1. Case # 85154: Bone marrow impression from a lame dog Presenter: Katie Boes Authors: Laurie O’Rourke, Geoffrey Saunders, Natalie Durrett Crawford, Nic Lambrechts, Jonathan Miller, Kurt Zimmerman Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

2. Signalment & History Signalment –2-year-old –Castrated male –Golden Retriever History –Chronic weight loss –Progressive left thoracic leg lameness Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

3. Physical Examination BCS 3/9 Left front limb –Grade 3/4 lameness –Muscle atrophy –Pain with shoulder flexion –Solid scapular mass Enlarged liver Abdominal distension Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

4. Imaging: Left Shoulder Radiographs –Well-circumscribed area of bony lysis at the scapular neck, surrounded by a soft tissue mass Ultrasound –Cortical lysis Loss of echogenic interface Loss of the distal acoustic shadowing Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

5. Imaging: Metastasis Check Abdominal ultrasound –Several soft tissue masses Thoracic radiographs –Enlarged heart –Unremarkable lung fields Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

6. Gross Findings Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

7. Samples Collected Cytopathology –Bone marrow impressions from the left scapula Histopathology –Perirenal mass, small intestine, liver, pancreas, spleen, kidney, lung –Not the left scapular mass Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

8. Left scapular bone marrow impression, Modified Wright’s Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

9. Left scapular bone marrow impression, Modified Wright’s Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

10. Perirenal mass, H&E Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

11. Perirenal mass, H&E Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

12. Perirenal mass, H&E Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

13. Special Stains & Immunohistochemistry StainResult Significance & Cell Origin Grimelius silver stainStrong (+)Chromaffin cell Vimentin(-)Not mesenchymal Cytokeratin AE1/3(-)Not epithelial SynaptophysinStrong (+)Neuroendocrine Chromatogranin AWeak (+)Neuroendocrine Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

14. Diagnosis Cytopathologic opinion of bone marrow –Consistent with metastatic neuroendocrine neoplasia Histopathologic diagnosis –Perirenal mass: malignant pheochromocytoma with metastases to the liver, pancreas, spleen, kidney, lung, and scapula bone, canine Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

15. Review: Neuroendocrine Cytologic Appearance Highly cellular Many free nuclei Cells exfoliate in loosely attached sheets Round to polygonal cells Indistinct cell borders –Occasionally distinct Nuclei are round to indented Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

16. Comments Histopathologic sections of the scapular mass were not taken, however… –Antemortem FNAs of the scapular mass and several intraabdominal masses revealed similar neoplastic cells as described in the postmortem bone marrow impression smear Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

17. Pheochromocytomas: Cell Origin & Signalment Type of paraganglioma tumor of the chromaffin cells arising from the adrenal medulla Uncommon tumor of older dogs –0.1% to 0.01% of all tumors in dogs –Mean age of 11 yrs (range of 1-15 yrs) No breed or sex predilection Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

18. Pheochromocytomas: Presenting Complaints None (incidental finding) –48-57% Non-specific Excessive catecholamine production –23-43% –Signs associated with hypertension –Panting, dyspnea, coughing, weakness, exercise intolerance Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

19. Pheochromocytomas: Clinical Diagnosis Routine blood and urine analysis –Variable and non-specific Measure catecholamines and their metabolites in blood and urine –Low availability –High technical difficulty and expense –False negatives due to cyclical excretion Catecholamine stimulation and suppression tests –Dangerous due to profound changes in blood pressure Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

20. Pheochromocytomas: Treatment & Survival Surgery is the treatment of choice –Mortality rates: 22-29% –Survival with complete removal: Up to 3.25 years Survival –No correlation between prognosis and histologic appearance in dogs –Neurologic disease, abdominal distension, and weight loss associated with advanced tumor stages Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

21. Acknowledgements VMRCVM’s Department of Biomedical Sciences Dr. Eric Schultze, Eli Lilly & Co. Dr. Christopher Ober, VMRCVM Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

22. References 1.Barthez PY, Marks, SL, Woo J, Feldman EC, Matteucci M. Pheochromocytoma in dogs: 61 cases (1984-1995). J Vet Intern Med. 1997;11:272-278. 2.Bouayad H, Feeney DA, Caywood DD, Hayden DW. Pheochromocytoma in dogs: 13 cases (1980-1985). J Am Vet Med Assoc. 1987;191:1610-1615. 3.Capen CC. Tumors of the adrenal gland. In: Moulton JE, ed. Tumors in Domestic Animals. 3rd ed. Berkeley, CA: University of California Press; 1990:576-583. 4.Gilson SD, Withrow SJ, Wheeler SL, Twedt DC. Pheochromocytoma in 50 dogs. J Vet Intern Med. 1994;8:228-232. 5.Raskin RE, Meyer DJ. Atlas of Canine and Feline Cytology. Philadelphia, PA: W. B. Saunders; 2001: 31-32. Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only

23. Questions? Presented at SEVPAC 2008 – Permission granted for use on SEVPAC website only