Neoplasia-Overview of Cancer and Carcinogenesis Flashcards
Briefly describe:
- Hyperplasia
- Metaplasia
- Dysplasia
Hyperplasia- excessive proliferation of cells due to a stimuli
Metaplasia- replacement of one mature epithelium type with a more resistant type due to chronic irritation
Dysplasia- loss of uniformity of individual cells and architectural orientation
What are the differences and similarities between hyperplasia and neoplasms❓
Differences: Hyperplasia: •follows normal stimuli •Growth : Degree of stimulation •Regress with cessation of stimulation •eg endometrial hyperplasia (⬆️estrogen)
Neoplasm:
•spontaneous
•growth without stimulus
•continues indefinitely
Similarities:
- Both involve cellular proliferation
- Sites of excessive mitosis often serve as fertile soil for genetic mutation
Give a few examples of metaplasia stating:
- Location
a. Normal epithelium
b. Metaplasic epithelium
c. Cause
- Bronchus
a. Pseudostratified ciliated columnar
⬇️
b.Squamous
c. Cigarette smoking - Oesophagus
a. Squamous
⬇️
b. Columnar mucous with goblet cells(Barrett’s)
c. Reflux - Stomach
a. Simple columnar
⬇️
b. Intestinal with goblet cells
c. H. pylori - Urinary bladder
a. Transitional epithelium
⬇️
b. Squamous
c. Stones, schistosoma infection - Cervix
a. Simple columnar
⬇️
b. Squamous
c. HPV, low PH
Metaplasia and dysplasia may be premalignant.
True or false
True
What features do dysplasia and neoplasia have in common❓
- Disorderliness
- ⬆️nucleocytoplasmic ratio
- Enlarged hyperchromatic nuclei
- Pleomorphism
The 3 grades of dysplasia include❓
- Mild
•lower 1/3rd of epithelium
•Reversible - Moderate
•lower 2/3rd of epithelium
•May be reversible - Severe
•full thickness of epithelium
•irreversible
List a few tumors that start with dysplasia
Bronchus Urinary bladder Cervix Vulva Penis
List a few pre-neoplastic lesions you know and their malignancy
PML: Bronchial dysplasia
M: Carcinoma
PML: Leukoplakia➡️Erythroplakia
M: Squamous cell carcinoma
PML: Dysplasic squamous papilloma
M: Squamous cell carcinoma
PML: Chronic atrophic gastritis
M: Gastric carcinoma
PML: Chronic ulcerative gastritis
M: Adenocarcinoma
PML: cervical dysplasia
M: Squamous cell carcinoma
PML: Endometrial hyperplasia
M: Endometrial carcinoma
PML: Liver cirrhosis
M: Hepatocellular carcinoma
PML: Solar keratosis
M: SCC of skin
Define “neoplasm”
- Abnormal mass of tissue
- Growth exceeds and is uncoordinated with that of normal tissues
- Persists in the same excessive manner after cessation of stimuli
The 5 properties of a neoplastic mass
- Autonomous
- Parasitic
- Purposeless
- Progressive
- Benign/Malignant
Define cancer
- Overgrowth of cells
- Acquired cumulative of genetic damage
- which confers growth advantage over normal cells
Malignant cells have three important features
List them
- Immortality
- Invasion
- Metastasis
What are the differences between normal and malignant cells❓
In malignant cells: •🚫Contact inhibition •⬆️Growth factor secretion •⬆️oncogene expression •🚫tumor suppressor genes
Cancer is among the 3 leading causes of death in developing counties
True or false
True
The five most common cancers in Nigeria include:
- Breast- 26.7%
- Cervix- 13.8%
- Liver- 11.8%
- Prostate- 11.7%
- Colorectal- 4.1%
List the common childhood cancers
- Burkitt’s lymphoma
- Retinoblastoma
- Nephroblastoma
- Sacromas
- Leukaemias
- Neuroblastomas
- Rhabdomyosarcoma
Tumors are classified based on behavior (benign or malignant) or based on its cell if origin
True or false
True
The difference between a benign and a malignant tumor is based on:
- Spread
- Growth rate
- Boundaries
- Relations
- Effects
Briefly draw contrasts
- Spread:
B: localized
M: Metastasize - Growth rate:
B: Slow
M: Rapid - Boundaries:
B: Circumscribed and encapsulated
M: Irregular, ill-defined, no capsule - Relations:
B: Compresses
M: Invades and destroys - Effects:
B: pressure effect
M: Destroys➡️Death
Tumors can be classified broadly into:
Benign epithelial
Malignant epithelial
Benign mesenchyma
Malignant mesenchyma
True or false
True
Benign tumors are generally named by attaching -oma to the cell of origin.
