Neoplasia Flashcards
neoplasia
abnormal tissue mass with uncoordinated, excessive growth; 3 defining criteria:
1) autonomous
2) clonal
3) proliferative
autonomous characteristic of neoplasia
growth independent of physiological signals
clonal characteristic of neoplasia
series of acquired mutations affecting a cell and ALL of its progeny
proliferative characteristic of neoplasia
mutations give neoplastic cells survival/growth advantage
benign neoplasms
1) localized and well-defined (may be encapsulated)
2) do NOT spread to other sites
3) growth usually recapitulates normal structures (cells look normal, relative to the tissue they are in)
benign neoplasms - nomenclature
-oma added to the cell of origin
*adenoma = benign glandular epithelial tumor
*fibroma = benign fibroblast tumor
*chondroma = benign cartilage tumor
*osteoma = benign bone tumor
papillary
visible fingerlike projections
polyp
visible projection above mucosa with a stalk
cystic
cyst/cavitary centers
malignant neoplasms
1) ill-defined growth
2) invasive (spread to and destroy adjacent structures)
3) metastasize (spread to non-contiguous, distant sites)
*requires interventional therapy
malignant neoplasm - nomeclature
*carcinoma = epithelial origin
(ex. adenocarcinoma, squamous cell carcinoma)
*sarcoma = mesenchymal origin
(ex. fibrosarcoma, liposarcoma)
differentiation of benign neoplasms
well-differentiated (close resemblance to normal)
differentiation of malignant neoplasms
*wide range of differentiation:
-well differentiated = closest resemblance to normal
-moderate = some resemblance to normal
-poor = little resemblance to normal
-undifferentiated = anaplasia, NO resemblance to normal
pleomorphism
variation in size/shape of cells (all cells look different from each other)
anaplasia characteristics
-pleomorphism
-abnormal nuclear morphology
-mitoses (increased and atypical)
-loss of polarity
-ischemic necrosis
metaplasia
replacement of one differentiated tissue with another
-chronic stress leads to reprogrammed stem cells
-typically reversible cell change
*precursor to malignancy
dysplasia
-“disordered growth”
-increased pleomorphism and increased mitotic activity
-may be reversible
*precursor to malignancy
typical sequence from normal to neoplastic
normal <-> hyperplasia <-> dysplasia <-> carcinoma
invasion
infiltration or destruction of surrounding tissues
(ex. mucosal layer invading the serosa of a tissue)
-sign of malignant (benign are non-invasive)
metastasis
spread of a tumor to physically distant, discontinuous sites
*unequivocally marks a neoplasm as malignant
*most reliable feature distinguishing malignant from benign
pathways of dissemination of metastasis
- seeding of body cavity or organ surfaces
- lymphatic spread
- hematogenous spread
seeding & metastasis
*involving an open body cavity
*peritoneal cavity is most common, but could also be pleural, pericardial, subarachnoid, etc
lymphatic spread & metastasis
*invade lymphatics to involve draining lymph nodes
**most common pathway for CARCINOMA dissemination
*pattern of nodal involvement follows natural lymphatic drainage (breast cancer to axillary nodes; lung cancer to hilar/mediastinal nodes)
hematogenous spread & metastasis
*direct invasion of blood vessels
**most common pathway for SARCOMA dissemination
*follow blood flow (veins more common than arteries; liver and lungs are most frequent sites of metastasis)
radiation and oncogenesis
UV radiation: mutations in oncogenes, tumor suppressor genes, formation of thymidine dimers
ionizing radiation: depends on type, length of exposure, etc
microbial agents and oncogenesis
-HPV & Epstein-Barre viruses (EBV)
-H. pylori
HPV oncogenesis
HPV can induce expression of oncoproteins
-E6: degrades p53, preventing apoptosis; activates telomerase
-E7: allows progression in cell cycle (binds RB and displaces E2F; blocks p21 and p27)
OVERALL EFFECT: immortalizes epithelial cells
EBV oncogenesis
-allows inappropriate expression of latency-phase genes
-EBNA and LMP
oncogenes
mutations in oncogenes turn them on and endow cell with self-sufficiency in growth; genes that accelerate cells and tell them to proliferate; “gain of function” process
*ONLY ONE COPY NEEDS TO BE MUTATED
growth factors
oncogenes that induce cellular growth
-some tumors induce autocrine loop, in which they synthesize the same growth factors to which the cell is responsive
-ex = PDGF (brain cancer)
growth factor receptors
oncogenes that mediate growth factor signals
-activation by growth factors cause dimerization and phosphorylation signaling cascade substrates
*constitutively dimerized/activated mutant receptors can be on without growth factor
*overexpression of normal forms of growth factor receptors
signal transducers
oncogenes that mediate signals to nucleus into different cascade events; mutations become “trapped” in active form
transcription factors
oncogenes that orchestrate the mitotic cycle
cell cyclers
oncogenes that orchestrate the cell cycle
tumor suppressor genes
mutations that lead to failed response to growth inhibitory signals; “loss of function” process that stops cellular proliferation
*BOTH COPIES MUST BE MUTATED
RB (retinoblastoma) gene
common tumor suppressor gene
-normal function = regulate G1-S transition
-mutations allow tumor cells to enter S phase unchecked
**require a DOUBLE HIT (both copies must be knocked out)
TP53 gene
common tumor suppressor genes
-normal function = slow down cell cycling in response to DNA damage, allowing repair or apoptosis
-mutations lead to no cell cycle arrest in tumor cells
**requires a DOUBLE HIT (both copies must be knocked out)
apoptosis regulators
disruption leads to immortalization of cells via evasion of cell death
-ex = BCL2 inhibits apoptosis; normally turned OFF in cells, but tumors can upregulate this gene and therefore they don’t undergo apoptosis
other features of oncogenesis
-replicative immortalization via upregulated telomerase (allows cells to continue to proliferate over time)
-angiogenesis to supply nutrients to tumor cells (tumor upregulates angiogenic factors)
-escape of immunosurveillance (down-regulate MHC class I)
warburg effect
tumor cells shift their metabolism to favor glycolysis, even with adequate oxygen, because it provides them a lot of other nutrients; provides a growth advantage in hypoxic tumor microenvironment; characteristic “glucose hunger” of tumor cells can be identified via PET scans
local problems associated with neoplasms
-space-filling can lead to obstruction
-tissue compression can lead to dysfunction and destruction
-surface ulceration can lead to bleeding and secondary infection
systemic problems associated with neoplasms
-cachexia
-paraneoplastic syndromes
paraneoplastic syndrome
clinical signs/symptoms that result from substances produced by the tumor and occurring remotely
include:
-hypercalcemia
-endocrinopathies
-hypercoagulability
tumor grade
pathology morphologic assessment (level of differentiation)
*low grade = well differentiated (better)
*high grade = poorly differentiated / anaplastic
tumor staging
determines the extent of SPREAD using the TMN system
TNM system
T = tumor size
N = node involvement
M = metastases
T (tumor size) of TMN system
T0 = in situ (non-invasive)
T1-T4 = increasing tumor size
N (node involvement) of TMN system
N0 = no regional lymph node involvement
N1 to N3 = increasing number of involved lymph nodes
M (metastases) of TNM system
M0 = no distant metastases
M1 = distant metastases
tumor markers
biochemical indicators of a tumor’s presence that are detectable in plasma
examples of tumor markers
-mucins (CA125, CA19-9)
-oncofetal antigens (AFP, CEA)
-specific proteins (PSA, immunoglobulins)
