Neoplasia Flashcards
1
Q
What is neoplasia?
A
new tissue growth that is unregulated, irreversible, and monoclonal
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)
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)
4
Q
Nomenclature for benign or malignant tumor of epithelial lineage?
A
Adenoma, papilloma; adenocarcinoma, papillary carcinoma
5
Q
Nomenclature for benign or malignant tumor of mesenchymal lineage?
A
Lipoma; liposarcoma
6
Q
Nomenclature for benign or malignant tumor of lymphocyte origin?
A
(does not exist); lymphoma/leukemia
7
Q
Nomenclature for benign or malignant tumor of melanocyte origin?
A
nevus (mole); melanoma
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
9
Q
Most common cancer by incidence?
A
- breast/prostate, 2. lung, 3. colon
10
Q
Most common cause of cancer mortality?
A
- lung, 2. breast/prostate, 3. colon
11
Q
How many divisions before early clinical symptoms?
A
30 divisions, cancer begins as a single mutated cell
12
Q
What is the goal of screening?
A
To catch dysplasia before it becomes carcinoma or carcinoma before clinical symptoms arise
13
Q
Pap smear
A
detects cervical dysplasia (CIN) before it becomes carcinoma
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
15
Q
Prostate Specific Antigen and digital rectal exam
A
detects prostate carcinoma before it spreads
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
17
Q
aflatoxins
A
Cause hepatocellular carcinoma in African countries, derived from Aspergillus, which can contiminate stored rice and grains
18
Q
Alkylating agents
A
Cause leukemia/lymphoma, side effect of chemotherapy
19
Q
Alcohol
A
squamous cell carcinoma of oropharynx and upper esophagus, and hepatocellular carcinoma
20
Q
Arsenic
A
Squamous cell carcinoma of the skin, lung cancer, and angiosarcoma, present in cigarette smoke
21
Q
Asbestos
A
Lung carcinoma and mesothelioma, exposure to asbestos is more likely to lead to lung cancer than mesothelioma
22
Q
Cigarette smoke
A
carcinoma of oropharynx, esophagus, lung, kidney, bladder, and pancreas. Most common carcinogen worldwide; polycyclic hydrocarbons are particularly carcinogenic
23
Q
Nitrosamines
A
Stomach carcinoma, found in smoked foods; responsible for high rate of stomach carcinoma in Japan
24
Q
Napththylamine
A
Urothelial carcinoma of bladder, derived from cigarette smoke
25
Vinyl chloride
Angiosarcoma of liver, occupational exposure; used to make polyvinyl chloride (PVC) used for pipes
26
Nickel, chromium, beryllium, or silica
Lung carcinoma, occupational exposure
27
EBV
Nasopharyngeal carcinoma, Burkitt lymphoma, and CNS lymphoma in AIDS, chinese male or individual in Africa, presents as a neck mass
28
HHV-8
Kaposi sarcoma - tumor or endothelial cells, found in 1. older eastern european males (excise lesion), 2. AIDS patients (treat virus), 3. patients with transplants
29
HBV (DNA) and HCV (RNA)
Hepatocellular carcinoma
30
HTLV-1
Adult T-cell leukemia/lymphoma
31
High-risk HPV (e.g., subtypes 16,18,31,33)
Squamous cell carcinoma of vulva, vagina, anus, and cervix; adenocarcinoma of cervix
32
Ionizing (nuclear reactor accidents and radiotherapy)
AML< CML, and papillary carcinoma of the thyroid, generates hydroxyl free radicals
33
Nonionizing (UVB sunlight is most common source)
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)
34
Explain the signal transduction scheme of RAS
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
35
How do cyclins and CDKs interact and what is an example
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
36
PDGF
growth factor oncogene, platelet-derived growth factor, causes overexpression of an autocrine loop, makes an astrocytoma
37
ERBB2 [HER2/neu]
growth factor receptor oncogene, epidermal growth factor receptor, causes amplification, subset of breast carcinomas
38
RET
growth factor receptor oncogene, neuronal growth factor receptor, point mutation, causes MEN 2A, MEN 2B and sporadic medullary carcinoma of thyroid
39
KIT
growth factor receptor oncogene, stem cell growth factor receptor, point mutation, gastrointestinal stromal tumor
40
RAS gene family
signal transducer oncogenes, GTP-binding protein, point mutation, carcinomal, melanoma, and lymphoma
41
ABL
signal transducer oncogenes, Tyrosine kinase, t(9;22) (philadelphia) with BCR, CML and some types of ALL
42
c-MYC
nuclear regulator oncogene, transcription factor, t(8;14) myc on 8 transferred to 14 involving IgH, burkitt lymphoma
43
N-MYC
nuclear regulator oncogene, transcription factor, amplification, neuroblastoma
44
L-MYC
nuclear regulator oncogene, transcription factor, amplification lung carcinoma (small cell)
45
CCND1 (cyclin D1)
cell cycle regulator oncogene, cyclin, t(11;14) involving IgH, mantle cell lymphoma
46
CDK4
cell cycle regulator oncogene, cyclin-dependent kinase, amplification, melanoma
47
example of tumor suppressor genes
p53 and Rb
48
Functions of p53
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
Tumor suppressor gene
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
Function of Rb
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
Function of Bcl2
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
3 important features of tumor development
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
What is the progression of tumor invasion and spread?
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
What type of spread is characteristic of carcinomas?
Lymphatic spread
55
What type of spread is characteristic of sarcomas?
Hematogenous
56
What are some hematogenous exceptions to carcinomas?
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
What is characteristic of ovarian carcinoma?
