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Kaplan Path > Neoplasia > Flashcards

Neoplasia Flashcards

1
Q

nitrosamines = carcinogen assoc with

A

gastric cancer

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2
Q

polycyclic aromatic hydrocarbons = carcinogen assoc with

A

bronchogenic carcinoma

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3
Q

asbestos = carcinogen assoc with

A
  • bronchogenic carcinoma, mesothelioma
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4
Q

chromium and nickel = carcinogen assoc with

A

bronchogenic carcinoma

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5
Q

arsenic = carcinogen assoc with

A
  • squamous cell carcinomas of skin and lung

- angiosarcoma of liver

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6
Q

vinyl chloride = carcinogen assoc with

A

angiosarcoma of liver

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7
Q

aromatic amines and as dyes = carcinogen assoc with

A

hepatocellular carcinoma

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8
Q

alkylating agents = carcinogen assoc with

A

leukemia, lymphoma, etc

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9
Q

benzene = carcinogen assoc with

A

AML

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10
Q

naphthylamine = carcinogen assoc with

A

bladder cancer (transitional cell)

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11
Q

how do we screen for potential carcinogens

A

Ames test

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12
Q

Hep B virus is associated with

A

hepatocellular carcinoma

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13
Q

EBV is associated with

A
  • burkitt lymphoma
  • B cell lymphomas in immunosuppressed patients
  • nasopharyngeal carcinoma (China)
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14
Q

HPV is associated with

A
  • benign squamous papillomas (warts - condyloma acuminatum)

- a variety of carcinomas (cervical, vulvar, vaginal, penile, anal

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15
Q

Ultraviolet B sunlight carcinogenesis

A
  • produces pyrimidine dimers in DNA –> transcriptional errors and mutations of oncogenes and TSG –> increases risk of skin cancer
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16
Q

xeroderma pigmentosum

A
  • AR
  • defect in DNA repair
  • pyrimidine dimers formed with UVB can’t be repaired –> skin cancer
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17
Q

when are cells most sensitive to radiation

A

during mitosis or G2

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18
Q

protooncogenes

A
  • normal cellular genes involved with growth and cellular differentiation
  • when protooncogenes get mutated–> oncogenes
  • oncogenes are derived from protooncogenes, either by a change in gene sequence –> new product (oncoprotein) or a loss of gene regulation resulting in overexertion of a normal gene product
  • oncogenes only need one hit to express symptoms (vs TSG need 2 hits)
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19
Q

hst-1 and int-2

  • tumor
  • gene product
  • MOA
A
  • oncogenes
  • tumor: cancer of stomach, breast, bladder, melanoma
  • gene product: growth factors: fibroblast growth factor
  • MOA: overexpression
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20
Q

sis

  • tumor
  • gene product
  • MOA
A
  • oncogene
  • tumor: astrocytoma
  • gene product: platelet derived growth factor
  • MOA: overexpression
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21
Q

erb-B1

  • tumor
  • gene product
  • MOA
A
  • oncogene
  • tumor: squamous cell carcinoma (SCC) of lung
  • gene product: growth factor receptors: epidermal growth factor receptor
  • MOA: overexpression
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22
Q

erb-B2

  • normal function
  • tumor
  • gene product
  • MOA
A
  • oncogene
  • receptor synthesis
  • tumor: breast, ovary, lung
  • gene product: epidermal growth factor receptor
  • MOA: Amplification (have more than 2 copies)
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23
Q

erb-B3

  • tumor
  • gene product
  • MOA
A
  • oncogene
  • tumor: breast
  • gene product: epidermal growth factor receptor
  • MOA: overexpression
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24
Q

ret

  • tumor
  • gene product
  • MOA
A
  • oncogene; tyrosine kinase
  • tumor: MEN II and III, familial thyroid (medullary) cancer
  • gene product: glial neurotrophic factor receptor (S100+)
  • MOA: point mutation
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25
Q

