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246 Cards in this Set
- Front
- Back
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What is the common name for nevus flammeus?
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birthmark
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What is a port-wine-stain and what is the clinical significance?
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Grows with child, thickens surface, no tendency to fade
Lesion in a trigeminal nerve distribution can be seen with Sturge-Weber syndrome |
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What does p53 (in regards to Cyclin D/CDK4) do?
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induces p21
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What does p27 (in regards to Cyclin D/CDK4) do?
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responds to TGF-beta
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What cancers is inhibitor p16 related to?
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somatic inactivation by mutation/deletion in wide variety of carcinomas
Germ-line mutations found in 20% of familial melanoma Inacivated by hypermethylation in HPV-related cancers (cervical) |
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What is an adenoma?
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Derived from or forming glands (also liver, kidney)
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What is a cystadenoma?
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Cystic masses arise from produce of neoplastic glandular cells
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What is a papilloma?
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forming finger-like projections
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What is a polyp?
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growth pattern projects above the skin or mucosal surface. May be neoplastic or non-neoplastic. Types = sessile, pedunculated, papillary
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What tissues form carcinomas?
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Epithelial tumors
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What tissues form sarcomas?
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tumors derived from mesenchyme
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What is nevus?
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a mole - benign
Common brown pigmented (melanin) - small, usually less than 0.5mm; circumscribed. Does not enlarge, change significantly over time |
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What 2 tumors are derived from the placenta?
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Hydatidiform Mole (benign)
Choriocarcinoma (malignant) |
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Where is a common place for a seminoma? What is it?
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a malignant germ cell epithelial tumor. Common in testis/ovaries
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What is a pleomorphic adenoma? is it benign or malignant?
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It is the most common neoplasm of the salivary gland - it is BENIGN (mixed tumor)
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What is the most common benign breast tumor?
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Fibroadenoma
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What is the most common kidney tumor of children ?
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Nephroblastoma (Wilms Tumor)
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What is a myxoma?
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Benign tumor of mesenchyme with a mucoid appearance
Most common tumor of the heart in adults - may kill the patient by virtue of location |
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What is a meningioma?
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benign neoplasm of covering of brain. Serious, possibly fatal due to location
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What is a neuroma?
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Benign tumor or nerve origin
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What is a glioma?
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always malignant! Neoplasm of the brain
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What is a heterotopia/choristoma?
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Small areas of mature tissue from one organ present within another, a developmental anomaly.
Ex: pancreatic/gastric tissue in a meckel's diverticulum, lingual thyroid, lacrimal gland tissue in conjunctiva, endometriosis (not a developmental anomaly) |
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What is a hemartoma?
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Focal malformation composed of proliferation of abnormal mixture of tissues native to the site.
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What is differentiation?
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The extent to which neoplastic cells resemble comparable normal cells. Benign tumor cells are indistinguishable from non-neoplastic cells of same type.
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What defines a grade 1 tumor?
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well differentiated, low grade
Tends to grow slowly |
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What defines a grade 2 tumor?
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moderately differentiated
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What defines a grade 3 tumor?
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poorly differentiated, high grade
tends to grow rapidly |
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What determines tumor grading?
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degree of differentiation
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What does anaplasia mean?
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lack of differentiation
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What is the origin of cancer?
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monoclonal origin, arises from mutations in progenitor or stem cell
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What defines tumor progression?
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acquisition of more aggressive behavior, greater malignant potential
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What is tumor heterogeneity?
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populations of cells that differ with respect to phenogtype
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What is the exception to the rule that benign tumors are encapsulated?
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hemangiomas
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What is carcinoma in situ?
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continuation of process of dysplasia
precancer, preinvasive involves the full thickness of epithelium, basement membrane intact |
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What are some synonyms for invasion?
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Infiltration
Extension |
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What is local extension refer to?
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direct tumor invasion of adjacent tissue or organ
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What is the definition of metastasis?
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Tumor implants discontinuously with the primary tumor (aka where the tumor started)
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What 2 malignancies do NOT metastasize?
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Gliomas
Basal Cell carcinomas |
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What are the 3 pathways of metastasis?
