Ch 7 Neoplasm Flashcards
(127 cards)
1
Q
New growth, resulting from genetic alterations that are passed down to progeny of the tumor cells. these genetic changes allow excessive and unregulated proliferation that becomes autonomous. This is termed as_.
A
Neoplasia
2
Q
The entire population of a neoplasm arising from a single cell that has incurred genetic changes where all the neoplastic cells are clones of one original altered cells. The term used for this is _
A
Clonality
3
Q
Characteristics of benign tumor include
A
- gross and microscopic appearances are considered relatively innocent, implying that it will remain localized
- does not spread to other sites
- amenable to local surgical removal
- encapsulated
4
Q
Characteristics of malignant tumors include
A
- Malignant tumors are referred to as cancers
- invade and destroy adjacent structures and spread to distant sites (metastasize)
- margins are not defined
- not encapsulated
5
Q
Benign epithelial neoplasms producing microscopically or macroscopically visible fingerlike or warty projections from epithelial surfaces are referred to as _
A
papillomas.
6
Q
What are cystadenomas?
A
benign epithelial neoplasms that form large cystic masses such as in the ovary
7
Q
Neoplasm that produces a macroscopically visible projection above a mucosal surface is known as _. Is it malignant or benign?
A
polyp.
Can be both malignant or benign
8
Q
Recognizable mature or immature cells or tissues belonging to more than one germ cell layer - originates from totipotential germ cells like in the ovary or testis. This is referred to as _
A
Teratoma
9
Q
What is a hamartoma?
A
disorganized but benign masses composed of cells indigenous to the involved site
10
Q
What are sarcomas?
A
- malignant tumors arising in solid mesenchymal tissues
- exmaples: fibrosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, gastrointestinal stromal tumors (GIST)
11
Q
What are some examples of malignant neoplasms that have inappropriate benign terminology?
A
- lymphoma
- melanoma
- mesothelioma
- seminoma
12
Q
What is a mixed tumor?
A
Tumors that contain epithelial component scattered within a myxoid stroma that may contain islands of cartilage or bone. All of the elements arise from a single clone capable of producing both epithelial and myoepithelial cells; thus the preferred designation of this neoplasm is pleomorphic adenoma.
- Usually seen in tumors of salivary glands
13
Q
Ovarian cystic teratoma (dermoid cyst) mainly differentiates along what germinal cell line to create a cystic tumor lined by skin replete with hair, sebaceous glands, and tooth structures?
A
Ectodermal
14
Q
What is meant by differentiation?
A
Differentiation refers to the extend to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells, both morphologiclaly and functionally.
15
Q
What is anaplasia?
A
Complete lack of differentiation. Anaplasia is a hallmark of malignancy.
16
Q
Anaplasia is often associated with many other morphologic changes such as pleomorphism which is defined as
A
Cancer cells with variation in size and shape. Ranges from small cells with an undifferentiated appearance to tumor giant cells many times larger than their neighbors. and some tumor giant cells has only a single huge polymorphic nucleus while other may have two or more large hyperchromatic nuclei.
17
Q
What are some characteristic features of anaplasia?
A
- pleomorphism
- abnormal nuclear morphology
- increased and abnormal mitosis and mitotic bodies
- loss of polarity
18
Q
What is paraneoplastic syndrome? Give example.
A
Highly anaplastic undifferentiated cells that which gives rise to new and unanticipated functions.
Example: bronchogenic carcinomas may produce croticotropin, parathyroid-like hormone, insulin, glucagon, and other hormoens
19
Q
What is metaplasia and what is almost always associated with?
A
Metaplasia is replacement of one type of cell with another type. Metaplasia Tissue damage, repair and regeneration.
20
Q
What is dysplasia and what are some characteristics?
A
disordered growth associated with constellation of changes that include a loss in the uniformity of the individual cells as well as loss in their architectural orientation.
- pleomorphic
- hyperchromatic
- abundant mitotic figures
21
Q
When dysplastic changes are marked and involve the full thickness of the epithelium but the lesion does not penetrate the basement membrane. This is known as _
A
Carcinoma in situ. It’s considered preinvasive neoplasm.
