Neoplasia complete Flashcards
Benign tumor origin
Epithelial or Connective tissue origin
Benign tumors of epithelial origin
Ectoderm, endoderm
Benign tumors of connective origin
mesoderm
Teratomas origin
Derives from ectoderm, endoderm, mesoderm
Origin of Carcinomas
Derive from squamous, glandular (adenocarcinoma), transitional epithelium
Origin of Sarcomas
Derive from connective tissue
Hamartoma
non-neoplastic overgrowth of tissue
Choristoma
normal tissue where it should NOT be
Neoplastic component of that determines the tumors biologic behavior
parenchyma (tissue that does the work)
Grade of cancer asks…
does the cancer resemble its parent tissue or not?
Features of Malignant tumors
↑ nuclear/cytoplasmic ratio; abnormal mitotic spindles
How many doubling times (cell cycles) are required b4 a tumor can be clinically evident
30
Benign and malignant tumors derive from a…
single precursor cell (monoclonality)
Why dont malignant tumors lose genetic material after multiple cell divisions?
d/t upregulation of telomerase activity
Feature of Basal cell carcinoma
invade tissue but do NOT metastasize
2nd most important criterion for malignancy
Invasion
Tissue resistant to invasion
Cartilage, elastic tissue
Loss of intercellular adherence (E-cadherin)
→ cell invasion
Extranodal metastasis (eg liver) has greater prognostic significance than…
nodal metastasis (TNM )
Routes of metastasis
lymphatic (carcinomas), hematogenous (sarcomas), seeding body cavities
Type of metastasis common w/ surface-derived ovarian cancers
Seeding
Bone metastasis
Vertebra MC site; paravertebral venous plexus
Feature of Osteoblastic metastasis
↑ serum alkaline phosphatase (dephosphorylates pyrophosphate which inhibits bone formation); seen in prostate cancer
Consequences of Osteolytic metastasis
hypercalcemia, pathologic fxs
Bone metastasis on X-ray
Osteoblastic-radiodense; Osteolytic-radiolucent
MC tissue metastasize to
Lymph node
2nd MCC death in US
Cancer
Lifetime risk for cancer
Men 〉 Women
Population w/ greatest overall risk for cancer
Blacks
MC cancer in children
Acute lymphoblastic leukemia (ALL)
Cancer incidence in men
Prostate 〉 Lung 〉 Colorectal
Cancer incidence in women
Breast 〉 Lung 〉 Colorectal
Incidence of gynecologic cancer
Endometrial 〉 Ovarian 〉 Cervical (lowest d/t pap smears)
MCC of cancer death in adults
Lung cancer
Cancer-related deaths in men
Lung 〉 Prostate 〉 colorectal
Cancer-related deaths in women
Lung 〉 Breast 〉 Colorectal
Most rapidly ↑ing cancer worldwide
Malignant melanoma
Cancer in china
Nasopharyngeal carcinoma 2ndary to EBV
Cancer in Japan
Stomach adenocarcinoma d/t smoked foods
Cancer of SE Asia
Hepatocellular carcinoma d/t Hep B and aflotoxins (produced by Aspergillus) in food
Cancer of Africa
Burkitts lymphoma d/t EBV and Kaposis sarcoma d/t HHV 8
AD cancer syndromes
Retinoblastoma, Familial Adenomatous Polyposis, Li-Fraumeni syndrome, Hereditary nonpolyposis colon cancer (Lynch syndrome), BRCA1 and BRCA2 genes
Retinoblastoma
point mutation inactivates RB suppressor gene; predisposition for osteogenic sarcoma in adolescence
Familial Adenomatous Polyposis (FAP)
inactivation of APC suppressor gene → malignant transformation of of polyps by age 50
Li-Fraumeni syndrome
inactivation of TP53 suppressor gene → ↑ risk for sarcomas, leukemia, carcinomas
Hereditary nonpolyposis colon cancer (HNPCC) aka Lynch syndrome
inactivation of DNA mismatch repair genes → cannot correct errors in nucleotide pairing; ↑ risk colorectal cancer w/o previous polyps
BRCA1 and BRCA2 genes
inactivation of genes ↑ risk for breast and ovarian cancer; can also be involved in Familial cancer syndromes
Autodomal recessive syndromes w/ defects in DNA repair
Xeroderma pigmentosum, Chromosome instability syndromes
Xeroderma pigmentosum