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Seeding
Lymphatic Mets Blood Borne Mets |
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What does seeding mean?
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Cancer breaks through to an open field and spreads onto surfaces of space. Ex: ovarian cancer, gastric carcinoma, pancreatic carcinoma, some intestinal malignancy, Lung cancer will seed pleura/pericardium
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What spreads via lymph system?
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carcinomas
oral cancer, breast cancer, lung cancer, colon cancer |
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What spreads via blood?
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sarcomas
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How is staging derived?
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from statistical studies of tumor outcomes. It varies for each organ.
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What are the most common cancers of adult males?
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1. prostate
2. lung 3. colon/rectum |
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What are the most common cancers of adult females?
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1. breast
2. lung 3. colon/rectum |
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What are the most common causes of cancer DEATH in adult males?
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1. Lung
2. Prostate 3. Colon/Rectum |
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What are the most common causes of cancer DEATH in adult females?
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1. Lung
2. Breast 3. Colon/Rectum |
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What cancers are associated with alcohol abuse?
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oropharynx
larynx esophagus hepatocellular carcinoma (2ary to cirrhosis) |
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What cancers are associated with tobacco smoke?
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head/neck/upper aerodigestive tract
Lip/mouth/oropharynx Larynx, lung, esophagus, pancreas, urinary tract, cervical |
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What cancers are associated with UV radiation?
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squamous cell carcinoma
malignant melanoma basal cell carcinoma |
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What is it about inflammation that predisposes to cancer?
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Cytokines! - they stimulate cell growth, increasing the pool of stem cells.
Also, inflammation generates ROS |
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What are some other acquired predispositions for cancer?
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Characterized by prolonged/increased regenerative and hyperplastic proliferations such as endometrial hyperplasia due to estrogen.
Repair from injury (burns) Cirrhosis of liver (hepatocellular carcinoma) Benign tumors rarely become malignant Hyperplasia --> Metaplasia --> Dysplasia |
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What are some characteristics of familial cancer syndromes?
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The genes tend to be related to sporadic tumors of the same type.
Familial clusters of cancer (2 or more relatives of index case). Tend to occur at younger age May have multiple or B/L Canceres Autosomal Dominant or multifactorial due to multiple low-penetrance alleles |
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What is Knudson's 2-Hit Hypothesis?
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Two mutations/"hits" of Rb gene required to produce Retinoblastoma. PT with familial RB inherits one defective gene copy in ALL cells = 1st hit. 2nd copy lost by somatic mutation = 2nd hit --> malignant transformation
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What percentage of breast cancer is due to the inherited cancer gene?
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~10%
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What are the BRCA-1 and BRCA-2 genes?
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Tumor suppressor genes (involved in transcription regulation) and DNA repair - homologous recombination.
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What are the 4 inherited autosomal recessive syndromes of defective DNA repair?
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1. Xeroderma Pigmentosum
2. Ataxia Telangiectasia 3. Bloom Syndrome 4. Fanconi's Anemia |
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What is the function of the bad DNA gene in Xeroderma Pigmentosa?
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Nucleotide Excision Repair gene
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What is the clinical manifestation of Xeroderma Pigmentosa?
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EXTREEEEEEME sensitivity to light
2000x increased risk of skin cancer (squamous/basal cell carcinoma and melanoma) skin cancers occur in childhood |
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What are the clinical manifestations of Ataxia Telangiectasia?
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Cerebellar Ataxia
Oculocutaneous telangiectasias IgA deficiency (recurrent infections) Sensitive to ionizing radiation, develop leukemia, lymphoma with exposure |
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What is the gene that is bad in Ataxia Telangiectasia?
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ATM (ataxia telangiectasia mutated) - gene results in chromosome fragility.
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What is the mechanism of damage in Ataxia Telangiectasia?
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ATM gene binds to damaged DNA; phosphorylates TP53 (p53).
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What is initiation? Promotion?
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Initiation: by a mutagen. Rapid, irreversible effect: permanent DNA damage but insufficient alone for tumor formation
Promotion: effect reversible. Promoters are not tumorigenic by themselves. Induce tumors in initiated cells. |
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What are direct acting initiators?