True or false
Give examples of benign mesenchyma tumors
True
Fibroma Osteoma Lipoma Haemagioma (blood vessel) Lymphangioma Chondroma Meningioma Neuroma Leiomyoma (smooth muscle) Rhabdomyoma (skeletal muscle)
Benign tumors are generally named by attaching -oma to the cell of origin.
True or false
Give examples of benign epithelial tumors
True
- Papilloma- raised above an epithelial surface
- Adenoma- forms glandular structures (parenchymal organs)
- Cystadenoma- forms glands and cystic spaces
- Nevus- benign tumor of melanocytes
- Trophoblastic tumor- hydratidiform mole (placenta)
- Polyps- in hollow organs, raised above mucosa
Malignant mesenchymal tumors are generally referred to as❓
List a few that you know
Sarcomas
Liposarcoma Osteosarcoma Chondrosarcoma Haemangiosacroma/Angiosacroma Leiomyosacroma Fibrosarcoma
Malignant epithelial tumors are generally referred to as❓
List a few that you know
Carcinomas
Adenocarcinoma
Squamous cell carcinoma
Melanocarcinoma/Melanomas
Choriocarcinoma (placenta)
*organ of origin should be specified eg SCC of cervix
Mixed tumors are tumors that have more than one neoplastic cell type.
List some examples
Pleomorphic adenoma of salivary gland (epithelial and mesenchymal components)
Fibroadenoma of breast (glandular epithelial and fibrous components)
Wilm’s Tumor of kidney (malignant) commonly affecting children
The difference between a carcinoma and a sarcoma is based on:
- Cell type
- Stroma
- Spread
- Metastasis
- Hemorrhage and necrosis
- Fatality
Briefly draw contrasts
- Cell type:
C: Epithelial
S: Mesenchymal - Storma:
C: Abundant
S: Scanty, fleshy - Spread:
C: Lymphatics 1st
S: Blood 1st - Metastasis:
C: Late
S: Early - Hemorrhage and necrosis:
C: Less frequent
S: Frequent - Fatality:
C: Relatively less
S: more fatal
What is a choriostoma❓
Is it a true tumor❓
An ectopic rest of normal tissue in an abnormal location
No
What is a harmatoma❓
Is it a true tumor❓
A mass of disorganized but mature specialized cells indigenous to the site
No
Seminomas (of the testis) and melanomas are benign tumors
True or false
False
- A teratoma is a…
- What are the common site of teratomas❓
- What is a monodermal teratoma called❓
1.
•Tumor with >1 neoplastic cell
•Derived from >1 germ cell layer
•Arise from totipotential cells in the gonads or in embryonic cell rests
•Can be mature/benign or immature/malignant
2.
