Neoplasia Flashcards
Is Neoplasia reversible?
No
Is hyperplasia reversible?
Yes
Neoplasia is caused by
genetic mutations
Is a tumor or neoplasm benign or malignant?
Can be either
Is Cancer benign or malignant?
Malignant-it can grow into the surrounding tissue and metastisize
What is an -oma
benign mesenchymal tumor
Glandular epithelial benign tumor
Adenoma
Papilloma
Benign- Raised spot on skin
Malignant mesenchymal tumor
Sarcomas
Epithelial tumors malignant
carcinomas
Glandular tumors malignant
carcinomas
Squamous epithelium malignant
squamous cell carcinoma
Adipose tissue benign and malignant tumor names
lipoma and liposarcoma
Fibrous tissue benign and malignant tumor
Fibroma and fibro sarcoma
Cartilage benign and malignant
chondroma and chondrosarcoma
Bone benign and malignant
Osteoma and osteosarcoma
Smooth muscle benign and malignant
Leiomyoma and leiomyosarcoma
How to treat cancer (2)
Chemo to kill cells or stop angionesis
Anaplastic
Cell does not look likely any normal cell (complete undifferentiaiton)
Benign tumors differentiated?
Well differentiated (they look like tissue they are from)
Malignant tumors differentiated
They are undifferentiated, some can even be aplastic
What characterizes a well-differentiated, moderately differentiated, poorly differentiated and anaplastic neoplasm?
a. How well does each resemble normal tissue?
Well differentiated resemble, undifferentiated or aplastic do not
Nucleus of cancer cells
Dark and bigger because more DNA
Describe the atypical cytology associated with malignant neoplasms and be able to recognize these features on a histological section of a tumor (4ish)
Pleomorphic nuclei and cells
Mitotic figures: DNA doubles and condenses-increased
Nuclei are dark, large-hyperchromatic
Increased cytoplasm to cell ratio
If comparing a microscopic image of a normal tissue with that of a neoplasm from the same type of tissue,
be able to identify if it is either a well differentiated benign neoplasm or a poorly differentiated or anaplastic malignant neoplasm.
Cells look similar-not exact. look for arrangement and if similar they are benign well differentiated.
Malignant can be any of these options…
If it looks like a random mess it is probably anaplastic
Define local invasion of a tumor and metastases.
Benign tumors-nearly all grow as a cohesive mass with a capsule around it
Metasisis or malignant tumors may grow and destroy surrounding tissue as well as distant sites..
What is the primary tumor, what is the secondary tumor?
Primary tumors are benign and do not metastasize
Secondary tumors metastasize and are MARKED AS MALIGNANT
What one characteristic definitively identifies a tumor as malignant?
It spreads-metastasizes
Tumors that are well demarcated with a surrounding capsule tend to be benign or malignant?
Benign
Liver tumors benign and malignant
hepatoma and hepatocellular carcinoma
Benign glandular epithelium tumor includes what (1)
Thyroid adenoma
Benign and malignant tumors of the urothelium
you will see the tumors of the epithelial layer of the bladder being called either urothelial papilloma/carcinoma or transitional cell papilloma/carcinoma.
Organ cuts of benign and malignant tumors appear how
An organ cut with a benign tumor is smooth/clean cut, malignant has been infiltrated and is a mess
Organ cuts of benign and malignant tumors appear how
An organ cut with a benign tumor is smooth/clean cut, malignant has been infiltrated and is a mess
Tumors that are not well demarcated and have infiltrated the ‘normal’ tissue tend to be benign or malignant?
Malignant
Compare the 3 main ways that cancers can spread or metastasize?
Which do carcinomas use more and which do sarcomas use more?
Seeding into a body cavity-neoplasms
Lymphatics-carcinomas mainly
Blood (hematogenous)-Sarcomas mainly
Which cancers can spread by seeding into a body cavity
More often from neoplasms that impinge upon body cavities, tumor; they must be adjacent to the cavity
Ex: GI tract tumor from ovary, breast carcinoma spreading to pleura
in lung
Which cancers tend to spread more often via lymphatics? By hematogenous spread?