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require no chemical transformation - highly reactive electrophilic: attach to DNA.
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What are indirect acting initiators?
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procarcinogens, are metabolized to ultimate carcinogen by P450 dependent enzymes.
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What is the effect of promoters?
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they induce sustained cell proliferation, induce hormones, phenols, drugs, etc
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What are some direct acting chemical carcinogens?
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Alkylating agents
Chemotherapy drugs Cyclophosphamide Cisplatin Busulfan Benzopyrene Vinyl Chloride Aflatoxin B1 |
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What is initiation? Promotion?
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Initiation: by a mutagen. Rapid, irreversible effect: permanent DNA damage but insufficient alone for tumor formation
Promotion: effect reversible. Promoters are not tumorigenic by themselves. Induce tumors in initiated cells. |
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What are direct acting initiators?
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require no chemical transformation - highly reactive electrophilic: attach to DNA.
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What are indirect acting initiators?
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procarcinogens, are metabolized to ultimate carcinogen by P450 dependent enzymes.
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What is the effect of promoters?
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they induce sustained cell proliferation, induce hormones, phenols, drugs, etc
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What are some direct acting chemical carcinogens?
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Alkylating agents
Chemotherapy drugs Cyclophosphamide Cisplatin Busulfan Benzopyrene Vinyl Chloride Aflatoxin B1 |
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What are some indirect acting chemical carcinogens?
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generally potent
Polycyclic aromatic hydrocarbons aromatic amines, amides, and azo dyes Nitrosamines Natural plant and microbial products |
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How does alcohol contribute to carcinogenesis?
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Alcohol is likely a promoter
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How does tobacco smoke contribute to carcinogenesis?
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Cigarrete smoke is an initiator. Benzo(a)pyrene and nitrosamines are major products. Promoters: multiple irritants in tobacco smoke and tobacco. Smoking is a multiplier/co-carcinogen for many other carcinogens including asbestos and radon gas
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What type of virus is HTLV-1 and what disease is it associated with?
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Oncogenic RNA virus - Retrovirus
Causes T cell leukemia/lymphoma (CD4 T lymphs) Infection of T-lymphs by HTLV-1 causes polyclonal expansion via Tax. Tax promotes genetic instability |
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What neoplasms are related to HPV infection?
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Squamous cell carcinoma
- vulva, vagina, cervix, penis, perianal = majority - sinuses, oral cavity, lung = minority |
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What are the features and actions of "high risk" (Carcinoma associated) HPV?
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High risk HPV: viral genome integrated into nuclear DNA
E2 viral repressor lost which promotes overexpression of E6 and E7. E6 protein inactivates p53 product degrades Bax, activates telomerase. E7 protein binds to Rb promoting cell progression of cell cycle. |
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What malignancies are associated with EBV?
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Hodgkin's Disease
Burkitt's Lymphoma B-cell Lymphoma (immunosuppressed) Nasopharyngeal carcinoma |
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What factors are responsible for the oncogenic effects of EBV?
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LMP-1
EBNA-2 vIL-10 (major transforming gene prevents activation of cytotoxic T cells) |
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Where is Burkitt's Lymphoma prevalent?
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Africa
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Where is nasopharyngeal carcinoma due to EBV prevalent?
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Southern China, Eskimos
Parts of africa |
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What viruses are associated with Hepatocellular carcinoma?
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Hepatitis B and C
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What is the mechanism of viral hepatitis causing cancer?
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chronic viral hepatitis with ongoing viral replication --> hepatocyte death. Hepatocyte death, regeneration and disruption of growth regulation -> cirrhosis. Genetic accidents arise in the regenerating cells. Multifactorial oncogenic effect: ongoing hepatocyte regeneration and environmetnal agents.
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Why is Hep B endemic in Asia & Africa?
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High rate of cancer due to virus being passed from mother to baby.
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How do 2 viruses work synergistically to cause Kaposi sarcoma? What are the viruses?
