Download PowerPoint - Practical Oncology Introduction

Practical Oncology
Wendy Blount, DVM
Housekeeping
• Handouts other than PowerPoint
slides are already in your notebook
• You will get copies of the PowerPoint
slides after each section
• Natalie is our “concierge”
• Course materials are downloadable
http://wendyblount.com
• Table of Contents, Abbreviations
• Blue subdividers
Housekeeping
• We’ll break the last 10 minutes of
every hour
• Lunch break is 11:50am-12:30pm
today
• Tomorrow, we will break from
11:30am to noon, and then start the
lunch program at noon
• PLEASE PARTICIPATE!!
• But take private conversations out in
the hall
Practical Medicine Philosophy
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)
Definitions
Hyperplasia
• Normal tissue response to noxious
stimuli
• Reversible when regeneration is
complete
Neoplasia
• Cell replication never “turns off”
Anaplasia
• Lack of cell differentiaion
Definitions
Malignant
• propensity to spread by recurring
locally and/or metastasizing
Mitotic Index
• Number of mitotic figures per high
power field
Definitions
Carcinoma
• Cancer arising from ectodermal or
endodermal tissues
Sarcoma
• Cancer arising from mesodermal
tissues
Definitions
Grade (based on histopathology)
• Grade I behaves most benignly
• Grade III behaves most malignantly
Stage (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
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 circumstances
Cancer most often arises from cells
that continually replicate
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
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
What Causes Cancer?
Lost Tumor Suppressor genes
• Normal people and animals have
these
• Lost in some individuals that will
have genetic tendencies to
particular pediatric cancers
– Retinoblastoma
– Osteosarcoma
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
What Causes Cancer?
Apoptosis defects
• Apoptosis – programmed cell death
• Important to growth equilibrium
• Some genetic mutations eliminate
apoptosis
What Causes Cancer?
It can take many years for a malignant
cell to produce a detectable tumor
• By the time you see the tumor, it has
been there for a very long time
What Causes Cancer?
Biology of metastasis
1. Cancer cells shed into blood or
lymphatics
2. Evade immune surveillance
3. Come to rest in capillary or
lymphatic vessel beds
4. Disrupt the basement membrane
(proteases, metalloproteinases)
5. New blood supply grows
(angiogenesis)
Treatment Modalities
Surgery and Radiation
• Local control
• Exception – whole body radiation for
lymphoma
– After 11 week chemo induction
– remission 16.5 months
Chemotherapy
• To manage widespread disease that is
chemo responsive
• To slow progression of metastatic
disease
Treatment Modalities
Metronomic Chemotherapy
• Low dose, long term chemo
• Generally well tolerated
• For less aggressive tumors
• For palliation for advanced tumor
stages
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?
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 for diagnosis
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
Cytology Basics
Thillai Koothan – Friendswood TX
Cytology Basics
7. Are cells round, epithelial or
mesenchymal?
1. Nuclei
•
•
round - round cells and epithelial cells
Nuclei and cytoplasm oblong - mesenchymal
cells
2. Clustering
•
•
With cell to cell adhesions - Epithelial cells
Separate cells - round cells or mesenchymal
cells
3. Cytoplasmic borders
•
•
distinct - round cells and epithelial cells
Indistinct – mesenchymal cells
Cytology Basics
7. Are cells round, epithelial or
mesenchymal? Mixed populations
– All three cell types present
•
•
anaplastic sarcoma
e.g., amelanotic melanosarcoma
– Multinucleated cells, mesenchymal
cells, histiocytic round cells
•
•
Malignant fibrous histiocytoma
aka PUSS
Cytology Basics
Round Cells
Cytology Basics
Mesenchymal Cells
Cytology Basics
Epithelial Cells
Cytology Basics
Anaplastic melanoma
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
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
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
Cytology Basics
Cytology Basics
Cytology Basics
Cytology Basics
Cytology Basics
Cytology Basics
Barton Cytologic Rubric
1. Is it inflammatory or noninflammatory?
2. Is it round cell, epithelial cell, or
mesenchymal cell?
3. Are there characteristics of
malignancy?
– Are they weak or strong?
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, testicles and bone marrow
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