Practical Oncology Round Cell Tumors

1. Practical OncologyRound Cell Tumors Wendy Blount, DVM

2. Round Cell Tumors • Lymphoma • Mast Cell Tumor • Plasma Cell Tumor • Extramedullary Plasmacytoma • Multiple myeloma • Histiocytic Disease • Transmissible Venereal Tumor

3. Diagnosis • Generally diagnosed with cytology, as they exfoliate well • May need histopathology if anaplastic • Immunohistochemistry if markedly anaplastic • Gives information about prognosis

4. Plasmacytoma • Round, button like tumors on the skin and mucous membranes • Technically malignant • Usually behave benignly if extramedullary • Surgery is curative if borders clean • Radiation curative if not resectable

5. Plasmacytoma

6. Plasmacytoma

7. Plasmacytoma Becky Hairgrove – Timpson TX Jennifer Cornish – Houston TX

8. Multiple Myeloma • Malignant plasma cells proliferate in bone marrow and are released into circulation • Malignant cells found in • Skeleton • Lymph nodes and spleen • Kidney and liver • Produce large amounts of a specific Ig or part of an Ig • Mono or biclonal gammopathy • Bence Jones protein is the light chain • heavy chain or paraprotein also possible

9. Multiple Myeloma Clinical Signs • Lethargy, anorexia weight loss • Lameness + pathologic fracture • PU-PD • Hyperesthesia • Hyperviscosity Syndrome • Immunosuppression – cytopenias in inhibition of humoral immunity • Cytopenias – anemia more common than leukopenia or thrombocytopenia • Hypercalcemia • Azotemia - hypercalcemia, renal infiltration, hyperviscosity

10. Multiple Myeloma Hyperviscosity syndrome (TP >10) • Heart failure • Reduced flow through small vessels • plasma volume expansion • volume overload • Myocardial hypoxia • Neurologic signs due to hypoxia • Seizures, disorientation, ataxia • Peripheral neuropathy

11. Multiple Myeloma Hyperviscosity syndrome (TP >10) • Bleeding diathesis • Capillary damage from hypoxemia • Inflammatory coagulopathy • Epistaxis, gingival bleeding • Retinal detachment, hyphema, secondary glaucoma, blindness • Renal ischemia

12. Multiple Myeloma Diagnosis – 2 of 5 • Paraproteinemia (monoclonal gammopathy) • Serum protein electrophoresis • Also caused by rickettsial disease • Osteolytic bone lesions (punched out) • Generalized osteopenia • Pathologic fractures • More common in dogs than cats • Radiograph spine, ribs and limbs • Biopsy lytic lesion and take bone marrow sample

13. Multiple Myeloma Diagnosis – 2 of 5 • >20% plasma cells in the bone marrow • DDx – atopy, rickettsial infection, FIP, Leishmania spp, heartworm disease • Bence Jones proteinuria • Not detected on urine dipstick • Infiltration of liver, spleen and skin with plasma cells (cats)

14. Multiple Myeloma Treatment • Treat hyperviscosity • diuresis • Whole blood or platelet rich plasma for bleeding diathesis • Treat hypercalcemia (pamidronate) • Plate pathologic fractures • Treat secondary infection • Treat renal failure • Chemotherapy melphalan and prednisone, with or without 1 dose cyclophosphamide

15. Multiple Myeloma Rescue Therapy – 3 week cycle • Week 1 – doxorubicin 30 mg/m2 IV • Start prednisone 1 mg/kg PO SID • Week 2, 3 – vincristine 0.7 mg/m2 • Wean off prednisone of possible

16. Multiple Myeloma Prognosis • Short term prognosis is good • median survival 540 days with treatment • Long term prognosis poor, as recurrence is expected • Bone pain and pathologic fractures main cause of morbidity and mortality • Negative prognostic indicators: • Hypercalcemia • Bence Jones proteinuria • Extensive bony lysis

