Chapter 7-Neoplasm Learning objectives Flashcards
1
Q
Define Cancer, Neoplasia, Tumor, Oncology and Clonal
A
Cancer: Malignant neoplasm
Neoplasia: New growth
Tumor: Neoplasm
Oncology: the study of Tumors/neoplasms
Clonal: Clones
2
Q
Define Benign and Malignant in common usage and as used by physicians.
A
Benign: Localized
Malignant: spreads
3
Q
Describe cell and tissue origins in determining the nomenclature of human neoplasms
and characterize the designations -oma, carcinoma and sarcoma.
A
- -Oma: Bening tumor
- Carcinoma: Malignant tumor from epithelium-any of 3 germ layers. (Adenocarcinoma = glandular)
- Sarcoma: From solid mesenchymal tissue (CT)
4
Q
What are the two basic tissue components of benign and malignant neoplasms?
A
- Parenchyma: Neoplastic cells-tumor cells
2. Stroma: supply (CT, BV, Immune system)
5
Q
Discuss the use of the terms polyp and adenoma in the GI tract
A
- Polyp: Benign or Malignant projection from mucosa (colon cancer)
- Adenoma: Benign EPITHELIAL neoplasm from GLANDS
6
Q
List examples of malignant neoplasms that have inappropriate benign terminology.
A
- ??
7
Q
Explain how a mixed tumor of the salivary gland is different from an adenoma of the colon.
A
Mixed Tumors: Contain epithelial components and myxoid stroma => islands of cartilage or bone
Adenoma Parenchyma will be relatively uniform
8
Q
Explain how a cystic teratoma of ovary fundamentally differs from a mixed tumor of salivary gland.
A
Mixed tumors: generally from 1 germ level (Epi +Myo = pleomorphic)
Teratoma: Multigerm layer (often from ovary(Dermoid Cyst)/testes)
9
Q
Define differentiated and anaplasia
A
Differentiated:
-The extent to which neoplastic parenchymal cells resemble corresponding normal parenchymal cells.
Anaplasia-Lack of diffentiation
10
Q
4 Malignant tumors
A
- Sarcoma
- Carcinoma
- Lymphoma
- Leukemia
11
Q
3 Benign Tumors
A
- Adenoma (epithelial-glands)
- Papilloma: Epithelial finger-like/warty projections
- Cystadenoma: Ovarian cysts etc
12
Q
1 Variable Tumor
A
Polyp
13
Q
Define desmoplasia
A
- Collagenous Stroma
14
Q
Define Scirrhous
A
- Stony/hard Stroma
- Often associated with breast tissue
15
Q
Explain why benign tumors are generally considered well differentiated.
A
Often keep most of the function of normal parenchyma
16
Q
List and describe histopathologic criteria used in employing the term anaplasia.
A
Anaplasia: lack of differentiation
-Malignant neoplasms are generally composed of poorly differentiated cells
17
Q
Compare and contrast metaplasia versus dysplasia.
A
Metaplasia: Change in cell type
Dysplasia: Loss in uniformity of the individual cells as well as loss in architectural orientation
18
Q
Define carcinoma in situ (CIS) and explain what distinguishes CIS from carcinoma
A
Dysplasia: Considered Carcinoma in situ when it is full thickness but does not invade basal layer
- Invasive once it crosses this basement membrane
- Metastatic action results in squamous epithelial carcinoma
- Does not always progress to cancer
19
Q
Delineate the most common histopathologic features used to assess rate of growth in a
neoplasm: Neoplastic growth accompanied by progressive…?
A
- infiltration
- Invasion
- Destruction of surrounding tissue
- Benign: grow as cohesive expansile masses that remain localized
20
Q
Delineate the most common histopathologic features used to assess rate of growth in a
neoplasm: needed for malignancy
A
Metastases is Key!!!
21
Q
Delineate the most common histopathologic features used to assess rate of growth in a
neoplasm: second best for malignancy determination
A
Invasiveness
22
Q
Define Anaplastic
A
Malignant neoplasms composed of poorly diff cells
23
Q
Nucleus:Cytoplasm
A
norm = 1:4 or 1:6
Abnormal = 1:1
24
Q
Anaplastic cell growth
A
Anarchy!
25
Large tumors have what at center?
