Canine mast cell tumors: diagnosis, treatment, and prognosis

References

• London C, Thamm D. Mast Cell Tumors. 5th ed. St Louis, MO: Saunders Elsevier; 2013.
   Google Scholar
• McNiel EA, Prink AL, O’Brien TD. Evaluation of risk and clinical outcome of mast cell tumours in pug dogs. Vet Comp Oncol. 2006;4(1):2–8.19754824
   PubMed Web of Science ®Google Scholar
• Downing S, Chien MB, Kass PH, Moore PE, London CA. Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. Am J Vet Res. 2002;63(12):1718–1723.12492288
   PubMed Web of Science ®Google Scholar
• Letard S, Yang Y, Hanssens K, et al Gain-of-function mutations in the extracellular domain of KIT are common in canine mast cell tumors. Mol Cancer Res. 2008;6(7):1137–1145.18644978
   PubMed Web of Science ®Google Scholar
• Jackson DE, Selting KA, Spoor MS, Henry CJ, Wiedmeyer CE. Evaluation of fixation time using Diff-Quik for staining of canine mast cell tumor aspirates. Vet Clin Pathol. 2013;42(1):99–102.23278320
   PubMed Web of Science ®Google Scholar
• Mullins MN, Dernell WS, Withrow SJ, Ehrhart EJ, Thamm DH, Lana SE. Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998–2004). J Am Vet Med Assoc. 2006;228(1):91–95.16426175
   PubMed Web of Science ®Google Scholar
• Thamm DH, Mauldin EA, Vail DM. Prednisone and vinblastine chemotherapy for canine mast cell tumor – 41 cases (1992–1997). J Vet Intern Med. 1999;13(5):491–497.10499735
   PubMed Web of Science ®Google Scholar
• Bostock DE. The prognosis following surgical removal of mastocytomas in dogs. J Small Anim Pract. 1973;14(1):27–41.4199921
   PubMed Web of Science ®Google Scholar
• Northrup NC, Roberts RE, Harrell TW, Allen KL, Howerth EW, Gieger TL. Iridium-192 interstitial brachytherapy as adjunctive treatment for canine cutaneous mast cell tumors. J Am Anim Hosp Assoc. 2004;40(4):309–315.15238561
   PubMed Web of Science ®Google Scholar
• Roberts SM, Severin GA, Lavach JD. Prevalence and treatment of palpebral neoplasms in the dog: 200 cases (1975–1983). J Am Vet Med Assoc. 1986;189(10):1355–1359.3793587
   PubMed Web of Science ®Google Scholar
• Jacobi S, Stanley BJ, Petersen-Jones S, Dervisis N, Dominguez PA. Use of an axial pattern flap and nictitans to reconstruct medial eyelids and canthus in a dog. Vet Ophthalmol. 2008;11(6):395–400.19046281
   PubMed Web of Science ®Google Scholar
• Barsotti G, Marchetti V, Abramo F. Primary conjunctival mast cell tumor in a Labrador Retriever. Vet Ophthalmol. 2007;10(1):60–64.17204130
   PubMed Web of Science ®Google Scholar
• Johnson BW, Brightman AH, Whiteley HE. Conjunctival mast cell tumors in two dogs. J Am Anim Hosp Assoc. 1988;24:439–442.
   Web of Science ®Google Scholar
• Thamm DH, Turek MM, Vail DM. Outcome and prognostic factors following adjuvant prednisone/vinblastine chemotherapy for high-risk canine mast cell tumour: 61 cases. J Vet Med Sci. 2006;68(6): 581–587.16820715
   PubMed Web of Science ®Google Scholar
• Fife M, Blocker T, Fife T, Dubielzig RR, Dunn K. Canine conjunctival mast cell tumors: a retrospective study. Vet Ophthalmol. 2011;14(3):153–160.21521438
   PubMed Web of Science ®Google Scholar
• Herman LH, Slaughter LJ, Martin DP. Malignant mastocytoma in a dog. J Am Vet Med Assoc. 1967;151(10):1322–1324.4965327
   PubMed Web of Science ®Google Scholar
• Patnaik AK, MacEwen EG, Black AP, Luckow S. Extracutaneous mast-cell tumor in the dog. Vet Pathol. 1982;19(6):608–615.6815869
   PubMed Web of Science ®Google Scholar
• Beck ER, Withrow SJ, McChesney AE, et al Canine tongue tumors: a retrospective review of 57 cases. J Am Anim Hosp Assoc. 1986;22(4):525–532.
