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Practical Oncology Round Cell Tumors

Practical Oncology Round Cell Tumors. Wendy Blount, DVM. Round Cell Tumors. Lymphoma Mast Cell Tumor Plasma Cell Tumor Extramedullary Plasmacytoma Multiple myeloma Histiocytic Tumors Transmissible Venereal Tumor Seminoma. Diagnosis.

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Practical Oncology Round Cell Tumors

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  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

  8. "Knowledge is power. Power to do evil ... or power to do good. Power itself is not evil. So knowledge itself is not evil."--Veronica Roth "Use your powers for good."--Common Sense and Wise Counsel

  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:

  28. “Those I love and admire for their strength and grace did not get that way because things worked out. They got that way because things went wrong, and they handled it. They handled it in a thousand different ways on a thousand different days, but they handled it. Those people are my superheroes.” --Elizabeth Gilbert (paraphrased)

  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

  49. "Most of us spend too much time on what is urgent and not enough time on what is important."-- Stephen Covey "Things don't have to change the world to be important."-- Steve Jobs

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

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