is associated with Plummer-Vinson Syndrome (↓ iron)?
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Squamous cell carcinoma of esophagus
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What neoplasms are associated with polycythemia?
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- Renal cell carcinoma
- Hepatocellular carcinoma |
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What neoplasms are associated with radiation exposure?
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- Leukemia
- Sarcoma - Papillary thyroid cancer - Breast cancer |
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What neoplasm is associated with SIADH?
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Small cell lung cancer
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What neoplasms are associated with tuberous sclerosis (facial angiofibroma, seizures, intellectual disability)?
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- Giant cell astrocytoma
- Renal angiomyolipoma - Cardiac rhabdomyoma |
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What neoplasm is associated with ulcerative colitis?
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Colonic adenocarcinoma
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What neoplasms are associated with xeroderma pigmentosum and albinism?
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- Melanoma
- Basal cell carcinoma - Especially squamous cell carcinoma of skin |
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What happens to activate an oncogene?
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Gain of function → ↑ cancer risk
Need damage to only 1 allele |
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What are the types of oncogenes?
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- BCR-ABL
- bcl-2 - BRAF - c-kit - c-myc - HER2/neu (c-erbB2) - L-myc - N-myc - ras - ret |
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What happens to activate a tumor suppressor gene?
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Loss of function → ↑ cancer risk
Both alleles must be lost for expression of disease |
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What are the types of tumor suppressor genes?
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- APC
- BRCA1 and BRCA2 - CPD4/SMAD4 - DCC - MEN1 - NF1 and NF2 - p16 - p53 - PTEN - Rb - TSC1 and TSC2 - VHL - WT1 and WT2 |
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What is the associated tumor and gene product of BCR-ABL?
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BCR-ABL (oncogene)
- Associated with CML and ALL - Gene product: tyrosine kinase |
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What is the associated tumor and gene product of bcl-2?
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bcl-2 (oncogene)
- Associated with follicular and undifferentiate lymphomas - Gene product: anti-apoptotic molecule (inhibits apoptosis) |
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What is the associated tumor and gene product of BRAF?
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BRAF (oncogene)
- Associated with melanoma - Gene product: serine / threonine kinase |
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What is the associated tumor and gene product of c-kit?
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c-kit (oncogene)
- Associated with gastrointestinal stromal tumor (GIST) - Gene product: cytokine receptor (for stem cell factor) |
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What is the associated tumor and gene product of c-myc?
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c-myc (oncogene)
- Associated with Burkitt lymphoma - Gene product: cytokine receptor (for stem cell factor) |
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What is the associated tumor and gene product of HER2/neu (c-erbB2)?
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HER2/neu (oncogene)
- Associated with breast, ovarian, and gastric carcinomas - Gene product: tyrosine kinase |
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What is the associated tumor and gene product of L-myc?
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L-myc (oncogene)
- Associated with lung tumor - Gene product: transcription factor |
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What is the associated tumor and gene product of N-myc?
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N-myc (oncogene)
- Associated with neuroblastoma - Gene product: transcription factor |
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What is the associated tumor and gene product of ras?
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Ras (oncogene)
- Associated with colon cancer, lung cancer, and pancreatic cancer - Gene product: GTPase |
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What is the associated tumor and gene product of ret?
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Ret (oncogene)
- Associated with MEN 2A and 2B - Gene product: tyrosine kinase |
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What tumor is associated with APC?
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APC (tumor suppressor)
- Associated with colorectal cancer (associated with FAP) |
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What is the associated tumor and gene product of BRCA1 and BRCA2?
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BRCA1 and BRCA2 (tumor suppressor)
- Associated with breast and ovarian cancer - Gene product: DNA repair protein |
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What is the associated tumor and gene product of CPD4/SMAD4?
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CPD4/SMAD4 (tumor suppressor)
- Associated with pancreatic cancer - Gene product: DPC = Deleted in Pancreatic Cancer |
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What is the associated tumor and gene product of DCC?
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DCC (tumor suppressor)
- Associated with colon cancer - Gene product: DCC = Deleted in Colon Cancer |
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What is the associated tumor and gene product of NF1?
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NF1 (tumor suppressor)
- Associated with Neurofibromatosis type 1 - Gene product: RAS GTPase activating protein (neurofibromin) |
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What is the associated tumor and gene product of NF2?
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NF2 (tumor suppressor)
- Associated with Neurofibromatosis type 2 - Gene product: Merlin (schwannomin) protein |
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What is the associated tumor and gene product of p16?
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p16 (tumor suppressor)
- Associated with melanoma - Gene product: cyclin-dependent kinase inhibitor 2A |
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What is the associated tumor and gene product of p53?
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p53 (tumor suppressor)
- Associated with most human cancers and Li-Fraumeni syndrome - Gene product: transcription factor for p21, blocks G1 → S phase |
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What tumor is associated with PTEN?
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PTEN (tumor suppressor)
- Associated with breast cancer, prostate cancer, and endometrial cancer |
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What is the associated tumor and gene product of Rb?
