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Neoplasia

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riosju10's version from 2016-06-11 15:39

Section

Objectives 1:
1.) Terms
Question Answer
Tumorswelling
NeoplamsNew growth, uninhibited, lack of organization, can be Benign OR malignant
Choristomanot neoplasm, normal tissue out of place, an ectopic rest of normal tissue
Hamartomanot neoplasm, mass of disorganized mature tissue indogenous to a particular sight (bronchal tissue in lung)-not derived from single cell type
oncologystudy of tumors / neoplasms
Clonalityentire population arises from single cell
Desmoplasiaformation of collagenous stroma in response to tumor or growth invasion
Parenchymafunctional parts of organ (hepatocyte in liver)
Stromastructural tissue of organs (connective tissue)
Adenomabenign epithelial (papillary adenoma = papilloma, cystic adenoma = cystadenoma)
Carcinomamalignant epithelial (adenocarinoma =glands, squamous cell carcinoma=epithelial)
-omabenign mesenchymal neoplasm (fibroma, leiomyoma, osteoma, chrodroma, lipoma)
-sarcomamalignant mesenchymal (fibrosarcoma, leiomyosarcoma, osteosarcoma, chrondros
differentiationthe extent to which neoplastic cells resemble comparable normal cells
Anaplasialack of differentiation
Pleopmorphismvariation in cell size and shape (morphology of malignancy)
Metaplasiachange from one adult type to another cell --> adapt to stress, predispose to cancer
Dysplasiadisordered growth, loss of normal polarity, but did not invade yet --> may develop to cancer
Metastasistumor implant discontinuous with primary tumor (ex. lung to bone)
Cachexiawasting syndrome, loss of apetite, atrophy of muscle, bone
Paraneoplastic syndromefrom effect of tumor (hormones, cytokines) cushing, hypoglycemia, etc
Gradeexpression of the level of differentiation of a malignant neoplasm
Stageextent of spread of cancer within the patient
Initiationalteration in a cell which causes permanent DNA damage --> capable of giving rise to tumor
Promotioninduction of tumors in initiated cells Carcinogenesis is two part process 1.) Initiation 2.) Promotion
Direct-acting agentsdo not require metabolic conversion to become carcinogenic
Indrect-acting agentsrequire metabolic conversion liver p450 enzymes
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2.) Classifying Benign v. Malignant Neoplasms
Question Answer
Benign Neoplasmcohesive, expansile mass, well differentiated, slow growth
Malignant neoplasminvade structures, spread, poor differentiation, grow rapidly, "cancer"
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3.) Nomenclature of benign and malignant tumors of different tissue types
Question Answer
Adenomabenign epithelial (papillary adenoma = papilloma, cystic adenoma = cystadenoma)
Carcinomamalignant epithelial (adenocarinoma =glands, squamous cell carcinoma)
-omabenign mesenchymal neoplasm (fibroma, leiomyoma, osteoma, chrodroma, lipoma)
-sarcomamalignant mesenchymal (fibrosarcoma, leiomyosarcoma, osteosarcoma, chrondros
Polypprojection above mucosal surface (benign or malignant)
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4.) Morphology of malignant neoplams
Question Answer
Malignant pleomorphism, abnormal nucleus (hyperchromasia, large nucleoli, increased nucleus/cytoplas), mitosis, loss of polarity (dysplasia), tumor giant cells, necrosis
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Malignant tumors have high turnover rate, chemo drugs will treat better

 

Question Answer
Direct seedingpenetration of tumor (ex. ovarian into GI)
Lymphatic spreadepithelial malignancies (thorugh lymph)
Hematogenous spreadmesenchymal malignancies (through blood)
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Section 1