Ischemia
26
Define Hemangioma
Tumor of tangled blood tissue
27
Tumor supressor genes that inhibit mitogenic signaling pathways (3)
1. APC
2. NF1
3. NF2
28
APC Protein and Fxn
Protein: Adenomatous polyposis coli protein
Fxn: Inhibitor of WNT signaling in colon epithelium - degrades B-catenin
29
APC is considered the...
gatekeeper of colonic neoplasia
30
APC bi-allelic loss
results in colon cancer-70%
31
APC Familial Syndromes
Familial colonic polyps and carcinomas
32
APC sporadic cancers: Carcinomas of (4)
1. Stomach
2. Colon
3. Pancreas
4. Melanoma
33
NF1 protein and function
P: Neurofibromin-1
Fxn: inhibitor of RAS/MAPK
34
NF1 familial syndromes
Neurofibromatosis type 1 (neurofibromas and malignant peripheral nerve sheath tumors)
35
NF1 sporadic cancers (2)
1. Neuroblastoma
| 2. Juvenile myeloid leukemia
36
NF2 P and F
P: Merlin
F: Cytoskeletal stability and Hippo pathway signaling
37
NF2 Familial syndromes
Neurofibromatosis type 2 (Acoustic schwannoma and meningioma)
38
NF2 Sporadic cancers: (2)
1. Schwannoma
| 2. Meningioma
39
Inhibitors of cell cycle progression (2)
1. RB
| 2. P53
40
RB p and fxn:
P: Retinoblastoma Protein
Fxn: Inhibitor of G1/S checkpoint
-Major proponent of 2-hit hypothesis
41
RB is considered the...?
govener of proliferation
42
Mutation of RB leads to
1. Gene amplification of CDK4/cyclin D
| 2. Loss of p16/INK4a
43
Virus-protein that inhibits RB?
E7 protein of HPV virus
44
Phosphorylation of RB... (2)
1. Turns it off
| 2. Activates E2F xsription factor
45
RB Familial Syndromes (3)
Familial Retinoblastoma Syndrome
1. Retinoblastoma
2. Osteosarcoma
3. Sarcomas
46
RB sporadic Cancers (3)
1. Retinoblastoma
2. Osteosarcoma
3. Carcinomas of breast/colon/lung
47
Inhb of pro-growth programs of metabolism and angiogenesis (1)
1. VHL
48
VHL P and F
P: Von Hippel Lindau
F: Inhb hypoxia-induced transcription factors (H1F1-alpha)
49
VHL is a component of what? What does it degrade?
1. Component of ubiquitin ligase
| 2. Degrades HIFs
50
What are HIFs?
HIFs alter gene expression in response to hypoxia
51
What type of mutation happens with VHL?
Loss of function
52
VHL: Increased RBC count can be associated with...?
-Paraneoplastic Syndrome
53
Tumors and cancers associated with RBC
1. CNS tumors
2. Renal Cysts
3. Neuroendocrine Tumors
4. Renal Cell Carcinomas
54
VHL: Familial Syndromes (4)
Von Hippel Lindau Syndrome
1. Renal Cell Carcinoma
2. Pheochromocytoma
3. Cerebellar Hamagioblastoma
4. Retinal Angioma
55
VHL: Sporadic cancers
Renal cell carcinoma
56
Are angiomas and hemangioblastomas malignant?
NO! Dude, just no.
57
Inhibitors of invasion and metastasis (1)
CDH1 (E-cadherin gene)
58
CDH1 P and F
P: E-cadherin
F: Cell adhesion, Inhb of cell motility
59
What does E-cadherin sequester?
B-catenin
60
What does B-catenin do?
Signals the WNT pathway
61
WNT pathway is related to?
Metastisis
62
CDH1 Loss of function results in?
Sporadic Carcinomas
-Loss of contact inhibition, cohesiveness and increased invasiveness
63
CDH1 Familial syndroms
Familial gastric carcinoma
64
CDH1 Sporadic Cancers (2)
1. Gastric Carcinoma
| 2. Lobular breast carcinoma
65
Enablers of genomic stability?
TP53
66
TP53 P and F
P: p53
F: Cell cycle arrest and apoptosis in resp to DNA dmg
67
TP53 is considered the guardian of the...?
genome
68
What chromosome is p53 on?
Chromosome 17
69
What does p53 regulate? (4)
1. G1/s progression
2. DNA repair
3. Cell Senescence
4. Apoptosis
70
DNA damage is sensed by?
ATM/ATR kinase family
71
How is P53 activated?
p53 is phosphorylated and released from MDM2 (inhibitor)
72
What does p53 do and what are its effects?
p53 up-regulates p21 and causes cell arrest
73
P53 is inactivated by what protein of what virus?
E6 of HPV
74
Therapeutic Implications of P53?
