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Pathoma > Neoplasia > Flashcards

Neoplasia Flashcards

1
Q

What is neoplasia?

A

new tissue growth that is unregulated, irreversible, and monoclonal

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2
Q

How can clonality be determined in females?

A

G6PD - multiple isoforms but only one inherited from each parent on X chromosome, one inactivated in females by lyonization, normal ratio of active isoforms in cells of any tissue = 1:1, 1:1 ratio maintained in hyperplasia (polyclonal), only one isoform present in neoplasia

Androgen receptor isoforms can also determine clonality (present on X chromosome)

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3
Q

How can clonality of B lymphocytes be determined?

A

Ig light chain phenotype, each B cell expresses 3:1 ratio of kappa to lambda light chains, ratio maintained in hyperplasia, ratio increases to >6:1 or inverted in lymphoma (monoclonal)

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4
Q

Nomenclature for benign or malignant tumor of epithelial lineage?

A

Adenoma, papilloma; adenocarcinoma, papillary carcinoma

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5
Q

Nomenclature for benign or malignant tumor of mesenchymal lineage?

A

Lipoma; liposarcoma

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6
Q

Nomenclature for benign or malignant tumor of lymphocyte origin?

A

(does not exist); lymphoma/leukemia

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7
Q

Nomenclature for benign or malignant tumor of melanocyte origin?

A

nevus (mole); melanoma

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8
Q

Leading cause of death in adults and children?

A

adult- 1. CV, 2. cancer, 3. chronic resp. disease

child-1.accident, 2. cancer, 3. congenital

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9
Q

Most common cancer by incidence?

A
  1. breast/prostate, 2. lung, 3. colon
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10
Q

Most common cause of cancer mortality?

A
  1. lung, 2. breast/prostate, 3. colon
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11
Q

How many divisions before early clinical symptoms?

A

30 divisions, cancer begins as a single mutated cell

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12
Q

What is the goal of screening?

A

To catch dysplasia before it becomes carcinoma or carcinoma before clinical symptoms arise

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13
Q

Pap smear

A

detects cervical dysplasia (CIN) before it becomes carcinoma

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14
Q

Mammography

A

detects in situ breast cancer (e.g., DCIS - ductal carcinoma in situ) before it invades or invasive carcinoma before it becomes clinically palpable

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15
Q

Prostate Specific Antigen and digital rectal exam

A

detects prostate carcinoma before it spreads

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16
Q

Hemoccult test (for occult blood in stool) and colonoscopy

A

detects colonic adenoma before it becomes colonic carcinoma or carcinoma before it spreads

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17
Q

aflatoxins

A

Cause hepatocellular carcinoma in African countries, derived from Aspergillus, which can contiminate stored rice and grains

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18
Q

Alkylating agents

A

Cause leukemia/lymphoma, side effect of chemotherapy

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19
Q

Alcohol

A

squamous cell carcinoma of oropharynx and upper esophagus, and hepatocellular carcinoma

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20
Q

Arsenic

A

Squamous cell carcinoma of the skin, lung cancer, and angiosarcoma, present in cigarette smoke

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21
Q

Asbestos

A

Lung carcinoma and mesothelioma, exposure to asbestos is more likely to lead to lung cancer than mesothelioma

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22
Q

Cigarette smoke

A

carcinoma of oropharynx, esophagus, lung, kidney, bladder, and pancreas. Most common carcinogen worldwide; polycyclic hydrocarbons are particularly carcinogenic

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23
Q

Nitrosamines

A

Stomach carcinoma, found in smoked foods; responsible for high rate of stomach carcinoma in Japan

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24
Q

Napththylamine

A

Urothelial carcinoma of bladder, derived from cigarette smoke

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25
Q

Vinyl chloride

A

Angiosarcoma of liver, occupational exposure; used to make polyvinyl chloride (PVC) used for pipes

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26
Q

Nickel, chromium, beryllium, or silica

A

Lung carcinoma, occupational exposure

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27
Q

EBV

A

Nasopharyngeal carcinoma, Burkitt lymphoma, and CNS lymphoma in AIDS, chinese male or individual in Africa, presents as a neck mass

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28
Q

HHV-8

A

Kaposi sarcoma - tumor or endothelial cells, found in 1. older eastern european males (excise lesion), 2. AIDS patients (treat virus), 3. patients with transplants

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29
Q

HBV (DNA) and HCV (RNA)

A

Hepatocellular carcinoma

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30
Q

HTLV-1

A

Adult T-cell leukemia/lymphoma

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31
Q

High-risk HPV (e.g., subtypes 16,18,31,33)

