Neoplasia 1 Nicols Definitions and Pics Flashcards
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What is a neoplasm ?
A neoplasm (tumor) is an autonomous irreversible clonal benign or malignant cell proliferation outside of normal control by contact inhibition, hormones, etc.
What are 5 adjectives that commonly describe neoplasms ?
- It is autonomous 2. Irreversible 3. Clonal 4. Benign (or 5) 5. Malignant
What is a metastasis ?
A secondary site of a tumor that is discontinuous with the first
What is a neoplasm of the mesenchyme cell layer ?
Sarcoma
What is a malignant neoplasm of epithelial cell origin ?
Carcinoma
What does the mesenchyme give rise to ?
Connective tissue, Bone Cartilage, muscle Ect.
How do carcinomas spread ?
Lymph system
How do sarcomas spread ?
Hematogenosus - Lung or the liver
How do ovarian carcinomas spread ?
Seeding of the body cavities or surfaces
What is a mixed germ cell tumor ?
Teratoma - which is a malignant neoplasm made up of one or more germ cell layer
What is a mass of mature disorganized tissue indigenous to its site and is a developmental abnormality
Hamartoma
What is an ectopic rest or a mass of normal tissue present outside its normal site, also a developmental anomaly
Choristoma
What is a macroscopic projection above a mucosal ( or epidermal ) surface or a nodule on a stalk or on that surface
A polyp
What is polyp on a stalk considered
A Pendunculated Polyp
What is a polyp that is flat with the surface it manifests ?
A Sessile Polyp
What is a benign epithelial neoplasm forming glands or derived from glands ?
An Adenoma
What is anaplasia ?
Lack of visual differentiation of tumor cells giving them the appearance of primitive unspecialized cells
What are the features of anaplastic cells
(1) larger size than differentiated cells, (2) higher nuclear / cytoplasmic ratio: larger nuclei, less cytoplasm, (3) pleomorphic (varying in size and shape).
What is a Dysplasia? and what are the two types ?
- An unorganized growth 1. Congenital - embryonically abnormal organization of cells and acquired cellular atypia usually premalignant, +/- reversible 2. Acquired - dysplasia of glandular epithelium is usually called “atypical hyperplasia” or “atypical adenomatous hyperplasia”.
What is the formation of abundant fibrous stroma by some carcinomas ?
Demoplasia
What is the difference between stroma and parenchyma ?
The stroma, you recall, is the infrastructural part of a tissue or organ, opposite of parenchyma, which is the functional (business) part.
Tissue with all the cytologic (individual cell) features of malignancy without visible invasion is called … ?
Carcinoma in situ
What are some of the common causes of cancer ?
smoking, obesity, alcohol, diet, human papilloma virus (HPV), ultraviolet light, asbestos and many other factors. Smoking is a cause of cancers of lung (90% of them), mouth, pharynx, larynx, esophagus, stomach, pancreas, kidneys, bladder and (to a smaller extent) many other types. Obesity is a cause of 14% of cancers of men and 20% of cancers of women in the US
What type of disease is neoplasia ?
Genetic
What are the six properties of malignant cells ?
(1) self-sufficiency in growth signals, (2) insensitivity to anti-growth signals, (3) evasion of apoptosis, (4) sustained angiogenesis, (5) limitless replicative potential and (6) the ability to invade tissue and metastasize.
What are the two major mutations that lead to cancer ?
Tumor suppressor genes normally apply brakes to cell proliferation. When mutated your cellular brakes wont work oncogene- is more like having you accelerator pinned to the floor
What does Rb do ?
*Rb binds to E2F when hypophosphorylated and sequesters E2F to prevent activation of Cyclin E (Halts cell cycle at G1-S)
*Rb is phosphorylated by Cyclin D CDK4/6 and releases E2F, –> transcription of S phase genes and the cell progresses through the cycle
**Normally when the cell reaches the M phase the phosphate groups are removed from Rb and it will rebind to E2F and the cell cycle will be inhibited
What does loss of control of Rb cause ? What is the mechanism ?
Retinoblastoma When Rb is phosphorylated by cyclin D-CDK4, cyclin D-CDK6 and cyclin E-CDK2 complexes, it releases E2F. E2 F then soon activates genes starting up cell proliferation.
**2 Hit mutant hypothesis
**Rb also stimulates macrophage, adipocyte, melanocyte and many other differentiation cell signals so loss of control is a big deal.
What does APC do ?
APC tumor suppressor gene controls intestinal stem cell proliferation by WNT signaling. The APC gene product breaks down beta-catenin so that it does not bind to transcription factor TCF that will allow the malignant transformation of neoplastic cells. This allows for down regulation of E-Cadeherin to decrease cellular adhesion.
What does p53 do ?
It prevents propagation of genetically damaged cells by binding to DNA, arresting the cell cycle to enable DNA repair and initiating apoptosis, if repair is impossible
What does MDM2 do to P53 ?
Resistance to p53 is mediated by an increase in a protein called MDM2, which destroys p53, or by E6 protein of HPV, which degrades p53. The response of a tumor to radiation or chemotherapy is mediated by p53, so resistance to p53 confers resistance to chemoradiotherapy.
NF-1 and NF-2 are tumor suppresser genes for what ?