   Web of Science ®Google Scholar
• Gieger TL, Theon AP, Werner JA, McEntee MC, Rassnick KM, DeCock HE. Biologic behavior and prognostic factors for mast cell tumors of the canine muzzle: 24 cases (1990–2001). J Vet Intern Med. 2003;17(5):687–692.14529136
   PubMed Web of Science ®Google Scholar
• Hillman LA, Garrett LD, de Lorimier LP, Charney SC, Borst LB, Fan TM. Biological behavior of oral and perioral mast cell tumors in dogs: 44 cases (1996–2006). J Am Vet Med Assoc. 2010;237(8):936–942.20946081
   PubMed Web of Science ®Google Scholar
• Elliott JW, Cripps P, Blackwood L, Berlato D, Murphy S, Grant IA. Canine oral mucosal mast cell tumours. Vet Comp Oncol. Epub November 11, 2013.
   Google Scholar
• Cahalane AK, Payne S, Barber LG, et al Prognostic factors for survival of dogs with inguinal and perineal mast cell tumors treated surgically with or without adjunctive treatment: 68 cases (1994–2002). J Am Vet Med Assoc. 2004;225(3):401–408.15328716
   PubMed Web of Science ®Google Scholar
• Sfiligoi G, Rassnick KM, Scarlett JM, Northrup NC, Gieger TL. Outcome of dogs with mast cell tumors in the inguinal or perineal region versus other cutaneous locations: 124 cases (1990–2001). J Am Vet Med Assoc. 2005;226(8):1368–1374.15844431
   PubMed Web of Science ®Google Scholar
• Newman SJ, Mrkonjich L, Walker KK, Rohrbach BW. Canine subcutaneous mast cell tumour: diagnosis and prognosis. J Comp Pathol. 2007;136(4):231–239.17399734
   PubMed Web of Science ®Google Scholar
• Thompson JJ, Pearl DL, Yager JA, Best SJ, Coomber BL, Foster RA. Canine subcutaneous mast cell tumor: characterization and prognostic indices. Vet Pathol. 2011;48(1):156–168.21078881
   PubMed Web of Science ®Google Scholar
• Thompson JJ, Yager JA, Best SJ, et al Canine subcutaneous mast cell tumors: cellular proliferation and KIT expression as prognostic indices. Vet Pathol. 2011;48(1):169–181.21160022
   PubMed Web of Science ®Google Scholar
• Northrup NC, Howerth EW, Harmon BG, et al Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference. J Vet Diagn Invest. 2005;17(6):561–564.16475514
   PubMed Web of Science ®Google Scholar
• Northrup NC, Harmon BG, Gieger TL, et al Variation among pathologists in histologic grading of canine cutaneous mast cell tumors. J Vet Diagn Invest. 2005;17(3):245–248.15945380
   PubMed Web of Science ®Google Scholar
• Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet Pathol. 1984;21(5):469–474.6435301
   PubMed Web of Science ®Google Scholar
• Kiupel M, Webster JD, Bailey KL, et al Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Vet Pathol. 2011;48(1):147–155.21062911
   PubMed Web of Science ®Google Scholar
• Takeuchi Y, Fujino Y, Watanabe M, et al Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: a retrospective cohort study. Vet J. 2013;196(3):492–498.23384436
   PubMed Web of Science ®Google Scholar
• Romansik EM, Reilly CM, Kass PH, Moore PF, London CA. Mitotic index is predictive for survival for canine cutaneous mast cell tumors. Vet Pathol. 2007;44(3):335–341.17491075
   PubMed Web of Science ®Google Scholar
• Elston L, Sueiro FA, Cavalcanti J, Metze K. The importance of the mitotic index as a prognostic factor for canine cutaneous mast cell tumors: a validation study. Vet Pathol. 2009;46(2):362–364.19261652
   PubMed Web of Science ®Google Scholar
• Baginski H, Davis G, Bastian RP. The prognostic value of lymph node metastasis with grade 2 MCTs in dogs: 55 cases (2001–2010). J Am Anim Hosp Assoc. 2014;50(2):89–95.24446400
   PubMed Web of Science ®Google Scholar
• Lejeune A, Skorupski K, Frazier S, et al Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999–2012). Vet Comp Oncol. Epub May 31, 2013.
