Neoplasia Flashcards
NEOPLASIA DEFINITION
abnormal mass of tissue that’s growth exceeds the surrounding normal tissue and grows without stimuli
Benign Neoplasm Definition
neoplasm which lacks the ability to invade, destroy tissue and metastasize
Malignant Neoplasm Definition
A neoplasm that possesses the ability to invade, destroy tissue and metastasize
Cancer definition
referring to all types of malignant neoplasms.
Urothelium
Transitional epithelium, lining majority of GU tract
Squamous stratified epithelium
multilayered flattened epithelial cells arranged on a basement membrane (mitosis occurs near BM)
Polyp
mass arising from a mucous membrane protruding into the lumen of a hollow viscus
Poly origin
epithelial cell origin
Sessile polyps
flat, arising directly from the mucosal epithelial layer
Pedunculated polyps
extending from the mucosa through a fibrovascular elongated stalk + surrounding epithelium
Cyst
outer capsule + inner surface lined with epithelium, hollow-cavity filled with mucin
Pseudocyst
lacks inner epithelial lining
Adeno-
glandular epithelial origin
Squamo-
flat, scale-like epithelial origin
Papillary
epithelial growth that extend outward as small nipple-like structure or protuberance
Papillo-
referring to a epithelial polyp
Myxo-
mucin producing mesenchymal origin
Rhabdomyo-
skeletal muscle mesenchymal origin
Leiomyo-
smooth muscle mesenchymal origin
Hemangio-
blood vessel mesenchymal origin
Lymphangio-
lymph vessel mesenchymal origin
Lympho-
lymphoid organ origin
Myelo-
myeloid origin: part of marrow- eosinophil, basophil, neutrophil, and monocyte
-oma
Benign neoplasm suffix
Carcinoma
malignant epithelial-derived cancer cells
Sarcoma
malignant mesenchymal-derived cells
Lymphoma
ALL are malignant lymphoid-derived cells
Myeloma
ALL are malignant marrow-derived cells
Leukemia
ALL are malignant hematologic-derived cells
Melanoma
Malignant neoplasm of melanocytic origin
Nevi
small benign melanocytic neoplasia
Myelodysplastic syndromes
hematologic dysplastic neoplasm
Plasmacytomas
discrete, solitary mass of plasma cells extramedullary or in bone
plasma cell dyscrasias
expansion of the number of monoclonal bone marrow plasma cells
Heterotopia
NOT NEOPLASTIC; congenital growth of microscopically normal cells or tissues in an abnormal location
Choristoma
NOT NEOPLASTIC; congenital growth of microscopically normal cells or tissues in an abnormal location
Hamartoma
NEOPLASTIC; excessive, focal overgrowth of cells and tissues native to the organ in which it occurs
Differentiation
degree to which the cellular constituents of a neoplasm resemble mature elements of the cell type
Differentiation of benign tumors
Highly differentiated
Differentiation of malignant tumors
tend to be less differentiated
Poorly differentiated tumors correlates with
advanced malignancy
Maturation
Directly related to differentiation; advancement of differentiation
Maturation of benign tumors
Very mature
Maturation of malignant tumors
tend to be less mature
Poorly maturated tumors correlate with
advanced malignancy
Dysplasia
Atypical nuclear and cytoplasmic changes which are considered PREmalignant
High grade dysplasia =
a lot of cellular atypia
Anaplasia
Atypical and aberrant changes within a cell or group of cells reflective of a MALIGNANT neoplastic changes
The greater the anaplasia
the more aggressive the tumor and the greater likelihood that the malignant cells become metastatic
Neoplastic rate of growth
When cellular replication and survival exceeds cellular loss
The greater the differentiation of a tumor, the _________ the growth
SLOWER; greater differentiation correlates with a slow growing tumor
In-situ carcinoma growth
Carcinomas begin to grow in the epithelium, but are confined by the basement membrane.
Why can’t you have in situ sarcomas?
Sarcomas derived from mesenchymal cells are not confined because there is no BM
What’s the difference between a high-grade dysplasia and in situ carcinoma?
