Neoplasia Flashcards
What are the stages of neoplastic progression?
- Normal cell: basal to apical differentiation.
- Hyperplasia: increased number of cells
- Dysplasia: abnormal proliferation of cells with loss of size, shape and polarity.
- Carcinoma In Situ: high N:C ratio & clumped chromatin, neoplastic cells have not yet invaded and encompass the entire thickness.
- Invasive Carcinoma: invasion of basement membrane via collegenase and hydrolases (Metalloproteases).
- Metastasis: reach blood or lymphatics and spread to distant site (seed soil theory: seed is a tumor embolus, soil is the distant site).
What are the hallmarks of a cancer?
Cancers are characterized by evasion of apoptosis, self sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replication potential, tissue invasion, and metastasis. It is essentially unregulated growth.
How to tumors evade immune surveillance?
Tudors evade immune surveillance by down regulating the expression of MHC class I on cells. Therefore the abnormal proteins that are usually displayed on MHC class I cannot be targeted by CD8 T-cells. This is necessary for tumor survival.
Differentiate hypertrophy and hyperplasia.
Hypertrophy involves an increase in cellular size and controlled by gene activation, protein synthesis, increased organelle production). It occurs in permanent cells such as nerve and muscle.
Hyperplasia is an increased number of cells from the production of stem cells.
What are the reversible -plasias and their characteristics?
Hyperplasia: increased number of cells.
Metaplasia: stress induced (smoking/GERD), one adult cell is replace by another.
Dysplasia: commonly pre-neoplastic (CIN) it is abnormal growth with loss of size, shape, polarity of the cell.
What are the irreversible -plasias and their characteristics?
Anaplasia: abnormal cells lacking differentiation, primitive looking, little to resemblance to tissue of origin.
Neoplasia: a clonal proliferation of cells that is uncontrolled, and excessive. It may be malignant or benign.
Desmoplasia: fibrous tissue formation in response to neoplasia.
What is the difference between Tumor Grade & Tumor Stage?
Tumor Grade is degree of cellular differentiation based on histological appearance of tumor. Graded I (well differentiated) - IV (poorly differentiated). It’s the character of the tumor itself.
Tumor stage is the degree of localization/spread based on site/size of primary lesion, spread to regional lymph nodes, presence of metastasis, and uses TNM Staging system. Tumor Stage has the best Prognostic value! T: size of Tumor. N: Node involvement. M: Metastasis (the most important prognostic value).
What is the difference between the term carcinoma and sarcoma?
Carcinoma implies epithelial origin, while sarcoma implies mesenchymal origin. Both are malignant.
What is the benign:malignant term describing tumors involving:
Melanocytes
Epithelium
Blood cells
Benign: Malignant
Melanocytes = nevus (mole):melanoma
Epithelium= adenoma:adenocarcinoma or papilloma:papillary carcinoma
Blood cells have no benign tumors and are termed leukemia/lymphoma.
What is the benign:malignant term describing tumors involving:
Blood vessels
Smooth muscle
Skeletal muscle
Benign:malignant
Blood vessels= hemangioma: angiosarcoma
Smooth muscle= leiomyoma:leiomyosarcoma
Skeletal muscle= rhabdomyoma:rhabdomyosarcoma
What is the benign:malignant term describing tumors involving: Connective Tissue Bone Fat >1 cell type
Benign:malignant Connective Tissue= fibroma:fibrosarcoma Bone= osteoma:osteosarcoma Fat= lipoma:liposarcoma >1 cell type= mature teratoma (women): mature & immature teratoma (men)
Compare the characteristics of a benign and malignant tumor:
Benign tumors are well differentiated, slow growing and organized, well demarcated and have a uniform nuclei, lack invasion, minimal mitotic activity and a low N:C ratio, mobile and not fixed in the tissue.
Malignant tumors are poorly differentiated, have erratic growth patterns, locally invasive, may metastasize, have lost polarity, are fixed to the surrounding tissue, nuclear polymorphism, high N:C ratio, high mitotic activity.