17. Histiocytic Disease • Histiocytoma • Cutaneous histiocytosis • Systemic histiocytosis • Localized histiocytic sarcoma • Malignant histiocytosis • aka disseminated histiocytic sarcoma

18. Histiocytoma • Single alopecic button like mass • Usually young dogs • Usually spontaneously regresses • Can take 2-3 months • Aspiration can induce regression • If large, may need to be resected • If >2 yrs old, remove for histopath • Rare in cats • Cytology – small lymphocytes may be more numerous than histiocytes

19. Histiocytoma

20. Cutaneous Histiocytosis (dogs) • Single mass or multiple masses • May regress spontaneously • May wax and wane over years, requiring multiple surgeries or immunosuppressive therapy • Prednisone 2 mg/kg PO SID, and taper as signs regress over 2-3 months • Cyclosporine 5 mg/kg PO SID-BID, taper • Leflunomide 2-4 mg/kg PO SID • Goal is trough level 20 mcg/ml, taper • Side effect vomiting

21. Systemic Histiocytosis • Familial in Bernese Mountain Dog • Slowly progressive disease • Cutaneous masses • Sometimes other organs are affected • Localized histiocytic sarcoma • Also retrievers and Rottweilers • Nodules occur around and infiltrate joints

22. Malignant Histiocytosis • Multi-system, rapidly progressive disease • Bernese Mountain dogs, retrievers, Rottweilers • Histiocytic infiltration of spleen, lymph nodes, lung, bone marrow, skin • Usually leads to death in weeks • Clinical signs • Weight loss, lethargy, anorexia • Coughing, dyspnea • Seizures, weakness, lameness • No effective treatment

23. TVT • The only known naturally occurring tumor that can be transplanted as an allograft • Transmitted by transplantation of cells onto abraded mucous membranes • During breeding • Nose to butt contact • In the nose, on the perineum, or on/in the reproductive tract • Begins as hyperemic papules • Progresses to multilobulated, ulcerated, bleeding mass

24. TVT • If untreated, can metastasize • Eye, skin, lips, oral and nasal cavities • Regional lymph nodes • Lungs, liver, brain • Abnormal karyotype with 59 chromosomes • Dogs normally have 78 • May occasionally spontaneously regress • Usually recur if surgically removed

25. TVT Treatment • Vincristine 0.7 mg/m2 IV weekly • Continue 2-3 weeks past resolution of disease • Usually 3-5 injections are required • If no response, doxorubicin 30 mg/m2 IV q3 weeks x 3 treatments • Radiation is also effective, but often reserved for those that do not respond to chemotherapy • Spay-neuter and do not allow to roam

26. Merry Vann – Coldspring TX Sean Penn – Lufkin TX

27. TVT

28. TVT

29. TVT

30. TVT

31. Round Cell Tumor Cytology • Covered Lymphoid Cells • Histiocyte – larger than lymphoblast • Round to indented nucleus • Scant to Moderate pale cytoplasm • Mast Cell – histiocyte w/ purple granules • TVT – histiocyte with clear vacuoles • Plasma Cells • Dark blue cytoplasm with central pallor • Perinuclear clear zone (Golgi zone) • Eccentric nucleus

32. Cytology • Rottweiler, sick with enlarged lymph nodes, spleen and liver – LN cytology • Dx – large cell lymphoma

33. Cytology • Button like alopecic skin mass

34. Cytology • Button like alopecic skin mass • Dx - Plasmacytoma

35. Cytology • Button like alopecic tumor • Dx – mast cell tumor

36. Cytology • Golden Retriever, sick with enlarged lymph nodes, spleen and liver • Dx – malignant histiocytosis

37. Cytology • Recurring button like alopecic masses • Dx – cutaneous histiocytosis

38. Cytology • alopecic tumor protruding from the naris, bleeds when bumped • Dx – TVT

39. Cytology • Infiltrative plaque-like skin masses • Dx – Multiple Myeloma