Seeding into a body cavity-neoplasms
Lymphatics-carcinomas mainly
Blood (hematogenous)-Sarcomas mainly
Explain why the liver and the lungs are the most common sites of metastasis from hematogenous spread.
all the blood goes through the lungs and the liver has the hepatic portal vein dumping into it
Define gain of function mutation/loss of function mutation.
Only need a mutation in one allele for gain of function mutation. .. If it is over-expressed too much protein is made or it is just always being made
LOF mutation:
In generic terms, describe the pathway leading from activation of a growth factor receptor to cell proliferation. (e.g. Activation of a growth factor receptor lead to a signaling pathway that…).
Proto-onco gene: GF binds receptor –> signaling pathway (Ras) –> increases transcription factor (Myc) –> increased protein production –> increased cell division and expression of CDK4
What defines a proto-oncogene,
Proto-onco gene: GF binds receptor –> signaling pathway (Ras) –> increases transcription factor (Myc) –> increased protein production –> increased cell division and expression of CDK4
What defines a proto-oncogene, an oncogene, a tumor suppressor gene?
b. Why is a mutation in one allele sufficient for an oncogene to contribute to carcinogenesis
Growth promoting proto-oncogenes: if mutated, over
expressed or always on or constitutively active (ex:
HER2, Ras, MYC, CDK4)
i. Cause uncontrolled growth or progression
through the cell cycle
ii. Only need a mutation in one allele
In this case if one allele has a mutation it will either produce to much protein or just always be on, either way you get more than you should
The largest percentage of liver metastases
arise from primary cancers in the: A. Breast B. Colon C. Esophagus D. Kidneys E. Lungs F. Skin
Colon
Why is a mutation in one allele sufficient for an oncogene to contribute to carcinogenesis, whereas both alleles need to be mutated with a tumor suppressor gene?
Need mutation in both alleles in order for nothing to be stopped or fixed…
Why is a mutation in one allele sufficient for an oncogene to contribute to carcinogenesis, whereas both alleles need to be mutated with a tumor suppressor gene?
Need mutation in both alleles in order for nothing to be stopped or fixed…
proto-oncogene, an oncogene, a tumor suppressor gene
c. How do they affect the cell cycle and cell growth and thereby cause malignant transformation? Use HER2, Ras, MYC and RB as examples.
Proto-onco genes: if these are mutated they produce too much GF causing cell growth… (i.e. HER2, Ras which turn on MYC and CDK4)
Growth inhibiting tumor suppressors such as Rb will inhibit growth and if their is two allele mutations it will lose function and lead to excessive proliferation
Onco-genes: drive the proliferation of cells, tumor suppressor
genes apply the breaks to cells (esp TP53, which is a tumor
suppressor/anti-oncogene)
proto-oncogene, an oncogene, a tumor suppressor gene?
d. Explain how mutations in the ‘guardian’ tumor suppressor genes (e.g. TP53) can contribute to malignant transformation and carcinogenesis.
Oncogenes drive the proliferation of cells, tumor suppressor
genes apply the breaks to cells- they reduce their activity and keep them in check…(esp TP53, which is a tumor
suppressor/anti-oncogene)
- Compare how mutations in anti-apoptotic genes, pro-apoptotic genes, and DNA repair genes contribute to carcinogenesis.
