Search strategy

For the construction and development of this study, an exploratory integrative literature review (ILR) and a meta-analysis were conducted. The integrative literature review is considered the broadest methodological approach because, in addition to allowing the researcher to include experimental and non-experimental studies for a comprehensive understanding of the analyzed phenomenon, it combines data from the theoretical literature and serves a wide range of purposes, such as: defining concepts, analyzing methodological problems on a particular topic, and reviewing theories and evidence.

This research was based on the following guiding question: what are the clinical aspects, diagnosis and treatment of cutaneous mast cell tumors in dogs? This question was formulated using the PICO strategy, an acronym for the words: P-Population; I- Interest; C- Control; O- Outcome, which is important for constructing the guiding question.

For the development of this research, the following steps were used: selection of the study's guiding questions; establishment of inclusion and exclusion criteria for sample selection; identification of information to be extracted from selected articles; data analysis; discussion of results; and presentation of the review.

Data collection

Data collection was conducted online, covering the period from 1990 to 2024. The search was carried out in databases such as SciELO, Scopus, Web of Science, and Science Direct, focusing on topics related to the clinical aspects, diagnosis and treatment of cutaneous mast cell tumors in dogs. The classification was based on that established by Patnaik et al. (88. Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Veterinary Pathology. 1984;21(5):469-474. https://doi.org/10.1177/030098588402100503
) and Kiupel et al. (99. Kiupel M, Webster JD, Bailey KL, Best S, DeLay J, Detrisac CJ, Fitzgerald SD, Gamble D, Ginn PE, Goldschmidt MH, Hendrick MJ, Howerth EW, Janovitz EB, Langohr I, Lenz SD, Lipscomb TP, Miller MA, Misdorp W, Moroff S, Mullaney TP, Neyens I, O’Toole D, Ramos-Vara J, Scase TJ, Schulman FY, Sledge D, Smedley RC, Smith K, Snyder PW, Southorn E, Stedman NL, Steficek BA, Stromberg PC, Valli VE, Weisbrode SE, Yager J, Heller J, Miller R. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Veterinary Pathology. 2011;48(1):147-155. https://doi.org/10.1177/0300985810386469
).

The health science descriptors used were “clinical aspects of cutaneous mastocytoma in dogs”, “diagnosis of cutaneous mast cell tumors in dogs”, “cutaneous mast cell tumors in dogs”, and “treatment of cutaneous mast cell tumors in dogs”. It is noteworthy that the search was conducted in a systematic manner, specifically within the aforementioned scientific databases, using the Boolean operators "AND" and/or "OR".

After selecting the studies, it was necessary to review and synthesize the information extracted to facilitate the management of the data obtained. For this purpose, a structured instrument was used, containing the following variables: Year; Article Title; Journal; Authors; Objectives or Research Question; and Results. This instrument was chosen because it ensured the extraction of all relevant data present in the scientific publications, minimizing the risk of transcription errors and guaranteeing the accuracy of information verification.

Inclusion and exclusion criteria

The inclusion criteria adopted for this study were: articles available in Portuguese and English, in full text; and related to the proposed topic. The exclusion criteria were: publications with incomplete or duplicate text, as well as dissertations, theses or monographs.

Data extraction and analysis

Data were extracted from the Materials and Methods and Results sections of the scientific articles selected for inclusion in the review. This involved extracting a phrase, word or set of words deemed relevant for the analysis of the collected data, which were subsequently discussed based on the theoretical framework.

Mast cells

Mast cells originated from hematopoietic precursors, although their development only occurred in tissues. There was a pathway that controlled the growth and development of mast cells, through a substance called precursor cell growth factor (SCF) or KIT ligand. SCF also controlled apoptosis, production, granulation, and chemotaxis of mast cells. SCF played an important role in the physiology and/or biochemistry of the mast cell tumors, as it binded to mast cell receptors encoded by an oncogene (c-kit). Another pathway that also produced mast cells involved cytokines derived from T cells (1010. Biase DD, Leo MD, Piegari G, D’Aquino I, Napoli ED, Mercogliano C, Calabria A, Pula A, Navas L, Russo V, Paciello O. Investigation of the Theragnostic Role of KIT Expression for the Treatment of Canine Mast Cell Tumors with Tyrosine Kinase Inhibitors. Veterinary Sciences. 2024;11(10):492. https://doi.org/10.3390/vetsci11100492
).