22
Q
True or false. dysplasia progresses to cancer
A
False.
23
Q
True or False Carcinoma in situ is malignant.
A
Falsed
24
Q
Explain how a CIN I looks different from a CIN III
A
In CIN I, there will be increased basilar proliferation around the basement membrane.
In CIN III shows full thickness change, filled with basilar cells. CIN III is indistinguishable from carcinoma in situ.
25
What's the next step after seeing CIN III on a pap smear?
Do a biopsy
26
Koilocytic atypia is usually seen histologically in what kind of cancer? what is meant by koilocytic atypia?
Cervical intraepithelial neoplasia, due to HPV infection. Koilocytic atypia means an squamous epithelium that has undergone a number of structural changes.
27
What are the two major determinants of differentation?
1. the noeplastic cells nuclei and cytoplasm
| 2. architectural relationship of the neoplastic cells to other neoplastic cells and non-neoplastic stroma
28
What are the four grades of differentiation?
- Well differentiated: closely resembles parent tissue
- Moderately differentiated: features of the original tissue type identifiable, but its not the dominant pattern, with additional atypia
- Poorly differentiated: a small minority of cellular constituents allow identification of the parent tissue; associated with cellular anaplasia
- Undifferentiated: tissue of origin cannot be discerned by histopathologic appearance of the neoplasm. always associated with anaplasia
29
In histology, if you see prominent keratin pearls, is that considered, well, moderately, poorly or undifferentiated?
Well differentiated.
30
Differentiate the benign and malignant based on degree of differentiation, rate of growth, local invasiveness, and distant spread.
Benign: well differentiated, slow growing, well circumscribed (may have capsule, does not invade and does not spread
Malignant: less well differentiated or even anaplastic, cells lose original function and may again unexpected function, grow faster, and poorly circumscribed and tend to invade surrounding normal tissues and has capability to metastasize.
31
Metastasis is THE most distinguished feature of malignancy, what is the next best reliable feature of malignancy?
Invasiveness
32
True or false, basal cell carcinoma usually do not metastasize.
True
33
True or false: urothelial cancers has a strong association with smoking
True
34
What is the common age group of testicular epithelial tumors?
15-34
35
True or False: Leiomyoma will most likely, if left untreated, progress to give rise to leiomyocarcinoma.
False. Most leiomyosarcoma occurs on their own not from leiomyoma.
36
Spread of tumor to sites that are physically discontinuous with the primary tumor is termed as:
Metastasis
37
It is said that gliomas and basal cell carcinomas of the skin invade early in their course. How likely is that they will metastasize?
Very unlikely
38
Dissemination of cancers occurs via what three routes?
1. direct seeding of body cavities or surfaces
2. lymphatic spread
3. Hematogenous spread
39
Direct seeding of body cavities or surfaces as a disemmination of cancers is a common route for what type of cancer and where does it go?
Carcinomas arising from ovaries and spreads to peritoneal surfaces
40
What is pseudomyxoma peritonei?
Mucus-secreting appendiceal carcinomas or ovarian carcinomas that fill the peritoneal cavity with a gelatinous neoplastic mass.
41
Carcinomas of the lung arising in the major respiratory passages metastasize first to which lymph nodes?
perihilar tracheobronchial and mediastinal nodes.
42
The first node in a regional lymphatic basin that receives lymph flow from the primary tumor is termed _
sentinel lymph nodes and these are the main and first nodes to be biopsied in breast cancer suspicion
43
Hematogenous spread is the main route of spread for what group of cancers?
Sarcomas.
44
When sarcomas metastasize, what are the first sites of metastasis?
Liver and lung
45
In the route of metastesis, what branches does renal cell carcinoma usually invade and where does it go from there?
Invades branches of renal vein and then the renal vein itself and moves upward in a snakelike fashion to the IVC.
