Neoplasia Flashcards
0
Q
neoplasm
A
abnormal mass of tissue; growth of which exceeds and is uncoordinated w/ that of the normal tissues and persists after cessation of the stimulus which evoked the change
1
Q
Neoplasia
A
New growth
2
Q
Neoplasms arise from…
A
cells that have proliferative capacity; **mature neurons and cardiac myocytes don’t give rise to turmors
3
Q
Things that can cause neoplasia
A
- mutations in genes that regulate growth
- apoptosis
- DNA repair
4
Q
Anaplastic / cellular atypia
A
lack of differentiated features (morphologically or functionally) in cancers
- pleomorphism
- enlarged hyperchromatic nuclei
- atypical mitoses
- bizarre cells
5
Q
What must cancers have?
A
Stem - like properties
- arise from tissue stem cells
- arise from more differentiated cells that transform and acquire the self renewal ability
6
Q
benign
A
microscopic and gross characteristics are considered to be innocent; WILL NOT METASTASIZE OR INVADE
7
Q
malignant
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tumors collectively referred to as cancer; CAN INVADE, DESTROY, METASTASIZE TO DISTANT SITES AND CAUSE DEATH
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Q
What do benign and malignant relate to?
A
the biological behavior rather than morphology
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Q
Primary descriptor of any tumor
A
cell of origin
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Q
secondary descriptor of any tumor
A
morphologic or functional characteristics
11
Q
Benign tumor suffix
A
- oma
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Q
Adenoma
A
benign, arises from a gland
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Q
epithelioma or papilloma
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benign and arise form epithelial cells
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Q
medullary
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soft and cellular w/ little stroma
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Q
comedo
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with a duct
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Q
Malignant tumor suffix for EPITHELIAL cancers
A
carcinoma
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Q
Malignant tumor suffix for cancers of MESENCHYMAL origin
A
sarcoma
18
Q
-emia
A
relationship to blood
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Q
Teratoma
A
benign tumor arising form germ cells (hair/teeth)
20
Q
Hamartoma
A
localized, disordered differentiation during EMBRYOGENESIS that results in disorganized composition of the tissue elements of an organ
21
Q
How may Hamartomas manifest?
A
either singly or in combination
1) abnormal quantity
2) abnormal structure
3) degree of maturation of the tissue components
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Q
Choriostoma
A
Ectopic islands of normal tissues
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Q
Hepatoma
A
malignant
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melanoma
malignant
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seminoma
malignant
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lymphoma
malignant
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Brenner tumor
malignant
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Hodgkin disease
malignant
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What 2 basic components do all tumors share? (both benign and malignant)
1) PARENCHYMA composed of transformed or neoplastic cells
| 2) STROMA - support tissue that is host derived and composed of connective tissue, blood vessels, and inflammatory cells
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What is the gold standard for diagnosing a cancer?
Routine microscopy (there are no reliable molecular indicators)
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Ewing sarcoma
malignant
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What criteria are used to assess the true biological nature of a tumor?
Histological correlation of histologic and cytologic patterns w/ clinical outcomes
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Fibrosarcoma and nodular fasciitis
Fibrosarcoma - malignant
Nodular fasciitis - benign; has a more alarming histologic appearance than many fibrosarcomas. Misdiagnosis can lead to unnecessary surgery.
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Benign tumors and histologic and cytologic characteristics
benign tumors tend to be histologically and cytologically similar to their tissues of origin
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Benign tumors and gross structure
May differ from tissue of origins; assume papillary and polypoid configurations
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Malignant tumor morphology
- differ from parent tissue
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What distinguishes malignant from benign tumors?
- differentiation and anaplasia
- rate of growth
- local invasion
- metastasis
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Tumor markers
- products of malignant neoplasms that can be detected in body fluids or in affected cells
- can sometimes identify the cell or origin for metastases or a poorly differentiated primary tumor
- preserve the characteristics of cells of origins or have specific protein products that define a certain neoplastic cell
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Types of markers include...
- immunoglobulins
- fetal proteins
- enzymes
- hormones
- cytoskeleton or junctional proteins
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Why do we need to identify the lineage of a neoplasm that is poorly differentiated or undifferentiated?