Seeding of the body cavities, involves the peritoneum
58
What are clinical features of benign tumors?
slow growing, well circumscribed, distinct, and mobile
59
What are clinical features of malignant tumors?
rapid growing, poorly circumscribed, infiltrative, and fixed to surrounding tissues and local structures
60
What are the histological features of benign tumors?
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
What are the histological features of malignant tumors (which are classically poorly differentiated - anaplastic)?
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
What is the immmunohistochemical stain associated with epithelium?
keratin
63
What is the immmunohistochemical stain associated with mesenchyme?
vimentin
64
What is the immmunohistochemical stain associated with muscle?
desmin
65
What is the immmunohistochemical stain associated with neuroglia?
GFAP
66
What is the immmunohistochemical stain associated with neurons?
neurofilament
67
What is the immmunohistochemical stain associated with prostate epithelium?
PSA
68
What is the immmunohistochemical stain associated with breast epithelium?
Estrogen Receptor
69
What is the immmunohistochemical stain associated with thyroid follicular cells?
Thyroglobulin
70
What is the immmunohistochemical stain associated with neuroendocrine cells (e.g. small cell carcinoma of lung and carcinoid tumors)?
chromogranin
71
What is the immmunohistochemical stain associated with melanoma, schwannoma and langerhans cell histiocytosis?
S-100
72
Serum tumor markers
useful for screening, monitoring response to treatment, and monitoring recurrence
elevated levels require tissue biopsy fr diagnosis of carcinoma
73
Grading of cancer
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
Staging of cancer
assessment of size and spread of a cancer, key prognostic factor, more than grade, determined after final surgical resection of the tumor
75
TNM staging system
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
Tumor Suppressor genes, functions, associated cancer: APC
Prevents nuclear transcription (degrades catenin, an activator of nuclear transcription)
Inherited mutation (AD): familial polyposis (colorectal carcinoma)
Somatic mutations: colon and stomach cancer
77
Tumor Suppressor genes, functions, associated cancer: BRCA1/BRCA2
regulates DNA repair
inherited mutation: female breast, ovary carcinomas; carcinoma male breast
78
Tumor Suppressor genes, functions, associated cancer: NF1
Inhibits RAS signal transduction; cell cycle inhibitor
Inherited mutation (AD): neurofibromatosis type 1: pheochromocytoma, Wilms tumor, neurofibrocarcomas
Somatic mutation: neuroblastoma
79
Tumor Suppressor genes, functions, associated cancer: NF2
Inherited mutation (AD): neurofibromatosis type II: bilateral acoustic neuromas (schwannoma), meningioma
Somatic mutation: schwannoma, meingioma
80
Tumor Suppressor genes, functions, associated cancer: p53
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
Tumor Suppressor genes, functions, associated cancer: RB1
inhibits G1 to S phase
inherited mutation (AD): retinoblastoma, osteogenic sarcoma
Somatic mutation: retinoblastoma, osteogenic sarcoma, carcinomas of breast, lung, colon
82
Tumor Suppressor genes, functions, associated cancer: TGF-beta
inhibits G1 to S phase
Inherited mutation: familial stomach cancer
Somatic mutation: pancreatic and colorectal carcinomas
83
Tumor Suppressor genes, functions, associated cancer: VHL
regulates nuclear transcription
inherited mutation (AD): von Hippel-Lindau syndrome: cerbellar hemangioblastoma, retinal angioma, renal cell carcinoma (bilateral), pheochromocytoma (bilateral)
84
Tumor Suppressor genes, functions, associated cancer: WT1
regulates nuclear transcription
inherited mutation (AD): Wilms tumor
Sporadic mutation: Wilms tumor
85
Azo Dyes
Used in paints, printing inks, varnishes, leather products, carpets, food products - heaptocellular carcinoma
86
Benzene
Component of light oil; used in printing industry, dry cleaning, paint, adhesives and coatings - Acute leukemia, Hodgkin lymphoma
87
Beryllium
Used in space industry (missle fuel and space vehicles; metal alloys in aerospace appliances and nuclear reactors) Bronchogenic carcinoma
88
Cadmium
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
cyclophosphamide
chemotherapy agent- transitional cell carcinoma of urinary bladder
90
Diethylstillbestrol (DES)
once used to treat women with threatened abortions, daughters exposed to mothers who took DES may develop clear cell carcinoma of vagina/cervix
91
Nickel
Nickel plating, by-product of stainless steel welding, ceramics, batteries, spark plugs - bronchogenic carcinoma, nasal cavity cancer
92
Radon and decay products
By-product of decay of uranium, hazard in quaries and underground mines - bronchogenic carcinoma
93
Silica
Chemical of silicon dioxide, rock quarries, sandblasting
94
Acanthosis nigricans
stomach carcinoma, black verrucous lesion
95
Eaton-Lambert syndrome
small cell carcinoma of lung, myasthenia gravis-like symptoms (e.g. muscle weakness); antibody directed against calcium channel
96
Hypertrophic osteoarthropathy
Bronchogenic carcinoma, periosteal reaction of distal phalanx (often associated with clubbing or nail)
97
Nonbacterial thrombotic endocarditis
mucus-secreting pancreatic and colorectal carcinomas, sterile vegetations on mitral valve
98
Seborrheic keratosis
stomach carcinoma, sudden appearance of numerous pigmented seborrheic keratoses (Leser-trelat sign)
99
superficial migratory thrombophlebitis
pancreatic carcinoma, release of procoagulants (trousseau sign)
100
nephrotic syndrome
lung, breast, stomach carcinomas- diffuse membranous glomerulopathy
101
Paraneoplastic syndrome
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.