A

Squamous cell carcinoma of vulva, vagina, anus, and cervix; adenocarcinoma of cervix

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32
Q

Ionizing (nuclear reactor accidents and radiotherapy)

A

AML< CML, and papillary carcinoma of the thyroid, generates hydroxyl free radicals

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33
Q

Nonionizing (UVB sunlight is most common source)

A

Basal cell carcinoma, squamous cell carcinoma, and melanoma of skin, results in formation of pyrimidine dimers in DNA, which are normally excised by restriction endonuclease (overrun process - xeroderma pigmentosum)

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34
Q

Explain the signal transduction scheme of RAS

A

Ras associated with growth factor receptors in an inactive GDP-bound state. REceptor binding causes GDP to be replaced with GTP, ativating ras. Activated ras sends growth signals to the nucleus. Ras inactivated itself by cleaving GTP to GDP via GTPase activating protein. Mutated ras inhibits activity of GTPase activating protein, prolonging activity of ras , resulting in increased growth signals

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35
Q

How do cyclins and CDKs interact and what is an example

A

cyclins and CDKs form a complex which phosphorylates proteins that drive the cell through the cell cycle. The cyclinD/CDK4 complex phosphorylates the retinoblastoma protein, which promotes progression through the G1/S checkpoint

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36
Q

PDGF

A

growth factor oncogene, platelet-derived growth factor, causes overexpression of an autocrine loop, makes an astrocytoma

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37
Q

ERBB2 [HER2/neu]

A

growth factor receptor oncogene, epidermal growth factor receptor, causes amplification, subset of breast carcinomas

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38
Q

RET

A

growth factor receptor oncogene, neuronal growth factor receptor, point mutation, causes MEN 2A, MEN 2B and sporadic medullary carcinoma of thyroid

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39
Q

KIT

A

growth factor receptor oncogene, stem cell growth factor receptor, point mutation, gastrointestinal stromal tumor

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40
Q

RAS gene family

A

signal transducer oncogenes, GTP-binding protein, point mutation, carcinomal, melanoma, and lymphoma

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41
Q

ABL

A

signal transducer oncogenes, Tyrosine kinase, t(9;22) (philadelphia) with BCR, CML and some types of ALL

42
Q

c-MYC

A

nuclear regulator oncogene, transcription factor, t(8;14) myc on 8 transferred to 14 involving IgH, burkitt lymphoma

43
Q

N-MYC

A

nuclear regulator oncogene, transcription factor, amplification, neuroblastoma

44
Q

L-MYC

A

nuclear regulator oncogene, transcription factor, amplification lung carcinoma (small cell)

45
Q

CCND1 (cyclin D1)

A

cell cycle regulator oncogene, cyclin, t(11;14) involving IgH, mantle cell lymphoma

46
Q

CDK4

A

cell cycle regulator oncogene, cyclin-dependent kinase, amplification, melanoma

47
Q

example of tumor suppressor genes

A

p53 and Rb

48
Q

Functions of p53

A
  1. In response to DNA damage, p53 slows the cell cycle and upregulates DNA repair enzymes
  2. If DNA repair is not possible, p53 induces apoptosis - p53 upregulates BAX, which disrupts Bcl2, cytochrome c leaks from the mitochondria activating apoptosis
49
Q

Tumor suppressor gene

A

both copies of gene must be knocked out for tumor formation (knudson two-hit hypothesis)

Loss seen in >50% of cancers

Germline mutation results in Li-Fraumeni syndrome (2nd hit is somatic), characterized by the propensity to develop multiple types of carcinomas and sarcomas

50
Q

Function of Rb

A

Rb regulates progression from G1 to S phase

  1. E2F necessary for transition to the S phase, Rb holds it
  2. E2F is released when RB is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex
  3. RB mutation = constitutively free E2F, allowing progression through cell cycle and uncontrolled cell growth
  4. Both copies of Rb gene must be knocked out
    - sporadic mutation = unilateral retinoblastoma
    - germline mutation = familial retinoblastoma (2nd hit somatic) characterized by bilateral retinoblastoma and ostesarcoma
51
Q

Function of Bcl2

A

Normally stabilizes the mitochondrial membrane, blocking release of cytochrome c, disruption of Bcl2 allows cytochrome c to leave the mitochondria and activate apoptosis

Bcl2 overexpressed in follicular lymphoma: t14;18) moves Bcl2 (chromosome 18) to the Ig heavy chain locus (chromosome 14) resulting in increased Bcl2 - mitochondrial membrane stabilized, prohibiting apoptosis

B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center accumulate, leading to lymphoma

52
Q

3 important features of tumor development

A

1- telomerase is necessary for cell immortality
2-angiogenesis (FGF and VEGF produced by tumor cells)
3- avoiding immune surveillance necessary for tumor survival - downregulating expression of MHC class I. immunodeficiency increases risk for cancer

53
Q

What is the progression of tumor invasion and spread?