abl

  • tumor
  • gene product
  • MOA
A
  • oncogene, tyrosine kinase activity; Chromosome 22 = philadelphia gene
  • tumor: CML, ALL (5%)
  • gene product: signal transduction proteins: bcr-abl fusion protein with tyrosine kinase activity (–> always on)
  • aka p210kD fusion protein
  • MOA: translocation t(9;22)
  • tyrosine kinase are signal transduction proteins –> fusion protein causes cells to grow/proliferate
  • DOC: imatinib –> blocks ATP binding site on tyrosine kinase
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26
Q

ki-ras

  • normal function
  • tumor
  • gene product
  • MOA
A
  • MC oncogene to be overexpressed
  • GTP signal transduction (gene product = GTPase)
  • tumor: lung, pancreas, colon; neurofibromas
  • gene product: GTP binding protein (signal transduction)
  • MOA: point mutation
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27
Q

c-myc

  • tumor
  • gene product
  • MOA
A
  • oncogene on Ch 8; normally fx = nuclear transcription factor
  • tumor: burkitt lymphoma (kids)
  • gene product: nuclear regulatory protein
  • MOA: translocation t(8;14) –> overexpression
  • promotes cellular proliferation:
  • when associated with p53, leads to apoptosis and
  • when associated with bcl-2 inhibits apoptosis
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28
Q

L-myc

  • tumor
  • gene product
  • MOA
A
  • oncogene on Ch 1
  • tumor: small cell lung carcinoma
  • gene product: nuclear regulatory protein (transcription factor)
  • MOA: amplification
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29
Q

N-myc

  • tumor
  • gene product
  • MOA
A
  • oncogene
  • tumor: neuroblastoma (if <18mo = better prognosis; if >18mo worse prognosis, spread)
  • gene product: nuclear regulatory protein (transcription factor)
  • MOA: amplification (2 = normal, the more copies you have the worse the prognosis)
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30
Q

bcl-1

  • tumor
  • gene product
  • MOA
A
  • oncogene
  • tumor: mantle cell lymphoma
  • gene product: cell cycle regulatory proteins: cyclin D protein
  • MOA: translocation t(11;14)
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31
Q

CDK4

  • tumor
  • gene product
  • MOA
A
  • oncogene
  • tumor: melanoma, glioblastomamultiforma (GBM)
  • gene product: cyclin dependent kinase
  • MOA: amplification
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32
Q

bcl-2

  • function
  • tumor
  • gene product
  • MOA
A
  • oncogene: overexpression –> fountain of youth
  • if doesn’t die, accumulates mutations until eventually develops cancer
  • tumor: follicular non hodgkins lymphoma (arises from B lymphocytes in LN)
  • MOA: translocation t(14;18) causes overexpression of Bcl-2 protein product–> prevents apoptosis of B lymphocytes (never die) –> follicular lymphoma = MC malignant lymphoma affecting adults in US
  • tumor genesis related to changes in regulation of apoptosis: normally bcl-2 prevents apoptosis, but here the bcl-2 regulator of apoptosis is overexpressed bc the translocation connects the immunoglobulin heavy chain gene on Ch14 (which turns on easily in B lymphocytes) to the bcl-2 gene on Ch 18
  • -> this leads to a situation where lymphocytes fail to die as expected and instead produce a tumor
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33
Q

tumor suppressor genes

A
  • encode proteins that regulate and suppress cell proliferation by inhibiting progression of the cell through the cell cycle
  • need 2 hits to express symptoms aka to knock out the TSG (vs oncogenes only need one hit)
  • 1st hit could be gremlin, 2nd hit = acquired
  • MOA of TSG varies. Ex)
  • p53 prevents a cell with damaged DNA from entering S-phase.
  • Rb prevents the cell from entering S-phase until the appropriate growth signals are present
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34
Q