1. Chemotherapy and irradiation help cure cancer by inducing DNA cell damage to cause apoptosis
75
Pt has 1 inherited TP53 gene mutation. What is the disease and what does it cause?
1. Li-Fraumeni Syndrome
| 2. 25-fold increase for cancer
76
TP53 bi-allelic is common in what population?
Anyone under 40 with 1 sarcoma
77
P53 Familial syndromes
Li-Fraumeni syndrome (diverse cancers)
78
Sporadic cancers of p53
Most human cancers
79
DNA repair factors?
BRCA1/BRCA2
80
BRCA1/BRCA2: P and F
P: Breast cancer 1 and 2
F: Repair breaks in dsDNA
81
BRCA1/BRCA2: Familial syndromes
1. Familial breast/ovarian carcinoma
| 2. Chronic Lymphocytic leukemia (BRCA2)
82
Unknown Mechenisms?
WT1
83
WT1 P and F
P: Wilms tumor-1
F: Transcription Factor
84
WT1 Familial Syndromes
Familial Wilms tumor (pediatric-kidney cancer)
85
WT1 sporadic Cancers: (2)
1. Wilms Tumor
| 2. Certain Leukemias
86
Upregulation Mechanisms (4)
1. BCR-ABL translocation (philadelphia chromosome)
2. BCL-2
3. MYC proto-oncogene
4. Oncofetal Antigens
87
BCR-ABL translocation (philadelphia chromosome): P and F
P: Tyrosine Kinase
F: Upreg cell proliferation
88
BCR-ABL translocation?
9 to 22: forms the active BCR-ABL
89
BCR-ABL translocation (philadelphia chromosome): Seen in? (2)
1. CML: Chronic myelogenous leukemia
| 2. ALL: Acute lymphoblastic leukemias (Most common malignancy in western children)
90
BCL-2 P and F
P: BCL2
F: Anti-apoptotic factor
91
BCL-2 translocation?
14: 18
| - Seen in 85% of B-cell lymphomas
92
BCL-2 translocation results in?
Cell unable to undergo apoptosis
93
This member of BCL-2 is seen to increase cell survival and drug resistance in cancers?
MCL-1
94
MYC Proto-oncogene P and F
P: MYC
F: activates many genes involved in cell growth
95
MYC uses what type of signaling? What does this signaling do?
1. RAS/MAPK signaling
| 2. follows stim of quiescent cells and upregulates telomerase
96
Oncofetal Antigens Proteins (2)
CEA (Carcinoembryonic antigen)
AFP (A-fetoprotein)
97
Oncofetal Antigens Proteins expressed at high levels when?
Specifically in cancer and fetal tissues
98
Oncofetal Antigens Proteins can be used as?
Marker for cancer
99
Oncogenes created by Translocations:
1. Philly chromosome-ALL and CML (9:22)
2. AML-Acute myeloid leukemia (15:17 or 8:21)
3. Burkitt Lymphoma (8:14)
4. Mantle Cell Lymphoma (11:14)
5. Follicular Lymphoma (14:18)
100
Philly chromosome is related to?
ALL and CML
101
ALL and CML have what translocation?
9:22
102
9:22 can also be considered
Pre-leukemia
-Myelo-proliferative syndrome
103
Is 9:22 prognosis good?
Yes
104
AML (Acute myeloid leukemia) translocations?
15:17 and 8:21
105
What can 15:17 translocation cause?
Pt can bleed out from DIC (disseminated intravascular coagulation)
106
8:14 translocation is?
Burkitt Lymphoma
107
Burkitt Lymphoma is what type of lymphoma?
B-cell related to MYC oncogene
108
14:18 translocation is related to?
Follicular lymphoma
109
14: 18 is required to diagnose
you guessed it... follicular lymphoma! (B-cell lymphoma)
110
11:14 is?
Mantle Cell Lymphoma (B-cell lymphoma)
111
Virus/Bacterial Oncogenesis/carcinogenesis (7)
1. HTLV-1
2. HPV
3. EBV (Burkitt Lymphoma)
4. HBV and HCV
5. Merkel Cell Polyomavirus
6. HHV-8
7. H. Pylori
112
HTLV-1 Is found in? (4)
Japan, Caribbean and parts of South America and Africa
113
HTLV-1 causes?
Adult T-cell leukemia/lymphoma (CD4+ T cell tumor)
114
HTLV-1 encodes what viral protein?
Tax
115
What does tax do?