Pro-apoptotic: have a LOF- too few of them
Anti-apoptotic: GOF-1 mutation-too many
DNA Repair genes: If you cannot repair DNA it will lead to cancer
There are several pro-apoptotic (e.g. BAX) and anti-apoptotic (e.g. BCL2) proteins. BCL2 has been show to be mutated in some lymphomas. The mutation is most likely a:
A. Gain of function mutation and both alleles are mutated B. Gain of function mutation and only one allele is mutated C. Loss of function mutation and both alleles are mutated D. Loss of function mutation and only one allele is mutated
B. Gain of function mutation and only one
allele is mutated
BRCA1 and BRCA2 are genes involved in breast cancer. They produce proteins that interacts with several other proteins to repair double-stranded breaks in DNA. Based on this, BRCA1 and BRCA2 would be considered:
A. Oncogenes
B. Tumor suppressor genes
B. Tumor Supressor Genes
Panitumumab is a monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR) and is approved for the treatment of K-Ras mutation-negative (wild-type), EGFR- overexpressing metastatic colorectal cancer. This drug will most likely lead to:
A. Activation of the downstream signaling
molecule, K-Ras
B. Cell cycle arrest
C. DNA repair
D. Increased transcription of anti-apoptotic
genes E. Necrosis
B. Cell cycle arrest
Panitumumab is a monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR) and is approved for the treatment of K-Ras mutation-negative (wild-type), EGFR- overexpressing metastatic colorectal cancer. This drug will most likely lead to:
A. Activation of the downstream signaling
molecule, K-Ras
B. Cell cycle arrest
C. DNA repair
D. Increased transcription of anti-apoptotic
genes E. Necrosis
B. Cell cycle arrest
Explain tumor progression and tumor heterogeneity.
This can explain what 3 things
Tumors become less well differentiated and more aggressive with
time via more mutations –> subpopulations of cells with new genetic
abnormalities
Progression and tumor heterogeneity can explain:
1. Why a primary tumor may respond to a chemotherapeutic
agent, but the secondary tumor (metastases) may not
2. Why, as time goes by, tumors are harder to treat (more
resistant to chemotherapy)
3. Why a recurrent tumor is usually resistant to therapy
tumor progression and tumor heterogeneity.
a. What role does genetic mutations play in this? (3)
They become harder to treat, less predictable, and less differentiated
Tumor progression and tumor heterogeneity….
b. How does this affect the response to therapy of the primary and metastatic tumors, and to recurrent tumors?
**Same 3 explanations of progression and heterogenecity
Progression and tumor heterogeneity can explain:
- Why a primary tumor may respond to a chemotherapeutic
agent, but the secondary tumor (metastases) may not - Why, as time goes by, tumors are harder to treat (more
resistant to chemotherapy) - Why a recurrent tumor is usually resistant to therapy
- Compare the number of possible doubling times between normal cells and cancer cells. Why is this important?
Cancer Cells have Limitless replicative potential..
Most normal cells have capacity for 60-70 doublings, but cancer cells need to be able to divide indefinitely
- Explain angiogenesis in a tumor.
Focus on: Briefly, what is VEGF, where is it produced and what does it do? Why is this important?
The tumors metastasize into vessels via breaking into the basement membrane… They can then spread to other tissue and will die and be necrotic if they do not get nutrients
Macrophage tries to eat tumor, can’t, both macrophage and tumor
release angiogenic growth factor VEGF (vascular endothelial growth
factor) –> growth of new blood vessels into the tumor
- Describe the problems with benign and malignant tumors.
(3)
a. What can happen if they impinge on other structures, have uncontrolled secretion of hormones or ulcerate through adjacent surfaces?
Clinical aspects of neoplasia
i. Problems with both malignant and benign tumors
1. Impingement on adjacent structures
2. Functional activity (e.g.: hormone production)
3. Ulceration through adjacent surfaces causing bleeding and
infections
- Describe the problems with benign and malignant tumors.
b. Define cachexia and explain the associated symptoms?
ii. Cachexia: loss of body mass that cannot be reversed nutritionally
1. Starvation: reduced food intake, decreased basal metabolic
rate
2. Cancer cachexia: reduced food intake, increased BMR
3. Both lead to loss of fat and lean muscle, profound weakness,
anorexia, anemia
iii. Management of cancer cachexia
1. Nutritional counseling, resistance training and increase of
physical activity, psychosocial support, symptom control