Question Answer
Bax/Bakpro-apoptosis gene,Bax mediates actions of P53 (tumor suppressor c17) "BAX- AX apoptosis"
bcl-2/BCL-CLanti-apoptosis gene (oncogene), Follicular lymphoma t(14,18) "Brings Cells 2 Life"
myc, CDK4growth promoting genes (oncogene) (c-myc=Burkitt's Lymphoma t(8;14)) "Makes Young Cells grow". N-myc = neuroblastoma
proto-oncogenesnormal, unmutated
growth factorsPDGF, TGF-alpha (platelet growth factor, transforming growth factor alpha). autocrine action
GF ReceptorsTyrosine kinase dimerize --> phosphorylation --> MAP cascade
Signal Transduction ProtienRAS, RAF, c-ABL tyrosine kinase, β-catenin (WNT Signaling)
Transcription Factorsmyc
Cell Cycle RegulationCyclin D,E, CDK4 "keeps cell cyclin"
Tumor Suppression GeneRBG (13), P53 (17)
RBGTumor suppressor, Chrom 13, Regulates G1/S. Hypophosphorylated (active) prevents transcription of Cyclin E by E2F. Thus inhibits G1/S transition.
P53Tumor suppressor, Chom 17, TP53 gene, 50% human tumors contain mutation, Li-Fraumeni. P53 inhibits CDK's that phosphorylate (inactivate) RB.
P53 Mechanismincrease BAX gene (apoptosis), increase p21 (CDK inhibitor,quiesence repair), inhibits MYC, CDK4 (growth promoters), inhibits BCL-2 (anti-aptosis gene)
APC/β-Catenin WNT PathwayAPC genes down regulate growth promoting signals from β-Catenin, mutations lead to "familial adenomatous polyposis" FAP Ch5, WNT receptor (APC is tumor suppressor gene)
p16-INK4a/p14-ARF (CDKN2A)p16-INK:inhibits cyclin D (CCND1) activation of CDK4/6 phosphorylation (inactivation) of RB (p16 tumor suppressor gene) chrom 9 melanoma
p14-ARF: inhibits MDM2 ubiquinidation (degradation) of P53 allowing p53 to upregulate p21 and inhibit CDK2 (RB phosphorylation)
CDK2phosphorylation of RB (inactive) --> allows cell cycle
TGF-βpotent inhibitor of cell proliferation by promoting CDKI (inhibitor) activation. Cancer cells mutate this pathway so it does not work --> unregulated cell growth and angiogenesis. More mutated TGF-Beta is produced which also inhibits T-cell immune response to tumor "T cells Get Fucked" --> pancreatic cancer "Teen Gets Farm --> pancreatic cancer Louie dad
PTENPhosphatase and TENsin homologue (chrom TEN10), inhibits in PI3K/AKT pathway (Cowden Syndrome) --> multiple hamartomas
NF1 proteinChrom 17, neurofibromin protein product. inhibits transduction of RAS proteins with GTPase activity of RAS (GDP is inactive), mutated in neurofibromatosis I (tumor suppressor gene) --> persistent activation of RAS-GTP
NF2 proteinChrom 22, merlin protein product; cells that lack merlin protein are insensitive to normal growth arrest from cell to cell contact --> tumors. Germline mutation in Neurofibrom Type II
VHL proteinChrom 3, von Hippel-Lindau Disease, no VHL-->no degradation of HIF1α-->angiogenesis (hemangioblastomas), hemangioma, benign endolymphatic sac tumors
WT1 proteinChrom 11, Wilms' Tumor (pediatric small blue tumors) WT1 is transcriptional activator of genes involved in rena gonadal differentiation
PTCH1 PTCH2PATCHED protein, cell membrane protein functions as receptor to for Hedgehog --> mutations = Gorlin Syndrome (nevoid basal cell carcinoma)
Extrinsic ApoptosisCD95/Fas death receptor
Intrinsic ApoptosisDNA damage
Ataxia TelangectasiaATM gene chromosome 11, DNA repair, 1.) Ataxia 2.) Telangectasia 3.) Decreased IgA (sinopulmonary infections), X-ray induced abnormalities
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Carcinogenic Infections:
Question Answer
aspergillus(Tx. Voroconazole) produces Aflotoxin B1 mutates P53 gene --> hepatocellular carcinoma (measure w. alpha fetoprotein marker)
vinyl chlorideliver angiosarcoma
UVradiationUVB sunlight causes DNA damage forming pyrimidine dimers. xeroderma pigmentosa (NER) defect thymidine dimer repair
Ionizing Radiationlong latent periods, most common is leukemia and thyroid cancer, big ugly cells. Large nucleus but also large cytoplasm. Ataxia Telangectasia.
HTLV-1human T cell leukemia virus type 1 is an RNA virus (retrovirdae). Tax gene --> protein product activates host cell genes to differentiate to T Cells and inactivates cell cycle inhibitor p16-INK (inhibits CDK4/6) --> leads to T cell proliferation/mutations "Flower cell" "High taxes like violets"
HPVDNA virus (papovirdae ds circular) genome integrated into host KNOW: High risk types are 16 and 18. Squamous carcinoma of cervix, oropharynx, anogenital. E6 protein degrades p53 & BAX. E7 protein binds RB and displaces E2F (like phosphate), inhibits p21. smoking makes worse. PAP smear (koilocytes), immunization
EBVDNA virus (herpesvirdae ds linear) infect B cells and immortalizes. t(8,14) activatates c-myc oncogene --> Burkitt's Lymphoma. EBV integrates into host cells viral latent membrane protein -1 (LMP-1) --> NF-kB, Nasopharyngeal carcinoma
HCV/HBVDNA virus (hepadnavirdae ds circular) hepatocelluar carcinoma --> chronic inflammation --> cirrhosis --> hepatocellular carcinoma