Compare the metaplasia that occurs in Barrett Esophagus vs that of Smoking
In Barrett Esophagus the metaplasia caused by GERD occurs in the normally nonkeratinized squamous epithelium of the esophagus to be replaced by glandular non-ciliated mucin producing columnar cells.
In smokers, the cilia is lost, and the affect on the bronchioles impacts the pseudostratified columnar cells to be replaced with squamous epithelium.
What is keratomalacia and what is it caused by?
Keratomalacia is a metaplasia of the conjunctiva caused by vitamin A deficiency and marked by the replacement of the thin squamous lining to a stratified squamous lining that is keratinized.
What is myositis ossificans?
Myositis ossificans is bony growth that occurs after contusion or strain. It is a metaplasia in which muscle is replaced with bone tissue.
What rank does cancer have in causes of death in adults and children in the US?
It is the 2nd leading cause of death followed by cerebrovascular. The primary cause of death remains cardiovascular disease.
What are the 3 main incidents and mortality of males and females with cancer?
Males: Incidence- prostate 32%, Lung 16%, colorectal 12%.
Death-lung 33% & Prostate 13%
Females: Incidence- Breast 32%, Lung 13%, colorectal 13%
Death-Death-lung 23% & Breast 18%
Give the oncogene and gene product for the following tumor associations:
Burkett’s Lymphoma
C-myc and transcription factor
Give the oncogene and gene product for the following tumor associations:
CML
abl; tyrosine kinase
Give the oncogene and gene product for the following tumor associations:
Follicular & undifferentiated lymphomas (inhibit apoptosis)
Bcl-2; anti-apoptotic molecule
Give the oncogene and gene product for the following tumor associations:
Breast, ovarian, and gastric carcinomas
erb-B2; tyrosine kinase
Give the oncogene and gene product for the following tumor associations:
Colon carcinomas
Ras; GTPase
Give the oncogene and gene product for the following tumor associations:
Lung tumor
L-myc; transcription factor
Give the oncogene and gene product for the following tumor associations:
Neuroblastoma
N-myc; transcription factor
Give the oncogene and gene product for the following tumor associations:
Multiple endocrine neoplasia types 2A &2B
Ret; tyrosine kinase
Give the oncogene and gene product for the following tumor associations:
Gastrointestinal stromatolites tumor (GIST)
C-kit; cytokine receptor
Give the tumor suppressor gene mutated & gene product for the following tumor associations:
Retinoblastoma and osteosarcoma
Rb; Rb when not phosphorylated holds E2F and blocks G1 to S phase transition of cell cycle.
Give the tumor suppressor gene mutated & gene product for the following tumor associations:
Most human cancers and Li-Fraumeni syndrome
p53; p53 normally induces apoptosis via increased expression of Bax and decreased expression of Bcl-2, which blocks the progression of G1 to S phase of the cell.
Give the tumor suppressor gene mutated & gene product for the following tumor associations:
Breast & ovarian cancer
BRCA1; DNA Repair protein
Give the tumor suppressor gene mutated & gene product for the following tumor associations:
Breast cancer only
BRCA2; DNA Repair protein
Give the tumor suppressor gene mutated & gene product for the following tumor associations:
Melanoma
p16
Give the tumor suppressor gene mutated for the following tumor associations:
Colorectal cancer associated with FAP
APC
Give the tumor suppressor gene mutated for the following tumor associations:
Wilm’s tumor
WT1
Give the tumor suppressor gene mutated for the following tumor associations:
Neurofibromatosis type 1 & 2
NF1 & NF2
Give the tumor suppressor gene mutated for the following tumor associations:
Pancreatic cancer
DPC
Deleted Pancreatic Cancer
Give the tumor suppressor gene mutated for the following tumor associations:
Colon cancer
DCC
Deleted Colon Cancer
Compare oncogenes and tumor suppressor genes and how they can cause cancer.
Oncogenes need damage to only 1 allele which causes a gain in function = cancer.
