VII- Neoplasia Flashcards
definition of neoplasm
clonal proliferation of cells that is uncontrolled and excessive
-irreversible change in cell type (metaplasia) and structure (dysplasia)
-benign or malignant
two components of neoplasm
- parenchyma - the monoclonal neplatic cells themselves, decides biological behavior of tumor
- stroma - CT/blood vessels/macrophages/lymphocytes that determine growth, spread, and mass consistency
hard mass = what stroma
abundant collagenous stroma
soft mass = what stroma
scant stroma
-tumor soft and fleshy
if benign @ epithelial tissue
ademoma
papilloma - finger like projections
if cavity or cyst then cystadenoma
features of benign tumors
- slow growth
- capsule present
- non invasive, non metastatic
- well differentiated
tumor-like conditions
- choristoma
- hamartoma
monoclonality of tumors
ALL TUMORS ARE MONOCLONAL so og from single precursor cell
-both benign and malignant
rubbery mass = what stroma
b/t soft and hard stroma status
if malignant @ epithelial tissue
carcinoma
if benign @ mesenchymal tissue
add -oma suffix
EXCEPTIONS: melanoma, lymphoma, seminoma, hepatoma, astrocytoma
if malignant @mesenchymal tissue
add -sarcoma suffix
polyp definition
club shaped growth projecting from mucosal surface into lumen of hollow viscus/organ
-bengin epithelial or hyperplasia
hematopoietic cell tumors
leukemia
-malignant from bone marrow stem cells
-CLL common for adults and ALL for peds
teratoma definition
tumor of 1+ parenchymal cell type so from more than one germ layer
-BUT all cells arise from single clone that can produce multi cell types
i.e. totipotent cells in gonads
non neoplastic lesions with -oma
granuloma
hematoma
choristoma
features of malignant tumors
- rapid growth
- no capsule
- invasive and metastatic potential
- range from well differentiated to poorly
features of sarcomas
- mesenchymal origin
- less common incidence vs carcinoma
- hematogenous initial spread
- poor prognosis
- early presentation
i.e. leiomyosarcoma (smooth m) or rhabdomyoSA (striated m)
features of carcinomas
- epithelial cell orgin
- more common than sarcomas
- lymphatic spread initially
- better prognosis
- late presentation
i.e. squamous cell CA, adenocarcinoma
carcinomas that spread hematogenously
exceptions to normal
- follicular CA of thyroid
- choriocarcinoma
- renal cell CA - invades renal vein
- hepatocellular CA invades hepatic vein
Four Carcinomas Route Hematogenously
choristoma
ectopic rest of normal tissue OR normal tissue in foreign location
ex. pancreatic tissue in mucosa of stomach
hamartoma def
disorganized benign mass of indigenous cells to invovled site
-developmental malformation
peutz-jeghers syndrome
hereditary intestinal polyposis syndrome aka autosomal dom
-polyps in GI tract and hyperpigmented macules @ lips and oral mucosa
determining B cell clonality
by Ig light chain phenotype
determining clonality of other cells
- glucose 6 phosphate dehydrogenase isoforms
- androgen receptor isoforms
pro-angiogenic factors
- VEGF
- bFGF
- HIF
-all are direct, indirect are Ras and myc by promoting
anti-angiogenic factors
- thrombospondin-1
- angiostatin
- endostatin
- tumstatin
rate of growth malignant
-rapid growth cancers highly susceptible to chemo
differentiation benign
-well differentiated bc only 1-10% are in cell cycle
-usually resemble normal mature cells/tissue
differentiation malignant
20-80% are in cell cycle so the rest of cells can differentiate varying
-may not resemble normal tissues
anaplasia (no resemblence to normal tissue) hallmark of high grade malignant tumor
indicators of tumor cell growth
- Ki-67
- PCNA
significance of mitotic figures
the more abnormal the mitotic figures (not metaphase, anaphase, prophase) the more likely malignancy
desmoplasia examples
- diffuse stomach cancer linitis plastica
- breast cancer
- prostate cancer
- cholangiocarcinoma
desmoplasia definitions
hyperplasia of activated fibroblasts + production of abundant collagen in stroma
recognizing cellular atypia
- cellular pleomorphism - vary in size and shape
- nuclear changes/pleomorphism
- inc ratio of nucleus:cytoplasm (1:1 instead of normal 1:5)
atypia definition
structural abnormality in a cell
-only in premalignant conditions and malignant tumors
cellular polarity
spatial diffs in shape, structure, function of cells
-if lost then can’t tell up from down of cell
P53 normally
- inhibits VEGF
- promotes thrombospondin-1
recognizing cellular atypia
- cellular pleomorphism - vary in size and shape
- nuclear changes/pleomorphism
- inc ratio of nucleus:cytoplasm (1:1 instead of normal 1:5)
role of invasion benign
tumors cells stay attached by adhesion molecules like E. cadherin
steps of invasion
- detachment of tumor cells from each other bc no E-cadherin
