Practical Oncology Round Cell Tumors Wendy Blount, DVM Round Cell Tumors • Lymphoma • Mast Cell Tumor • Plasma Cell Tumor • Extramedullary Plasmacytoma • Multiple myeloma • Histiocytic Disease • Transmissible Venereal Tumor Diagnosis • Generally diagnosed with cytology, as they exfoliate well • May need histopathology if anaplastic • Immunohistochemistry if markedly anaplastic • Gives information about prognosis 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 Plasmacytoma Plasmacytoma 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 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 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 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 Multiple Myeloma Diagnosis – 2 of 5 1. Paraproteinemia (monoclonal gammopathy) • Serum protein electrophoresis • Also caused by rickettsial disease 2. 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 Multiple Myeloma Diagnosis – 2 of 5 3. >20% plasma cells in the bone marrow • DDx – atopy, rickettsial infection, FIP, Leishmania spp, heartworm disease 4. Bence Jones proteinuria • Not detected on urine dipstick 5. Infiltration of liver, spleen and skin with plasma cells (cats) 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 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 Multiple Myeloma x x Multiple Myeloma Prognosis • Short term prognosis is good • median survival 540 days (2.5 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 Histiocytic Disease • • • • • Histiocytoma Cutaneous histiocytosis Systemic histiocytosis Localized histiocytic sarcoma Malignant histiocytosis • aka disseminated histiocytic sarcoma 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 Histiocytoma 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 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 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 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 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 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 TVT TVT TVT TVT 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 Cytology • Rottweiler, sick with enlarged lymph nodes, spleen and liver – LN cytology • Dx – large cell lymphoma Cytology • Button like alopecic skin mass Cytology • Button like alopecic skin mass • Dx - Plasmacytoma Cytology • Button like alopecic tumor • Dx – mast cell tumor x x Cytology • Golden Retriever, sick with enlarged lymph nodes, spleen and liver • Dx – malignant histiocytosis Cytology • Recurring button like alopecic masses • Dx – cutaneous histiocytosis Cytology • alopecic tumor protruding from the naris, bleeds when bumped • Dx – TVT Cytology • Infiltrative plaque-like skin masses • Dx – Multiple Myeloma