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117 Cards in this Set
- Front
- Back
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What is a neoplasm?
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A neoplasm is a growth that is uncoordinated from the normal tissues and it also exceeds the rate of growth of normal tissues even when the stimuli for growth is removed
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What is a tumor
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Tumor = swelling.
Commonly used as a synonym of neoplasia. Tumor does not equal cancer, therefore neoplasia does not equal cancer. |
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What are the ways to classify a tumor
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Benign vs Malignant
Epithelial vs Mesenchymal (origin) Differentiation (well vs poor vs moderate) |
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How do benign tumors look compared to malignant ones in how they resemble normal tissues
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Benign tissues resemble normal tissue. Malignant tissues vary in their resemblance to normal tissue
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Benign tumors end in
Malignant tumors end in |
Oma
Carcinoma or sarcoma |
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What are the growth rates for benign vs malignant tumors?
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Benign tumors grow slow
Malignant vary in their growth rate |
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How does the invasiveness of benign vs malignant tumors vary
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Benign are usually encapsulated and therefore not invasive.
Malignant are usually invasive |
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Benign vs malignant tumors in terms of metastasis?
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Benign tumors do not metastasize
Malignant tumors metastasize |
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Where do epithelial tumors arise from? What kinds of cells involved?
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Epithelial tumors arise from ecto/endo derm. Types of epithelial cells involved are squamous (skin), respiratory, transitional (bladder), ducts, glands
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Are epithelial tumors benign or malignant
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They are either benign or malignant
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Where do mesenchymal tumors arise from? What kinds of cells are involved?
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Arise from the mesoderm; involves adipocytes, muscle cells, cartilage, bone, and blood vessels.
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Hematolymphoid tumors are those that involve
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Lymphomas, leukemias, ie basically immune cells. They are malignant
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Melanocyte tumors originate from what kind of cells? Are they benign or malignant
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They originate from neural crest cells. They are benign (nevus) or malignant (melanoma)
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What is an adenoma
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A benign glandular epithelium
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What are mixed tumors
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Mixed tumors can be either malignant or benevolent, but they involve both epithelial and mesenchymal components.
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What are teratomas
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Teratomas are predominantly benign. But they have totipotent cells and they are composed of tissues from multiple germ layers.
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What is a carcinoma
What is a sarcoma |
A carcinoma is a malignant, epithelial tumor
A sarcoma is a malignant, mesenchymal tumor |
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What is a hamartoma
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This is a mass of disorganized, mature tissue that has all the right components histologically, but is disorganized.
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What is a choriostoma
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A choriostoma is an ectopic tissue in a foreign location
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What is differentiation/grade
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This is the extent to which tumor cells morphologically and functionally resemble the normal tissue counterpart
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What are the categories of differentiation/grade
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Well differentiated (resemble normal tissue); evidence of maturation function
Moderately differentiated (in between) Poorly differentiated (primitive and vague resemblance) - no functionality anaplastic = complete lack of differentiation |
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What are some of the features you would see in an anaplastic cell
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Pleomorphism, dark nuclei, high N/C ratio, bizzare mitoses, loss of polarity
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How can you classify tumors by their spread?
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In situ- has not penetrated basement membrane
Locally invasive = malignant Metastatic = malignant |
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What do clincal stages classify tumor based off
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TNM = tumor size, nodal involvement, metastasis
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Describe carcinoma in situ
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This is a preinvasive lesion that is frequently seen in proximity to the invasive tumor. No penetration below the basement membrane. Dysplasia is present
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What is dysplasia
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Dysplasia is a component of carcinoma in situ. This is similar to an anaplastic cell (loss of polarity, increased mitoses, loss of maturation, crowded nuclei)
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What does local invasion involve
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Involves the tumor cells migrating through BM
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What are the 2 malignant tumors that do not metastasize
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Basal cell carcinoma and gliomas
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Where are the sites of metastasis for tumors
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Lungs, Liver, Vertebra, Brain, Lymph nodes
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What are the pathways for metastatic spread
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Hematogenously, Seeding, and Lymphatics
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Describe hematogenous spreading of metastasis
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Most common for sarcoma spread mostly in veins - goes to portal, vena cava, and paravertebral plexus
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Descirbe the pathways for lymphatic spread
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Usually for carcinomas. Sentinel nodes are the first LN to drain the tumor.
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What is seeding?
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Seeding of body cavities is when the peritoneal cavity is usually involved. IN this, tumor cells displace from the mass and implant in serosal surfaces. Common in Ovarian cancer and lung cancers.
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What are the most common types of pediatric cancer?