Nothing, virtually impossible to tell
Encapsulated
Benign neoplasms: limited cohesive expansion
Unencapsulated
Malignant neoplasms: have the capacity for local infiltration and invasion leading to extensive tissue destruction
If an in situ carcinoma cell undergoes genetic alterations that allow it to invade the BM, it is now
a microinvasive carcinoma that has the ability to enter vessels if it comes into contact
Metastasis
tumor cells ability to leave their primary site or origin (primary neoplasm) and spread to a distant area of the body (separated in space) where they implant and replicate
Metastasis can occur via
direct seeding, lymphatic spread or hematogenous spread
Metastasis: lymphatic spread
tumor embolus is carried by lymph until it reaches a point where it lodges and begins to grow (generally at regional lymph nodes)
Lymphatic spread from breast cancer generally occurs at
axillary lymph nodes
Metastasis: Hematogenous spread
tumor embolus is carried by blood vessels, there are no gate keepers - wide-spread
Secondary Brain tumor indicates
Hematogenous spread, there is no lymph to brain
Metastasis: Direct seeding
the cancer is exposed to a cavity and cancer cells are carried in the fluid within the cavity and carried to another surface
Benign Neoplasm Characteristics
Encapsulated, well-differentiated, limited growth due to contact inhibition, freely moveable upon palpation due to capsule, no local invasion
Malignant Neoplasm Characteristics
Well-differentiated to undifferentiated, loss of maturity, loss of tissue and cellular organization, nuclear atypia, increased levels of mitoses, large nucleus, tumor giant cells, non-encapsulated, fixed position, often necrotic of hemorrhaging, local invasion, capacity to metastasize
Malignant tumor cell features
Large nucleus, abnormal increased mitoses, large, multi-nucleated cells, mitotic figures
Grading
Related to degree of differentiation of malignant neoplasm - phenotypic property
grade 1 neoplasms
well differentiated
Grade 4 neoplasms
poorly differentiated
High grade tumors have more
atypical cells and atypical mitotic figures, higher capacity to metastasize
Low anaplastic potential
low-grade tumor
Staging
classification of a tumor based on the extent of spread throughout the human body as determined by the UICC and AJC
Staging considers
tumor size, the degree of regional lymph node involvement and the presence or absence of metastasis
AJCC Staging
TNM (tumor size, number of nodes, metastasis)
pT2N2 versus T2N2
‘p’ indicates pathologists staging based on the tissue biopsy; other indicates clinical staging based on diagnostics
Incidence of cancer types is due to
environmental (geographical) and genetic determinants
Cancer incidence in males
14% lung, 33% prostate, 11% colorectal
Cancer incidence in females
33% breast, 12% lung, 11% colorectal
Mortality from cancer in males
31% lung, 10% colorectal, 10% prostate
Mortality from cancer in females
25% lung, breast 15%, 11% colorectal
Autosomal dominant inherited cancer syndromes
means the person is born with a mutation in one gene and only needs to acquire 1 mutation in the other gene throughout life for cancer to develop (1 mutation = increased risk of cancer)
Sporadic cancer
requires 2 mutations to occur throughout life, 1 in each chromosome, which is less likely to occur than if born with a mutation
Familial Retinoblastoma
pt is heterozygous for Rb gene - when a mutation is acquired sporadically in the normal Rb gene chromosome (usually UV light), the patient becomes homozygous for mutant Rb gene, and retinoblastoma occurs
Examples of Autosomal dominant inherited cancer syndromes
Retinoblastoma, MEN syndrome, Familial Adenomatous polyposis, hereditary nonpolyposis colon cancer, Li-Fraumeni Syndrome
Li Fraumeni Syndrome
autosomal dominant p53 mutation, predisposes a person to a variety of cancer developments
Autosomal Recessive Syndromes of Defective DNA Repair
pt is homozygous for the defective gene, inherits 2 copies of the mutated gene which puts them at increased risk for cancer