Treatment decisions can be based on tumor markers that are present
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Tumor marker roles outside of determining lineage
- can be used to screen for cancer
- can be used to follow progression or resolution of cancer
- can be therapeutic targets
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PSA
prostate-specific antigen
screen for prostate carcinoma
evaluate for recurrence
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CEA
carcinoembyronic antigen
GI malignancies progression or recurrence
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CA 125
ovarian carcinoma progression or recurrence
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HER2
therapeutic target for breast cancer
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Immunohistochemistry
using antibodies to visualize certain tissues bound antigens
- conjugate an antigen to PEROXIDASE and there is a reaction that yields a color change
- conjugate the antibody to something that is fluorescent
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Tumor markers - immunohistochemical methods of diagnosis
| CARCINOMAS
- uniformally express cytokeratins (CKs)
- prostatic carcinoma produces PSA
- thyroid carcinomas can produce THYROGLOBULIN
- breast cancers can have ESTROGEN AND PROGESTERONE RECEPTORS
- LEWIS A ANTIGEN in PANCREATIC AND GASTROINTESTINAL CANCER
- CA125 for ovarian cancer
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Chromogranins
Tumor markers - immunohistochemical methods in diagnosis
NEUROENDOCRINE TUMORS
contained in neurosecretory granules
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Synaptophysin
Tumor markers - immunohistochemical methods in diagnosis
NEUROENDOCRINE TUMORS
- contained in adrenal and pancreatic islet cells
- neuroblastoma, pheochromocytoma, medullary thyroid carcinoma
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Antibodies to peptide hormones produced
Tumor markers - immunohistochemical methods in diagnosis
NEUROENDOCRINE TUMORS
- insulin, gastrin, ACTH, serotonin, somatostatin
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Tumor markers - immunohistochemical methods in diagnosis
| MALIGNANT MELANOMA
- may appear undifferentiated, unpigmented
- express HMB-45 and S-100
- NOT POSITIVE FOR CYTOKERATINS
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Tumor markers - immunohistochemical methods in diagnosis
| MALIGNANT LYMPHOMAS
- LCA (leukocyte common antigen)
- CD markers for B or T cells
- see lambda or kappa chains expressed on B cells (expression of only one type is consistent w/ a monoclonal B cell lymphoma)
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Tumor markers - immunohistochemical methods in diagnosis
| VASCULAR TUMORS
- antibodies against Factor VIII (8) - related antigen [CD31]
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Tumor markers - immunohistochemical methods in diagnosis
| PROLIFERATING CELLS
- PCNA (proliferating cell nuclear antigen) illustrates tumor growth rate
- look for cycling cells where growth is not usually present [Ki-67]
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Tumor markers - immunohistochemical methods in diagnosis
| SOFT TISSUE SARCOMAS
- express VIMENTIN (anchoring organelles and having shape/form to cells
- express DESMIN (in smooth or striated muscle fiber derived neoplasms)
- MUSCLE SPECIFIC ACTING
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Invasion and metastases
local invasion and capacity to metastasize to distant sites are unique to malignant cells and responsible for many cancer deaths
metastases allow the cancer to persist EVEN AFTER SURGICAL RESECTION OF THE PRIMARY TUMOR
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Carcinoma in situ
- dysplastic changes are marked and INVOLVE THE ENTIRE THICKNESS OF THE EPITHELIUM
- CONTAINED BY THE BASEMENT MEMBRANE
- PREINVASIVE NEOPLASM
- CURABLE
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When is an in situ stage not defined?
in situations in which cancers arise from cells that are not confined by a basement membrane (such as connective tissue cells, lymphoid elements, and hepatocytes)
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Fistula
abnormal connection/passageway between 2 epithelium-lined organs or vessels
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invasion
growth within a tissue
- enlarge and infiltrate throughout the tissue
- can result in obstruction or functional insufficiency
extension beyond primary site
- tumor may secondarily impair the function of an adjacent organ
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Most common cause of cancer death
metastases
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What is metastases?
- migration to a noncontiguous site
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How does metastases occur?
via hematogenous, lymphatic, or direct seeding routes
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Hematogenous metastases - common invasion sites
capillaries and venules (more thin walls)
thicker vessels are more resistant
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Where are metastases common??
Liver and lungs
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Place where mets can lodge and extend
lymph nodes
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Lymphatic capillaries _________ a basement membrane
Lack
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Initial sign of disease for lymphatic metastases
Lymph nodes enlarge
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Regional lymphatic metastases of the breast
Metastases primarily begin via lymphatics
| *nodal involvement is on prognostic significance
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Regional lymphatic metastases of the breast - Cancers arising laterally
Axillary nodes
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Regional lymphatic metastases of the breast - cancers arising medial
internal mammary nodes
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Sentinel node
"first lymph node" to where the cancer will drain
| - locate w/ a tracer such as die or scintigraphy (radioactive tag)
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skipped metastases
- metastases are more distant
| - prognosis is worse
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Direct seeding of metastases
Tumor cells are released into a BODY CAVITY
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Example of direct seeding of metasteses
ovary (mesentery or bowel can be involved)
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Tumor-Associated Host Cells
- significant number of cells within tumor mass
- fat cells, macs and leukocytes, fibroblasts, vascular endothelial cells, neural cells
- nontumor cells can define the cancer behavior
- CONCEPT OF PRODUCTS W/ MUTUALLY OPPOSITE EFFECTS
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Tumor-Associated Host Cells - Macrophages and Leukocytes
Macs will produce enzymes to digest basement membranes
- MMPs, cathepsins, u-PA
Macs promote inflammation and angiogenesis
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Tumor-Associated Host Cells - Adipocytes
- Express a MMP that promotes cancer movement through the MATRIX
- stimulate macs to secrete pro inflammatory cytokines through leptin production
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Adhesion molecules
Promote the entire process: necessary for invasion, metastases, and growth at the distant site
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Integrins
interaction BETWEEN CELLS and between CELLS and EXTRACELLULAR MATRIX
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Selectins
Binding between TUMOR CELLS and NONMALIGNANT TUMOR-ASSOCIATED CELLS
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Cadherins
Interaction AMONG TUMOR CELLS
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IgCAM superfamily (immunoglobulin cell adhesion molecule)
binding both AMONG TUMOR CELLS and BETWEEN TUMOR CELLS AND TUMOR-ASSOCIATED CELLS
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Upper limits of tumor diameter that can be supported w/o additional "supply line"
2mm diameter
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VEGF
Vascular Endothelial Growth Factor
- Made by tumor cells
- Most significant amount is made by connective tissue, platelets, and TAMS
- acts on vascular endothelium to induce proliferation toward the source
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TAMs
Tumor Associated Macrophages
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VEGF, FGF, EGF, TGF-alpha
TAMs
- growth factors for tumors
- mitogens for endothelial cells
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Cytokines (TNF-alpha, IL-8)
TAMs
TNF can be pro and anti-tumor
IL-8 can stimulate angiogenesis
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TNF in low quantities
anti-tumor
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TNF in high quantities
favors angiogenesis and environment for tumors to grow
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In normal cells, GF interaction is...
