Pathoma: Principles of Neoplasia Flashcards
definition of neoplasia
new tissue growth that is unregulated, irreversible, and monoclonal
definition of monoclonal
the neoplastic cells are derived from a single mother cell
How is clonality of B lymphocytes determine
Ig light chain phenotype
Immunoglobulin composed of heavy and light chains that is either kappa or lambda
normal kappa to lambda is 3:1
monoclonal is 6:1 or inverted 1:3
benign neoplastic tumors
remain localized and do not metastasize
malignant neoplastic tumors
invade locally and have the potential to metastasize
Epithelium tumors nomenclature - benign and malignant
Benign: adenoma, papilloma
Malignant: adenocarcinoma, Papillary carcinoma
Mesenchyme tumors nomenclature - benign and malignant
Benign: lipoma
Malignant: liposarcoma
lymphocyte tumors nomenclature - benign and malignant
Benign: does not exist
Malignant: lymphoma, leukemia
Melanocyte tumors nomenclature - benign and malignant
Benign: Nevus
Malignant: Melanoma
most common cancers by incidence in adults
1) breast/prostate
2) lung
3) colorectal
most common cause of cancer mortality
1) lung
2) breast/prostate
3) colorectal
definition of carcinogens
agents that damage DNA, increasing the risk for cancer
What is the associated cancer with this carcinogenic chemical:
Aflatoxins
Hepatocellular carcinoma
Derived from aspergillus, which can contaminate stored rice and grains
What is the associated cancer with this carcinogenic chemical:
Alkylating agents
leukemia/lymphoma
side effect of chemo
What is the associated cancer with this carcinogenic chemical:
alcohol
squamous cell carcinoma of oropharynx and upper esophagus,
hepatocellular carcinoma
What is the associated cancer with this carcinogenic chemical:
arsenic
squamous cell carcinoma of skin, lung cancer, and angiosarcoma of liver
arsenic is present in cigarette smoke
What is the associated cancer with this carcinogenic chemical:
nitrosamines
stomach carcinoma
found in smoked foods
responsible for high rate of stomach carcinoma in Japan
What is the associated cancer with this carcinogenic chemical:
naphthylamine
urothelial carcinoma of bladder
derived from cigarette smoke
What is the associated cancer with this carcinogenic chemical:
vinyl chloride
angiosarcoma of liver
occupational exposure
used to make PVC
What is the associated cancer with this carcinogenic chemical:
nickel, chromium, beryllium, or silica
lung carcinoma
occupational carcinoma
What is the associated cancer with this carcinogenic chemical:
asbestos
lung carcinoma and mesothelioma
exposure to asbestos is more likely to lead to lung cancer than mesothelioma
What is the associated cancer with this carcinogenic chemical:
cigaretter smoke
carcinoma of oropharynx, esophagus, lung, kidney, bladder, and pancreas
most common carcinogen worldwide, polycyclic hydrocarbons are particularly carcinogenic
What is the associated cancer with this carcinogenic oncogenic virus:
EBV
nasopharyngeal carcinoma, burkitt lymphoma, and CNS lymphoma in AIDS
What is the associated cancer with this carcinogenic oncogenic virus:
HHV-8
Kaposi Sarcoma
What is the associated cancer with this carcinogenic oncogenic virus:
HBV and HCV
Hepatocellular carcinoma
What is the associated cancer with this carcinogenic oncogenic virus:
HTLV-1
Adult T-cell leukemia/lymphoma
What is the associated cancer with this carcinogenic oncogenic virus:
High-risk HPV (16,18,31,33)
squamous cell carcinoma of vulva, vagina, anus, and cervix, adenocarcinoma of cervix
What is the associated cancer with radiation:
ionizing (nuclear reactor accidents and radiotherapy)
AML, CML, and papillary carcinoma of the thyroid
generates hydroxyl free radicals
What is the associated cancer with radiation:
nonionizing (UVB sunlight is most common source)
basal cell carcinoma, squamous cell carcinoma, and melanoma of skin
results in formation of pyrimidine dimers in DNA, which are normally excised by restriction endonuclease
Function
Mechanism
associated tumor of:
PDGFB
platelet-derived growth factor
overexpression, autocrine loop
astrocytoma