- attachment to matrix by laminin
- degradation of ECM by tumor cells, fibroblasts, inflamm cells, collagenase/MMP for type IV BM collagen
- migration of tumor cells by binding fibronectin and secreting motility factor
metastatic cascade
- invasion of BM
- movement thru ECM
- vascular dissemination
- homing
role of metastasis malignant
unequivocally marks a tumor malignant
-CD44 !!! favors metastasis
tumor grading mechanisms
- conventional - degree of differentiation with H and E stain, mitotic index
- uptake of BrdU - higher uptake higher grade tumor
TNM tumor staging
T = size of primary tumor
N = nodal involvement
M = distant metaastases
cancer incidence
2 cause of death (heart dz is 1)
- prostate or breast
- lung
- colon
primary tumors that metastasis to brain
LUBMECK
-lung > breast > melanoma/colon/kidney
primary tumors that metastasis to liver
- colon
- stomach
- pancreas
primary tumors that metastasis to bone
- prostate (blastic) and breast (mixed)
- lung, thyroid, kidney (all lytic)
4 grades
- well differentiated
- moderately
- poorly
- nearly aplastic
cervical dysplasia grading
- mild - confined to basal 1/3 of epi
- moderate- confined to basal 2/3 of epi
- severe - more than 2/3 but less than 3/3
- carcinoma in situ - full thickness dysplasia
4 common acquired pre-cancerous conditions
- oral leukoplakia
- barret esophagus
- chornic ulcerative colitis
- hep B and C
gene translocation CML
abl from 9 > bcr on 22
bcr-abl hybrid inc tyrosine kinase activity
-philadelphia chromosome
gene translocation Burkitt lymphoma
c-myc from 8 > Ig heavy chain on 14
-inc myc protein
gene translocation follicular B cell lymphoma
14 > 18
BCL-2 genes prevent mitochondrial leakage of cytochrome c (so no apoptosis)
BRAF oncogene
inc serine/threonine kinase
-non hodgkin lymphoma, melanoma
oral leukoplakia
starts as hyperlasia/hyperkeratosis
leads to mild-severe dysplasia
ends with squamous cell carcinoma
Barretts esophagus progression
glandular metaplasia in lower esophagus > dysplasia > adeoCA of esophagus
chronic ulcerative colitis progression
to dysplasia then adenoCa of colon
hepatitis infection progression
- B or C
- macronodular cirrhosis
- hepatocellular carcinoma
HER2 oncogene
inc receptor tyrosine kinase
-breast and gastric carcinoma
MYC- L1 oncogene
inc transcription
-lung tumors
N-MYC oncogene
inc transcription
-neuroblatomas
RET oncogene
inc receptor tyrosine kinase
-medullary thyroid cancer
APC
colorectal cancer
-normally downregs B-catenin to prevent accumulation
-pathologic by WNT signalling
p53
most human cancers
-activates p21 to block G1 to S phase so apoptosis by BAX
-also inhibited by E6 and E7 from HPV
VHL
von hippel lindau dz aka renal carcinomas + hemangioblastomas (benign), renal cysts
-normally tumor suppressor gene that inhibits HIF-1a
RB
retinoblastomas, osteosarcoma, soft tissue sarcoma
-blocks G1 to S phase
-both alleles inactivated for cancer
telomerase role in cancer
telomere shortening and loss of function can activate p53
-expression can be inc by E6
psammoma body
- papillary thyroid carcinoma
- papillary renal cell carcinoma
- serous papillary cystadenocarcinoma ovary
- meningioma
- malignant mesothlioma
concentric spherules with calcification
two steps of chemical carcinogenesis
- initiation by chemicals, perm DNA damage irreversible
- promotion - induces tumors but not affect DNA itself
chems can be direct without transformation or indirection need metabolism
UVB and skin cancer
UVB causes DNA damage from pyrimidine dimers
-if defective repair enzymes then esp susceptible
viral carcinogens
- HBV encodes HBx that activates growth promoting genes and inhibits p53, also chronic liver injury regen hyperplasia
- HCV gives chronic liver cell injury and regen
- EBV = burkitts, hodgkin, nasopharyngeal
- HPV 16, 18, 31
- HTLV1 via tax gene
- HIV
- HHV-8 kaposi sarcoma
bacterial carcinogens
H pylori via CagA cytotoxin
-gastric lymphoma MALT, gastric carcinoma
key paraneoplastic syndromes
- cushing syndrome - ACTH, small cell lung carcinoma
- SIADH - ADH, small cell lun carcinoma
- polycythemia- EPO, renal cell carcinoma, hepatocellular carcinoma, leiomyoma
- hypercalcemia - PTHrP, squamous cell carcinoma lung/head/neck
IHC markers
- thyroglobulin = thyroid cancer
- CD10/CALLA = acute lymphobalstic leukemia
- placental alkaline phosphatase = seminoma
- vWF, CD31 = vascular neoplasms
epithelial cell markers
cytokeratin or keratin or epithelial membrane antigen (EMA)
hormonal carcinogens
estogren
contraceptive hormones
anabolic steroids
mesenchymal origin markers
vimentin or desmin or muscle specific actin
neuronal tumor origin markers
neuron specific enolase NSE
chromogranin
synaptophysin
NSE also stains for small cell carcinoma lung and carcinoids