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Leukemia and lymphomas (ALL most common - acute lymphoblastic lymphoma)
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What are the most common cancers in men and women by incidence
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Men - Prostate, lung, colon
Women - breast, lung, colon |
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What is important to note about trends for cancer in men? Women
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Lung and colorectal cancers are on the decline.
Women - breast is down, lung is up, colorectal down. |
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Which race/sex combination has the highest cancer incidence? Lowest?
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Highest = black men
Lowest = black women |
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What is the second leading cause of death in the US
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Cancer
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What cancers take the most lives in men and women
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Lung, prostate, colorectal in that order
Lung, breast, colorectal in that order |
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What are the autosomal dominant cancer syndromes
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Retinoblastoma
FAP Li Fraumeni HNPCC |
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For AD cancer syndromes, is it 1 or 2 hits?
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2 hits. THe first hit is inherited, but it needs a second hit to manifest.
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What happens with the Rb gene in retinoblastoma
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Rb normally has a hold on a trasncription factor E2F. With mutations in Rb, E2F is not regulated, you get osteosarcoma and retinoblastoma
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What is familial adenomatous polyposis
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100s of polyps on the colon -> gives the potential for trasnformation to malignancy. Prophylaxis - removing colon. Caused by a mutation of APC gene, which down regulates Beta catentin. Beta catenin complexes with TCF a transcription factor, and this leads to lots of growth factors being produced = cancer.
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What happens in Li Fraumeni syndrome?
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This is an inheritance of mutated p53 (an apoptosis initiator). This increases risk of cancers 25X over normal people- and you are younger and get many cancers.
Cancers implicated are sarcomas carcinomas leukemias |
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What prophylactic measures can be taken in BRCA1 mutations
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Mastectomies and salpingoophorectomies (ovary and FT)
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BRCAs are rare or common in sporadic cancers?
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Rare to have both mutations occur sporadically. Typically follows the AD pattern.
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Does BRCA mutations account for the majority of breast cancers
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No. Only about 3% of all breast cancers, but does make up 25% of familial cancers.
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How are defective DNA repair syndromes inherited typically
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Usually AR except for HNPCC which is AD. This means you need 2 hits for these diseases.
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What are the DNA repair systems we have in our body
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Recombination repair
Nucleotide excision repair Mismatch repair |
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HNPCC is a defect in what kind of DNA repair system
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Defect in DNA mismatch repair. MSH2 and MLH1 genes are involved. No polyps usually.
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What is Xeroderma pigmentosum
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A defect in nucleotide excision repair (thymidine dimers). Autosomal recessive condition. Photosensitivity, high skin cancer risk, neurological abnormalities.
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What are familial cancer syndromes
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In these syndromes, the pattern of inheritance is not clearly defined. They have early onset, with multiple bilateral tumors, and two or more close relatives affeted. 10-20% of breast cancers are familial.
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What kind of genetic alterations are the key to carcinogenesis. How can these alterations happen
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Point mutations, balanced translocations, gene deletions, gene amplifications/overexpression
These alterations are either acquired or inherited |
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What kinds of gene targets does cancer affect
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Protooncogenes are activated
Tumor supressor genes are inactivated Antiapoptosis genes are activated apoptotic genes are inhibited DNA repair genes are inhibited |
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What is a protooncogene
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A protooncogene is a normal regulatory gene involved in regulated cell growth. They encode things like GF, GF receptors, signal transducers, transcription factors, cell cycle regulators
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What is an oncogene. What is their inheritance pattern.
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These are constitutively active and DOMINANT. They upregulate cell proliferation in cancer cells.
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Is the SIS gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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The sis gene is a protooncogene. It is overexpressed in cancer. Tumors that result include astrocytoma and osteosarcoma.
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Is the ERB-B2/Her2 gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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ERB-B2 is a protooncogene. It is amplified in cancer. Breast and ovary are examples.
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Is the cKIT gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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cKIt is a protooncogene. It undergoes a point mutation, giving GISTS (gastrointestinal stromal tumors)
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Is the Ras gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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Ras is a protooncogene. It undergoes a point mutation in cancer. Lung and pancreas are affected.
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What are familial cancer syndromes
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In these syndromes, the pattern of inheritance is not clearly defined. They have early onset, with multiple bilateral tumors, and two or more close relatives affeted. 10-20% of breast cancers are familial.
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Is the Abl gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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Abl is a protooncogene. It is translocated in cancer. CML and ALL tumors occur.