Ovary/Testes
Mediastinum
Sacrococcygium
- Struma ovarii
What are the differences between a benign and a malignant teratoma❓
Tumor components:
B: mature, well-differentiated structures
M: primitive, undifferentiated structures
Grossly:
B: Cystic
M: Solid
Prognosis:
B: Good
M: fatal outcome
Cancer risk increases with age
True or false
True
H. pylori predisposes one to❓
Gastric adenocarcinoma
Mucosal associated lymphoid tissue, MALT lymphoma
What microorganism predisposes an individual to hepatocellular carcinoma❓
Hepatitis B/C virus
What microorganism predisposes an individual to cervical cancer❓
Human papilloma virus
An infection by Epstein Barr virus could lead to which neoplasms❓
Nasopharyngeal carcinoma
Burkitt’s lymphoma
An infection by HIV could lead to which neoplasms❓
High grade B cell lymphoma
An exposure to schistosoma haematobium could lead to ❓
Squamous cell carcinoma of the urinary bladder
Exposure to benzene commonly leads to what neoplasm❓
Leukaemia
Aniline dyes used in rubber industries could lead to what type of cancer❓
Bladder cancer
Ultraviolet and X-ray exposure can lead to❓
Cancer of the:
- Skin
- Breast
- Thyroid
Cancer of the lungs can be due to exposure to pollution from burning fuels
True or false
True
Intake of tobacco can lead to which cancers❓
Mouth Lungs Breast Stomach Pancreas Cervix
Alcohol intake can lead to which cancers❓
Breast
Stomach
Liver
An overweight or obese individual may come down with what type of neoplasms❓
Esophagus Breast Colon Kidney Uterus cancers
Early exposure to sex could predisposed an individual to cancer of the cervix
True or false
True
Having multiple sexual partners is a rush factor for which cancers❓
Cervix (HPV)
Liver (HBV)
Colorectal cancers could be contributed to by high animal protein and fat diet
True or false
True
Aflatoxin from Aspergillus flavus commonly seen in poorly preserved grains like groundnuts are associated with which cancer❓
Hepatocellular carcinoma (HBV)
List factors that could predispose an individual to cervical cancer
Multiple sex partners Early exposure to sexual partners Smoking Poverty Immune deficiency (HIV) Poor nutrition Lack of micronutrients
List factors that could predispose an individual to prostrate cancer
⬆️serum androgen levels Black race >40 years \+ve family history Obesity ⬆️fat diet
List the inherited cancer syndromes that you know
Retinoblastoma
Familial adenomatous polyposis
Neurofibromatosis
Multiple endocrine neoplasm (MEN)
List the familial cancers that you know
Breast
Colon
Ovary
Brain
Autosomal recessive syndromes of defective DNA repair include:
Ataxia talengiectasia
Xeroderma pigmentosum
Bloom’s syndrome
Fanconi anemia
What are the diagnostic methods for tumors❓
- Histology (paraffin/frozen section)
- Cytology (FNAC, Pap smear effusions)
- Immunocytochemistry
- Molecular (oncogenes)
- Flow cytometry
- Tumor markers
The prevention of cancer includes:
Primary:
•Lifestyle modification
•Vaccination against infectious agents
Secondary: •Early detection- BSE (breast self examination) Clinical breast examination (1-3yrs age20-39) Mammography screening (annually >40)
Prophylaxis
Prompt treatment
A pap smear should be done annually in women >18yrs or with commencement of sexual activity
True or false
True
A pap smear should be done mid cycle or second half of the cycle
True or false
True
No sexual intercourse or douching should occur 24hours before a pap smear
True or false
True
The HPV/DNA testing should be done for women in what age group❓
A -ve HPV/DNA testing can be repeated after❓
30years of age
5-10years
What screening options are available for prostate cancer❓
Digital rectal exam
Prostrate Specific Antigen test
Characteristics of neoplasms include:
Differentiation/anaplasia
Rate of growth
Local invasion
Metastasis
What is differentiation in this context❓
Microscopic resemblance of a tumor to normal cells morphologically and physiologically
Anaplasia is a lack of differentiation, hence a poorly differentiated tumor is probably malignant
True or false
True
A poorly differentiated tumor or an anaplasic tumor is also known as a high grade tumor
True or false
True
What is a low grade tumor❓
A high grade tumor is❓
A well differentiated tumor
A poorly differentiated tumor
Will a well differentiated tumor retain its functions❓
Yes.
Or unanticipated functions emerge.
What are the histologic features of malignant tumors❓
- Pleomorphism
- Hyperchromatism
- ⬆️nucleocytoplasmic ratio
- Coarsely clumped chromatin
- Large, multiple, prominent nucleoli
- Mitoses (bizarre and numerous)
- Tumor giant cells
- Disorderliness/disorientation
Most benign tumors are encapsulated except❓
Haemangioma
Some malignant tumors may have a pseudocapsule. Give an example
Wilm’s Tumor
Metastasis is an important hallmark of malignancy except in ❓
Basal cell carcinoma of skin
Malignant glial tumors of the brain
- What are the most common sites of metastasis❓
2. What is the most uncommon site of metastasis❓
1. Lungs Liver Bone Brain Kidney
- Spleen
Metastatic cascade is broadly divided into❓
Invasion of extracellular matrix
Vascular dissemination and homing of tumor cells
Describe the metastatic cascade that occurs in cells that acquire a metastatic potential.
