practical oncology wendy blount, dvm. definitions cancer the state in which normal growth...

Practical Oncology

Wendy Blount, DVM

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

completeNeoplasia• Cell replication never “turns off”Anaplasia• Lack of cell differentiaion

Definitions

Malignant• propensity to spread by recurring

locally and/or metastasizingMitotic Index• Number of mitotic figures per high

power field

Definitions

Carcinoma• Cancer arising from ectodermal or

endodermal tissuesSarcoma• Cancer arising from mesodermal

tissues

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

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

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• The are 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

• With senescence, odds of aberrant cell division increases– Exposure to carcinogens– Infection by viruses carrying oncogenes– Physical damage by trauma or irritation

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)

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

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

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

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

Cytology BasicsJulie Bradford – Tyler TX

Melissa Riley – Houston TXRosalie Cooper-Chase – Crockett TX

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 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?

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

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