Function
Mechanism
associated tumor of:
ERBB2 (HER2/neu)
Epidermal growth factor receptor
amplification
subset of breast carcinomas
Function
Mechanism
associated tumor of:
RET
neural growth factor receptor
point mutation
MEN2A, MEN 2B and sporadic medullary carcinoma of thyroid
Function
Mechanism
associated tumor of:
KIT
stem cell growth factor receptor
point mutation
gastrointestinal stromal tumor
Function
Mechanism
associated tumor of:
RAS gene family
GTP-binding protein
point mutation
carcinomas, melanoma, and lymphoma
Function
Mechanism
associated tumor of:
ABL
tyrosine kinase
t(9:22) with BCR
CML and some types of ALL
Function
Mechanism
associated tumor of:
c-Myc
transcription factor
t(8:14) involving IgH
burkitt lymphoma
Function
Mechanism
associated tumor of:
N-Myc
transcription factor
amplification
neuroblastoma
Function
Mechanism
associated tumor of:
L-myc
transcription factor
amplification
lung carcinoma (small cell)
Function
Mechanism
associated tumor of:
CCND1 (cyclin D1)
cyclin
t(11:14) involving IgH
mantle cell lymphoma
Function
Mechanism
associated tumor of:
CDK 4
cyclin dependent kinase
amplification
melanoma
p53
tumor suppressor
regulates progression of the cell cycle from G1 to S phase
slows cell cycle when damage is present
if repair is not possible, upregulates BAX -> disrupts Bcl2 -> induces apoptosis
Knudson two hit hypothesis
both copies of p53 gene must be knocked out for tumor formation
Rb
tumor suppressor
hold E2F transcription factor which is necessary for transition to S phase from G1
sporadic Rb mutation
both hits are somatic
characterized by unilateral retinoblastoma
germline Rb mutation
familial retinoblastoma - 2nd hit is somatic
bilateral retinoblastoma and osteosarcoma
Bcl2
prevents apoptosis in normal cells
stabilizes mitochondrial membrane, blocking release of cytochrome c
over expressed in follicular lymphoma
telomerase is necessary for
cell immortality
cancers often have upregulated telomerase, which preserves telomeres
angiogenesis
necessary for tumor survival and growth
FGF and VEGF often produced by tumor cells
how do tumor cells evade immune surveillance
downregulating expression of MHC I
normally, the abnormal proteins would be displayed by MHC I and destroyed by CD8+
lymphatic spread is characteristic of
carcinomas
hematogenous spread is characteristic of
sarcomas and some carcinomas
seeding of body cavities is characteristic of
ovarian carcinoma
which often involves the peritoneum
Benign tumors histologic features
organized growth uniform nuclei low nuclear to cytoplasmic ratio minmal mitotic activity lack of invasion no met potential
malignant tumor histology
disorganized growth nuclear pleomorphism and hyperchromasia high nuclear cytoplasmic ratio high mitotic activity with atypical mitosis invasion
well differentiated
low grade
resembles normal parent tissue
poorly differentiated
high grade
does not resemble parent tissue
grading
determines prognosis
staging
more important than grade
assessment of size and spread of cancer
TNM staging of a tumor
T - tumor - size and/or depth of invasion
N - spread to regional lymph nodes, 2nd most important prognostic factor
M - metastasis - single most important prognostic factor
Immunohistochemical stain assoc. with which tissue:
keratin
epithelium
Immunohistochemical stain assoc. with which tissue:
vimentin
mesenchyme
Immunohistochemical stain assoc. with which tissue:
desmin
muscle
Immunohistochemical stain assoc. with which tissue:
GFAP
neuroglia
astrocytes
Immunohistochemical stain assoc. with which tissue:
neurofilament
neurons
Immunohistochemical stain assoc. with which tissue:
PSA
prostatic epithelium
Immunohistochemical stain assoc. with which tissue:
ER
breast epithelium
Immunohistochemical stain assoc. with which tissue:
thyroglobulin
thyroid follicular cells
Immunohistochemical stain assoc. with which tissue:
chromogranin
neuroendocrine cells (small cell carcinoma of lung and carcinoid tumors)
Immunohistochemical stain assoc. with which tissue:
S-100
melanoma, Schwannoma, and Langerhans cell histiocytosis