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Human Herpesvirus 8 (KS) and HIV
KS is a neoplastic proliferation of BVs or vessel-forming mesenchyme. Primitive mesenchyme or endothelial cells are infected by KS virus. Cytokines and tat gene product from HIV infected CD4 T lymphs induce KS-infected cell proliferation. |
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What malignancy/malignancies are associated with Helicobacter pylori?
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Adenocarcinoma of the stomach
Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) Cog-A - containing strains = adenocarcinoma |
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What infections/diseases are caused by H. pylori?
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Chronic gastritis and ulceration
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What is cachexia?
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Loss of body fat and lean body mass w profound weakness, anorexia, and anemia. Mediated through soluble agents secreted by tumor and by host immune response.
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What tumor agents are indicated in cachexia?
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PIF, LMF, and Pro-inflammatory cytokines.
Cytokines + PIF activation of ubiquitin proteasome pathway lead to myosin degradation |
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Define paraneoplastic syndrome.
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Hormone elaboration by nonendocrine tumors.
Effects remote from a tumor not explained by elaboration of hormones indigenous to tumor. |
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What are 2 types of paraneoplastic syndromes?
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Endocrinopathies (ex: polycythemia due to renal tubular carcinoma, Cushings Syndrome, Myasthenic Syndrome - Lambert-Eaton Syndrome)
Syndromes due to antibodies (Ab mediated progressive muscle weakness - Ab against calcium channels, Paraneoplastic Acanthosis Nigricans) |
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What is blood marker CEA for?
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colon cancer
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What is blood marker Alpha-Fetoprotein for?
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liver and testicular cancer
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What is blood marker beta-HCG for?
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choriocarcinoma
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What is blood marker PSA for?
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Prostate cancer
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What are blood markers VMA, HVA, and NSE for?
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Neuroblastoma
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What is blood marker CA-15-3 for?
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breast cancer
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What is blood marker CA-125 for?
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ovarian cancer
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What cancer is associated with arsenic and arsenic compounds?
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lung, skin, hemangiosarcoma
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What cancer is associated with asbestos?
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lung, mesothelioma, GI (esophagus, stomach, large intestine)
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What cancer is associated with benzene?
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leukemia, hodgkin lymphoma
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What cancer is associated with Beryllium and beryllium compounds?
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lung
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What cancer is associated with cadmium and cadmium compounds?
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prostate
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What cancer is associated with chromium compounds?
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lung
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What cancers is associated with nickel compounds?
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nose, lung
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What cancer is associated with radon and its decay products?
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lung
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What cancers are associated with vinyl chloride?
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angiosarcoma, liver
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What 4 things can a frozen section may be used for?
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presence or absence of malignancy
Presence or absence of inflammation/organisms Whether surgical margins are free of neoplasm (basal cell carcinoma) Whether diagnostic tissue is present |
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What is the intermediate filament associated with carcinomas, mesotheliomas?
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Keratins
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What cancers are associated with keratins?
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carcinomas, mesotheliomas
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What is the intermediate filament associated with muscle tumors, smooth and striated?
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Desmin
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What cancers are associated with Desmin?
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Muscle tumors, smooth and striated
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What intermediate filament is associated with mesenchymal tumors, some carcinomas?
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vimentin
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What cancers are associated with vimentin?
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Mesenchymal tumors, some carcinomas
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What intermediate filament is associated with gliomatous tumors?
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Glial Filaments
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What cancer is associated with Glial filaments?
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Gliomatous tumors
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What intermediate filament is associated with neuronal tumors?
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Neurofilaments
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What cancer is associated with neurofilaments?
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neural tumors
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What 2 things can flow cytometry measure?
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Cell characteristics such as membrane antigens and DNA content of tumor cells
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Which subset of DNA content is generally associated with a poor prognosis?
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aneuploid
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Which CD markers are for T cells?
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1, 3, 4, 5, 8
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Which CD markers are for B cells?
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10, 19, 20, 21, 23
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Which CD markers are for Monocytes/macrophages?
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11, 13, 14, 15
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Which CD markers are for NK cells?
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16, 56
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Which CD markers are for stem cells?
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34
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Which CD markers are for activation marker?
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30
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Which CD markers are present on all leukocytes?
