Subcutaneous mast cell tumours: A prospective multi-institutional clinicopathological and prognostic study of 43 dogs.
canine
cytograding
lymph node metastasis
mastocytoma
prognosis
Journal
The Veterinary record
ISSN: 2042-7670
Titre abrégé: Vet Rec
Pays: England
ID NLM: 0031164
Informations de publication
Date de publication:
08 Jul 2023
08 Jul 2023
Historique:
revised:
27
02
2023
received:
28
10
2022
accepted:
06
04
2023
medline:
10
7
2023
pubmed:
24
5
2023
entrez:
24
5
2023
Statut:
ppublish
Résumé
Canine subcutaneous mast cell tumours (ScMCTs) reportedly have a good prognosis. However, biomarkers that can be used to predict outcome are currently limited. A multicentre prospective study was conducted to identify new prognostic markers. Dogs with a first occurrence of ScMCT were enrolled upon primary tumour removal and regional lymphadenectomy. In the absence of metastasis, dogs were monitored, while dogs with overtly metastatic lymph nodes (histological node 3, HN3) received adjuvant vinblastine. Forty-three dogs were enrolled: 15 (34.9%) had at least one HN3 lymph node and received vinblastine, and 28 (65.1%) were monitored. Three tumours harboured exon 8 and 9 c-kit mutations. Eight (18.6%) dogs experienced tumour progression, and five (11.6%) died of MCT-related causes. The 1- and 2-year survival rates were 90% and 77%, respectively. Variables significantly associated with an increased risk of progression included high cytograde, a mitotic count (MC) greater than 4/10 high-power fields (hpf) and Ki67-index greater than 23. An MC greater than 4/10 hpf was also associated with an increased risk of tumour-related death. Regional rather than sentinel lymphadenectomy was performed in these dogs. Dogs were enrolled in oncology referral centres, constituting a different population compared to previous studies. ScMCTs have a good prognosis. However, the metastatic rate at admission was higher in this study than previously reported, and a subset of tumours were associated with a fatal outcome despite multimodal treatment. Proliferative activity and cytograding may predict more aggressive behaviour in ScMCTs.
Sections du résumé
BACKGROUND
BACKGROUND
Canine subcutaneous mast cell tumours (ScMCTs) reportedly have a good prognosis. However, biomarkers that can be used to predict outcome are currently limited.
METHODS
METHODS
A multicentre prospective study was conducted to identify new prognostic markers. Dogs with a first occurrence of ScMCT were enrolled upon primary tumour removal and regional lymphadenectomy. In the absence of metastasis, dogs were monitored, while dogs with overtly metastatic lymph nodes (histological node 3, HN3) received adjuvant vinblastine.
RESULTS
RESULTS
Forty-three dogs were enrolled: 15 (34.9%) had at least one HN3 lymph node and received vinblastine, and 28 (65.1%) were monitored. Three tumours harboured exon 8 and 9 c-kit mutations. Eight (18.6%) dogs experienced tumour progression, and five (11.6%) died of MCT-related causes. The 1- and 2-year survival rates were 90% and 77%, respectively. Variables significantly associated with an increased risk of progression included high cytograde, a mitotic count (MC) greater than 4/10 high-power fields (hpf) and Ki67-index greater than 23. An MC greater than 4/10 hpf was also associated with an increased risk of tumour-related death.
LIMITATIONS
CONCLUSIONS
Regional rather than sentinel lymphadenectomy was performed in these dogs. Dogs were enrolled in oncology referral centres, constituting a different population compared to previous studies.
CONCLUSIONS
CONCLUSIONS
ScMCTs have a good prognosis. However, the metastatic rate at admission was higher in this study than previously reported, and a subset of tumours were associated with a fatal outcome despite multimodal treatment. Proliferative activity and cytograding may predict more aggressive behaviour in ScMCTs.
Substances chimiques
Vinblastine
5V9KLZ54CY
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2991Informations de copyright
© 2023 British Veterinary Association.
Références
Thompson JJ, Pearl DL, Yager JA, Best SJ, Coomber BL, Foster RA. Canine subcutaneous mast cell tumour: characterization and prognostic indices. Vet Pathol. 2011;48:156-8.
Thompson JJ, Yager JA, Best SJ, Pearl DL, Coomber BL, Torres RN, et al. Canine subcutaneous mast cell tumours: cellular proliferation and KIT expression as prognostic indices. Vet Pathol. 2011;48:169-81.
Gill V, Leibman N, Monette S, Craft DM, Bergman PJ. Prognostic indicators and clinical outcome in dogs with subcutaneous mast cell tumours treated with surgery alone: 43 cases. J Am Anim Hosp Assoc. 2020;56:215-25.
Newman SJ, Mrkonjich L, Walker KK, Rohrbach BW. Canine subcutaneous mast cell tumour: diagnosis and prognosis. J Comp Pathol. 2007;136:231-9.
Thompson JJ, Morrison JA, Pearl DL, Boston SE, Wood GA, Foster RA, et al. Receptor tyrosine kinase expression profiles in canine cutaneous and subcutaneous mast cell tumours. Vet Pathol. 2016;53:545-58.
Chen P, Marconato L, Sabattini S, Kiupel M. Mutations in exons 8 and 11 of c-kit gene in canine subcutaneous mast cell tumours and their association with cell proliferation. Vet Sci. 2022;9:493-502.
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;7:130-8.