Tumor suppressor genes need a “double hit” to two alleles which causes a loss in function = cancer.
What neoplasms are associated with Down Syndrome?
ALL , AML
What neoplasms are associated with Xeroderma pigmentosum and albinism?
Melanoma, basal cell carcinoma, and especially squamous cell carcinomas of the skin.
What neoplasm is associated with chronic atrophic gastritis, pernicious anemia, and post surgical gastric remnants?
Gastric carcinoma
What neoplasms are associated with tuberous sclerosis (facial angiofibroma, seizures, & mental retardation)?
Astrocytoma, angiomyolipoma, and cardiac rhabdomyoma.
What neoplasm is associated with actinic keratosis?
Squamous cell carcinoma of the skin
What neoplasm is associated with Barret’s esophagus?
Esophageal adenocarcinoma (metaplasia to mucin secreting columnar cells.
What neoplasm is associated with Plummer-Vinson syndrome (atrophic glossitis, esophageal webs, anemia, all due to iron deficiency) ?
Squamous cell carcinoma of the esophagus
What neoplasm is associated with Cirrhosis ( alcohol, Hepatitis B/C) ?
Hepatocellular carcinoma
What neoplasm is associated with Ulcerative colitis?
Colonic adenocarcinoma
What neoplasms are associated with Paget’s disease of bone?
Secondary osteosarcoma and fibrosarcoma.
What neoplasm is associated with immunodeficiency states?
Malignant lymphomas
What neoplasms are associated with AIDS?
Aggressive malignant Non-Hodgekin’s Lymphoma & Kaposi’s Sarcoma.
What neoplasm is associated with autoimmune diseases ( ie Hashimoto’s Thyroiditis, myasthenia gravis)?
Lymphoma
What neoplasm is associated with Acanthosis nigricans (hyperpigmentation and epidermal thickening)?
Visceral malignancy (stomach, lung, & uterus).
What neoplasm is associated with Dysplastic nevus?
Malignant melanoma
What neoplasms are associated with Radiation exposure?
Sarcoma & Papillary thyroid cancer.
What is cachexia and what is it mediated by?
Cachexia: Loss of weight, muscle atrophy, fatigue, and loss of appetite in somebody not actively trying to lose weight. It occurs in chronic diseases (ie cancer, AIDS, HF, and TB).
It is mediated by TNFalpha (nicknamed cachectin), IFNgamma, & IL-6.
What type of cancer does ionizing radiation (nuclear reactor accident /radiotherapy) cause and what is its method of damage?
Ionizing radiation causes AML, CML, & Papillary carcinoma of thyroid. It’s method of cellular damage is via free radicals.
What types of cancer does non-ionizing radiation (UVB sunlight) cause and what is its method of damage?
Non-ionizing radiation causes basal cell carcinoma, squamous cell carcinoma, and melanoma.
It’s method of damage is via the formation of pyrimidine diners in the skin which are normally excised by restriction endonucleases.
What is cachexia and what is it mediated by?
Cachexia is loss of weight, muscle atrophy, fatigue, and loss of appetite in somebody not actively trying to loss weight. It occurs in chronic disease (ie cancer, AIDS, HF, and TB).
It is mediated by TNFalpha (nicknamed cachectin), IFNgamma, & IL-6.
What type of cancer does ionizing radiation (nuclear reactor accident /radiotherapy) cause and what is its method of damage?
Ionizing radiation causes AML, CML, & Papillary carcinoma of thyroid. It’s method of cellular damage is via free radicals.
What types of cancer does non-ionizing radiation (UVB sunlight) cause and what is its method of damage?
Non-ionizing radiation causes basal cell carcinoma, squamous cell carcinoma, and melanoma.
It’s method of damage is via the formation of pyrimidine diners in the skin which are normally excised by restriction endonucleases.
Aflatoxins are produced by what, affect which human organ, and predispose to what cancer?
Aflatoxins are produced by the fungi Aspergillus found in contaminated grains, affect the liver, and predispose to Hepatocellular carcinoma.