H.pyloribacterial infection, 2 types of gastric malignancy (gastric adenocarcinoma from chronic gastritis and metaplasia and lymphoma MALToma) --> seaguls on slide
Hepatocellular carcinomaHep B, Hep C, aflotoxin (apergillus) --> test for Hepatocellular carcinoma w. alpha-fetoprotein marker
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Question Answer
erb-B2 (HER-2)growth factor receptor is overexpressed is 25% breast cancer, Tx, Trastuzumab (herceptin), monoclonal antibody against receptor (oncogene)
APC Genechrom 5q21germline APC mutation --> familial adenomatous polyposis (hundreds of polyps--> colorectal cancer) NOTE: most sporadic adenomas and carcinomas of colon result from mutation of gene (tumor suppressor) "FAP Five" APC normally binds Beta-catenin
BCL-2 Geneanti-apoptosis, t(14;18)(q32;q21) translocation causes over expression of BCL-2 --> follicular lymphoma, translocation used to diagnose lymphoma, FISH techniques (oncogene)
MSH-2 and MLH-1DNA mismatch repair genes hereditary nonpolyposis colon cancer (HNPCC) aka Lynch Syndrome, Autosomal Dominant- defect in mismatch DNA repair
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Pathology of Neoplasia:
Question Answer
paraneoplastic syndromessymptoms that cannot be explained by local or distant spread of tumor and endogenous hormones. ex. lung cancer producing ACTH (corticotropin -->cushing)
lung cancerassociated with many paraneoplastic syndromes (cushings ACTH, hypercalcemia PTH, hyponatremia low ADH)
carcinoid syndrome5-HIAA (seratonin) release from metastatic malignant carcinoma tumors, flushing, hypertension, diarrhea
renal cell carcinomapolycythemia, release of EPO
Lambert-Eaton Syndromeparaneoplastic syndrome thymoma, or lung cancer. Antibodies against calcium channels, no Ach release (better with movement) Mysthenia Gravis: Ach receptors blocked, fatigue
Acanthosis nigricansthickening/darkening of skin
Hypertrophic osteoarthropathyswelling of hand, arthritis
Gradelevel of differentiation (I-IV. well - poorly differentiatied), how much do they look like normal counterparts
Stageextend of spread of cancer (TNM: Tumor size, Node involvement, Metastasis) Tis: tumor in situ (not invasive yet)
Frozen sectionon the fly histo analysis while in surgery, but induces many artifacts
Fine Needle AspirateFNA used for palpable lesions, thyroid (can diagnose thyroid carcinoma w. FNA), lymph node
Metaplastic squamousinfected HPV , see koilocyte, hyperchromasia, pleomorphism
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Classify Undifferentiated Neoplasm:
Question Answer
Cytokeratincarcinomas (epithelial origin) used to classify undifferentiated neoplasm
Vimentinsarcomas
Glil fibrillary acidic protein (GFAP)gliomas
P100melanoma
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Site of Origin:
Question Answer
ProstatePSA (Prostate Specific Antigen)
ThyroidTTF1 (thyroid transcription factor 1)
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Prognosis Markers:
Question Answer
ER/PR Breast Cancerrespond better to antiestrogen therapy
HER-2 positiverespond to Trastuzumab (herceptin) --> monoclonal antibody against the receptor
t(9:22)Bcr-abl philadelphia chromosome (CML) chronic myeloid leukemia
t(14:18)bcl-2 follicular lymphoma
t (8;14)c-myc Burkitts Lymphoma
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First Aid: Tumor Suppressor Genes --> both alleles must be lost for expression of disease "need to loss both foot and e brake"
Question Answer
Rb13q Retinoblastoma, osteosarcoma
BRCA117q Breast and ovarian cancer
BRCA213q Breast cancer "unlucky 13"
p5317p, most human cancers, Li-Fraumeni syndrome
p169p, Melanoma ("MelaNoma is on Nine")
APC5q Colorectal cancer, associated w. FAP "FAP Five"
WT111p Wilms' Tumor "IL =11"
NF117q Neurofibromatosis I, cutaneous neurofibromas, optic gliomas, pheochromocytomas
NF222q Neurofibromatosis II, acoustic schwannomas, meningiomas, and ependymomas
DPC18q Pancreatic cancer "Deleted in Pancreatic Cancer"
DCC18q Colon cancer "Deleted in Colon Cancer"
MEN1Parathyroid, pancreas, pituitary (3 P's)
PTENbreast cancer, prostate cancer, endometrial cancer
TSC1/2tuberous sclerosis
VHLvon Hippel-Lindau, renal cell carcinoma
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First Aid: Oncogenes: Gain of function leads to cancer. Need damage to only 1 allele. Only need one gas pedal
Question Answer
bcr/ablCML (chronic myeloid leukemia) t(9;22)philly, ALL
c-mycBurkitt's Lymphoma t(8;14)
bcl-2Follicular lymphoma (inhibits apoptosis) t(14;18)
erb-B2 (HER2/neu)Breast, ovarian, gastric cancer
rascolon carcinoma, lung, pancreatic cancer
L-mycLung tumor "L -lung"
N-mycneuroblastoma "N- neuro"
retMultiple Endrocrine neoplasia IIA/B, medullary thyroid cancer
c-kitgastrointestinal stromal tumor (GIST)
brafmelanoma, non hodgkin lymphoma
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