🚫Ability to adhere to each other (get detached)
⬆️Ability to adhere to BM and ECM
Degradation of ECM
Migration through the ECM
Cells form aggregates within vessels
Migrate through BM of secondary site
Formation of tumor emboli at secondary sites
What does a “grade” mean❓
Level of microscopic resemblance of tumor cells to normal similar cells of origin
Prostatic carcinoma is graded using❓
Gleason’s system
SCC of cervix is graded using❓
Extent of keratin formation
How are tumors graded❓
Grade I- Well differentiated
Grade II- Moderately differentiated
Grade III- Poorly differentiated
Grade IV- Nearly anaplastic
Staging refers to❓
Extent of tumor spread based on:
Size of primary tumor
+/-lymphatic spread
+/-distant blood borne metastasis
The two systems used in staging cancers are❓
1. TNM: Tumor size [0-4] Node [0-3] Distant metastasis [M0/M1]
- AJC:
I-IV
Tis stage of a cancer depicts❓
Carcinoma in-situ
Tumor limited to the epithelium
T2 stage of a cancer depicts❓
Larger, more invasive within the primary organ site
T3 stage of a cancer depicts❓
Larger and/or invasive beyond margins of primary organ site
N1
N2
N3
stages of cancer depict❓
N1: regional lymph node involvement
N2: extensive lymph node involvement
N3: More distant lymph node involvement
Carcinogenesis refers to❓
Malignant transformation of normal cells by carcinogenic agents (physical, chemical or microbiological)
- Give some examples of physical carcinogens you know
- What are their effects❓
- What cancers could be involved❓
1. Ionization radiation X-ray Radiotherapy UV light Atomic energy
- Chromosomal changes in cell mutation
3. Melanocarcinoma Basal cell ca SSC of Skin Leukemia Thyroid Breast
Chemical carcinogens can be:
- Direct acting
- Indirect acting
- Promoters
Describe the mechanisms of these three categories in carcinogenesis
- •Electrophylic region easily forms covalent bonds with DNA
•eg alkylating agents like anti cancer drugs
- •Have to be converted to active metabolites in the liver
•eg polycyclic hydrocarbon in the cigarette
Beta-naphthylamine in anyline dye
- Aflatoxin B1
The general sequence of chemical carcinogens include:
- Initiation- DNA alteration and subsequent cell division (mitosis)
- Promotion- proliferation of initiated cell at the expense of normal cells
- Effect: progression/dormancy/regression
- An exposure to arsenic could to lead to what cancer❓
2. Who are the people most exposed to it❓
- Lung
Liver
Skin - Mining
Pesticide workers
- An exposure to asbestos could to lead to what cancer❓
2. Who are the people most exposed to it❓
1.
Lung
Mesothelioma
- Construction workers
- An exposure to benzene could to lead to what cancer❓
2. Who are the people most exposed to it❓
1.
Leukemia
- Petroleum
Rubber
Chemical workers
- An exposure to chromium could to lead to what cancer❓
2. Who are the people most exposed to it❓
1.