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Rb (tumor suppressor)
- Associated with retinoblastoma and osteosarcoma - Gene product: inhibits E2F, blocks G1 → S phase |
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What is the associated tumor and gene product of TSC1?
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TSC1 (tumor suppressor)
- Associated with tuberous sclerosis - Gene product: Hamartin protein |
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What is the associated tumor and gene product of TSC2?
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TSC2 (tumor suppressor)
- Associated with tuberous sclerosis - Gene product: Tuberin protein |
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What is the associated tumor and gene product of VHL?
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VHL (tumor suppressor)
- Associated with von Hippel-Lindau disease - Gene product: inhibits hypoxia inducible factor 1a |
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What tumor is associated with WT1 and WT2?
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WT1 and WT2 (tumor suppressor genes)
- Associated with Wilms Tumor (nephroblastoma) |
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What is the use and limitations of "tumor markers"?
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- Should not be used as the primary tool for cancer diagnosis
- They may be used to monitor tumor recurrence and response to therapy, but definitive diagnosis can be made only via biopsy |
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What is alkaline phosphatase a tumor marker of?
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Metastases to bone, liver, Paget disease of bone, and seminoma (placental ALP)
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What is α-Fetoprotein a tumor marker of?
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- Normally made by fetus
- Hepatocellular carcinoma, hepatoblastoma, yolk sac (endodermal sinus) tumor, testicular cancer, mixed germ cell tumor (co-secreted with β-hCG) |
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What is β-hCG a tumor marker of?
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- Hydatidiform moles and Choriocarcinoma (gestational trophoblastic disease), and testicular cancer
- Commonly associated with pregnancy |
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What is CA-15-3/CA-27-29 a tumor marker of?
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Breast cancer
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What is CA-19-9 a tumor marker of?
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Pancreatic adenocarcinoma
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What is CA-125 a tumor marker of?
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Ovarian cancer
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What is calcitonin a tumor marker of?
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Medullary thyroid carcinoma
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What is CEA a tumor marker of?
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CarcinoEmbryonic Antigen
- Very non-specific but produced by ~70% of colorectal and pancreatic cancers - Also produced by gastric, breast, and medullary thyroid carcinomas |
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What is PSA a tumor marker of?
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Prostate Specific Antigen
- Used to follow prostate adenocarcinoma - Can also be elevated in BPH and prostatitis - Questionable risk/benefit for screening |
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What is S-100 a tumor marker of?
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Neural crest origin (eg, melanoma, neural tumors, schwannomas, Langerhans cell histiocytosis)
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What is TRAP a tumor marker of?
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Tartrate-Resistant Acid Phosphatase (TRAP)
- Hairy cell leukemia (B-cell neoplasm) "TRAP the hairy animal - largely replaced by flow cytometry" |
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What cancers are associated with EBV?
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- Burkitt lymphoma
- Hodgkin lymphoma - Nasopharyngeal carcinoma - CNS lymphoma (in immunocompromised patients) |
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What cancers are associated with HBV and HCV?
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Hepatocellular Carcinoma
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What cancers are associated with HHV-8?
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Kaposi-Sarcoma associated herpesvirus
- Body cavity fluid B-cell lymphoma |
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What cancers are associated with HPV?
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Cervical and penile/anal carcinoma (16, 18)
- Head and neck or throat cancer |
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What cancers are associated with H. pylori?
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Gastric adenocarcinoma and MALT lymphoma
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What cancers are associated with HTLV-1?
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Adult T-cell Leukemia / Lymphoma
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What cancers are associated with liver flukes (Clonorchis sinensis)?
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Cholangiocarcinoma
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What cancers are associated with Schistosoma haematobium?
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Bladder cancer (squamous cell)
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What organ does Aspergillus affect? How?
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Aspergillus releases Aflatoxins → Liver → Hepatocellular Carcinoma
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What organ do Alkylating Agents affect? How?
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Alkylating agents → Blood → Leukemia / Lymphoma
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What organ do Aromatic Amines (eg, Benzidine, 2-Naphthylamine) affect? How?
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Aromatic Amines → Bladder → Transitional Cell Carcinoma
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What organ does Arsenic affect? How?
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Arsenic:
- Liver → Angiosarcoma - Lung → Lung cancer - Skin → Squamous cell carcinoma |
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What organ does Asbestos affect? How?
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Asbestos → Lung → Bronchogenic Carcinoma > Mesothelioma
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What organ does Carbon Tetrachloride affect? How?
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Carbon Tetrachloride → Liver → Centrilobular Necrosis and Fatty change
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What organ does cigarette smoke affect? How?
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Cigarette smoke:
- Bladder → Transitional cell carcinoma - Esophagus → Squamous cell carcinoma / Adenocarcinoma - Kidney → Renal cell carcinoma - Larynx → Squamous cell carcinoma - Lung → Squamous cell and small cell carcinoma - Pancreas → Pancreatic adenocarcinoma |
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What organ do Ethanol affect? How?
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Ethanol → Liver → Hepatocellular carcinoma
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What organ does ionizing radiation affect? How?