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45
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What are the main uses for FISH?
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detection of viral infections
detection of specific DNA or RNA sequences in tissue sections or cell preps |
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What is special about FISH as compared to standard karyotyping?
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can be performed on cells in dividing and resting stages
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What does PCR make?
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millions of copies of DNA sequences
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What does a DNA microarray analysis measure?
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expression levels of several thousand genes
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What 6 areas are genomic approaches having an impact on?
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1. tumor classification
2. prognostic markers 3. predictive indicators or drug response 4. the development of new drug therapies 5. strategies for monitoring disease 6. management of susceptibility to cancer |
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What 2 features are helpful to divide blood vessels into benign vs. malignant categories?
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1. degree of well formed vascular channels present
2. Extent of regularity of the endothelial cell proliferation |
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What are the 3 categories of hemangiomas?
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Capillary
Juvenile Cavernous |
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Where are capillary hemangiomas predominantly found?
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skin
SubQ tissues Mucous membranes |
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What are the characteristics of a pyogenic granuloma?
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Peduncular red nodules on skin, oral mucosa (rapidly growing, bleeds easily, often ulcerated)
Proliferating capillaries with edema and acute & chronic inflammation 1/3 develop after a trauma |
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Where do glomus tumors occur?
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distal portions of digits under the nail
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What are glomus tumors composed of?
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branching vascular channels
aggregates, nests, and masses of specialized glomus cells |
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What distinctive clinical symptom do glomus tumors have?
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extremely painful, arising from smooth muscle cells of glomus body
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What causes a bacillary angiomatosis?
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infectious disease, non-neoplastic proliferation of vessels in skin, lymph nodes and visceral organs
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Who gets bacillary angiomatosis?
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HIV patients or immunocompromised patients.
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How would you treat a bacillary angiomatosis?
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macrolide anitbx - erythromcyin
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What are the 2 intermediate grade blood vessel tumors?
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Hemangioendothelioma
Kaposi's Sarcoma |
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What is the underlying infectious cause of Kaposi sarcoma?
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Human Herpesvirus 8
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What are the 4 types of Kaposi Sarcoma?
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Chronic (classic, European Form)
Lymphadenopathic (African Kaposi's) Transplant-Associated AIDS associated |
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What are the microscopic hallmarks of the later stage of Kaposi Sarcoma?
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plump, spindle-shaped stromal cells with irregular, angulated, slit-like spaces filled with red cells
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What are 3 types of malignant blood vessel tumors?
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Angiosarcoma
Hemangiopericytoma |
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What 3 carcinogens are hepatic angiosarcomas associated with?
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Arsenic
Thorotrast Polyvinyl Chloride (PVC) |
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What are the 2 types of lymphangiomas?
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simple and cavernous
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What is the other term for cavernous lymphangioma?
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Cystic hygroma
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Where are cystic hygromas located? In whom do they occur?
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at the base of the neck in children
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What syndrome are cystic hygromas associated with?
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Turner's Syndrome
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How many alleles effected for oncogenes?
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one
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How many alleles effected for tumor suppressors?
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two
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What neoplasms are most associated with RAS?
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frequent in adenocarcinomas (pancreatic, colon carcinomas)
Common in hematologic malignancies |
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What is RAS?
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GTP binding protein - transduction activator
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How does a RAS oncogene arise?
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point mutations especially in response to a chemical injury
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How is RAS activated?
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in response to growth signal via GDP --> GTP, results in transduction via RAS/RAF/MAP
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Describe RAS inactivation.
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Intrinsic GTPase activity of normal RAS
GAP (GTPase-activating proteins) NF-1 (a tumor suppressor) |
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Describe mutated RAS.
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It evades GAP (GTPase-activating proteins)
Remains bound to GTP and activated |
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How is ABL activated?
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by translocation of t(9:22) - Philadelphia Chromosome.
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Describe the ABL mechanism of oncogenicity
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Fusion of ABL with BCR results in persistent transduction.
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What neoplasm is most associated with ABL activation?
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Chronic Myelogenous Leukemia (CML)
some acute lymphoblastic leukemias |
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What is ABL?
