1. Practical Oncology Soft Tissue Sarcomas Wendy Blount, DVM

2. Soft Tissue Sarcomas Locally invasive, but slow to metastasize Fibrosarcoma (FSA) Hemangiopericytoma (HPA) Nerve sheath tumor, Schwannoma Leiomyosarcoma (LMSA) Spindle cell tumor Liposarcoma (LPSA) Different from infiltrative lipoma Myxosarcoma (MXSA) Pleomorphic Undifferentiated Sarcoma (PUS) Aka malignant fibrous histiocytoma (MFHA)

3. Soft Tissue Sarcomas A few behave differently – not included here Hemangiosarcoma (HSA) Lymphangiosarcoma Rhabdomyosarcoma Soft tissue osteosarcoma Synovial cell sarcoma

4. Soft Tissue Sarcomas Often extend beyond the visible mass Microscopic tendrils know what you have before you excise FNA all masses except SGA prior to excision Send out for cytologic evaluation if necessary Not enough experience Not enough time Can be difficult to distinguish from fibroplasia, especially if inflammatory Send stained and unstained – Giemsa stain is superior for some features Take a quick look to make sure you have adequate cells other then RBC

5. Diagnosis Often cytological diagnosis is “sarcoma” May need histopathology for definitive diagnosis Excision biopsy (“en bloc” excision) is best for diagnosis If unresectable, may need to get incisional biopsy Best excision for large mass is done after CT scan If dirty margins, re-excise or radiation therapy (if histopath indicates radiation)

6. Cytology

7. Cytology Wispy cytoplasm with streaming tails

8. Cytology Occasional binucleate cell Round to oval nuclei, inconspicuous nucleoli

9. Kristina Lemm – Houston TX Shawn Penn – Lufkin TX

10. Cytology Wispy cytoplasm with streaming tails Occasional binucleate cell Round to oval nuclei, inconspicuous nucleoli

11. Cytology Wispy cytoplasm with streaming tails Occasional binucleate cell Round to oval nuclei, inconspicuous nucleoli Cells in whorls, rare mitotic figures Hemangiopericytoma

12. Cytology

13. Cytology Blunt ended nuclei, indistinct cell borders Parallel alignment

14. Cytology Blunt ended nuclei, indistinct cell borders Parallel alignment Variation in cell and nucleus size

15. Cytology Blunt ended nuclei, indistinct cell borders Parallel alignment Variation in cell and nucleus size Intranuclear inclusions Leiomyosarcoma

16. Cytology Spindle shaped cells with minimal cytoplasm Oval nuclei

17. Cytology Spindle shaped cells with minimal cytoplasm Oval nuclei Characteristics of malignancy Fibrosarcoma

18. Cytology Anaplastic Sarcoma

19. Cytology Fibroma

20. Cytology

21. Cytology

22. Cytology Individual polyhedral cells with basophilic foamy cytoplasm Round to oval nuclei with prominent nucleoli

23. Cytology Individual polyhedral cells with basophilic foamy cytoplasm Round to oval nuclei with prominent nucleoli Characteristics of malignancy Liposarcoma

24. Cytology Non-staining, large ballooning cytoplasm Collapsed cells with scan, lacy cytoplasm Peripherally compressed nuclei Lipoma or Infiltrative Lipoma Well differentiated liposarcoma

25. Cytology Well differentiated fusiform & stellate cells

26. Cytology Low cellularity with granular background

27. Cytology Well differentiated fusiform & stellate cells Low cellularity with granular background Occasional multinucleate cells Mucin stains with Alcian blue stain Myxosarcoma

28. Cytology Large multinucleate cells Spindle/mesenchymal cells

30. Cytology Large multinucleate cells Spindle/mesenchymal cells Histiocyte-like round cells

31. Cytology Large multinucleate cells Spindle/mesenchymal cells Histiocyte-like round cells

32. Cytology Large multinucleate cells Spindle/mesenchymal cells Histiocyte-like round cells Malignant Fibrous Histiocytoma Pleomorphic Undifferentiated Sarcoma

33. Surgery The mainstay of treatment for STSA 3 cm lateral borders to visible mass 1 fascia layer deep to visible mass May appear to be encapsulated, but are not Pseudocapsule made up of tumor cells Still respect the border rules “shelling out” results in recurrence

34. Radiation If histopath indicates likely radiation responsiveness STSA not terribly radiation responsive unless high MI 20-30% response rate for gross disease Results in long disease free interval when post-surgical disease is microscopic 4-5 years For tumors that can not be adequately re- excised Taking more tissue not possible Dirty borders after re-excision

