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Clinical pathology case
- 1. Clinical Pathology Case Emily Jones
- 2. Case Presentation •10 year old female neutered DSH •Ataxia •Inappetance •Treated with Meloxicam for 1 week ▫ No improvement
- 3. Haematological Abnormalities ↓Hb 9.4 g/dl (10.0-15.0) ↓ HCT 29.4 % (30-45) ↓ WBC 4.46 x 109 (5.5-15.5) ↓ Lymphocytes 0.446 x 109 (1.5-7.0) ↑Total Protein 154 g/l (60-85) ↓ Albumin 15 g/l (26-36) ↑ Globulin 139 g/l (27-45) ↓ A:G Ratio 0.1 g/l (0.35–1.5)
- 4. Problem list • Ataxia • Inappetance • Severe hyperglobuminemia • Moderate to severe lymphopenia • Mild leukopenia • Moderate hypoalbuminemia • Mild anaemia
- 5. Differential Diagnosis • Hyperglobulinemia 1. Chronic antigen stimulation and inflammation secondary to infection, immune mediated diseases or neoplasia. (Polyclonal) - Feline Infectious Peritonitis 2. Neoplasia. (Monoclonal) - Multiple Myeloma - Lymphoma
- 6. Feline Infectious Peritonitis • Hyperglobulinemia • Lymphopenia • Neutophilia • Anaemia
- 7. Further investigations • FCoV antibody titre 0 • Alpha-1 AGP 280 ug/ml
- 9. Multiple Myeloma • Lymphoproliferative neoplasia • Rare in cats (<1% malignant tumours) • Median age 12-14 years • Unknown etiology • Develops in multiple BM sites • Variable clinical signs
- 10. Further Investigation • Spinal radiographs - ID bone lesions • Bone Marrow biopsy - ≥ 10% plasma cells (normal: <4%)
- 11. References • Bienzle, D. 'Multiple Myeloma In Cats: Variable Presentation With Different Immunoglobulin Isotypes In Two Cats'. Veterinary Pathology 37.4 (2000): 364-369. Web. • Weber, NA, and CS Tebeau. 'An Unusual Presentation Of Multiple Myeloma In Two Cats'. Journal of the American Animal Hospital Association 34.6 (1998): 477-483. Web. • Diagnosis and clinical signs of feline infectious peritonitis in the central nervous system • Vetsurgerycentral.com,. 'Multiple Myeloma'. N.p., 2015. Web. 12 Mar. 2015. • DACVP, Jackie. 'An Overview Of Multiple Myeloma In Dogs And Cats'. dvm360.com. N.p., 2015. Web. 12 Mar. 2015.
Editor's Notes
- Presented to the referring vet with ataxia and inappetance. No vomiting, PUPD, weight loss, temperature normal. Samples submitted; EDTA blood smear, Heparin blood tube, serum gel blood tube.
- These are the haematological abnormalities. Mild anaemia Moderate leukopenia, lymphopenia Marked hyperproteinemia with a severe hyperglobulinemia but a moderate hypoalbuminemia. The A:G ratio is therefore decreased.
- This is our problem list from the information we have so far. The most significant clinical pathology finding is the severe hyperglobulinemia.
- So we’ll look at the main differentials for a cat with hyperglobulinemia. There are two broad causes of an elevated globulin; the first is due to chronic antigen stimulation. This happens because of an infection or immune mediated disease. The most likely cause of this in cats would be Feline infectious peritonitis, a disease caused by coronavirus. The referring vet had a suspicion of FIP so as well as haematology they requested an FIP profile which also includes: -Feline coronavirus antibodies - Αlpha 1 Acid glycoproteins
- Non-effusive (dry) FIP: Haematology often reveals a non-regenerative anaemia, lymphopaenia and mild neutrophilia, with a left shift However FIP generally occurs in younger cats and there is normally other clinical signs including ascites or a pleural effusion
- The coronavirus titre came back as 0 which means this cat has never been infected with coronavirus and seroconverted. This result allows us to rule out FIP as this disease occurs when coronavirus mutates in the body. FCoV Antibody Titre ≥ 640 High FCoV antibody titre 160-320 Moderate FCoV antibody titre ≤ 80 Low FCoV antibody titre Alpha 1 acid glycoprotein is one of a number of acute phase proteins produced by the liver in response to a wide range of inflammatory stimuli, including infectious and non-infectious diseases. Healthy cats are usually < 1500 g/mL = Reduced index of suspicion for FIP ≥1500 g/mL = Increased index of suspicion for FIP Increased concentrations of 1-AGP are not specific for FIP but can be a useful diagnostic marker for the disease when combined with other clinical and laboratory findings. Serum electrophoresis to determine whether the increase in globulin is monoclonal or polyclonal – this will help us to come to a diagnosis.
- The serum electrophoresis showed a monoclonal IgG hyperglobulinemia, this new clinical evidence suggests that neoplasia is involved. The most common cause of monoclonal hyperglobulinemia in cats is multiple myeloma. Monoclonal gammopathy has been described in cats with lymphosarcoma and is primarily because of the increased production of IgG from a clone of immunoglobulin producing cells. Clinical signs are primarily associated with hyperviscosity resulting in ophthalmic, neurologic, hematologic, and renal abnormalities. Clinical signs in cats with monoclonal gammopathy are nonspecific and include anorexia and lethargy Protein electrophoresis and immunoelectrophoresis help establish a diagnosis after the recognition of an abnormally elevated total serum protein concentration. Differentials for a monoclonal gammopathy in a cat include multiple myeloma, amyloidosis, and benign hyperglobulinemia. Multiple Myeloma – consists of a clonal proliferation of malignant plasma cells that usually produce an immunoglobulin. The tumor originates in the bone marrow and may involve other organs to varying degrees. Affected individuals generally are hyperglobulinemic. In dogs and cats two (or three?) of the following four signs must be present to make a diagnosis of Multiple Myeloma: - paraproteinemia - osteolytic lesions - more than 20% plasma cells in bone marrow biopsies - Bence Jones (light chain) proteinuria.
- Clinical signs vary depending on the systemic distribution of malignant cells and the amount of immunoglobulins secreted – hyperviscocity syndrome, renal disease, hypercalcaemia (para). Signs associated with multiple myeloma, which are often nonspecific and insidious in onset, include lethargy, weakness, and anorexia. The pathologic conditions associated with multiple myeloma are related to the effects of the circulating paraprotein as well as organ or bone marrow dysfunction due to neoplastic infiltration. Multiple myeloma is a B cell malignancy characterized by the infiltration and growth of plasma cells in the bone marrow
- 25-66% of MM cases have visible bone lesions Treatment - Chemotherapy agents Melphalan - alkylating agent is an oral medication that must be given daily to the patient Prednisone - a steroid increases the efficacy of melphalan and is typically discontinued after 2 months of treatment Cyclophosphamide - an alkylating agent can be used in place of melphalan or in combination with melphalan. Some oncologists will use this agent only in cases that have high calcium levels in the blood or if the tumor is widespread Chlorambucil - an alkylating agent can be used to treat MM In a study of 60 dogs treated for MM, 43% had a complete remission, 49% had partial remission, and 8% did not respond to treatment at all. Plasma cells (black arrows) are characterized by an eccentric nucleus, basophilic cytoplasm, and perinuclear clear zone/Golgi. Mitotic figures are present (white arrow) (Wright's stain; 500X).