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a non-receptor Tyrosine Kinase
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What is MYC's oncogenic function?
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activates transcription by DNA binding
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What are gatekeeper genes?
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They regulate cell growth - brakes to cell proliferation
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What is loss of heterozygosity?
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Pt born with one defective/mutated copy in familial cancer syndromes.
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What are 3 examples of cancers arising from loss of heterozygosity?
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Rb - familial retinoblastoma
WT1 - Wilms Tumor (nephroblastoma) VHL: von Hippel Lindau - clear cell renal carcinoma |
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What is the function of CpG islands?
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They inactivate the 2nd X chromosome (common in promoter regions of genes)
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What rare p53's functions?
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suppressor - p21
DNA repair apoptosis - Bax Senescence (melanoma vs nevus) |
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How is p53 mutated?
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by benzo(a)pyrene in tobacco smoke
aflatoxin UV light |
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What is the familial syndrome associated with p53?
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LiFraumeni - germ line heterozygous p53 mutation confers 25x risk of cancer by age 50. Many types of cancer can occur: breast, sarcoma, brain tumors, leukemia, adrenal cortical.
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What is cellular senescence?
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loss of cell's ability to complete mitosis due to irreversible arrest of cell cycle. It is a protective response in cells in which oncogenes have been activated. Characteristic of benign tumors. Cells remain viable.
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What genes confer the property of cellular senescence?
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p53 and Rb
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What is the gene product of APC?
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beta-catenin
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What is APC?
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tumor suppressor gene.
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What are 2 functions of beta-catenin?
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binds to E-cadherin, maintains cell-to-cell cohesion/adhesiveness
Component of WNT signally pathway (translocates to nucleus as transcription factor) |
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What is the gene product function of E-cadherins?
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Glycoprotein glues between epithelial cells. Loss favors malignant phenotype - disintegrated cells invade, metastasize. Common in many visceral cancers and breast cancer
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What is the gene product function of TBGF-beta?
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Stimulates CDKI's p21 and p15. Inhibits transcription of CDKs, cyclins, MYC, Signaling pathway SMAD.
Mutations in the factor or pathway, occur in pancreatic cancers, colon, and gastric cancers |
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What is the gene product function of NF-1?
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Codes for neurofibromin (one of the brakes on RAS). GTPase activating protein - inactivates RAS.
Neurofibromatosis Type I occures w/ one germline mutant allele. Loss of 2 alleles leads to continuously active RAS and Neurofibrosarcoma. |
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What is the gene product function of NF-2?
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Merlin - Neurofibromin 2. Homologous to RBC cytoskeletal protein. Cell-to-cell junctions and signaling functions. Mechanism of carinogenesis unknown. Schwannomas and Meningiomas
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What is PTEN?
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Phosphate and Tensin homologue
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What is the function of PTEN?
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potent tumor suppressor gene!
2nd most frequent gene mutation in cancers. It dephosphorylates proteins and lipids. Impacts multiple signaling pathways, including p53 and RAS. Brake on pro-survival/pro-growth pathway PI3K/AKT. |
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What syndrome is associated with PTEN familial mutation?
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Cowden syndrome: benign skin appendage hemartomas
Increased risk for cancers: esp breast. |
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What cancers are seen in sporadic monoallelic loss of PTEN?
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breast
colon prostate lung brain |
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What cancer is seen in homozygous mutation of PTEN?
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endometrial
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What is VHL?
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suppressor gene
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What cancers are seen due to germline mutation of VHL gene?
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Hereditary renal cell carcinoma - most common kidney cancer of adults. Both genes inactive in the most common form of sporadic renal cell carcinoma.
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What is the function of VHL?
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blocks the production of VEGF
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What is the function of HIFa? What is it?
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regulates VEGF, PDGF
Hypoxia inducible factor (VHL gene) |
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What chromosome is related to WT-1?
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Chromosome 11p13
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What is the function of WT-1?
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Tumor suppressor activity: growth activity.
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What is the oncogenic activity of WT-1?
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transcription activator of genes involved in renal and gonadal development, RNA processing, anti-apoptotic activity.