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Ionizing Radiation → Thyroid → Papillary Thyroid Carcinoma
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What organ do Nitrosamines (smoked foods) affect? How?
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Nitrosamines → Stomach → Gastric cancer
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What organ does Radon affect? How?
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Radon → Lung → Lung Cancer (2nd leading cause after cigarette smoke)
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What organ does Vinyl Chloride affect? How?
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Vinyl Chloride → Liver → Angiosarcoma
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What hormones/agents can be elevated abnormally in Paraneoplastic Syndromes?
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- 1,25-(OH)2 D3 = Calcitriol
- ACTH - ADH - Antibodies against presynaptic Ca2+ channels at NMJ - Erythropoietin - PTHrP |
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What neoplasms can increase/release Calcitriol (1,25-(OH)2 D3)? What is the effect?
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Paraneoplastic Syndrome:
- Hodgkin Lymphoma - Some non-Hodgkin Lymphomas *Causes hypercalcemia |
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What neoplasms can increase/release ACTH? What is the effect?
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Paraneoplastic Syndrome:
- Small cell lung carcinoma *Causes Cushing Syndrome |
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What neoplasms can increase/release ADH? What is the effect?
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Paraneoplastic Syndrome:
- Small cell lung carcinoma - Intracranial neoplasms *Causes SIADH |
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What neoplasms can increase/release antibodies against presynaptic Ca2+ channels at NMJ? What is the effect?
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Paraneoplastic Syndrome:
- Small cell lung carcinoma *Causes Lambert-Eaton myasthenic syndrome (muscle weakness) |
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What neoplasms can increase/release Erythropoietin? What is the effect?
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Paraneoplastic Syndrome:
- Renal cell carcinoma - Thymoma - Hemangioblastoma - Hepatocellular carcinoma - Leiomyoma - Pheochromocytoma *Causes polycythemia |
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What neoplasms can increase/release PTHrP? What is the effect?
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Paraneoplastic syndromes:
- Squamous cell lung carcinoma - Renal cell carcinoma - Breast cancer *Causes hypercalcemia |
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Which paraneoplastic syndrome(s) can cause hypercalcemia? Associated neoplasms?
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1,25-(OH)2-D3 (Calcitriol)
- Hodgkin lymphoma - Some non-Hodgkin lymphomas PTHrP - Squamous cell lung carcinoma - Renal cell carcinoma - Breast cancer |
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Which paraneoplastic syndrome(s) can cause Cushing Syndrome? Associated neoplasms?
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ACTH
- Small cell lung carcinoma |
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Which paraneoplastic syndrome(s) can cause SIADH? Associated neoplasms?
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ADH
- Small cell lung carcinoma - Intracranial neoplasms |
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Which paraneoplastic syndrome(s) can cause Lambert-Eaton myasthenic syndrome (muscle weakness)? Associated neoplasms?
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Antibodies against presynaptic Ca2+ channels at NMJ
- Small cell lung carcinoma |
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Which paraneoplastic syndrome(s) can cause polycythemia? Associated neoplasms?
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Erythropoietin
- Renal cell carcinoma - Thymoma - Hemangioblastoma - Hepatocellular carcinoma - Leiomyoma - Pheochromocytoma |
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What is the appearance/content of a psamomma body?
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Laminated, concentric, calcific spherules
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What are the causes of psamomma bodies?
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PSaMMoma bodies:
- Papillary carcinoma of thyroid - Serous papillary cystadenocarcinoma of ovary - Meningioma - Malignant mesothelioma |
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What are the most common causes of cancer in males?
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- Prostate (32%)
- Lung (16%) - Colon / rectum (12%) |
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What are the most common causes of cancer in females?
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- Breast (32%)
- Lung (13%) - Colon / rectum (13%) |
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What are the most common causes of cancer mortality in males?
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- Lung (33%)
- Prostate (13%) |
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What are the most common causes of cancer mortality in females?
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- Lung (23%)
- Breast (18%) |
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How has lung cancer incidence changed in males and females?
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- Dropped in men
- Not changed significantly in women |
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What are the top two leading causes of death in US?
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- 1st = Heart Disease
- 2nd = Cancer |
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What are the common sites of metastasis?
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- Brain
- Liver - Bone |
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What are the most common tumors that metastasize to the brain?
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Lung > Breast > Genitourinary > Osteosarcoma > Melanoma > GI
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How common are brain tumors from metastasis?
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50% of brain tumors are from metastasis
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What is the typical appearance of brain tumors from metastasis?
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Multiple well-circumscribed tumors at gray/white matter junction
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What are the most common tumors that metastasize to the liver?
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Colon >> Stomach > Pancreas
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What are the most common sites of metastasis after the regional lymph nodes?
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Liver and lung after the regional lymph nodes
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What are the most common tumors that metastasize to the bone?
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Prostate, Breast > Lung > Thyroid
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Where do metastases to the bone preferentially affect?
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Whole-body bone scans show tumor predilection for axial skeleton
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What are the characteristics of bone metastases from the prostate?
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Osteoblastic
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What are the characteristics of bone metastases from the breast?
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Osteoblastic and Osteolytic
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