35. Radiation For tumors that are too large for “en bloc” excision Neoadjuvant therapy Palliative therapy Shrink tumor Pain control When margins are “clean but close” When concurrent condition precludes anesthesia or surgery Coagulopathy (VWDz, hemophilia) Renal failure Radiation may not be better, as it requires multiple sedations

36. Radiation For limb sparing tumor treatment when post- amputation mobility difficulties expected Response rate for radiation alone is poor when compared to radiation + surgery When you have hemangiopericytoma Chemotherapy STSA tend to be chemotherapy unresponsive

37. Prognosis Local control is usually curative Staging is a low yield procedure, but indicated prior to starting extensive or expensive treatment 3 views thoracic radiographs Aspirate draining lymph nodes (maybe abdominal US)

38. Prognosis Local control is usually curative Staging is a low yield procedure, but indicated prior to starting extensive or expensive treatment 3 views thoracic radiographs Aspirate draining lymph nodes (maybe abdominal US)

39. Feline Sarcoma Vaccine Associated Sarcoma (VAS) Vaccine Associated Fibrosarcoma Vaxosarcoma Feline Injection Site Sarcoma Emerged in the mid 1980’s FISS Update

40. Usually a fibrosarcoma but can also be PUS Rhabdomyosarcoma Mast cell tumor Soft tissue osteosarcoma Liposarcoma Chondrosarcoma Undifferentiated sarcoma FISS Update

41. Relationship between FISS and chronic inflammatory responses following trauma or injections, including vaccination some long-acting medications even foreign materials such as suture and microchips Incidence varies widely between 1 per 1000 and 1 per 16,000 vaccinated cats. FISS Update

42. In cats younger than typical fibrosarcoma Adjuvant and foreign bodies found within the tumors Site specific, correlating with common injection sites More aggressive behavior than the typical fibrosarcoma Some but not all are associated with feline sarcoma virus (FeSV) infection FISS Update

43. Especially FeLV and rabies vaccines When local laws began requiring rabies vaccination in cats, incidence of FISS increased – FeLV is deadly and infects cats at 1-2% of well cats – Rabies is rare but is deadly to people THEORY – More appropriate extended feline vaccination protocols should help – Vaccination annually with Purevax should be better than triennially with an adjuvanted vaccine Merial Purevax has been out for more than 10 years FISS Update

44. Virbac Pharmacovigilance project (Europe) – Adverse event reports 2000-2009 – McGahie, 2012 (WSAVA) – FISS has a possible relationship with recombinant subunit FeLV vaccine as well – FISS rate 1 per 500,000 vaccinations – No such relationship found for the Purevax rabies vaccine FISS Update

45. Diagnosis Post-vaccination granulomas are common If they fail to resolve within 3-4 weeks, if they grow at all after the first week, or if they are larger than 2 cm, they should be removed for histopath – Treated like other soft tissue sarcomas at this point – 3 cm borders – One fascia layer deep FISS Update

46. Treatment If FISS is confirmed, treatment should be prompt and aggressive Consider referral for more surgery – CT scan prior to surgery – Wide, wide margins Possible radiation and/or chemo depending on tumor site and histopath report Neoadjuvant therapy for large masses FISS Update

47. Prognosis Median survival variable, but can be more than 2 years with surgery alone (average age 6 years) Almost 4 years survival with surgery and radiation Prognosis is worse if bone is invaded and the tumor can not be removed by bilateral trapezius muscle excision Distant metastasis is rare, but it makes prognosis worse 84% of those treated with neoadjuvant epirubicin were alive at 6 years – Less aggressive tumors were selected for therapy – 10% died of chemo induced renal failure FISS Update

48. FISS Client Handout FISS Update

50. Acknowledgements Philip J. Bergman, DVM, MS, PhD, DACVIM (Oncology) Philip J. Bergman, DVM, MS, PhD, DACVIM (Oncology) VIN Consultant, CMOfficer BrightHeart Vet Centers Louis-Philippe de Lorimier, DVM, ACVIM (Oncology) Louis-Philippe de Lorimier, DVM, ACVIM (Oncology) VIN Consultant, Univ Ill Urbana-Champaign Karri A. Meleo, DVM, ACVIM (Oncology), ACVR Karri A. Meleo, DVM, ACVIM (Oncology), ACVR VIN Consultant, Vet Oncol Serv, Edmonds, WA Mark Rishniw, BVSc, MS, ACVIM (SAIM), ACVIM (Cardiology) Mark Rishniw, BVSc, MS, ACVIM (SAIM), ACVIM (Cardiology) VIN Consultant, Clin Res Coord, Ithaca, NY Kurt R. Verkest, BVSc, BVBiol, MACVSc (Small Animal) Kurt R. Verkest, BVSc, BVBiol, MACVSc (Small Animal) VIN Associate Editor, Univ Queensland, Australia