46
Cancers arising from mutation in oncogenes is usually due what kind of mutation?
gain-of-function mutation
47
Cancers arising from mutation in tumor suppressors like RB and p53 is usually due what kind of mutation?
Loss-of-function mutation
48
Carcinogenesis results from_
accumulation of complementary mutations in a stepwise fashion over time.
49
What is a driver mutation?
Mutation that contribute to the development of the malignant phenotype.
50
what is a initiating mutation?
the first driver mutation that starts a cell on the path to malignancy
51
what is a passenger mutation?
Driver mutations that increases frequency of mutations that have no phenotypic consequence,
52
By the time a tumor grows to clinical attention, how many cell doubling has it undergone?
minimum 30 cell doubling
53
How does a call or group of cells reach tumor progression state?
Darwinian contest. Competition between tumor cells for access to nutrients and microenvironmental niches and subclones with the capacity to overgrow their predecessors tend to win and dominate the tumor mass and replace the other cells with more malignant subclones and overtime becomes more aggressive.
54
what are the 8 hallmarks of cancer?
1. self-sufficiency in growth signals
2. insensitivity to growth-inhibitory signals
3. altered cellular metabolism
4. Evasion of apoptosis
5. Limitless replicative potential (immortality)
6. Sustained angiogenesis
7. Ability to invade and metastasize
8. ability to evade host immune response
55
How do cancer cells acquire limitless replicative potential?
Transformation of normal cells via acquired genetic lesions that impart a stem-like state on a more mature cell.
- Cells acquire lesions that inactivate senescence signals and reactivate telomerase which act together to convey limitless replicative potential
56
For each of the following, identify the most common cancer that can arise with mutation:
A. Activation of EGF receptor tyrosine kinase by point mutation
B. activation of HER2 receptor tyrosine kinase by gene amplification
C. Activation of JAK2 tyrosine kinase by point mutation
D. Activation of ABL nonreceptor tyrosine kinase by chromosomal translocation and creation of a BCR-ABL fusion gene
E. Increased expression of MYC by deregulation through chromosomal translocation
F. amplification of NMYC
G. CDK4 amplification or point mutation
```
A. Lung cancer
B. Breast Cancer
C. Myeloproliferative disorders
D. CML, ALL
E. Burkitt lymphoma, and other hematologic malignancies
F. Neuroblastoma
G. Glioblastoma, melanoma, sarcoma
```
57
What is the normal function of APC and what cancer arises if it's mutated?
Normal function: inhibitor of WNT signaling pathway
Cancer: Familial colonic polyps and carcinomas, Carcinomas of stomach, colon, pancreas, and melanoma
58
what is the normal function of NF1 and what cancer can arise if mutated?
Normal function: Inhibitor of RAS/MAPK signaling
Cancer: neuroblastoma, juvenile myeloid leukemia
59
What is the normal function of NF2 and what cancer can arise if mutated?
Normal function: cytoskeletal stability, Hippo pathway signaling
Cancer: Schwannoma, meningioma
60
What is the normal funciton of RB and what cancer can arise if mutated?
Normal Function: Inhibitor of G1/S transition
Cancer: Retinoblastoma, osteosarcoma, carcinomas of breast, colon, lung
61
What is the normal function of VHL and what cancer can arise if mutated?
Normal function: inhibitor of hypoxia induced transcription factor
Cancer: Renal cell carcinoma. also associated with Von Hippel Lindau Syndrome
62
What is the normal function of CDH1 (E-cadherin) and what cancer arise if mutated?
Normal function: Cell adhesion, inhibition of cell motility.
Cancer: Gastric carcinoma, lobular carcinoma
63
what is the normal function of WT1 and what cancer can arise if mutated?