Vinyl Chloride is produced by what, affect which human organ, and predispose to what cancer?
Vinyl Chloride affect the liver, and predispose to angiosarcoma.
CCl4 are produced by what, affect which human organ, and predispose to what cancer?
CCl4 are an occupational hazard in the production of PVC, affect the liver, and predispose to centrilobular necrosis & fatty change.
Nitrosamines are produced by what, affect which human organ, and predispose to what cancer?
Nitrosamines are found in smoked foods, affect the stomach, and cause gastric cancer.
Cigarette smoke produced what harmful chemical, affect which human organs, and predispose to what cancers?
Cigarette smoke produces polycyclic hydrocarbons. They are the cause of cancer in the following organs:
Larynx-squamous cell carcinoma
Lung-squamous & small cell carcinomas
Kidney-renal cell carcinoma (invades renal a.)
Bladder-transitional cell carcinoma.
Asbestos affect which human organ, and predispose to what cancer?
Asbestos affect the lung and cause mesothelioma and bronchogenic carcinoma.
Note that you are most likely to get lung cancer but mesothelioma is specifically caused by asbestos.
Aresenic which is also found in cigarette smoke, affects which human organ, and predisposes to what cancers?
Arsenic affects the skin and liver. In the skin it causes squamous cell carcinoma and in the liver it causes angiosarcoma.
Naphthalene (aniline) dyes also produced by cigarette smoke affect which human organ, and predispose to what cancer?
Napthalene (aniline) dyes affect the urothelium of the bladder and cause transitional cell carcinoma.
Alkylation agents are produced by what, affect which human organ, and predispose to what cancer?
Alkylating agents are a side effect of chemotherapy and disseminate in the blood. They can cause leukemia and lymphoma.
The following microbe is associated with what cancer?
HTLV-1
Adult T-cell Leukemia/lymphoma
The following microbe is associated with what cancer?
HBV, HCV
Hepatocellular carcinoma
The following microbe is associated with what cancer?
EBV
EBV: Burkitt’s Lymphoma, Hodgekin’s Lymphoma, and nasopharyngeal carcinoma.
The following microbe is associated with what cancer?
HPV
HPV is associated with cervical cancer (16,18), Penile/anal cancer.
The following microbe is associated with what cancer?
HHV-8
HHV-8 Kaposi’s sarcoma, body cavity fluid B-cell lymphoma.
The following microbe is associated with what cancer?
HIV
Primary brain (CNS) Lymphoma
The following microbe is associated with what cancer?
H-pylori
Gastric adenocarcinoma and lymphoma.
The following microbe is associated with what cancer?
Schistosoma haematobium
Found in Egypt it can cause squamous cell carcinoma of transitional epithelium in the bladder.
Small cell lung carcinoma is associated with paraneoplastic syndrome secreting what hormone/agent and has what type of effect?
Small cell carcinoma secreted ACTH or ACTH-like peptide and caused Cushing’s syndrome. They also cause ADH and cause SIADH. Also produce anti-bodies against calcium channels at neuromuscular junction and cause Lambert-eaton syndrome (muscle weakness).
Intracranial neoplasm is associated with paraneoplastic syndrome secreting what hormone/agent and has what type of effect?
Intracranial neoplasms secrete ADH and cause SIADH.
Squamous cell lung carcinoma, renal cell carcinoma, amd breats cancer are associated with paraneoplastic syndrome secreting what hormone/agent and has what type of effect?
PTH-related peptide, TGFbeta, TNF, & IL-1 cause hypercalcemia.
Thymoma is associated with paraneoplastic syndrome secreting what hormone/agent and has what type of effect?
Thymoma produces antibodies against presynaptic calcium channels at neuromuscular junction. It causes Lambert-Eaton syndrome (muscle weakness).
Leukemias and lymphomas are associated with paraneoplastic syndrome secreting what hormone/agent and has what type of effect?