VHL

  • function
  • chromosome
  • tumor
A
  • TSG, normal protein product inhibits hypoxia inducible factor 1a
  • chromosome: 3p25
  • function: regulates nuclear transcription
  • tumor: von hippel-lindau disease (bilateral renal cell carcinoma, pheochromocytoma, hemangioblastomas), renal cell carcinoma
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35
Q

WT-1

  • function
  • chromosome
  • tumor
A
  • TSG, regulates nuclear transcription
  • chromosome: 11p13
  • tumor: wilms tumor
  • WT-1 is by PAX-6 so they’re knocked out together–> WAGR syndrome: kid has aniridia look for films tumor
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36
Q

WT-2

  • function
  • chromosome
  • tumor
A
  • TSG, regulates nuclear transcription
  • chromosome: 11p15
  • tumor: wilms tumor
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37
Q

Rb

  • chromosome
  • function
  • tumor
A
  • TSG
  • chromosome: 13q14 (13 looks like B)
  • function: Inhibits E2F; blocks G1 to S phase of cell cycle
  • tumor: retinoblastoma, osteosarcoma (sunburst, codmans triangle)
  • MOA: “policeman of checkpoints”
  • if have familial Rb have 40% chance of other tumor developing
  • if familial type of RB: develops early, both eyes. born with 1 germline mutation and acquire point mutation.
  • if sporadic (non-familial) type: both alleles inactivated in somatic mutation in one of the retinoblasts –> occurs later in life; unilateral.
  • assoc with retinoblastoma, osteogenic sarcoma, breast cancer
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38
Q

p53

  • function
  • chromosome
  • tumor
A
  • TSG (TP53), MC knocked out in most cancers!!
  • p53 activates p21, inhibits G1 to S phase, repairs DNA, activates BAX
  • chromosome: 17p13.1
  • tumor: Li fraumeni (Li looks like an upside down 17)
  • lung, breast, colon, etc
  • p53 tells Rb to stop cell and if no it lets cytochrome c out of mitochondria –> apoptosis
  • p53 is often knocked out in malignant tumors
  • p53 promotes apoptosis in mutated cells by stimulating bax synthesis.
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39
Q

BRCA-1

  • chromosome
  • function
  • tumor
A
  • TSG
  • chromosome: 17q12-21
  • function: regulates DNA repair
  • tumor: hereditary breast, ovarian, pancreatic, colon and prostate cancers
  • “there are 17 letters in angelina jolie-pitt”
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40
Q

BRCA-2

  • chromosome
  • function
  • tumor
A
  • TSG
  • chromosome: 13q12-13
  • function: regulates DNA repair
  • tumor: hereditary breast cancer
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41
Q

APC

  • chromosome
  • function
  • tumor
A
  • TSG
  • chromosome: 5q21 (5 letters in colon)
  • function: prevents nuclear transcription
  • negative regulator of β-catenin/WNT pathway
  • tumor: Adenomatous Polyps and Colon cancer; FAP
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42
Q

DCC

  • chromosome
  • tumor
A
  • TSG
  • chromosome: 18q21
  • tumor: colon cancer
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43
Q

NF-1

  • chromosome
  • tumor
A
  • TSG; turns off ras
  • chromosome: 17q11.2
  • gene product: neurofibromin (Ras GTPase activating protein)
  • tumor: neurofibromas, cafe au last spots, lisch nodules
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44
Q

NF-2

  • chromosome
  • tumor
A
  • TSG
  • chromosome: 22q12
  • gene product: merlin (Schwannomin protein)
  • tumor: schwannomas of acoustic nerve = acoustic neuromas, meningiomas
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45
Q

keratin

  • normal tissue
  • tumors
A
  • intermediate filament
  • normal tissue: all epithelial cells
  • tumors: carcinomas
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46
Q

vimentin

  • normal tissue
  • tumors
A
  • intermediate filament
  • normal tissue: mesenchymal cells
  • tumors: sarcomas
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47
Q

desmin

  • normal tissue
  • tumors
A
  • intermediate filament
  • normal tissue: muscle cells; actin also found in muscle
  • tumors: uterine leiomyoma, rhabdomyosarcoma
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48
Q

neurofilament

  • normal tissue
  • tumors
A
  • intermediate filament
  • normal tissue: CNS and PNS neurons, neural crest derivatives
  • tumors: pheochromocytoma, neuroblastoma
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49
Q

glial fibrillary acidic protein (GFAP)