Normal function: Transcription factor
Cancer: wilm's tumor
64
what cancer is associated with translocation 9;22
CML
65
What cancer is associated with translocation 8;21 and 15;17
AML
66
What cancer is associated with translocation 8;14
burkitt lymphoma
67
what cancer is associated with translocation 11;14
Mentle cell lymphoma
68
what cancer is associated with translocation 14;18
Follicular lymphoma
69
What cancer is associated with translocation 11;22
Ewing sarcoma
70
What cancer is associated with translocation 7;21
Prostatic adenocarcinoma
71
_ is a major transcriptional regulator of cell growth that activates expression of many genes that are involved in cell growth; can upregulate telomerase; can act to reprogram somatic cells into pluripotent stem cells
MYC
72
_ is a tumor suppressive pocket protein that binds E2F transcription factors in its hypophosphorylated state, repventing G1/S transition
RB
73
_ is a tumor suppressor that acts mainly through p21 to cause cell cycle arrest. Causes apoptosis by inducing the transcription of pro-apoptotic genes like BAX.
p53
74
```
Which of the following are DNA repair factors?
A. WT1
B. BRCA1, BRCA2
C. TP53
D. CDH1
E. RB
F. APC
G. NF1
```
B. BRCA1, BRCA2. Frequently mutated in breast cancer
75
When RB is _ exerts antiproliferative effects by binding and inhibiting E2F transcription factors that regulate genes required for cells to pass through G1-S phase.
hypophosphorylated
76
The antiproliferative effect of RB is abrogated in cancers mainly through which general mechanism?
1. Loss of function mutation affecting RB gene
2. Gene amplification of CDK4 and Cyclin D genes
3. Loss of cyclin-dependent kinase inhibitors (p16/INK4a)
4. Viral oncoproteins that bind and inhibit RB (E7 protein of HPV)
77
Li-Fraumeni syndrome is associated with inheritance of a mutated copy of what gene?
TP53
78
MDM2 normally acts as an inhibitor of what protein?
P53
79
what HPV protein specifically targets to inactivate p53?
E6
80
Which gene encodes a factor that negatively regulates the WNT pathway in colonic epithelium by promoting the formation of a complex that degrades beta-catenin?
APC
81
_ is mutated in familial adenomatous polyposis and is associated with development of thousands of colonic polyps and early onset colon carcinoma.
APC
82
Germline loss-of-function mutation in _ is associated with autosomal dominant familial melanoma.
CDKN2A. A complex locus that encodes two tumor suppressive proteins, p16/INK4a, a cyclin-dependent kinase inhibitor that augments RB function and ARF which stabilizes p53.
83
_ encodes a component of a ubiquitin ligase that is responsible for degradation of hypoxia-induced factors (HIF) transcription factors that alter gene expression in response to hypoxia
VHL
84
Germline loss of function mutation in _ causes von Hippel-Lindau syndrome,, an autosomal dominant disorder associated with a high risk of renal cell carcinoma and pheochromocytoma
VHL
85
In greater than 85% of follicular B cell lymphomas _ is over expressed due to 14;18 translocation.
BCL2 gene
86
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Which of the following types of cancer an effective treatment with conventional chemo or irradiation?
A. Testicular teratocarcinomas
B. Lymphoblastic leukemias
C. Lung Cancer
D. Colorectal Cancer
E. A and B
F. C and A.
```
E. A and B.
In testicular teratocarcinomas and acute lymphoblastic leukemias both have wild type TP53 and so with conventional chemo or irradiation, you can induce DNA damage and TP53 would induce apoptosis. But with lung cancer or colorectal cancer, TP53 is mutated and a mutated TP53 won't respond to conventional chemo or irradiation.
87
Tumor cells needs adequate vascularization in order to thrive. In growing tumors, hypoxia triggers angiogenesis through the action of _ on transcription of the proangiogenic factor _.
HIF-1a
| VEGF
88
Ability to invade tissues, a hallmark of malignancy, occurs in what four steps?
1. loosening of cell-cell contact
2. degradation of ECM
3. attachment of novel ECM components,
4. migration of tumor cells
89
Tumor cells is able to accomplish cell-cell contact loss by inactivating _ through a variety of pathways.
E-cadherins
90
what genes are important epithelial tumor metastasis genes that promote epithelial-mesenchymal transition?