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What kind of genetic alterations are the key to carcinogenesis. How can these alterations happen
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Point mutations, balanced translocations, gene deletions, gene amplifications/overexpression
These alterations are either acquired or inherited |
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What kinds of gene targets does cancer affect
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Protooncogenes are activated
Tumor supressor genes are inactivated Antiapoptosis genes are activated apoptotic genes are inhibited DNA repair genes are inhibited |
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What is a protooncogene
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A protooncogene is a normal regulatory gene involved in regulated cell growth. They encode things like GF, GF receptors, signal transducers, transcription factors, cell cycle regulators
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What is an oncogene. What is their inheritance pattern.
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These are constitutively active and DOMINANT. They upregulate cell proliferation in cancer cells.
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Is the SIS gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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The sis gene is a protooncogene that produces Beta- PDGF. It is overexpressed in cancer. Tumors that result include astrocytoma and osteosarcoma.
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Is the ERB-B2/Her2 gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result? What are its prognostic, predictive, and treatment qualities?
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ERB-B2 is a protooncogene. It is amplified in cancer. Breast and ovary are examples. ERB B2 /Her 2 is poor prognosis, predicts poorly to estrogen therapy. Hereptin/Trastuzumab = antibody against receptor. Binds GF receptor and recruits immune cells to destroy the cell.
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Is the cKIT gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result? What is the treatment.
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cKIt is a protooncogene. It undergoes a point mutation, giving GISTS (gastrointestinal stromal tumors). Treatment is Imatinib/Gleevec (which is a tyrosine kinase inhibitor).
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Is the Ras gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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Ras is a protooncogene. It undergoes a point mutation in cancer and is the single most common abnormality of oncogenes. When Ras is mutated it loses its GTPase activity and stays on. Lung and pancreas are affected.
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Is the Abl gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result? What is the treatment
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Abl is a protooncogene. It is translocated in cancer. CML and ALL tumors occur. This translocation leads to loss of regulatory control. Can be treated with Gleevec.
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Is the myc gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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Myc is a protooncogene. IT is translocated and amplified, leading to lots of transcription. Burkit lymphoma (c) and neuroblastoma (N) result
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Is the cyclin D1 gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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Cyclin D1 is a protooncogene. It is translocated in cancer - mantle cell lymphoma results.
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Is the Rb gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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Rb is a tumor supressor. IT is mutated, resulting in retinoblastoma and osteosarcoma.
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Is the APC/Beta catenin gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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It is a tumor supressor gene that is mutated, affecting GI and pancreas.
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Is the p53 gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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p53 is a tumor supressor. It is mutated, resulting in many cancers.
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Is the BRCA1 gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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It is a tumor supressor that is mutated, resulting in breast and ovary cancer.
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Is the bcl2 gene a protooncogene, tumor supressor, or antiapoptotic? How is it altered in cancer? What kind of tumors result?
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It is an antiapoptotic gene. It is translocated. Lymphomas result.
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Are cyclins expressed all the time? Are CDKs expressed all the time?
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cyclins are cyclic and are not expressed all the time. CDKS are expressed all the time.
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What are pro apoptotic genes? Anti apoptotic genes
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Pro = Bax
Anti = Bcl2 |
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What are direct acting carcinogens? Do they need processing?
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Direct acting carcinogens are electrophiles that react with electron rich nucleic acids. They do not need processing.
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What is an indirect acting carcinogen
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These need to be metabolized by P450s to be active. They then target the nucleic acids.
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CYP1A1. What does it metabolize/detoxify? Who has highly inducible forms/deletions?
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CPY1A1 metabolizes polycyclic aromatic hydrocarbons. 10% of caucasians have an inducible form that leads to increased carcinogens.
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Glutathione S transferase. What does it metabolize/detoxify. Who has highly inducible forms/deletions
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50% of caucasians have deletions in GST, which detoxifies polycyclic aromatic hydrocarbons. This leads to increased carcinogens.
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What are initiators? Are they direct or indirect? What kind of damage do they cause?
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Initiators are chemicals that cause permanent DNA mutations. They are both the direct and the indirect. They can cause permanent or repairable damage. They attack specific regions of DNA.
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What are promoters?
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These are chemicals that enhance the proliferation of mutated cells. This encouragement of proliferation gives you a chance to acquire more mutations.
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What is the most important carcinogen in tobacco smoke
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Polycyclic aromatic hydrocarbons. They are initiators. Tobacco smoke causes Lung, bladder, and laryngeal/oral carcinoma.
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What are the 2 mechs by which viruses, bacteria, and parasites cause oncogenesis?
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They 1)integrate in the genome and overexpress their proteins that affects cell growth
2) They stimulate inflammatory response and subsequent regeneration gives the chance to accumulate more mutations |
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What conditions is HPV implicated in
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Verruca vulgaris, cervical cancer
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What is HPVs mechanism of oncogenesis?