  • normal tissue
  • tumors
A
  • intermediate filament
  • normal tissue: glial cells (i.e. astrocytes, oligodendrocytes, ependymal cells)
  • tumors: astrocytomas, ependymomas
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50
Q

increased AFP in pregnant woman

A

neural tube defects

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51
Q

decreased AFP in pregnant woman

A

down syndrome

52
Q

AFP: tumor marker for

A

hepatoma (HCC), nonseminomatous testicular germ cell tumors (yolk-sac –> fetal proteins)

53
Q

β- hCG: tumor marker for

A
  • trophoblastic tumors (mole), choriocarcinoma

- from placental cells

54
Q

calcitonin: tumor marker for

A
  • used for medullary carcinoma of the thyroid
  • c cells –> neural crest –> S100
  • surrounded by amyloid
55
Q

carcinoembryonic antigen (CEA) : tumor marker for

A
  • Major associations: colorectal and pancreatic cancers
  • minor associations: gastric, breast, medullary thyroid carcinomas
  • CA15-3, CA-125, CA19-9
  • Kaplan: carcinomas of the lung, pancreas, stomach, breast and colon (colorectal and pancreatic adenocarcinomas*)
56
Q

CA-125: tumor marker for

A

malignant ovarian epithelial tumors (surface derived ovarian CA)

57
Q

CA19-9: tumor marker for

A

malignant pancreatic adenocarcinoma

58
Q

placental alkaline phosphatase: tumor marker for

A

seminoma

59
Q

biopsy when PSA is >

A
  • biopsy when PSA is >10
  • normal: 0-4
  • PSA increased in BPH and prostatitis
60
Q

CA-15-3: tumor marker for

A

breast carcinoma

61
Q

sarcoma

A

Sarcomas are tumors that arise from “mesenchymal” tissues such as bone, muscle, connective tissue, cartilage and fat.
- all sarcomas are vimentin +

62
Q

carcinoma

A
  • epithelial cell tumors that become malignant
  • Most cancers (>90%) arise from “epithelial” tissues, such as the inside lining of the colon, breast, lung or prostate.
  • usually affect older people.
  • all carcinomas are keratin +
63
Q

S100 + seen in

A

melanoma and neural tumors

64
Q

ionizing radiation (ie hiroshima) puts you at risk for developing

A
  • AML

- papillary carcinoma of thyroid

65
Q

familial Rb

A
  • every cell in body has 1 Rb gene knocked out at birth

- if get 2nd mutation –> bilateral Rb and osteogenicsarcoma

66
Q

Li fraumeni syndrome

A
  • every cell missing 1 p53 (has p53 mutation) at birth
  • if get 2nd p53 mutation –> cancer all over body
  • colon, prostate, breast, sarcoma, lymphoma, etc
67
Q

S-100

A
  • melanoma and cells that come from neural crest
68
Q

these cancers spread via hematogenous spread

A
  • most sarcomas
  • renal cell carcinoma (bc of proximity to large renal vein)
  • hepatocellular carcinoma (bc of the presence of the hepatic sinusoids)
  • follicular carcinoma of thyroid
  • choriocarcinoma (bc of its propensity to seek vessels
69
Q

seeding of body cavities occurs commonly in

A

ovarian carcinoma

70
Q

familial melanoma mutation

A

p16 (TSG) mutation on chromosome 9

71
Q

dysplastic nevus syndrome

A
  • multiple dysplastic nevi
  • micro: cytological and architectural atypia
  • AD
  • CMM1 gene on Ch 1
  • increased risk of developing malignant melanoma
72
Q