Tax activates growth/survival pathways (PI3K/AKT, NF-kB) in T cells
116
This virus causes benign warts, cervical cancer (squamous cell carcinoma) and oropharyngeal cancer?
HPV
117
What are 2 HPV viral proteins and what do they do?
E6: binds RB
E7: binds p53
Both proteins neutralize their proteins.
118
Ubiquitous herpes virus implicaed in pathogenesis of Burkitt lymphoma and B-cell lymphoma in Pt with T-cell immunosupression
EBV
119
70-85% of hepatocellular carcinomas are related to what virus?
HBV and HCV
120
Oncogenic effects HBV/HCV are?
multifactorial
121
What is the dominant effect of HBV/HCV?
Immunologically mediated chronic inflammation and hepatic injury.
122
What are the proteins of HBV and HCV that activate signals, leading to increased carcinogenesis?
HBV: HBx protein
HCV: Core protein
123
This virus causes neuro-endocrine skin cancer
Merkel Cell Polymomavirus
124
Kaposi sarcoma is caused by what virus?
HHV-8
125
Where do you often see Kaposi Sarcoma skin lesions?
In AIDS pts
126
What does KS look like?
Skin lesions of LE, (genitalia, mouth/gums/hard palate, GI and resp. tract) nodular/blotches. Appear red/purple and usually raised/palpable
127
This bacteria is involved with pathogenic genes like CagA and can stim GF pathways.
H. Pylori
128
Chronic infection of H. pylori can lead to?
MALT lymphoma of the stomach
-Caused by B-cell proliferations/a monoclonal B-cell tumor.
129
Paraneoplasmic Syndromes: Endocrinopathies (5)
1. Cushings Syndrome
2. SIADH (Syndrome of inappropriate ADH)
3. Hypercalcemia
4. Hypoglycemia
5. Polycythemia
130
This syndrome causes Intracranial neoplasms and small cell carcinoma of the lung.
What is its mech?
1. SIADH (syndrome of Inappropriate ADH)
| 2. ADH or ANH (atrial natriuretic hormone)
131
This causes pancreatic carcinoma, Neural tumors and small cell carcinoma?
What is its mech?
1. Cushings Syndrome
| 2. ACTH or ACTH like things
132
What cancers results in Hypercalcemia? (4)
1. Squamous cell carcinoma of lung
2. Breast Carcinoma
3. Renal Carcinoma
4. Adult T-cell leukemia/lymphoma
133
What is the mech of hypercalcemia?
PTH-related protein (PTHRP)
2. TGF-alpha
3. TNF
4. IL-1
134
The mechanism of action for this syndrome involve Insulin/insulin-like substances
Hypoglycemia
135
Cancers causing Hypoglycemia? (3)
1. Ovarian Carcinoma
2. Fibrosarcoma
3. Other mesenchymal sarcomas
136
These cancers may result in Polycythemia? (3)
1. Renal carcinoma
2. Cerebellar Hamangioma
3. Hepatocellular carcinoma
137
What is the mech of Polycythemia?
Erythropoietin
138
"other" types of Paraneoplasms? (4)
1. Neuromyopathic (nerve + Muscle)
2. Acanthosis Nigricans
3. Hypertrophic Osteoarthropathy (Clubbing of fingers)
4. Trousseau Syndrome (Migratory Thrombophlebitis)
139
Gastric carcinoma, lung carcinoma, uterine carcinoma can all generate what?
What is the causal Mech?
1. Acanthosis Nigricans
| 2. Immunologic secretion of EGF (epidermal growth factor)
140
Myasthenia gravis causes?
Neuromyopathic (N and M)
141
Myasthenia gravis can be a result of what cancers?
1. Bronchogenic Carcinoma
| 2. Thymic Neoplasms
142
CNS and PNS disorders are caused by?
Breast carcinoma
143
Hypertrophic Osteoarthropathy looks like?
Clubbing of fingers
144
What cancers can cause finger clubbing/hypertrophic osteoarthropathy?
1. Bronchogenic carcinoma
| 2. Thymic neoplasms
145
Pancreatic carcinoma and Bronchogenic carcinoma can cause?
Trousseau Syndrome (Migratory Thrombophlebitis)
146
1. Progressive loss of body fat.
2. Profound weakness, anorexia and anemia
This is? What causes number 2?
1. Cachexia
| 2. The release of factors by tumor or host immune cells
147
Tumor grades?
1. Poor
2. Mild
3. Moderate
- Done by pathologists
148
Tumor stages?
Metastisis = stage 3
Does the cancer spread?
Number of nodes/size?
-Oncologists do this