TWIST and SNAIL
91
Which hallmark of cancer is considered the "holy grail of oncology" and why?
Evasion of host defense, due to the promise of therapies that enable the host immune system to recognize and destroy cancer cells is finally coming to fruition largely due to a clearer understanding of the way by which cancer cells evade the host response.
92
Patients with _ syndrome have defects in mismatch repair system, leading to development of carcinomas of the colon. These patient's genomes show microsatellite instability, characterized by changes in length of short repeats throughout the genome.
HNPCC
93
Patients with _ are highly sensitive to the sun. they have defect in the nucleotide excision repair pathway and are at increased risk for development of cancer of the skin exposed to sun's UV light, because of an inability to repair _
xeroderma pigmentosum
| inability to repair pyrimidine dimers.
94
COX2 inhibitors have been shown to decrease incidence of _1_ and are now approved for treatment of patients with _2_.
1. Colonic adenomas.
| 2. Familial adenomatous polyposis
95
Cancer-enabling inflammation induces what three conditions?
1. Anemia
2. Fatigue
3. Cachexia
96
MLL1 and MLL2 responsible for histone methylation are mutated in 90% of which childhood cancers?
- Acute leukemia
| - follicular lymphoma
97
Mutation in this gene which normally functions as nucleosome positioning/chromatin remodeling is mutated in 100% of malignant rhabdoid tumor.
SNF5
98
_ is a very good example of chemical carcinogen associated with a mutational "hotspot". It is a naturally occurring agent produced by some strains of a mold called aspergillus which can grow on improperly stored grains and nuts. There is a strong correlation of dietary level of this food contamiant and the incidence of what _ carcinoma in parts of African and Far East.
Aflatoxin b1
| hepatocellular carcinoma.
99
The carcinogenicity of UVB light is due to formation of _ in DNA
pyrimidine dimers
100
Ionizing radiation whats mainly what kind of damage?
Chromosome breakage, translocation, and less frequently point mutation.
101
With radiation-induced cancers, which ones are common and which organs are relatively resistant to radiation-induced neoplasia?
Most frequent are myeloid leukemias (tumors of granulocytes and their precursors); cancers of thyroid follows closely in the young.
Skin, bone, and GI tract are relatively resistant to radiation-induced neoplasia.
102
```
Which of the following are oncogenic RNA viruses?
A. HTLV-1
B. HPV
C. EBV
D. HBV
E. Merkel cell polymavirus
F. HHV-8
G. HIV
```
A. HTLV-1 is the only oncogenic RNA virus listed.
B-F are all oncogenic DNA viruses.
HIV is not a transforming virus, in other words NOT oncogenic virus
103
Which virus is endemic in Japan, the Caribbean, and parts of South America and Africa that causes adult T-cell Leukemia/lymphoma?
HTLV-1 via viral protein Tax
104
Which oncoproteins of HPV that bind to Rb and p53 to neutralize their function and is associated with benign warts, cervical cancer, and/or oropharyngeal cancer?
E6 (binds to RB)
| E7 (binds to P53)
105
EBV has been implicated in the pathogenesis of _ and _ in patients with immunosuppression (HIV infection, transplant recipient)
Burkitt's lymphomas and B-cell lymphomas
106
70-85% of hepatocellular carcinomas worldwide are caused by which viruses?
hepatitis B virus and hepatitis C virus
107
H. pylori is associated with what cancers?
gastric adenocarcinoma and MALT lymphoma via pathogenicity genes such as CagA.
108
In cancer related cachexia is associated with what features? what's the leading suspected mediator?
- loss of both fat and lean muscle
-elevated basal metabolic rate
-evidence of systemic inflammation
TNF is the leading mediator of immune responses
109
What is the most common endocrinopathy associated with paraneoplastic syndrome?
Cushing syndrome. 50% of these pts have carcinoma of the lung (small-cell type)
110
What is the most common paraneoplastic syndrome?