A

Epithelial tumors normally attached via E-cadherin, downreg. of E-cadherin leads to dissociation of attached cells, cells attach to laminin and destroy basement membrane (collagen type IV) via collagenase. Cells attach to fibronectin in the ECM and spread locally. Entrance to vascular/lymphatic spaces = metasasis

54
Q

What type of spread is characteristic of carcinomas?

A

Lymphatic spread

55
Q

What type of spread is characteristic of sarcomas?

A

Hematogenous

56
Q

What are some hematogenous exceptions to carcinomas?

A
  1. Renal cell carcinoma (invades renal vein)
  2. Hepatocellular carcinoma (invades hepatic vein)
  3. Follicular carcinoma of the thyroid
  4. Choriocarcinoma (malignancy of placental cells)
57
Q

What is characteristic of ovarian carcinoma?

A

Seeding of the body cavities, involves the peritoneum

58
Q

What are clinical features of benign tumors?

A

slow growing, well circumscribed, distinct, and mobile

59
Q

What are clinical features of malignant tumors?

A

rapid growing, poorly circumscribed, infiltrative, and fixed to surrounding tissues and local structures

60
Q

What are the histological features of benign tumors?

A
  1. organized growth
  2. uniform nuclei
  3. low nuclear to cytoplasmic ratio
  4. minimal mitotic activity
  5. lack of invasion (of basement membrane or local tissue)
  6. No metastatic potential (absolute distinction between benign and malignant)
61
Q

What are the histological features of malignant tumors (which are classically poorly differentiated - anaplastic)?

A
  1. disorganized growth (loss of polarity)
  2. Nuclear pleomorphism and hyperchromasia
  3. High nuclear to cytoplasmic ratio
  4. High mitotic activity with atypical mitosis
  5. Invasion (through basement membrane or into local tissue)
  6. Metastatic potential hallmark of malignancy
62
Q

What is the immmunohistochemical stain associated with epithelium?

A

keratin

63
Q

What is the immmunohistochemical stain associated with mesenchyme?

A

vimentin

64
Q

What is the immmunohistochemical stain associated with muscle?

A

desmin

65
Q

What is the immmunohistochemical stain associated with neuroglia?

A

GFAP

66
Q

What is the immmunohistochemical stain associated with neurons?

A

neurofilament

67
Q

What is the immmunohistochemical stain associated with prostate epithelium?

A

PSA

68
Q

What is the immmunohistochemical stain associated with breast epithelium?

A

Estrogen Receptor

69
Q

What is the immmunohistochemical stain associated with thyroid follicular cells?

A

Thyroglobulin

70
Q

What is the immmunohistochemical stain associated with neuroendocrine cells (e.g. small cell carcinoma of lung and carcinoid tumors)?

A

chromogranin

71
Q

What is the immmunohistochemical stain associated with melanoma, schwannoma and langerhans cell histiocytosis?

A

S-100

72
Q

Serum tumor markers

A

useful for screening, monitoring response to treatment, and monitoring recurrence

elevated levels require tissue biopsy fr diagnosis of carcinoma

73
Q

Grading of cancer

A

microscopic assessment of differentiation (how much cancer resembles the tissue in which it grows) takes into account architectural and nuclear features

  1. well differentiated (low grade) resembles normal parent tissue
  2. poorly differentiated (high grade) does not resemble parent tissue
    important for determining prognosis; well differentiated better than poorly differentiated
74
Q

Staging of cancer

A

assessment of size and spread of a cancer, key prognostic factor, more than grade, determined after final surgical resection of the tumor

75
Q

TNM staging system

A

T- tumor (size solig organ and/or depth of invasion rubular)
N- spread to reginal lymph nodes; second most important prognostic factor
M- metastasis; single most important prognostic factor

76
Q

Tumor Suppressor genes, functions, associated cancer: APC

A

Prevents nuclear transcription (degrades catenin, an activator of nuclear transcription)

Inherited mutation (AD): familial polyposis (colorectal carcinoma)