TGF-β

  • function
  • cancers
A
  • Function: inhibits G1 to S phase

- associated cancer: pancreatic and colorectal cancers

73
Q

LN:

  • B cells are located in the
  • T cells are located in the
A
  • B cells are located in the Follicles of LN

- T cells are located in the paracortex (around LN)

74
Q

t(8;14)

A

burkitt’s lymphoma

75
Q

t(9;22)

A

CML (Chronic myelogenous leukemia)

76
Q

t(14;18)

A

B cell follicular lymphoma

77
Q

Lesch Nyhan Syndrome

  • genetic mutation
  • effect
  • clinical symptoms
A
  • X-linked Recessive
  • enzyme deficiency: hypoxanthine - guanine phosphoribosyltransferase (HGPRT)
  • normally involved in in salvaging the purines hypoxanthine and guanine
  • clinical: MR, hyperuricemia (gout), self mutilation
78
Q

Vit D resistant rickets

  • genetic mutation
  • effect
  • clinical symptoms
A
  • X-linked recessive

- defects in renal and GI reabsorption of phosphates –> defective bone mineralization (i.e. osteomalacia)

79
Q

Alport’s Syndrome

  • genetic mutation
  • effect
  • clinical symptoms
A
  • X-linked recessive

- hereditary glomerulonephritis w/ nerve deafness (see kidney)

80
Q

hyperhomocystinemia

A
  • inborn error of metabolism
  • homocysteine levels: >100 micromol/L
  • due to low folate and Vit B12 intake –> increased incidence of vascular disease
81
Q

bence jones protein = tumor marker for

A

multiple myeloma, waldenstrom’s macroglobulinemia

82
Q

tonofilaments

A
  • important EM finding in epithelial tumors
83
Q

weibel palade bodies

A

important EM finding in angiosarcomas

84
Q

neurosecretory granules

A

important EM finding in neuroendocrine tumors

85
Q

birbeck granules

A
  • important EM finding in histolytic tumor (i.e. histiocytosis X = CD-1 positive)
  • looks like tennis racket
86
Q

CD45

A

leukocyte malignancies (common leukocyte antigen)

87
Q

neuroendocrine tumors are + for

A

S100 and neuron specific enolase (NSE)

88
Q

cytokeratin is found in

A

carcinomas

89
Q

EMA is found in

A

carcinomas (EMA= epiehtlial membrane antigen)

90
Q

vimentin is found in

A

tumors of mesenchymal tissue

91
Q

desmin is found in

A

muscle derived sarcomas

92
Q

trousseau’s is associated with

A
  • pancreatic adenocarcinoma (bc excess mucin production)

- aka superficial migratory thrombophlebitis

93
Q

NBTE (nonbacterial thrombotic endocarditis) associated with

A

mucous secreting colon and pancreatic adenocarcinomas

94
Q

hypertrophic osteoarthropathy

A
  • clubbing of the nails with an underlying periosteal reaction of bone of distal phalanx that’s associated with primary lung cancer (bronchogenic carcinoma)
95
Q

eaton lambert syndrome

A
  • myasthenia gravis like symptoms (i.e. muscle weakness)
  • antibodies directed against calcium channel
  • associated with small cell CA of lung
96
Q

Cushing’s syndrome

A
  • increased cortisol –> cushing’s syndrome (lemon on a stick appearance)
  • ectopic ACTH release –> increased cortisol
  • associated cancers = small cell cancer of lung, medullary carcinoma of thyroid
97
Q

hyponatremia

  • endocrinopathy
  • associated cancer
A
  • ectopic ADH release

- associated with small cell cancer of lung

98
Q

hypocalcemia

  • endocrinopathy
  • associated cancer
A
  • calcitonin

- associated with medullary carcinoma of thyroid

99
Q

gynecomastia

  • endocrinopathy
  • associated cancer
A
  • β-hCG

- choriocarcinoma of testes

100
Q

hypercalcinoma

  • endocrinopathy (cause)
  • associated cancer
A
  • MC paraneoplastic syndrome
  • malignancy accounts for 40% of all cases. Causes:
    1. release of PTH related peptide (PTHrP) - metastasis to bone not necessary)
  • in squamous cell carcinoma of lung and renal cell carcinoma
  • labs: hypercalcemia and decreased serum PTH
    2. osteolytic bony metastasis** (release of osteolytic factors PGE2, IL-1)
  • seen in breast cancer
101
Q