paracrine in nature
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In neoplastic cells, GF interactions have...
an autocrine loop
| - part of the immortality these cells have
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Examples of autocrine loops
Glioblastomas secrete PDGF and have receptors
Sarcomas secrete TGF-alpha and have receptors
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Oncogenes induce GF genes to...
Overproduce
this does not induce neoplastic transformation (does not make cancer)
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Quiescent intervals
tumor dormancy - present in cancer growth
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Tumor dormancy
presence of cancers, either primary or metastatic, that do not enlarge to the point of being clinically detectable
Tumor cells in G0 phase of the cell cycle
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Causes of tumor dormancy
growth arrest secondary to signaling
proliferation = death
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Monoclonal
1 cell transforms; all of its progeny make up the tumor
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Polyclonal
several cells transform, giving way to identical clones that make up this tumor; a little bit harder to treat depending on how each reacts
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Most cells are of what origin?
Monoclonal origin
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Spike on serum electrophoresis
indicates monoclonal transformation in the gamma regions (right)
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Tumor heterogeneity
the genotypic and phenotypic variation that occurs
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Clonal evolution
progressive accumulation of new mutations as they proliferate
Darwinian-style selection, "survival of the fittest" of tumors governs which subclones will succeed, die, metastasize, or remain localized
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3 different mechanisms responsible for mutations
1) chromosomal instability
2) microsatellite instability
3) aberrant DNA methylation
106
Genomic instability as a contributor to cancer development - Chromosomal instability
additions and deletions of various sizes
results in
- aneuploidy (imbalance in chromosomal numbers)
- gene amplification (increase in gene copy number)
- loss of heterozygosity (loss of allele out of a pair)
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Oncogenes
mutated genes that promote autonomous cell growth in cancer cells
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Proto oncogenes
"unmutated" cellular counterparts
| - normal cell that can become an oncogene due to mutations or increased expression
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Oncoproteins
Gene products
- lack regulatory components
- do not depend on signals or GFs for production
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Where were oncogenes originally found?
in the oncogenically activated state in retroviruses and transformed cells
- so oncogenes are in the normal non-oncogenically activated state in non-transformed cells
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Oncogene activation by mutation
- includes point mutations, deletions, and translocations
- Point mutations: result in alterations usually involving critical protein regulatory regions
- leads to uncontrolled continuous activity of the mutated protein
- activation is associated w/ somatic alterations due to unregulated growth
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c-ras
first human oncogene identified
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Oncogene activation by gene amplification
- redundant replication of genomic DNA
| - karyotypic abnormalities: double-minute chromosomes (DMs) and homogenous staining regions (HSRs)
114
Double minutes (DMs)
"mini-chromosome structures" w/o centromeres
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Homogenous staining regions (HSRs)
segments of chromosomes lacking normal alternating light and dark staining bands (more genes, segments appear longer)
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Oncogene activation by chromosomal translocation
- found in leukemias and lymphomas
- keys are the proto-oncogene and the breakpoint cluster region
- hybrid oncogene results in aberrant protein w/ high tyrosine kinase activity (mitogenic and antiapoptotic signals)
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Example of oncogene activation by chromosomal translocation
Philadelphia chromosome (bcr/abl fusion gene)
- translocation in CML fuses c-abl gene, normally located at 9q34 w/ the bcr gene at 22q11
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Another example of oncogene activation chromosomal translocation
Burkitt lymphoma
c-myc gene, located at chromosome band 8q24 under control of regulatory elements from the immunoglobulin heavy chain locus located at 14q32
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Gain-of-function mutations
mutations giving increased activity