UV light → cross links adjacent pyrimidines (C&T) producing pyrimidine dimers; ↑ risk of skin cancer like basal cell carcinoma, squamous cell carcinoma
Chromosome instability syndromes
Chromosomes susceptible to damage by ionizing radiation and drugs→to cancer
Examples of Chromosome instability syndromes
Fanconi anemia, ataxia telangiectasia, bloom syndrome
Precursor of squamous cell carcinoma
Actinic (solar) keratosis
Most important factor in ↓ risk for cancer
Cessation of smoking
Name something that ↓ risk for hepatocellular carcinoma
HBV immunization
Name something that ↓ risk for cervical cancer
Human papillomavirus immunization
Least common gynecologic cancer in US
Cervical cancer
Test most responsible for ↓ incidence/mortality rate for cervical cancer
Cervical pap smear
Prostate-specific antigen (PSA)
more sensitive (yes,yes) than specific (no,no)
Rx H. pylori infection
↓ risk for developing gastric lymphoma/adenocarcinoma
Rx GERD
↓ risk for distal adenocarcinoma of esophagus
MC type of mutation in cancer
Point mutations
Genes involved in normal growth and repair
Proto-oncogenes
Genes that protect against unregulated cell growth
Suppressor genes
Antiapoptosis genes (prolife)
BCL2 gene family
apoptosis gene
BAX gene; activated by TP53 if DNA damage is excessive; BAX gene inactivates BCL2 antiapoptosis gene
Proto-oncogenes
ABL, HER (ERBB₂), MYC, N-MYC, RAS, RET, SIS
ABL
Nonrecptor tyrosine kinase; t(9;22); CML, chr. 22 Philadelphia chr
HER (ERBB₂)
Receptor synthesis; amplification mutation; Breast carcinoma (marker of aggression)
MYC
Nuclear transcription; t(8;14); Burkitts lymphoma
N-MYC
Nuclear transcription; amplification mutation; Neuroblastoma
RAS
GTP signal transduction; Point mutation; leukemia; lung, colon, pancreatic cancer
RET
Receptor synthesis; Point mutation; Multiple Endocrine Neoplasia IIa/IIb (MEN) syndromes
SIS
Growth factor synthesis; Overexpression; Osteogenic sarcoma, astrocytoma
Tumor suppressor genes
APC, BRCA1/BRCA2, RB, TGF-β, TP53, VHL, WT₁
Mutation common to tumor suppressor genes
Point mutation
APC
prevents nuclear transcription; Famililal adenomatous polyposis
BRCA1/BRCA2
Regulated DNA repair; Breast ovary, prostate cancers
RB
Inhibits G₁ to S phase; Retinoblastoma, osteogenic sarcoma, breast carcinoma
TGF-β
Inhibits G₁ to S phase; pancreatic and colorectal carcinomas
TP53
Inhibits G₁ to S phase, Repairs DNA, activates BAX; Lung, colon, breast carcinomas; Li-Fraumeni syndrome: breast carcinoma, brain tumors, leukemia, sarcomas
VHL
Regulates nuclear transcription; Von Hippel-Lindau syndrome; cerebellar hemanioblastoma, retinal angioma, renal cell carcinoma (bilateral), pheochromocytoma (bilateral)
Pheochromocytoma
Neuroendocrine tumor of medulla of adrenal glands; secretes excessive catacholamines
WT₁
Regulates nuclear transcription; Wilms tumor
Fxn of DNA repair genes
correct errors in nucleotide pairing; excise pyrimidine dimers
Enzymes involved in dimer excision
endonuclease, exonuclease, polymerase, ligase
Agent most responsible for cancer and cancer deaths in the US
Tobacco
Sequence of chemical carcinogenesis
Initiaion → promotion→ progression
Aflatoxin (from aspergillus)
HCC in assoc. w/ Hep B
Alcohol
Squamous cell carcinoma or oropharynx and upper/middle esophagus; pancreatic and Hepatocellular carcinomas
Alkylating agents
Malignant lymphoma
Arsenic
Squamous cell carcinoma of skin, lung cancer, liver angiosarcoma
Asbestos
Bronchogenic carcinoma, pleural mesothelioma
Benzene
Acute Leukemia
Beryllium
Bronchogenic carcinoma
Chromium
Bronchogenic carcinoma
Cyclophosphamide
Transitional cell carcinoma of urinary bladder
Diethylstilbestrol (DES)
Clear cell carcinoma of vagina/cervix
β-Naphthylamine (aniline dyes)
Transitional cell carcinoma of urinary bladder
Nickel
Bronchogenic carcinoma
Oral Contraceptives
Breast, cervical carcinomas