Examples of Autosomal Recessive Syndromes
Xeroderma pigmentosum, Ataxia-telangiectasia, Fanconi anemia, HNPCC, Bloom Syndrome
Familial Clustering
No clear defined transmission pattern, but som egene specificity; early age of onset, tumors in 2+ relatives
Acquired Preneoplastic Disorders Include
Preceding inflammatory conditions, viral infection, chemical carcinogenesis, pre-existing benign neoplasm
Growth-promoting proto-oncogenes
normal functional gene that regulates growth and differentiation, that when mutated is likely to lead to cancer due to its regulatory functions in a normal cell. Proto-oncogene -> mutation -> oncogene
Oncogenes may alter
GFs, GFRs, signal transduction proteins, nuclear regulatory proteins, cell cycle regulators
sis gene
oncogene that increases GF production
erb-B2 gene
oncogene that increases GF receptors
ras gene
oncogene that encodes for a mutated signal transducer protein (constitutively active)
myc gene
oncogene coding for mutant TF (nuclear regulatory proteins); active w/o signal transduction
Mutation examples
point mutation, chromosomal rearrangement, gene amplification
Burkitt’s Lymphoma - c-myc mutation type
chromosomal rearrangement of 8 and 14
n-myc mutation type
gene amplification
anti-oncogenes
regulate nuclear transcription, cell cycle, signal transduction, stimulate cell surface suppressor molecules; normally act as BRAKES to cell cycle
Growth inhibiting cancer suppressor genes (anti-oncogenes)
Normally suppress growth, but when mutated can no longer suppress growth
Genes which regulate apoptosis
prevent or promote programmed cell death
Multi-step carcinogenesis
requires a mutation that activates an oncogene AND suppresses an anti-oncogene, followed by clonal expansion and neoplasm formation
Point mutation example
retinoblastoma
Examples of anti-oncogenes
Rb, p53, BRCA1-2
Clonal expansion characteristic
polyclonal cell population
malignant cells have a high number of cells in G1-M phase
G1-M phase
Malignant neoplasms have the ability to recruit
angiogenesis
Angiogenesis - Proto-oncogenic regulation
Stimulate blood vessel growth.
Angiogenesis - Tumor suppressor gene regulation
Normally inhibit blood vessel growth, unless mutated
an invasive tumor that has gained the ability to breach basement membrane has likely undergone genetic alteration and now has the ability to bind
laminin of basement membrane
monoclonal expansion –>
heterogeneity of the cell population overtime due to mutations in various daughter cells leading to sub-types of cells with various capabilities
In situ transformation to invasive carcinoma
Cell must lose adhesion molecules to adjacent cells, obtain an active collagenase to break down ECM, tumor cells then bind to laminin receptors of BM
Intravasation
attach and invade the BM of the vessel and migrate through the tight junctions of the endothelial cells
Satellite nodules
earliest example of metastasis (intra-organ metastasis)
Secondary tumor
arises in a distant location from primary
Chemical initiator
causes a change in the cell which makes it susceptible to the development of a neoplasm. Initiation alone is insufficient for neoplasia to occur
2 types of initiators
Direct acting agent and Indirect acting agents
Indirect acting agents
Require in-vivo metabolic conversion into an active definitive carcinogen (metabolite or free radicals)
v-onc
proto-oncogene mutation due to viral transduction
c-onc
proto-oncogene mutation due to influences that alter their function in situ
p53 is an example of
tumor suppressor (anti-oncogene)
Rb is an example of
tumor suppressor (anti-oncogene)
BRCA-1/2 is an example of
tumor suppressor (anti-oncogene)
Direct acting initiator
Require no chemical transformation to induce their carcinogenic potential
chemical initiators are
mutagenic at the molecular level inducing mutations in oncogenes
Promoters
themselves are not mutagenic. Rather they stimulate activation and production of enzymes capable of inducing cell growth and proliferation.