Somatic mutations: colon and stomach cancer

77
Q

Tumor Suppressor genes, functions, associated cancer: BRCA1/BRCA2

A

regulates DNA repair

inherited mutation: female breast, ovary carcinomas; carcinoma male breast

78
Q

Tumor Suppressor genes, functions, associated cancer: NF1

A

Inhibits RAS signal transduction; cell cycle inhibitor

Inherited mutation (AD): neurofibromatosis type 1: pheochromocytoma, Wilms tumor, neurofibrocarcomas

Somatic mutation: neuroblastoma

79
Q

Tumor Suppressor genes, functions, associated cancer: NF2

A

Inherited mutation (AD): neurofibromatosis type II: bilateral acoustic neuromas (schwannoma), meningioma

Somatic mutation: schwannoma, meingioma

80
Q

Tumor Suppressor genes, functions, associated cancer: p53

A

Inhibits G1 to S phase. Repairs DNA, inhibits BCL2 antiapoptosis gene (initiates apoptosis)

Inherited mutation (AD): Li-Fraumeni syndrome: breast carcinoma, brain tumors, leukemia, sarcomas

Somatic mutation: most human cancers

81
Q

Tumor Suppressor genes, functions, associated cancer: RB1

A

inhibits G1 to S phase

inherited mutation (AD): retinoblastoma, osteogenic sarcoma

Somatic mutation: retinoblastoma, osteogenic sarcoma, carcinomas of breast, lung, colon

82
Q

Tumor Suppressor genes, functions, associated cancer: TGF-beta

A

inhibits G1 to S phase

Inherited mutation: familial stomach cancer
Somatic mutation: pancreatic and colorectal carcinomas

83
Q

Tumor Suppressor genes, functions, associated cancer: VHL

A

regulates nuclear transcription

inherited mutation (AD): von Hippel-Lindau syndrome: cerbellar hemangioblastoma, retinal angioma, renal cell carcinoma (bilateral), pheochromocytoma (bilateral)

84
Q

Tumor Suppressor genes, functions, associated cancer: WT1

A

regulates nuclear transcription

inherited mutation (AD): Wilms tumor

Sporadic mutation: Wilms tumor

85
Q

Azo Dyes

A

Used in paints, printing inks, varnishes, leather products, carpets, food products - heaptocellular carcinoma

86
Q

Benzene

A

Component of light oil; used in printing industry, dry cleaning, paint, adhesives and coatings - Acute leukemia, Hodgkin lymphoma

87
Q

Beryllium

A

Used in space industry (missle fuel and space vehicles; metal alloys in aerospace appliances and nuclear reactors) Bronchogenic carcinoma

88
Q

Cadmium

A

Industrial industries where ore is being smelted; electroplating; welders who have welded on cadmium-containing alloys or worked with silver solders; found in some batteries - prostate and lung cancer

89
Q

cyclophosphamide

A

chemotherapy agent- transitional cell carcinoma of urinary bladder

90
Q

Diethylstillbestrol (DES)

A

once used to treat women with threatened abortions, daughters exposed to mothers who took DES may develop clear cell carcinoma of vagina/cervix

91
Q

Nickel

A

Nickel plating, by-product of stainless steel welding, ceramics, batteries, spark plugs - bronchogenic carcinoma, nasal cavity cancer

92
Q

Radon and decay products

A

By-product of decay of uranium, hazard in quaries and underground mines - bronchogenic carcinoma

93
Q

Silica

A

Chemical of silicon dioxide, rock quarries, sandblasting

94
Q

Acanthosis nigricans

A

stomach carcinoma, black verrucous lesion

95
Q

Eaton-Lambert syndrome

A

small cell carcinoma of lung, myasthenia gravis-like symptoms (e.g. muscle weakness); antibody directed against calcium channel

96
Q

Hypertrophic osteoarthropathy

A

Bronchogenic carcinoma, periosteal reaction of distal phalanx (often associated with clubbing or nail)

97
Q

Nonbacterial thrombotic endocarditis

A

mucus-secreting pancreatic and colorectal carcinomas, sterile vegetations on mitral valve

98
Q

Seborrheic keratosis

A

stomach carcinoma, sudden appearance of numerous pigmented seborrheic keratoses (Leser-trelat sign)

99
Q

superficial migratory thrombophlebitis

A

pancreatic carcinoma, release of procoagulants (trousseau sign)

100
Q

nephrotic syndrome

A

lung, breast, stomach carcinomas- diffuse membranous glomerulopathy

101
Q

Paraneoplastic syndrome

A

a disease or symptom that is the consequence of cancer in the body but, unlike mass effect, is not due to the local presence of cancer cells.

Pathoma (3 decks)

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