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What happens in homozygous inactivation of WT-1?
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Familial Wilms Tumor (nephroblastoma) - pediatric renal cancer
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What cancer is characterized by BCL-2 overexpression?
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B-cell lymphoma
t(14:18) activates transcription of BCL-2 Resistant to therapy |
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What are the apoptotic effects of p53?
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upregulates BAX
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What are the apoptotic effects of PTEN?
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upregulates BAD (autophagy facilitation)
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What inherited and sporadic malignancy is associated with defective mismatch repair?
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Hereditary nonpolyposis colon cancer - inherited defect in one of the two alleles for mismatch repair gene - acquired defect in 2nd gene/allele
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What are the most common genes and what defect accumulates in the genome of mismatch repair?
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Genes: MLH-1 MSH-2
They are spell checkers of DNA , they proofread and correct defects. Microsatellite instability can be detected (tandem repeats of up to 6 nucelotides) in the genome. Sporadic mutations occur in 15% of all colon cancers |
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What inherited disease is associated with defective nucleotide excision repair?
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Xeroderma Pigmentosum
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What genes are involved in DNA repair by homologous recombination?
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BRCA-1
BRCA-2 ATM |
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What does BRCA-1 gene do?
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regulates estrogen receptor activity
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What factors are proangiogenic?
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VEGF - transcription controlled by hypoxia-inducing factor HIFa, RAS, MAP, MYC
Basic fibroblastic growth factor (bFGF) - released by proteases from ECM |
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What factors are anti-angiogenic?
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Thrombospondin-1: induced by p53
Agents produced in response to tumor by proteolytic cleavage of ECM (collagen, plasminogen, tranthyretin) - angiostatin - endostatin - vasculostatin |
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What are the features of tumor vessels?
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Tumor vessels are tortuous, irregular, and leaky (due to increase in VEGF) and grow continuously
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What factors are involved in tumor invasion?
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loss of E-cadherins
reduced catenin protein degradationof basement membrane, interstitial CT Matrix Metalloproteinase (Type IV collagenase) Cathepsin D Urokinase plasminogen factor |
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How might metastases occur?
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formation of tumor embolis/cell collections w/ adherent platelets
Coagulation factors Single cells Adhesion to endothelium (CD44). Extravasation (grow through wall of cessel) |
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What are the outcomes of metastases?
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circulation of cells
dormancy tumor cell products |
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What is the Warburg Effect?
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Even in the presence of ample oxygen, cancer cells shift their glucose metabolism away from the oxygen hungry, but efficient, mitochondria to glycolysis. Aerobic glycolysis. The glucose hunger of tumors is used to visualize them via PET scanning
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How do PET scans work?
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Inject the patient with 18F-fluorodeoxyglucose which will be taken up into the tumor cells.
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What is an example of Tumor SPECIFIC antigens?
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BCR-ABL
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What are some examples of Tumor ASSOCIATED antigens?
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Prostatic Acid Phosphatase
Oncofetal antigens - alpha-fetoprotein CEA CD20 in B cell lymphoma Her2/Neu p53, RAS HPV E7 |
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What is the primary mechanism of antitumor immune activity?
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CTLs (CD8+ cells)
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What are some other cells that are involved in antitumor effector mechanisms in tumor immunity?
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NK cells - destroy w/o prior sensitization
Macrophages: cell killing by ROS Antibodies against tumor antigens |
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What is the status of the immune system by the time cancer is diagnosed? What are the mediators?
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Balance is switched from immunostimulatory to immunosuppression. Switch from TH1 to TH2 (Ab production)
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What are the functions of TGF-beta in cancer?
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Tumor suppressor gene. Produced by Treg cells and fibroblasts in the stroma of invasive cancer. Effects related to invasion include: increased angiogenesis, increased deposit of ECM, immunosuppression
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Describe a cardiac myxoma.
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Benign, uncommon.
Clinical: ball-valve obstruction -- heart failur Fragmentation with systemic embolization possible systemic inflammatory reaction - fever due to IL-6 from tumor 90% are in atria, L>R by 4:1. Morphology: sessile or pedunculated; Myxoid (gelatinous), mesenchymal cells |
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What is the most common neoplasm of the heart in infants?
