Principles of Neoplasia Flashcards
Tumors derived from what lineage?
Monoclonal
Neoplasia growth characteristics
Unregulated, irreversible, monoclonal
Clonality determined by:
G6PD or androgen receptor isoforms
Clonailty of B lymphocytes determined from
Ig light chain
Kappa:Lambda = 3:1 ratio
Hyperplasia maintains ratio
Lymphoma: monoclonal
Which is monoclonal? Benign or malignant tumors?
BOTH
Epithelium tumor prefix
adeno or papill
Mesenchyme are what tissues and prefix
Lipo (fat)
Osteo (bone)
Chondro (cartilage)
Agio (blood vessel)
Are there benign lymphcyte tumors?
NO- all are malignant and called lymphoma/leukemia
Melanocyte
Nevus: benign
Melanoma: malignant
Cancer begins as what?
How many divisions until earliest clinical symptoms arise?
A single mutated cell
30 divisions
Each double results in increased what?
Mutations
Pap smear screens for?
Cervical dysplasia
Mammography screens for?
In situ breast cancer (DCIS often calcifies)
PSA/DRE screens for?
Prostate carcinoma
Hemoccult test and colonoscopy screen for?
Colonic adenoma (before it becomes carcinoma)
Cancer formation initiated by?
DNA mutations
Chemical agent: Alfatoxin
HCC
From aspergillus
Chemical agent: alkylating agent
Leukemia/lymphoma
Chemical agent: alcohol
SCC of oropharyrnx & upper esophagus
Pancreatic carcinoma
HCC
Chemical agent: Arsenic
SCC of skin, lung
Angiosarcoma of liver
Chemical agent: asbestos
Lung carcinoma
Mesothelioma
What 3 chemicals will you find in cigarette smoke?
Arsenic
Naphthyalmine
*Polycyclic hydrocarbons
Chemical agent: nitrosamines
Stomach cancer - smoked foods (Japan)
Intestinal vs diffuse type
Nitrosamine related to intestinal type
Chemical agent: napthylamine
Urothelial carcinoma of bladder
Chemical agent: cigarette smoke
Carcinoma of oropharynx, esophagus, lung, kidney, bladder
Chemical agent: vinyl chloride
Angiosarcoma of liver
PVC in pipes
Chemical agent: nickel, chromium, beryllium, silica
Lung carcinoma
Oncogenic viruses: EBV
Nasopharyngeal carcinoma
1. Chinese male
2. African individual (region of Africa)
Neck mass
Burkitt lymphoma
CNS lymphoma in AIDS
Oncogenic viruses: HHV-8
Kaposi Sarcoma
Endothelial cells
- Eastern European Males (older) - excise lesions
- AIDS pts
- Transplants - immunosuppressed
Oncogenic viruses: HBV/HC
HCC
Oncogenic viruses: HTLV-1
Adult T-cell leukemia/lymphoma
Oncogenic viruses: High risk HPV
SCC of vulva, vagina, anus, cevix
Adenocarcinoma of cervix
Radiation: Ionizing (nuclear reactor accidents & radiotherapy)
AML, CML, papillary carcinoma of thyroid
Hydroxyl free radicals generated and hit DNA causing damage
Oncogenic viruses: Nonionizing (UVB most common)
BCC, SCC, melanoma
Form pyrimidine dimers in DNA
Disrupted systems include
Proto-oncogenes
Tumor suppressor genes
Regulators of apoptosis
Proto-oncogenes essential for
cell growth and differentiation
Oncogene leads to
unregulated cell growth
4 categories of oncogenes
- GF
- GF receptors
- Signal transducers
- Cell cycle regulators
GF oncogene: PDGFB
Astrocytoma
Overexpression of PDGFB Growth factor - overgrowth of the cell/division
GF Receptor: ERBB2 (HER2/neu)
Breast carcinoma
Amplification
Epidermal GF receptor
GF Receptor: RET
MEN2A, 2B
Sporadic medullary carcinoma of thyroid
Point mutation
Neural GF Receptor
GF Receptor: KIT
GI stromal tumor
Point mutation
Stem cell GF receptor
Signal transducers: RAS gene family
Carcinoma, melanoma, lymphoma
Point mutation
GTP biding protein (instead of inactive form of RAS-GDP)
Signal transducers: ABL
CML and some ALL
t(9,22) with BCR
Tyrosine Kinase
What defines CML?
