practical oncology wendy blount, dvm. definitions cancer the state in which normal growth...
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Practical Oncology
Wendy Blount, DVM
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Definitions
Cancer• The state in which normal growth
controlling mechanisms are permanently impaired, permitting progressive growth of cells without reaching growth equilibrium
Growth Equilibrium• Production of new cells = cell death• No net gain of tissue (liver) (heart)
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Definitions
Hyperplasia• Normal tissue response to noxious
stimuli• Reversible when regeneration is
completeNeoplasia• Cell replication never “turns off”Anaplasia• Lack of cell differentiaion
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Definitions
Malignant• propensity to spread by recurring
locally and/or metastasizingMitotic Index• Number of mitotic figures per high
power field
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Definitions
Carcinoma• Cancer arising from ectodermal or
endodermal tissuesSarcoma• Cancer arising from mesodermal
tissues
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Definitions
Grade (based on histopathology)• Grade I behaves most benignly• Grade III behaves most malignantlyStage (based on tests to determine
extent of tumor invasion)• Stage I is the least invasive• Stage 4-5+ are most invasive, and
often carry poor prognosis for cure
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What Causes Cancer?
Genetic derangement of the things that normally eventually turn cell replication off
Faulty differentiation of pluripotent stem cells
NOT anaplasia of differentiated cells• Except in rare circumstancesCancer most often arises from cells
that continually replicate
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What Causes Cancer?
Cancer is a disease of aging• odds of aberrant cell division
increases• Immune surveillance weakens• Cell repair mechanisms fail• Genetic injury by exposure becomes
more likely– Exposure to carcinogens– Infection by viruses carrying oncogenes– Physical damage by trauma or irritation
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What Causes Cancer?
Oncogenes• Virus RNA that causes cancer when
incorporated into host genes• Oncogenes make growth factors that
are most often kinases• Basis of the new TKI anticancer
drugs
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What Causes Cancer?
Lost Tumor Suppressor genes• Normal people and animals have
these• The are lost in some individuals that
will have genetic tendencies to particular pediatric cancers– Retinoblastoma– Osteosarcoma
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What Causes Cancer?
Cancer Cell Immortalization• Normally a cell line eventually dies
out because the telomeres required for cell division are used up
• Telomerase allows extension of the telomeres for cell division ad infinitum
• Telomerase products are sold as health food supplements to combat aging
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What Causes Cancer?
Apoptosis defects• Apoptosis – programmed cell death• Important to growth equilibrium• Some genetic mutations eliminate
apoptosis
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What Causes Cancer?
It can take many years for a malignant cell to produce a detectable tumor
• With senescence, odds of aberrant cell division increases– Exposure to carcinogens– Infection by viruses carrying oncogenes– Physical damage by trauma or irritation
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What Causes Cancer?
Biology of metastasis1. Cancer cells shed into blood or
lymphatics2. Evade immune surveillance3. Come to rest in capillary or
lymphatic vessel beds4. Disrupt the basement membrane
(proteases, metalloproteinases) 5. New blood supply grows
(angiogenesis)
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Treatment Modalities
Surgery and Radiation• Local control• Exception – whole body radiation for
lymphomaChemotherapy• To manage widespread disease that
is chemo responsive• To slow progression of metastatic
disease
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Treatment Modalities
Metronomic Chemotherapy• Low dose, long term chemo• Generally well tolerated• For less aggressive tumors• For palliation for advanced tumor
stages
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Cytology Basics
1. Is cellularity adequate? – are there plenty of cells?– Are the cells those you intended to
sample?– Are there cells other than RBC?
2. If there are few cells, is it possibly a cyst or hematoma?
3. Are the nucleated cells WBC or other cells?
4. If WBC, are they lymphoid cells?
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Cytology Basics
5. Are the lymphoid cells uniform or of various stages?– Various stages indicates inflammatory
lymphoid response– All lymphoblasts – large cell lympoma– All plasma cells – plasmacytoma,
myeloma– All lymphocytes can be normal in
lymph node or spleen• Lymphocytic tumors can require
histopathology
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Cytology Basics
6. If non-lymphoid WBC, what kind?– Neutrophils – suppurative– Degenerate toxic neutrophils – septic– Neutrophils + macrophages –
pyogranulomatous– Macrophages – granulomatous– Eosinophils, basophils – allergic, parasitic– Mott cells, plasma cells – chronic
antigenic stimulation– Fibroblasts can accompany chronic
inflammation
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Cytology Basics
7. Are cells round, epithelial or mesenchymal?1. Nuclei
• round - round cells and epithelial cells• Nuclei and cytoplasm oblong with mesenchymal
cells
2. Clustering • Epithelial cells are clustered – look for cell-to-cell
adhesions• No cell-to-cell adhesion with round cells or
mesenchymal cells
3. Cytoplasmic borders are distinct for round cells and epithelial cells
– All three cell types present• anaplastic sarcoma
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Cytology BasicsJulie Bradford – Tyler TX
Melissa Riley – Houston TXRosalie Cooper-Chase – Crockett TX
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Cytology Basics
Round Cells
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Cytology Basics
Mesenchymal Cells
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Cytology Basics
Epithelial Cells
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Cytology Basics
Anaplastic melanoma
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Cytology Basics
8. Are there characteristics of malignancy?– Cells aren’t normally found there– Increased blast cells– Changes in nucleus• Increased, abnormal mitotic figures
– Especially odd number of poles
• Hyperchromatic nucleus• Prominent or abnormal nucleoli• Unexpected multinucleation
– Especially different sizes
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Cytology Basics
8. Are there characteristics of malignancy?– Changes in cytoplasm• Loss of differentiation
– Changes in Cell• Increased N:C ratio (nucleus takes over
the cell)• Cell polymorphism – variation in size and
shape
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Cytology Basics
9. Is sufficient inflammation present to explain dysplasia?– No – strong characteristic of
malignancy– Mesothelial cells, macrophages and
fibroblasts can look very dysplastic in response to severe inflammation
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Cytology Basics
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Cytology Basics
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Cytology Basics
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Cytology Basics
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Cytology Basics
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Cytology Basics
Barton Cytologic Rubric1. Is it inflammatory or non-
inflammatory?2. Is it round cell, epithelial cell, or
mesenchymal cell?3. Are there characteristics of
malignancy?– Are they weak or strong?
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Cytology Basics
Technique Tips• Try “coring” with needle only prior
to attaching a syringe for aspiration• Start with a 22 or 25 gauge needle• If inadequate cellularity, try a
bigger needle and/or aspiration• Use a 10-12cc syringe to spray the
sample quickly onto a slide• Smear gently – vertical for lymph
nodes and testicles
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Cytology Basics
“Malignant” is a reasonable cytologic diagnosis
“Benign” is almost never a cytologic diagnosis
Cytology can not distinguish malignancy from wicked inflammation
If the lump changes, aspirate it again