   Google Scholar
• Krick EL, Billings AP, Shofer FS, Watanabe S, Sorenmo KU. Cytological lymph node evaluation in dogs with mast cell tumours: association with grade and survival. Vet Comp Oncol. 2009;7(2):130–138.19453367
   PubMed Web of Science ®Google Scholar
• Hume CT, Kiupel M, Rigatti L, Shofer FS, Skorupski KA, Sorenmo KU. Outcomes of dogs with grade 3 mast cell tumors: 43 cases (1997–2007). J Am Anim Hosp Assoc. 2011;47(1):37–44.21164163
   PubMed Web of Science ®Google Scholar
• Marconato L, Marchetti V, Francione D, et al Morphometrical approach for predicting regional lymph node micrometastatic load in canine mast cell tumours: preliminary results. Vet Comp Oncol. 2008;6(3):162–170.19178676
   PubMed Web of Science ®Google Scholar
• Murphy S, Sparkes AH, Blunden AS, Brearley MJ, Smith KC. Effects of stage and number of tumours on prognosis of dogs with cutaneous mast cell tumours. Vet Rec. 2006;158(9):287–291.16517820
   PubMed Web of Science ®Google Scholar
• Chaffin K, Thrall DE. Results of radiation therapy in 19 dogs with cutaneous mast cell tumor and regional lymph node metastasis. Vet Radiol Ultrasound. 2002;43(4):392–395.12175005
   PubMed Web of Science ®Google Scholar
• Rassnick KM, Bailey DB, Russell DS, et al A phase II study to evaluate the toxicity and efficacy of alternating CCNU and high-dose vinblastine and prednisone (CVP) for treatment of dogs with high-grade, metastatic or nonresectable mast cell tumours. Vet Comp Oncol. 2010;8(2): 138–152.20579327
   PubMed Web of Science ®Google Scholar
• Cayatte SM, McManus PM, Miller WH, Scott DW. Identification of mast cells in buffy coat preparations from dogs with inflammatory skin diseases. J Am Vet Med Assoc. 1995;206(3):325–326.7751239
   PubMed Web of Science ®Google Scholar
• McManus PM. Frequency and severity of mastocytemia in dogs with and without mast cell tumors: 120 cases (1995–1997). J Am Vet Med Assoc. 1999;215(3):355–357.10434973
   PubMed Web of Science ®Google Scholar
• Stockham SL, Basel DL, Schmidt DA. Mastocytemia in dogs with acute inflammatory diseases. Vet Clin Pathol. 1986;15(1):16–21.15334338
   PubMedGoogle Scholar
• Endicott MM, Charney SC, McKnight JA, Loar AS, Barger AM, Bergman PJ. Clinicopathological findings and results of bone marrow aspiration in dogs with cutaneous mast cell tumours: 157 cases (1999–2002). Vet Comp Oncol. 2007;5(1):31–37.19754799
   PubMed Web of Science ®Google Scholar
• Finora K, Leibman NF, Fettman MJ, Powers BE, Hackett TA, Withrow SJ. Cytological comparison of fine-needle aspirates of liver and spleen of normal dogs and of dogs with cutaneous mast cell tumours and an ultrasonographically normal appearing liver and spleen. Vet Comp Oncol. 2006;4(3):178–183.19754814
   PubMed Web of Science ®Google Scholar
• Stefanello D, Valenti P, Faverzani S, et al Ultrasound-guided cytology of spleen and liver: a prognostic tool in canine cutaneous mast cell tumor. J Vet Intern Med. 2009;23(5):1051–1057.19656285
   PubMed Web of Science ®Google Scholar
• Book AP, Fidel J, Wills T, Bryan J, Sellon R, Mattoon J. Correlation of ultrasound findings, liver and spleen cytology, and prognosis in the clinical staging of high metastatic risk canine mast cell tumors. Vet Radiol Ultrasound. 2011;52(5):548–554.21689203
   PubMed Web of Science ®Google Scholar
• Simpson AM, Ludwig LL, Newman SJ, Bergman PJ, Hottinger HA, Patnaik AK. Evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc. 2004;224(2):236–240.14736068
   PubMed Web of Science ®Google Scholar