Leukemia and lymphoma produce hyperurecenia due to excess nucleic acid turnover (cytotoxic therapy). It causes gout and urate nephropathy.
Renal cell carcinoma is associated with paraneoplastic syndrome secreting what hormone/agent and has what type of effect?
Renal cell carcinoma:
EPO = polycythemia
PTHrelated peptide, TGFbeta, TNF, & IL-1 = hypercalcemia
Hemagioblastoma, Hepatocellular carcinoma, renal cell carcinoma, and pheoochromocytoma are associated with paraneoplastic syndrome secreting what hormone/agent and has what type of effect?
Hemagioblastoma, Hepatocellular carcinoma, renal cell carcinoma, and pheoochromocytoma generate EPO and cause polycythemia.
What are psammoma bodies and in which diseases are they found in?
Psammoma bodies are mineralized bodies composed usually of a central capillary surrounded by concentric whorls in various stages of hyaline change and mineralization. Psammoma bodies are round microscopic calcific collections. It is a form of dystrophic calcification. Necrotic cells forms the focus for surrounding calcific deposition.
They can occur in benign and malignant epithelial tumors (such as papillary ovarian or thyroid carcinoma).
PPASSMM
Papillary adenocarcinoma of thyroid
Prolactinoma
Adenocarcinoma of lung
Serous papillary cystadenocarcinoma of ovary
Somatostatinoma
Meningioma
Malignant mesothelioma
What is the tumor marker for thyroid medullary tumor?
Calcitonin
Thyroid medullary carcinoma
What is the tumor marker for Pancreatic adenocarcinoma?
CA-19-9
For pancreatic adenocarcinoma
What is the tumor marker for hairy cell leukemia (B cell neoplasm)?
TRAP - tartrate-resistant acid phosphatase
“TRAP the hairy animal”
What is the tumor marker for neuroblastoma, lung and gastric cancer?
Bombesin
For neuroblastoma, lung, and gastric cancer
What is the tumor marker for bone metastasis, obstructive biliary disease, and Paget’s disease?
Alkaline phosphatase
For bone metastasis (phosphate storage with active enzyme site) and bike duct has phosphatase enzyme.
What is the tumor marker for melanoma, neural tumors, and astrocytes?
S-100
For melanoma, neural tumors and astrocytes
“MAN look at that S-100 car”
What is the tumor marker for ovarian and malignant epithelial tumors?
CA-125
For ovarian and malignant epithelial tumors
What is the tumor marker for hydatidiform moles, choriocarcinomas, & gestational trophoblastic tumors?
Beta-hCG
for H(hydatidiform moles)
C(choriocarcinomas)
G(gestational trophoblastic tumors)
What is the tumor marker for Hepatocellular carcinomas, and nonseminiferous germ cell tumors of the testes such as yolk sac tumor?
Alpha-fetoprotein
Normally made by fetus. Hepatocellular carcinoma and nonseminiferous germ cell tumors.
This tumor marker is very nonspecific but produced by 70% of colorectal and pancreatic cancers, also produced by gastric, breast, and thyroid medullary carcinomas.
CEA - carcinoembryonic antigen
Very nonspecific but produced by 70% of colorectal and pancreatic cancers; also produced by gastric, breast, and thyroid medullary carcinomas.
What is the tumor marker for prostrate carcinoma?
PAP (prostatic acid phosphatase)
This tumor marker is used to screen for prostrate carcinomas and elevated in BPH & prostatiitis.
PSA - Prostate specific antigen.
Metastatic bone tumors are far more common than primary tumors. Rank 5 sites that a bone tumor may have seeded from.
Prostate, breast > lung > thyroid, testicles.
If a blastic metastatic bone tumor was found, which site would it have most likely come from?
Prostate: blastic bone tumor
If a lytic metastatic bone tumor was found, which site would be the most likely for it to have come from?
Lung: lytic bone tumor
If a metastatic mix of lytic and blastic bone tumors were found, which site would it most likely have come from?
Breast: lytic & blastic bone tumor
