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 Tumors • Transmissible Venereal Tumor • Seminoma

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. 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

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9. Multiple Myeloma Clinical Signs • Lethargy, anorexia weight loss • Lameness + pathologic fracture • PU-PD • Hyperesthesia • Hyperviscosity Syndrome • Immunosuppression – cytopenias & inhibition of humoral immunity • 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 & resulting renal failure

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 • 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

14. 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

15. 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

16. 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

17. 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)

18. Multiple Myeloma Treatment • Treat hyperviscosity • diuresis • Whole blood or platelet rich plasma for bleeding diathesis • Treat hypercalcemia (see LSA) • (Plate pathologic fractures) • Treat secondary infection • Treat renal failure • Chemotherapy

19. Multiple Myeloma Standard Chemotherapy • Melphalan 0.1 mg/kg PO SID x 10 days, then 0.05 mg/kg PO QOD thereafter • Prednisone 0.5 mg/kg PO SID x 10d, then QOD • with or without 1 dose cyclophosphamide 200 mg/m2 IV Pulse Chemotherapy • Melphalan 7 mg/m2 PO SID x 5 days, repeat every 3 weeks • Prednisone 0.5 mg/kg PO SID x 10d, then QOD

20. 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 if possible

21. Multiple Myeloma Prognosis • Short term prognosis is good • median survival 540 days (1.5 years) 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

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

23. 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

24. Histiocytoma

25. 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

26. Histiocytic Sarcoma • Familial in Bernese Mountain Dog • Slowly progressive disease • Cutaneous masses • Sometimes other organs are affected • Nodules can occur around and infiltrate joints • Also retrievers and Rottweilers

27. Poppie • 6 yr F Miniature Pinscher • CC: urine has been dark • Urinalysis: 4+ bilirubin, USG 1.024 • CBC, panel: ALT 322, SAP 633, bili 1.8 • Abdominal US:

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29. Poppie • 6 yr F Miniature Pinscher • CC: urine has been dark • Urinalysis: 4+ bilirubin, USG 1.024 • CBC, panel: ALT 322, SAP 633, bili 1.8 • Abdominal US: • BMBT: 1 minute 5 seconds • Liver Cytology: mild cholestasis • Tx: amoxicillin x 3 weeks, milk thistle, recheck 30 days

30. Poppie • Recheck 2 weeks: urine • cleared up, now dark again • Appetite has been a little off • Mild icterus noted on exam • CBC, panel: ALT 752, SAP1433 • bili 2.1 • BMBT: 1 minute 10 seconds • Abdominal US:

31. Poppie • Recheck 2 weeks: urine • cleared up, now dark again • Appetite has been a little off • Mild icterus noted on exam • CBC, panel: ALT 752, SAP1433 • bili 2.1 • BMBT: 1 minute 10 seconds • Abdominal US:

32. Poppie • Recheck 2 weeks: urine • cleared up, now dark again • Appetite has been a little off • Mild icterus noted on exam • CBC, panel: ALT 752, SAP1433 • bili 2.1 • BMBT: 1 minute 10 seconds • Abdominal US:

33. Poppie • Recheck 2 weeks: urine cleared, now dark again • Appetite has been a little off • Mild icterus on exam • CBC, panel: ALT 752, SAP1433, bili 2.1 • BMBT: 1 minute 10 seconds • Abdominal US: • many nodules 1-30mm, rounded and bumpy liver margins • Liver Cytology: histiocytic sarcoma • Poppy’s dam died of the same tumor, at the same age

34. Poppie • Lessons from Poppie: • Never hesitate to repeat • the ultrasound, to check • for progression of disease • Repeat FNA as well, even if no sonographic change • Recheck as soon as 14-30 days if looking for neoplasia

35. Teleah Grand, DVM Poppie • Lessons from Poppie: • Never hesitate to repeat • the ultrasound, to check • for progression of disease • Repeat FNA as well, even if no sonographic change • Recheck as soon as 14-30 days if looking for neoplasia

36. 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

37. 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

38. 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

39. 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 recurs if surgically removed

40. 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

41. TVT

42. TVT

43. Round Cell Tumor Cytology • Lymphoid Cells – see LSA section • 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 – special lymphoid cell • Dark blue cytoplasm with central pallor • Perinuclear clear zone (Golgi zone) • Eccentric nucleus

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

45. Cytology • Button like alopecic skin mass • Dx - plasmacytoma

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

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

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

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50. Cytology • alopecic tumor protruding from the nostril, bleeds when bumped • Dx – TVT