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Rhabdomyoma - rare benign tumor or hemartoma
May produce obstruction Occurs in infants/children in first year of life |
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What aggressive primary malignancy occurs in the heart?
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cardiac angiosarcoma - aggressive, metastasizing, usually fatal
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What is the unit used to calculate/describe the dose of radioactive iodine given to a pt?
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Curies/Becquerels
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How is the unit of the dose of external beam radiation calculated?
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Grays
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What units are used to record annual radiation exposure in a worker?
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Siverts (mSv)
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What cells are most radiosensitive?
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Rapidly dividing cells:
hematopoietic cells (esp lymphs) germ cells GI epithelium salivary glands skin endothelium |
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When is a cell most vulnerable to radiation injury?
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Cells in G2, M are most sensitive
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What is the pathogenesis of radiation injury?
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Cross-linkage of DNA, proteins
Cleavage of bonds DNA breaks, DNA damage (most serious) double stranded breaks, repair by homologous recombination, nonhomologous end joining (more common) --> produces chromosomal aberrations |
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Describe acute radiation injury.
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cell death.
Endothelium is major target to radiation injury: apoptosis, endothelium cell death, and cytokine release causes burns. Damage to intestinal crypt cells cause GI syndrome of radiation sickness |
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Describe chronic injury.
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Vascular injury, fibrosis of wall with obliteration
thrombosis telangiectasias Ischemia of organs supplied by scarred vessels fibrosis due to ischemia, loss of stem cells |
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What is the latency period for radiation exposure of the big disasters of Hiroshima, Chernobyl, and Fukushima?
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10-20 years
(at least 2) |
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What cancers are associated with radiation exposure of Hiroshima, Chernobyl, and expected from Fukushima?
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Children: thyroid, breast, GI, GU
Adults: Acute leukemias 20x more likely |
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What is the most common neoplasm of childhood? Is it benign/malignant?
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Hemangioma - benign
Common locations = skin of face and scalp |
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What is Sturge-Weber syndrome?
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Port-wine-stain malformation that has an intertrigeminal distribution. Vascular anomalies extend into eye, meninges, risk for glaucoma
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What is a teratoma? Where is it most commonly located?
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arise from totipotent germ cell rests. Contains tissue from all 3 germ layers.
Most common location of childhood = sacrococcygeal |
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What are some big differences about pediatric cancers as opposed to adult cancers?
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5x higher risk for death from a cause other than their primary cancer
Get secondary cancers Histology = blastomas |
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Where is the most common location of neuroblastoma?
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Adrenal medulla
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What is the derivation of a neuroblastoma?
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primordial neural crest of the sympathetic ganglia
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What is the behavior of a neuroblastoma?
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Microscopic lesions tend to remain silent and spontaneously regress
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What are the symptoms of a neuroblastoma?
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Abdominal mass
Fever Weight loss Mets to bone = bone pain Respiratory problems orbit mets common "blueberry muffin" appearance |
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What is the most common renal tumor of childhood?
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Wilm's Tumor aka Nephroblastoma
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What are the genes related to genetic predisposition for Wilm's Tumor?
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WT-1
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What are the 3 genetic diseases with increased risk for Wilm's Tumor?
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WAGR
Denys-Drash Beckwith-Wiedman Syndrome |
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What is WAGR?
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Wilms tumor - WT-1 gene
Aniridia (absent iris), genital malformation, mental retardation. Chromosome 11p deletion. Deleted region includes PAX6 gene for the irises. Risk for Wilm's Tumor = 30% |
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What is Deny-Drash Syndrome?
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Male pseudohermaphroditism and nephropathy, renal failure. Missense mutation WT1 gene. Risk for Wilm's tumor for both = 90%. Screen for both until grown
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What is the microscopic morphology of Wilm's Tumor?
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Small round blue cells
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What chromosome is RB on?
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13
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What is the microscopic morphology of Retinoblastoma?
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Small round blue cells forming Flexner-Wintersteiner Rosettes.
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