t(9,22) (Philadelphia chromosome)
Ph+ ALL
t(9,22) ALL
Nuclear regulators: c-MYC
Burkitt Lymphoma (B cell)
t(8,14) involving IgH IgHeavy chain on 14 Translocation with Myc gene on 8 Myc sits on Heavy chain so it will get turned on "starry sky" appearance
Transcription factor
Nuclear regulators: n-MYC
Neuroblastoma
Amplification
Nuclear regulators: l-MYC
Lung cell carcinoma (small cell)
Cell cycle regulators: CCND1 (cyclin D1)
Mantle cell lymphoma
t(11, 14) involving IgH
Cyclin
G1-S phase
cyclin D1 on chromosome 11
Cell cycle regulators:CDK4
Melanoma
Amplification
Cyclin-dependent kinase
p53 regulates what?
cell cycle: G1 to S phase
p53 sees mutation: call in DNA repair enzymes
OR
too damaged and will call in BAX to destroy BCL2 - which stabilizes CYT C, so induces apoptosis
LI Fraumeni syndrome
one mutation in p53 inherited
increased risk for multiple types of carcinoma and sarcomas
Rb regulates
Progression from G1 to S
Needs E2F to do this (normally bound by RF) and needs to be phosphorylated
and then will release E2F
Phosphoylated by Cyclin D/CDK4 complex
Allows cell to go from G1 to S
If mutation in Rb - forms tumor from released E2F
Sporadic mutation of Rb
unilateral retinoblastoma
Germline mutation of Rb
bilateral retinoblastoma and osteosarcoma
Bcl2 normally stablizes mito membrane preventing release of
Cytochrome C
What happens when cytochrome C is released from mito?
Activates apoptosis - releases caspases
Bcl 2 overexpressed in what?
Follicular lymphoma
t(14,18) Bcl 2 (18) to Ig heavy chain (14) results in increased Bcl2
What is necessary for cell immortality?
Telomerase: upregulated in cancers
GF in angiogenesis for tumor growth and survival
FGF and VEGF
Fibroblast GF
Vascular endothelial GF
How do tumors cells avoid immune surveillance?
CD8” cells detect and destroy mutated cells by detecting the abnormal cells presented on MHC I
Tumor cells downregulate MHC I
How does cancer spread occur?
Down regulation of E-Cadherin leading to dissociation of attached cells
Cells attach to laminin and destroy BM (type 4 collagen) - via collagenase
Cells attach to fibronectin in ECM and spread locally
Either gain access to BV or lymphatics
What type of spread is characteristic of carcinomas?
Lymphatic spread
Initial spread is to regional draining lymph nodes
What type of spread is characteristic of sarcomas (and some carcinomas)?
Hematogenous spread
What are the exceptions of carcinomas that spread hematogenously instead of thru the lymphatics
RCC
HCC
Follicular carcinoma of the thyroid
Choriocarcinoma (placental tissue - trophoblasts)
RCC spreads into what vein?
Renal
HCC spreads into what vein?
Hepatic
How does ovarian carcinoma spread?
Seeding
“omental caking”
Characteristics of benign tumors
Slow growing
Well circumscribed
Distinct
Mobile
Characteristics of malignant tumors
Rapid growing
Poorly circumscribed
Infilitrative
Fixed to surrounding tissue
Histologic features of benign tumors
Organized growth Uniform nuclei Low nuclear to cytoplasmic ratio Minimal mitotic activity Lack of invasion No metastatic potential
Histologic features of malignant tumors
Disorganized growth Nuclear pleomorphism w/ hyperchromasia High nuclear to cytoplasmic ratio High mitotic activity Invasion
Absolute distinguishing feature between malignant and benign?
BENIGN NEVER METASTASIZE!
Intermediate filaments: keratin
epithelium
Intermediate filaments: vimentin
Mesenchyme
Intermediate filaments: Desmin
Muscle
Intermediate filaments: GFAP
neuroglia
Intermediate filaments: Neurofilament
Neurons
PSA
prostate epithelium
ER
breast epithelium
Thyroglobulin
Thyroid follicular cells
Chromogranin
Neuroendocrine cells
Carcinoid is best, small cell carcinoma worst
S-100
Melanoma
What’s useful for screening, monitoring response to tx, monitoring recurrence?
Serum tumor markers - proteins released by tumor
Elevated levels of tumor serum marker requires what for dx of carcinoma?
Biopsy
1 prognosis factor for cancer for staging?
Size and spread
Single most prognostic factor
Metastasis