Neurofibramatosis
TGF-Beta is a tumor supressor gene for what cancer ?
TGF-Beta is a potent inhibitor of cell proliferation. It binds to the TGF-B receptor, dimerizes, and upregulates many CDKI’s and downregulates many proligerative genes such as MYC, CDK2, CDK4.
What is WT-1 a tumor supressor for ?
Wilms Tumor
Patched PCTH is a tumor supressor for what
Basal Cell carcinoma of the skin
What does the NF-1 gene do ?
The NF-1 gene product neurofibromin activates a GTPase, creating GDP that binds to cell membrane RAS protein, making it inactive so that RAS does not transduced growth factor signals for proliferation. Inherited mutation causes neurofibromatosis, type 1, with numerous benign neurofibromas due to second hit mutations.
What does the von Hippel Lindau gene do ?
Von Hippel Lindau gene product causes ubiquitination and degradation of hypoxia inducible transcription factor-1 that would yield increased PDGF and VEGF and tumor angiogenesis, if left around. Germ line VHL mutation causes kidney cancer, pheochromocytoma (adrenal medullary tumor), retinal angioma and other tumors with second hit mutations.
What do oncogenes do ?
Drive Autonomous cell growth in many cancers
What is HER-2
HER2, formerly called Her2/neu or ERB-B2, is an EGFR receptor overexpressed in 20% of breast cancers, which often respond to blocking the overexpressed receptor with a monoclonal antibody called trastuzumab or two newer agents, lapatinib or pertuzumab.
How do you diagnose overexpressed HER-2 ?
The overexpression can be diagnosed by immunohistochemical staining of the protein in tissue sections. This overexpression is on a continuum and the staining is graded 0 to 3. Response to targeted therapy is primarily to grade 3 overexpression, but there are fluorescent in situ hydridization (FISH) tests for the amplification of the gene that causes the overexpression of the growth receptor and these are more sensitive than immunohistochemistry for the gene product.
What is the current guideline for positive FISH ?
The current guideline is that FISH is called positive if there is an average of more than six copies per nucleus (for test systems without an internal control probe) or an HER2/CEP 17 ratio of more than 2.2 where CEP is a centromeric probe for chromosome 17 on which HER2 resides
What is K-Ras ?
K-RAS oncogene codes for a GTPase in the cytoplasm on the inner side of the cell membrane bound to the EGFR. K-RAS carries out signal transduction from cytoplasm to nucleus when EGFR binds growth factors, transducing signals for the cell to proliferate.
What happens when growth factors bind to EFGR ?
Binding of growth factors to EGFR causes the K-RAS GTPase to make more GDP that generates proteins that ultimately enter the nucleus to deliver the signal.
What happens when K-RAS is messed up ?
If K-RAS is messed up, running all the time, even when not transducing a growth factor signal, upstream therapy directed against the EGFR won’t work.
What can cause mutations in K-Ras ? What is mutated K-Ras associated with ?
Mutations in the K-RAS proto-oncogene caused by as little as a single nucleotide substitution cause it to become constitutively activated in about 40% of colon carcinomas.
Neoplasm ?
autonomous irreversible clonal benign or malignant cell proliferation outside of normal control by contact inhibition, hormones, etc.
Malignancy ?
when a neoplasm invades and / or metastasizes.
Metastasis ?
secondary site of tumor discontinuous with the primary site.
Carcinoma ?
malignant neoplasm of epithelial cell origin.
Sarcoma ?
malignant neoplasm of mesenchyme-derived tissue.
Teratoma ?
benign or malignant neoplasm with components of more than one germ cell layer, usually all three (ectoderm, mesoderm, endoderm).
Hamartoma ?
developmental anomaly creating mass of mature but disorganized tissue indigenous to its site.
Choristoma ?
ectopic rest or a mass of normal tissue present outside its normal site, a developmental anomaly.
Polyp ?
macroscopic projection above a mucosal (or epidermal) surface or bump or nodule on a stalk in or on that surface.
Adenoma ?
benign epithelial neoplasm forming glands or derived from glands.
Anaplasia ?
lack of visible differentiation of malignant tumor cells, giving them the appearance of primitive unspecialized cells.
Dysplasia ?
disordered growth, 2 types: (1) congenital embryonically abnormal organization of cells or (2) acquired cellular atypia, usually premalignant.
Demoplasia ?
reactive formation of abundant fibrous stroma by some carcinomas.
Carcinoma in Situ ?
tissue with all the cytologic (individual cell) features of malignancy without visible invasion
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Benign Breast Tumor
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Cut Surface of the pancreas showing tan white cancer
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Memorize that shit
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Metastatic Colon Cancer in a Lymph Node
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Review this
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Ovarian Teratoma making hair and sebum
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Sub Pleural Chondoma
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Pedunculated Colon Polyp
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Sessile Colon Polyp
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Adenona of the Colon
What is the origin of this ?
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No Idea … ANAPLASIA
What are the arrows poiniting to ?
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Dysplasia below and between the arrows
What is this ?
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Gastric cancer with Desmoplasia
What is this ?
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Anaplasia with abnormal Tripolar mitoses
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Tan and white lung cancer invading pink and grey lung
What are these ?
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Neurofibromas
What is the gold tissue ?
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Renal Cell Carcinoma