Practical Oncology Soft Tissue Sarcomas

1. Practical OncologySoft 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 • Wispy cytoplasm with streaming tails • 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 • Well differentiated fusiform & stellate cells • 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. FISS Update • Feline Sarcoma • Vaccine Associated Sarcoma (VAS) • Vaccine Associated Fibrosarcoma • Vaxosarcoma • Feline Injection Site Sarcoma Emerged in the mid 1980’s

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

41. FISS Update 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.

42. FISS Update • 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

43. FISS Update • 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

44. FISS Update • 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

45. FISS Update 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

46. FISS Update 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

47. FISS Update 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

48. FISS Update FISS Client Handout

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