Suami H, Yamashita S, Soto-Miranda MA, Chang DW. Lymphatic territories (lymphosomes) in a canine: an animal model for investigation of postoperative lymphatic alterations. PLoS One. 2013;8:e69222.
De Swarte M, Alexander K, Rannou B, D'anjou M-A, Blond L, Beauchamp G. Comparison of sonographic features of benign and neoplastic deep lymph nodes in dogs. Vet Radiol Ultrasound. 2011;52:451-6.
Weishaar KM, Thamm DH, Worley DR, Kamstock DA. Correlation of nodal mast cells with clinical outcome in dogs with mast cell tumour and a proposed classification system for the evaluation of node metastasis. J Comp Pathol. 2014;151:329-38.
Guerra D, Faroni E, Sabattini S, Agnoli C, Chalfon C, Stefanello D, et al. Histologic grade has a higher-weighted value than nodal status as predictor of outcome in dogs with cutaneous mast cell tumours and overtly metastatic sentinel lymph nodes. Vet Comp Oncol. 2022;20:551-8.
Marconato L, Stefanello D, Kiupel M, Finotello R, Polton G, Massari F, et al. Adjuvant medical therapy provides no therapeutic benefit in the treatment of dogs with low-grade mast cell tumours and early nodal metastasis undergoing surgery. Vet Comp Oncol. 2020;18:409-15.
Veterinary Co-operative Oncology Group. Veterinary co-operative oncology group-common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.0. Vet Comp Oncol. 2004;2:194-213.
Dores CB, Milovancev M, Russell DS. Comparison of histologic margin status in low-grade cutaneous and subcutaneous canine mast cell tumours examined by radial and tangential sections. Vet Comp Oncol. 2018;16:125-30.
Meuten DJ, Moore FM, George JW. Mitotic count and the field of view area: time to standardize. Vet Pathol. 2016;53:7-9.
Webster JD, Yuzbasiyan-Gurkan V, Miller RA, Kaneene JB, Kiupel M. Cellular proliferation in canine cutaneous mast cell tumours: associations with c-KIT and its role in prognostication. Vet Pathol. 2007;44:298-308.
Giantin M, Vascellari M, Morello EM, Capello K, Vercelli A, Granato A, et al. c-KIT messenger RNA and protein expression and mutations in canine cutaneous mast cell tumours: correlations with post-surgical prognosis. J Vet Diagn Invest. 2012;24:116-26.
Camus MS, Priest HL, Koehler JW, Driskell EA, Rakich PM, Ilha MR, et al. Cytologic criteria for mast cell tumour grading in dogs with evaluation of clinical outcome. Vet Pathol. 2016;53:1117-23.
Stefanello D, Buracco P, Sabattini S, Finotello R, Giudice C, Grieco V, et al. Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous mast cell tumours: 386 cases (2009-2014). J Am Vet Med Assoc. 2015;246:765-69.
Pecceu E, Serra Varela JC, Handel I, Piccinelli C, Milne E, Lawrence J. Ultrasound is a poor predictor of early or overt liver or spleen metastasis in dogs with high-risk mast cell tumours. Vet Comp Oncol. 2020;18:389-401.
Miller RL, Van Lelyveld S, Warland J, Dobson JM, Foale RD. A retrospective review of treatment and response of high-risk mast cell tumours in dogs. Vet Comp Oncol. 2016;14:361-70.
Marconato L, Polton G, Stefanello D, Morello E, Ferrari R, Henriques J, et al. Therapeutic impact of regional lymphadenectomy in canine stage II cutaneous mast cell tumours. Vet Comp Oncol. 2018;16:580-9.
Ferrari R, Marconato L, Buracco P, Boracchi P, Giudice C, Iussich S, et al. The impact of extirpation of non-palpable/normal-sized regional lymph nodes on staging of canine cutaneous mast cell tumours: a multicentric retrospective study. Vet Comp Oncol. 2018;16:505-10.
Chalfon C, Sabattini S, Finotello R, Faroni E, Guerra D, Pisoni L, et al. Lymphadenectomy improves outcome in dogs with resected Kiupel high-grade cutaneous mast cell tumours and overtly metastatic regional lymph nodes. J Small Anim Pract. 2022;63:661-9.
Brocks BAW, Bertram CA, Bartel A, Kirpensteijn J, Collins-Webb A, Catlin C, et al. Internal tandem duplication of exon 8 of c-kit is associated with longer total survival in canine cutaneous mast cell tumours. Vet Pathol. 2021;58:315-24.
Bertram CA, Aubreville M, Gurtner C, Bartel A, Corner SM, Dettwiler M, et al. Computerized calculation of mitotic count distribution in canine cutaneous mast cell tumour sections: mitotic count is area dependent. Vet Pathol. 2020;57:214-26.
Mendez SE, Drobatz KJ, Duda LE, White P, Kubicek L, Sorenmo KU. Treating the locoregional lymph nodes with radiation and/or surgery significantly improves outcome in dogs with high-grade mast cell tumours. Vet Comp Oncol. 2020;18:239-46.
Ferrari R, Chiti LE, Manfredi M, Ravasio G, De Zani D, Zani DD, et al. Biopsy of sentinel lymph nodes after injection of methylene blue and lymphoscintigraphic guidance in 30 dogs with mast cell tumours. Vet Surg. 2020;49:1099-108.
Ferrari R, Boracchi P, Chiti LE, Manfredi M, Giudice C, De Zani D, et al. Assessing the risk of nodal metastases in canine integumentary mast cell tumours: is sentinel lymph node biopsy always necessary? Animals. 2021;11:2373.