Polycyclic hydrocarbons
Squamous cell carcinoma: oral cavity, midesophagus, larynx, lung; Adenocarcinoma: pancreas, kidney; Transitional cell carcinoma: urinary bladder, renal pelvis
Silica
Bronchogenic carcinoma
Oncogenic RNA viruses
HCV , HTLV-1 (human T-cell lymphotropic virus)
HCV
produces postnecrotic cirrhosis; HCC
HTVL-1 (Human T-cell lymphotropic Virus)
Activates TAX gene, stimulates polyclonal T-cell proliferation, inhibits P53; T-cell leukemia and lymphoma
Oncogenic DNA viruses
EBV, HBV, HHV-8, HPV 16 and 18
EBV
Promotes polyclonal B cell proliferation, which ↑ risk for t(8;14); Burkitts lymphoma, CNS lymphoma in AIDS, mixed cellularity Hodgkins lymphoma, nasopharyngeal carcinoma
HBV
activates proto-oncogenes, inactivates p53; HCC
HHV-8
acts via cytokine released from HIV and HSV; Kaposis sarcoma in AIDS
HPV 16 and 18
Type 16: E6 gene product inhibits P53, Type 18: E7 inhibits RB; squamous cell carcinoma of vulva, vagina, cervix, anus, larynx, oropharynx
Pathogens and cancer
Viruses 〉 bacteria 〉 parasites
MC cancer d/t ionizing radiation
AML (acute myeloblastic leukemia) or CML (chronic myeloblastic leukemia)
MC cancer d/t excessive UV light exposure
Basal cell carcinoma
Squamous cell carcinoma in physical injury
3rd degree burns; chronically draining sinuses (chronic osteomyelitis)
Most effective host defense against cancer
Cytotoxic CD8 T cells
Most important prognostic factor
Staging criteria; TNM system
Least to most important prognostic factor
T 〈 N 〈 M (most important)
Molecule involved in Cachexia
TNF-α secreted by macrophages and tumor cells→suppresses appetite in hypothalamus and stimulates apoptosis
MC anemia in cancer
Anemia of chronic dz; normocytic anemic w/ corrected reticulocyte count 〈 3 %
Hemostasis abnormality in malignancy
Thrombogenic
MCC of death in cancer
Gram - sepsis
Skin abnormality that may be assoc. w/ stomach cancer
Acanthosis nigricans; black, verrucoid-appearing lesion
Signs of ectopic hormone production
hypercalcemia, hyponatremia, hypoglycemia, hypercortisolism, polycythemia
Eaton-Lambert syndrome
Small cell carcinoma of lung; Myasthenia gravis-like Sxs (muscle weakness); Ab against Ca channel
Hypertrophic osteoarthropathy
Bronchogenic carcinoma; Periosteal rxn of distal phalanx (often assoc. w/ clubbing of nail)
Nonbacterial thrombotic endocarditis
Mucus-secreting pancreatic and colorectal carcinomas; sterile vegetations on mitral valve
Seborrheic keratosis
Stomach carcinoma; Sudden appearance of numerous pigmented seborrheic keratoses (leser-Trélat sign)
Superficial migratory thrombophlebitis
Pancreatic carcinoma; Release of procoagulants (Trousseaus sign: hypercoagulability)
Nephrotic syndrome
Lung, breast, stomach carcinomas; Diffuse membranous glomerulopathy
Cushing syndrome
ACTH; small cell carcinoma of lung, medullary carcinoma of thyroid
Gynecomastia
hCG; Choriocarcinoma (testis)
Hypercalcemia
PTH-related protein: Renal cell carcinoma, 1° squamous cell carcinoma of lung, breast carcinoma; Calcitriol (VitD): malignant lymphoma (contain α1-hydroxylase)
Hypocalcemia
Calcitonin; Medullary carcinoma of thyroid
Hypoglycemia
Insulin-like facter; HCC
Hyponatremia
ADH; small cell carcinoma of lung
2° Polycythemia
EPO; Renal cell and Hepatocellular carcinoma
α-fetoprotein (AFP)
HCC, yolk sac tumor of ovary or testis
Bence Jones Protein
Multiple myeloma, Waldenströms macroglobulinemia
CA 15-3
Breast cancer
CA 19-9
Pancreatic, colorectal carcinomas
CA 125
Surface-derived ovarian cancer (eg serous cystadenocarcinoma; helpful in distinguishing malignant from b9
Carcinoembryonic antigen (CEA)
Colorectal and pancreatic carcinomas
Lactate dehydrogenase
Malignant lymphoma
Cytokeratin
epithelial origin
Vimentin
Connective tissue origin
Desmin
Muscle
GFAP
Neuroglia
Neurofilaments
Neurons
CD45+
Malignant lymphoma