Examples of direct-acting initiators
alkylating agents, cyclophosphamide, chlorambucil, busulfan, melphalan, immunosuppressants
direct-acting initiators are
weak carcinogens
Examples of indirect-acting initiators
Polycyclic aromatic hydrocarbons, Aromatic amines/azo dyes, Aflatoxin B1 – Produced by Aspergillus flavus, Nitrosamines and amides
Polycyclic aromatic hydrocarbons
indirect-acting initiator, potent carcinogen, can cause skin, colon, lung, bladder cancer, sarcoma
Aromatic amines/azo dyes
indirect-acting initiator, activated by the cytochrome P-450 oxygenase activator systems, associated with HCC
β-naphthylamine
indirect-acting initiator, present in aniline-dyes, associated with bladder cancer
Aflatoxin B1
indirect-acting initiator, Produced by Aspergillus flavus, when Hep B infected person is exposed = increased risk of HCC
Nitrosamines and amides
indirect-acting initiator, common food preservatives activated by gut bacteria, gastrointestinal carcinomas
Exogenous promoters
Saccharin and cyclamates, Diethylstilbestrol (DES), Exogenous hormones
Endogenous Promoters
Hormones, Bile salts/Dietary Fat
UV exposure
causes pyrimidine dimers in DNA that overrides the body’s inherent Nucleotide Excision Repair (NER) mechanisms
UV exposure primarily causes
cutaneous malignancies
UV, electromagnetic, particulate, radon
Many can act directly by inducing DNA breaks or indirectly by generating free radicals
Cytotoxic viruses
inject their DNA/RNA into a cell, this becomes incorporated into cells DNA and causes mutations/altered genes
HPV
DNA oncogenic virus
HPV Types 16 and 18 are associated with
invasive squamous cell carcinoma
HPV Types 1, 2, 4, 7 are associated with
Benign squamous papillomas
HPV Types 6 and 11 are associated with
Genital lesions with low malignant potential
Epstein Barr virus (EBV)
DNA oncogenic virus
EBV is associated with
Burkitt’s Lymphoma, B-cell lymphoma
HBV virus
DNA oncogenic virus
HBV is associated with
HCC esp in combo with Aflatoxin B1
Kaposi virus
DNA oncogenic virus
Kaposi virus KSHV is associated with
development of AIDS related Kaposi sarcoma
Human T cell leukemia virus (HTLV-1)
RNA oncogenic virus
Human T cell leukemia virus (HTLV-1) is associated with
T cell leukemia/lymphoma
Hep C virus
RNA oncogenic virus
Hep C virus is associated with
HCC
Helicobacter pylori
gastric bacteria associated oncogenesis (gastric carcinoma, MALT lymphoma)
MALT lymphoma caused by h/ pylori can be treated with
abx
Local effects from tumor on host
Effects caused at site due to tumor growth
Hormonal effects from tumor on host
tumors may possess the ability to secrete hormones or hormone-like factors
Small cell cancer of the lung often secretes
ACTH causing Cushing’s Syndrome
Cachexia
systemic effect due to tumor, causing increased TNF-alpha and cytokine release, resulting in increased basal metabolic rate, in addition to tumor cells increased need for nutrients
Paraneoplastic syndrome
Constellation of physical findings that are in association to products of the tumor
migratory thrombophlebitis
Malignancies associated with hypercoagulability
Tumor lysis syndrome
group of metabolic complications that can occur after treatment of cancer: hyperkalemia, hyperphosphatemia, hyperuricemia and hyperuricosuria, hypocalcemia, and consequent acute uric acid nephropathy and acute renal failure
Anti-tumor defenses include
CTL, NK, Macrophages, immunosurveillance, immunotherapy against tumor antigens
Histology
staining and viewing tissue morphology and cells in relation to another
Cytology
Cellular staining to look for characteristics of individual cells
DNA probe
look for specific DNA sequences characteristic of cancer type
Carcinoembryonic Antigen (CEA):
colon cancer
Alpha-Fetoprotein (AFP):
HCC
Beta Subunit Human Chorionic Gondotropin (β-HCG):
choriocarcinoma
CA-125
ovarian cancer
Flow cytometry
use to quantify B and T cells
exfoliative cytology
scrape away epithelium and stain
Fine needle aspiration
insertion of a needle into the neoplasm to collect fluid and cells