• Fulcher RP, Ludwig LL, Bergman PJ, Newman SJ, Simpson AM, Patnaik AK. Evaluation of a two-centimeter lateral surgical margin for excision of grade I and grade II cutaneous mast cell tumors in dogs. J Am Vet Med Assoc. 2006;228(2):210–215.16426187
   PubMed Web of Science ®Google Scholar
• Pratschke KM, Atherton MJ, Sillito JA, Lamm CG. Evaluation of a modified proportional margins approach for surgical resection of mast cell tumors in dogs: 40 cases (2008–2012). J Am Vet Med Assoc. 2013;243(10):1436–1441.24171373
   PubMed Web of Science ®Google Scholar
• Schultheiss PC, Gardiner DW, Rao S, Olea-Popelka F, Tuohy JL. Association of histologic tumor characteristics and size of surgical margins with clinical outcome after surgical removal of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc. 2011;238(11):1464–1469.21627510
   PubMed Web of Science ®Google Scholar
• Jaffe MH, Hosgood G, Kerwin SC, Hedlund CS, Taylor HW. Deionised water as an adjunct to surgery for the treatment of canine cutaneous mast cell tumours. J Small Anim Pract. 2000;41(1):7–11.10713976
   PubMed Web of Science ®Google Scholar
• Grier RL, Di Guardo G, Myers R, Merkley DF. Mast cell tumour destruction in dogs by hypotonic solution. J Small Anim Pract. 1995;36(9):385–388.8583766
   PubMed Web of Science ®Google Scholar
• Michels GM, Knapp DW, DeNicola DB, Glickman N, Bonney P. Prognosis following surgical excision of canine cutaneous mast cell tumors with histopathologically tumor-free versus nontumor-free margins: a retrospective study of 31 cases. J Am Anim Hosp Assoc. 2002;38(5):458–466.12220031
   PubMed Web of Science ®Google Scholar
• Seguin B, Leibman NF, Bregazzi VS, et al Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996–1999). J Am Vet Med Assoc. 2001;218(7):1120–1123.11318363
   PubMed Web of Science ®Google Scholar
• Weisse C, Shofer FS, Sorenmo K. Recurrence rates and sites for grade II canine cutaneous mast cell tumors following complete surgical excision. J Am Anim Hosp Assoc. 2002;38(1):71–73.11804319
   PubMed Web of Science ®Google Scholar
• Misdorp W. Incomplete surgery, local immunostimulation, and recurrence of some tumour types in dogs and cats. Vet Q. 1987;9(3):279–286.3118558
   PubMed Web of Science ®Google Scholar
• Seguin B, Besancon MF, McCallan JL, et al Recurrence rate, clinical outcome, and cellular proliferation indices as prognostic indicators after incomplete surgical excision of cutaneous grade II mast cell tumors: 28 dogs (1994–2002). J Vet Intern Med. 2006;20(4):933–940.16955819
   PubMed Web of Science ®Google Scholar
• Brocks BA, Neyens IJ, Teske E, Kirpensteijn J. Hypotonic water as adjuvant therapy for incompletely resected canine mast cell tumors: a randomized, double-blind, placebo-controlled study. Vet Surg. 2008;37(5):472–478.18986315
   PubMed Web of Science ®Google Scholar
• Murphy S, Sparkes AH, Smith KC, Blunden AS, Brearley MJ. Relationships between the histological grade of cutaneous mast cell tumours in dogs, their survival and the efficacy of surgical resection. Vet Rec. 2004;154(24):743–746.15224593
   PubMed Web of Science ®Google Scholar
• Donnelly L, Mullin C, Balko J, et al Evaluation of histological grade and histologically tumour-free margins as predictors of local recurrence in completely excised canine mast cell tumours. Vet Comp Oncol. Epub March 4, 2013.
   Google Scholar
• Kry KL, Boston SE. Additional local therapy with primary re-excision or radiation therapy improves survival and local control after incomplete or close surgical excision of mast cell tumors in dogs. Vet Surg. Epub January 6, 2014.