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E6 and E7 of HPV are overexpressed. E6 inhibits p53.
E7 inhibits Rb and p53. Low risk = hpv 6,11 |
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EBV is implicated in
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Burkit lymphoma
Lymphomas HIV/endemic And post transplant B cell disorders |
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What is the mechanism of oncogenesis in hepatitis viruses
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They issue is that they cause chronic liver injury and then the regeneration prolbme is where mutations can occur. This is the problem in cirrhosis - the hep C causes inflammation and the body tries to repair, but then each repair increases the risk for developing abnormalities, acting as a precursor to hepatocellular carcinoma HCC.
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Helicobacter pylori is implicated in. It is similar to the mechanism of
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Gastric adenocarcinomas
Maltomas Similar to hepatocellular carcinoma mechanism (regeneration repeatedly) |
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What are the 2 forms of radiation
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X rays and gamma rays (ionization)
and UV light (implicated in melanomas, and basal/squamous carcinomas) |
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What are 2 host reactions to cancer
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Antitumor defense
Physical effects (cachexia, anemia, hemostasis abnormality, fever, paraneoplastic syndrome) |
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What is the antitumor defense
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Cytotoxic T cells (CD8 T cells) recognize antigens in the context of MHC molecules.
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What kind of things to CD8 cells recognize
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Antigens which could be
altered cell surface lipids/proteins oncogene products aberrant self proteins overexpressed proteins viral proteins etc |
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What drug is a good anti tumor drug. What is it used for
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Rituxan. It is a monoclonal anti-CD20 antibody that takes out B cells sine B cells are in lymphomas.
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If we have anti tumor immunity, why does cancer still develop
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Tumor cells can express immuno supressant proteins, can alter MHC genes, can fail to produce an antigen etc.
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What is cachexia
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It is a wasting disease- loss of body fat and lean body mass. Profound weakness and anorexia occurs dt cytokines.
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What kind of blood responses can occur due to cancer?
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Anemia (so malnutrition can cause lack of clotting factors or invasion of bone marrow etc)
OR hypercoagulability (tumors produce procoagulants - in pancreatic cancer/trousseau syndrome and acute promyelocytic leukemia DIC) |
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Paraneoplastic syndromes occur in what % of cancer patients? What are paraneoplastic syndromes
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10.
These are syndromes that occur unreleated to the spread of a tumor (like a tumor secreting hormones). These include endocrinopathies, skin, nerve, muscle, bone , soft tissue, vascular syndromes. |
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What is cushings syndrome
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High levels of cortisol can be caused by high ACTH. This is a paraneoplastic syndrome. You have obesity and a moon face.
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Squamous cell carcinoma produces what paraneoplastic syndrome
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Hypercalcemia. This can be due to Parathyroid hormone related protein (increase calcium resorption in kidney, causes release of Ca++ from bones)
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What is the lifetime risk of breast cancer
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1/8 for women. 200k new cases/yr with 40k deaths
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Strong risk factors for breast cancer
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Age, female, 2 first degree relatives affected, mutations, breast cancer, hyperplasia
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moderate risk factors for breast cancer
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1 first degree relative, chest radiation, high bone density
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Minor risk factors are related to circulating hormones
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First preg after 30, early menarche, obesity, oral contraceptives...etc all give more time for estrogen circulation
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Majority of breast cancers are what type of cancer?
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Adenocarcinomas. Invasive ductal is most common. Invasive lobular less common (rarely have Her 2 amplified).
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What are the prognostic indicators for breast cancer
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Morphology (size, lymph node involvement, tumor grade)
ER status (most are ER +) Her2 status - 20-25% of cancers; more aggressive. |
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do well differentiated tumors have a low grade or a high grade
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LOW grade
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How do you test for ER receptor
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Immunohistocompatibility Complex C testing.
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ER receptor works how
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Dimerizes and ligand dependent transcription factor.
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What is the difference between prognostic and predictive
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Prognostic is expected course of disease. Predictive is likelihood of response to treatment
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Her 2 belongs to what receptor family? How does it work
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Epidermal growth factor receptor. IT has tyrosine kinase activity. It is overexpressed in 20% of breast cancers and can be detected by IHC. Gene can be detected by fish.
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What happens to Her 2 in breast cancer
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IT is amplified. Herceptin (trastuzumab) is given as tx. It recruits cell mediated immunity to kill tumor cells.
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What are the heritable breast cancer risks
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BRCA 1 mutations
Li Fraumeni Syndrome Cowden syndrome (PTEN) |