Lung
- Metal workers
Electroplaters
- An exposure to leader dust could to lead to what cancer❓
2. Who are the people most exposed to it❓
- Nasal
Bladder cancers - Shoe manufacturers
- An exposure to naphthylamine could to lead to what cancer❓
- Who are the people most exposed to it❓
- Bladder
- Dye
Rubber
Chemical workers
- An exposure to radon could to lead to what cancer❓
2. Who are the people most exposed to it❓
- Lung
- Underground mining
- An exposure to soot, tars and oils could to lead to what cancer❓
- Who are the people most exposed to it❓
- Lung
Liver
Skin - Coal
Gas
Petroleum workers
- An exposure to vinyl chloride could to lead to what cancer❓
- Who are the people most exposed to it❓
- Liver
- Rubber
PVC manufacturing
- An exposure to wood dust could to lead to what cancer❓
2. Who are the people most exposed to it❓
- Nasal
- Furniture making
Tumors are monoclonal
True or false❓
What does this mean❓
True
A tumor mass results from a clonal expansion of a single progenitor cell that has incurred genetic change
The targets of mutation include❓
Tumor promoter
Tumor suppressor
Apoptotic genes
DNA repair genes
An infection by what virus can cause a T-cell leukemia❓
HTLV-1
What organism predisposes an individual to cholangiocarcinoma❓
Liver fluke
What are proto-oncogens❓
Normal constituents of the cell that promote normal cell growth and differentiation
They are also known as tumor promoters
What are oncogenes❓
- Gene sequences that can transform normal cell to cancer cells
- Derived from proto-oncogenes
- Produce onco-proteins (growth factors, membrane products and proteins that control growth and differentiation)
Are tumor promoters dominant or recessive❓
What does this mean❓
Dominant
Only one mutant allele of the gene need to be present to cause transformation
What could lead to the conversion of proto-oncogenes➡️oncogens❓
•Point mutations:
ras
•Translocation:
c-myc in Burkitt’s lymphoma
c-abl in CML
•Amplification:
n-myc in neuroblastoma
c-erb in breast carcinoma
Are tumor suppressor dominant or recessive❓
What does this mean❓
Abnormalities that can lead to cancer are❓
Recessive
Two alleles of the gene must be damaged to transform cells
Deletion or inhibition
Give examples of the antioncogens you know
Rb
p53
APC
NF-1, NF-2
BRCA-1, BRCA-2
WF-1 genes
Apoptotic genes may be dominant or recessive.
A deletion of an apoptotic gene may lead to cancer.
True or false
Give examples
True
p53
c-myc
bcl-2 gene in b-cell lymphoma
- DNA repair genes are the care-taker genes.
- Are they dominant or recessive❓
- Inactivation of these genes with lead to❓
- Give a few examples
- Recessive
- Both alleles must be lost to induce genomic instability
- Increased mutation of all other genes including those that control cell division
- BRCA-1, BRCA-2 in breast ca
MLH1, MSH2 mutation in HNPCC
List some effects of malignant tumors on the host
Compression eg pituitary adenoma on optic chaism
Functional activity eg insulinoma
Hemorrhage
Secondary infection
Infarction/Rupture
Cancer cachexia
Paraneoplastic syndrome
What are paraneoplastic syndromes❓
Classify them
A symptom complex that occurs in a cancer patient that cannot be explained by local/distant spread of the tumor
Endocrinopathies Dermatological Nerve and muscle Bone and joint Vascular/heamatological
- Cushing’s syndrome is a paraneoplastic syndrome that may be observed in which carcinomas❓
- What is it’s feature❓
- Small cell ca of the lungs
Pancreatic carcinoma
Neural tumors
2.
Secretion of ACTH-like substances
- Paraneoplastic Syndrome of Hyponatrimia may be a complication of which cancers❓
- What is it’s feature❓
- Small cell ca
Intracranial tumors - Inappropriate ADH secretion
- Paraneoplastic Syndrome of Hypoglycemia may be a complication of which cancers❓
- What is it’s feature❓
1.
Fibrosarcoma
HCC
2.
Insulin-like substances
- Carcinoid syndrome is a paraneoplastic syndrome that may be a complication of which cancers❓
- What is it’s feature❓
- Bronchial adenoma (carcinoid)
Pancreatic ca
Gastric ca
2. Secretion of: Serotonin Bradykinin Histamine
- Paraneoplastic Syndrome of Hypercalcaemia may be a complication of which cancers❓
- What is it’s feature❓
- Squamous cell carcinoma
2. Secretion of: •Parathormone-like substance •IL-1 •TNF-alpha •TGF-alpha
- Paraneoplastic Syndrome of Polycythemia may be a complication of which cancers❓
- What are their features❓
- Renal cell ca
HCC
Cerebellar haemangioma - Erythropoietin