Hypercalcemia associated with osteolysis induced by cancer like MM, and production of calcemic humoral substances by extraosseous neoplams (this is the only true paraneoplastic hypercalcemia)
111
what are some forms of neuromyopathic paraneoplastic syndromes?
- peripheral neuropathies,
- cortical cerebellar degeneration
- polymyopathy resmebling polymyositis
- myasthenic syndrome similar to myasthenia gravis
112
What is acanthosis nigricans?
a form of paraneoplastic syndrome characterized by grayblack patches of thickened, hyperkeratotic skin with velvety appearance. These lesion appear even before the cancer comes to clinical attention
113
what cancer is commonly associated with hypertrophic osteoarthropathy form of paraneoplastic syndrome? How is it characterized?
Lung carcinoma.
| Hypertrophic osteoarthropathy is characterized by periosteal new bone formation, arthritis, and clubbing of digits
114
Migratory thrombophlebitis as a form of paraneoplastic syndrome is associated with what cancers?
Carcinomas of the pancreas or lung
115
What cancer produces DIC, as a paraneoplastic syndrome?
acute promyelocytic leukemia and prostatic adenocarcinoma
116
In grading a cancer what feature is taken into account?
Microscopic assessment of differentiation. Takes into account architectural and nuclear features.
117
What does staging take into account?
Staging of solid tumor is based on size of primary lesion, its extent of spread to regional lymph nodes, and presence or absence of blood-borne metastases.
118
What staging system is current used and explain the system.
TNM system.
T for primary tumor (T1-T4 based on size)
N for regional lymph nodes (N0-N3 based on increasing involvement of lymph nodes)
M for metastases: number of mets. M0 means no mets
119
In determining the nature of a mass lesion, in evaluating the margins of an excised cancer to ascertain that entire neoplasm, what kind of excisional section would you request?
quick-frozen section
120
Fine-needle aspiration involves aspirating cells and attendant fluid with a small-bore needle followed by cytologic examination of stained smear. This method is most commonly used for assessment of what kind of cancers?
Readily palpable lesions in sites such as breast, thyroid, and lymph nodes. With more modern techniques it can be used for deep-seated structures like pelvic lymph nodes and pancreas.
121
This cancer detection method is widely used to screen for carcinoma of the cervix, often at an in situ stage, but also used for suspected malignancy in which tumor cells are easily accessible or shed like endometrial carcinoma, lung carcinoma, bladder and prostatic tumors, and gastric carcinomas. what are it's limitations?
Cytologic smears
Limitation: it's only helpful to screen for malignancy, but the findings often fall short of diagnosing a specific cell type. Can't help to decide treatment option or prognosis.
122
For the detection of antigenic characteristics such as protein expresison, to aid in characterizing the cell of origin, as well as provide info in selection of treatment protocols, what cancer detection method would be useful?
immunohistochemistry
123
Flow cytometry is mainly used for what kind of tumors?
liquid tumors like B and T cell lymphomas and leukemias and myeloid neoplasms. Helps rapidly and quantitatively measure several individual cell characteristic. Can help identify more than one type of antigen (via monoclonal ab) unlike immunohistochemistry
124
What is circulating tumor cells method best used for?
Detection quantification and characterization of rare solid tumors like carcinomas, melanoma circulating blood. Used in clinical research.
125
Melanoma, papillary thryoid carcinoma, hairy cell leukemia, langerhans cell histiocytosis, and colon adenocarcinoma all have mutation in what protein?
BRAF. being able to identify that BRAF was mutated in all of those cancers is the future of cancer diagnosis and targeted therapy. It's accomplished by Molecular profiling of tumors.
126
PS, CEA, and AFP assay lack both specificity and sensitivity required for the early detection of cancer, but they are useful for detection of what?
Recurrences after excision. With successful resection of the tumor, these markers disappear from the serum; their persistence or reappearance almost always signifies tumor lurking within
127
For each of the following tumor marker indicate the associated cancer:
A. HCG
B. CA-125
C. Immunoglobulin
A. Testicular tumors
B. ovarian tumors
C. MM and other secretory plasma cell tumors.