acanthiosis nigricans

A

associated with stomach carcinoma

102
Q

prolactinoma

A
  • secretes excess prolactin –> amenorrhea, infertitility and calactorrhea
  • pituitary tumosr
103
Q

somatotropic adenoma

A
  • tumor secreting excess growth hormone –> gigantism in children and acromegaly in adults
104
Q

adrenal adenoma

A
  • increased cortisol –> Cushing’s syndrome
  • incrased mineralocorticoids –> Conn’s syndrome
  • increased sex hormone –> adrenogenital syndrome
105
Q

granulosa theca cell tumor causes

A

hyperestrinism

106
Q

sertoli/leydid cell tumor causes

A

excess androgen

107
Q

cachexia is caused by

A
  • TNF-α (aka cachectin)

- suppresses appetite center in hypothalamus and increases mobilization of FA from adipocytes (increased catabolism)

108
Q

right sided colorectal carcinoma causes what hematological association?

A

iron deficiency anemia

109
Q

macrocytic anemia due to folate deficiency from rapid tumor growth is seen in

A

leukemias and lymphomas

110
Q

chronic lymphocytic leukemia has what hematological association?

A

autoimmune hemolytic anemia

111
Q

myelophthisic anemia =

A

anemia related to metastasis to BM

112
Q

CDKN2A

A
  • TSG
  • p16, blocks G1 –> S phase
  • seen in melanoma and pancreatic cancer
113
Q

DPC4

A
  • TSG Deleted in Pancreatic Cancer

- aka SMAD4

114
Q

ALK

A
  • oncogene
  • gene product: receptor tyrosine kinase
  • associated neoplasm: lung adenocarcinoma
115
Q

BRAF

A
  • oncogene
  • gene product: serine/threonine kinase
  • assoc w: melanoma, non-hodgkin lymphoma, papillary thyroid carcinoma
116
Q

c-kit

A
  • oncogene
  • gene product: cytokine receptor
  • assoc w: GI stromal tumor (GIST)
117
Q

α-fetoprotein

A
  • associated cancers: hepatocellular carcinoma, hepatoblastoma, yolk sac tumor, mixed germ cell tumor
  • normally made by fetus; transiently high in pregnancy
  • high levels assoc with near tube and abdominal wall defects
  • low levels assoc with Downs
118
Q

β-HCG

A
  • associated cancers: Hydatidiform moles, Choriocarcinomas, Gestational trophoblastic disease
  • produced by synctiotrophoblasts of placenta
119
Q

CA15-3

A

associated with breast cancer

120
Q

calcitonin

A

associated with medullary thyroid carcinoma (alone and in MEN2A and MEN2B)

121
Q

P-glycoprotein

A
  • AKA multi drug resistance protein 1 (MDR1)
  • pumps out toxins (including chemo)
  • classically seen in adrenocortical carcinoma but also expressed by other cancer cells (colon, liver)
122
Q

CA27-27

A

associated with breast cancer

123
Q

polycythemia associated with

A
  • increased EPO

- RCC, HCC, hemangioblastoma, pheochromocytoma, leiomyoma

124
Q

myasthenia gravis is associated with what cancer (as a paraneoplastic syndrome)

A
  • thymoma

- ab against postsynaptic ACh receptors at NMJ

125
Q

lambert-eaton is associated with what cancer (as a paraneoplastic syndrome)

A
  • small cell lung cancer

- ab against presynaptic (P/Q type) calcium channels at NMJ

Kaplan Path (8 decks)

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