1. Practical Oncology Wendy Blount, DVM

2. 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)

3. Definitions Hyperplasia Normal tissue response to noxious stimuli Reversible when regeneration is complete Neoplasia Cell replication never “turns off” Anaplasia Lack of cell differentiaion

4. Definitions Malignant propensity to spread by recurring locally and/or metastasizing Mitotic Index Number of mitotic figures per high power field

5. Definitions Carcinoma Cancer arising from ectodermal or endodermal tissues Sarcoma Cancer arising from mesodermal tissues

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. What Causes Cancer? Apoptosis defects Apoptosis – programmed cell death Important to growth equilibrium Some genetic mutations eliminate apoptosis

13. 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

14. 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)

15. Treatment Modalities Surgery and Radiation Local control Exception – whole body radiation for lymphoma Chemotherapy To manage widespread disease that is chemo responsive To slow progression of metastatic disease

16. Treatment Modalities Metronomic Chemotherapy Low dose, long term chemo Generally well tolerated For less aggressive tumors For palliation for advanced tumor stages

17. 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?

18. 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

19. 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

20. 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

21. Cytology Basics Julie Bradford – Tyler TX Melissa Riley – Houston TX Rosalie Cooper-Chase – Crockett TX

22. Cytology Basics Round Cells

23. Cytology Basics Mesenchymal Cells

24. Cytology Basics Epithelial Cells

25. Cytology Basics Anaplastic melanoma

26. 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

27. 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

28. 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

29. Cytology Basics

34. Barton Cytologic Rubric 1.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?

35. 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

36. 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