   Google Scholar
• Frimberger AE, Moore AS, LaRue SM, Gliatto JM, Bengtson AE. Radiotherapy of incompletely resected, moderately differentiated mast cell tumors in the dog: 37 cases (1989–1993). J Am Anim Hosp Assoc. 1997;33(4):320–324.9204467
   PubMed Web of Science ®Google Scholar
• LaDue T, Price GS, Dodge R, Page RL, Thrall DE. Radiation therapy for incompletely resected canine mast cell tumors. Vet Radiol Ultrasound. 1998;39(1):57–62.9491519
   PubMed Web of Science ®Google Scholar
• Hahn KA, King GK, Carreras JK. Efficacy of radiation therapy for incompletely resected grade-III mast cell tumors in dogs: 31 cases (1987–1998). J Am Vet Med Assoc. 2004;224(1):79–82.14710881
   PubMed Web of Science ®Google Scholar
• Poirier VJ, Adams WM, Forrest LJ, Green EM, Dubielzig RR, Vail DM. Radiation therapy for incompletely excised grade II canine mast cell tumors. J Am Anim Hosp Assoc. 2006;42(6):430–434.17088389
   PubMed Web of Science ®Google Scholar
• al-Sarraf R, Mauldin GN, Patnaik AK, Meleo KA. A prospective study of radiation therapy for the treatment of grade 2 mast cell tumors in 32 dogs. J Vet Intern Med. 1996;10(6):376–378.8947870
   PubMed Web of Science ®Google Scholar
• Dobson J, Cohen S, Gould S. Treatment of canine mast cell tumours with prednisolone and radiotherapy. Vet Comp Oncol. 2004;2(3):132–141.19379301
   PubMedGoogle Scholar
• Carlsten KS, London CA, Haney S, Burnett R, Avery AC, Thamm DH. Multicenter prospective trial of hypofractionated radiation treatment, toceranib, and prednisone for measurable canine mast cell tumors. J Vet Intern Med. 2012;26(1):135–141.22176473
   PubMed Web of Science ®Google Scholar
• Cooper M, Tsai X, Bennett P. Combination CCNU and vinblastine chemotherapy for canine mast cell tumours: 57 cases. Vet Comp Oncol. 2009;7(3):196–206.19691648
   PubMed Web of Science ®Google Scholar
• Rassnick KM, Bailey DB, Flory AB, et al Efficacy of vinblastine for treatment of canine mast cell tumors. J Vet Intern Med. 2008;22(6):1390–1396.19000249
   PubMed Web of Science ®Google Scholar
• Rassnick KM, Moore AS, Williams LE, et al Treatment of canine mast cell tumors with CCNU (lomustine). J Vet Intern Med. 1999;13(6): 601–605.10587263
   PubMed Web of Science ®Google Scholar
• Vail DM, von Euler H, Rusk AW, et al A randomized trial investigating the efficacy and safety of water soluble micellar paclitaxel (Paccal Vet) for treatment of nonresectable grade 2 or 3 mast cell tumors in dogs. J Vet Intern Med. 2012;26(3):598–607.22390318
   PubMed Web of Science ®Google Scholar
• Veterinary Cooperative Oncology Group. Common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.1. Vet Comp Oncol. Epub July 20, 2011.
   Google Scholar
• Bailey DB, Rassnick KM, Kristal O, Chretin JD, Balkman CE. Phase I dose escalation of single-agent vinblastine in dogs. J Vet Intern Med. 2008;22(6):1397–1402.19000250
   PubMed Web of Science ®Google Scholar
• Kristal O, Rassnick KM, Gliatto JM, et al Hepatotoxicity associated with CCNU (lomustine) chemotherapy in dogs. J Vet Intern Med. 2004;18(1):75–80.14765735
   PubMed Web of Science ®Google Scholar
• Skorupski KA, Hammond GM, Irish AM, et al Prospective randomized clinical trial assessing the efficacy of Denamarin for prevention of CCNU-induced hepatopathy in tumor-bearing dogs. J Vet Intern Med. 2011;25(4):838–845.21689156
   PubMed Web of Science ®Google Scholar
• Hahn KA, Oglivie G, Rusk T, et al Masitinib is safe and effective for the treatment of canine mast cell tumors. J Vet Intern Med. 2008;22(6):1301–1309.18823406
   PubMed Web of Science ®Google Scholar
• Hahn KA, Legendre AM, Shaw NG, et al Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors. Am J Vet Res. 2010;71(11):1354–1361.21034327
   PubMed Web of Science ®Google Scholar
• London CA, Hannah AL, Zadovoskaya R, et al Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res. 2003;9(7):2755–2768.12855656
   PubMed Web of Science ®Google Scholar
• London CA, Malpas PB, Wood-Follis SL, et al Multi-center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clin Cancer Res. 2009;15(11): 3856–3865.19470739
   PubMed Web of Science ®Google Scholar
• Bernabe LF, Portela R, Nguyen S, et al Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose. BMC Vet Res. 2013;9:190.24079884
   PubMed Web of Science ®Google Scholar
• Mitchell L, Thamm DH, Biller BJ. Clinical and immunomodulatory effects of toceranib combined with low-dose cyclophosphamide in dogs with cancer. J Vet Intern Med. 2012;26(2):355–362.22303814
   PubMed Web of Science ®Google Scholar
• Robat C, London C, Bunting L, et al Safety evaluation of combination vinblastine and toceranib phosphate (Palladia®) in dogs: a phase I dose-finding study. Vet Comp Oncol. 2012;10(3):174–183.22235914
   PubMed Web of Science ®Google Scholar