Mast cells were present in almost all organs and tissues of the most diverse animal species, with their highest incidence in places with contact with external antigens, such as skin, lungs and gastrointestinal tract. In addition, a small concentration could be evidenced in lymph nodes in the paracortical region (1111. Sabattini S, Faroni E, Renzi A, Ghisoni G, Rigillo A, Bettini G, Pasquini A, Zanardi S, Guerra D, Marconato L. Longitudinal lymph node step-sectioning for the identification of metastatic disease in canine mast cell tumor. Veterinary Pathology. 2022;59(5):768-772. https://doi.org/10.1177/03009858221088780
).

The binding of immunoglobulin E with the receptor became the most relevant mechanism of activation of mast cells. However, processes such as maturation, as well as differentiation and degranulation were modulated by the KIT ligand (22. Rissi DR, Miller AD, Demeter EA, Church ME, Koehler JW. Diagnostic immunohistochemistry of primary and secondary central nervous system neoplasms of dogs and cats. Journal of Veterinary Diagnostic Investigation. 2024;36(2):153-168. https://doi.org/10.1177/104063872312218
).

For mast cell identification, ideal staining preparation included Romanovsky and Giemsa staining, due to the granular affinity for basic dyes such as toluidine blue. The granules were intensely stained red or wine-colored, a characteristic termed metachromasia. This mast cell characteristic was important for the diagnosing and identifying the histopathological grade of mast cell tumors (55. Minnoye S, Vos SD, Beck S, Duchateau L, Hubers M, David S, Fortrie R, Rooster HD. Histopathological features of subcutaneous and cutaneous mast cell tumors in dogs. Acta Veterinaria Scandinavica. 2024;66(1):53. https://doi.org/10.1186/s13028-024-00775-5
).

General aspects

Mast cell tumors are characterized as a neoplastic proliferation of mast cells, which originate in the bone marrow and connective tissue, and are also known as histiocytic mast cell tumors or mast cell sarcoma (1212. Ivashkiv BB, Mysak AR. Skin mastocytoma in dogs, complex treatment and survival of animals. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies. Series: Veterinary Sciences. 2024;26(115):159-174. https://doi.org/10.32718/nvlvet11523
).

Mastocytoma is a cutaneous or subcutaneous tumor (Figure 1 a,b,c), occurring more frequently in canine species. They represent between 16 % and 21 % of cutaneous neoplasms and 11 % to 15 % of skin tumors, of which 11 % to 27 % are malignant (22. Rissi DR, Miller AD, Demeter EA, Church ME, Koehler JW. Diagnostic immunohistochemistry of primary and secondary central nervous system neoplasms of dogs and cats. Journal of Veterinary Diagnostic Investigation. 2024;36(2):153-168. https://doi.org/10.1177/104063872312218
-33. Pinello K, Amorim I, Pires I, Canadas-Sousa A, Catarino J, Faísca P, Branco S, Peleteiro MC, Silva D, Severo M, Niza-Ribeiro J. Vet-OncoNet: Malignancy analysis of neoplasms in dogs and cats. Veterinary Sciences. 2022;9(10):535. https://doi.org/10.3390/vetsci9100535
, 1313. Engdahl K, Saellström S, Hedhammar AÅ, Dimopoulou M, Rönnberg H. The epidemiology of mast cell tumours in insured dogs in Sweden. Preventive Veterinary Medicine. 2025:242(1):106589. https://doi.org/10.1016/j.prevetmed.2025.106589
).

Cause and degrees of mast cell tumors in dogs

The cause of mast cell tumors is not fully understood, but some studies have demonstrated alterations in the stem cell factor receptor (KIT), responsible for encoding the juxtamembrane domain of the tyrosine kinase receptor (SCF), in canine mast cell tumor (33. Pinello K, Amorim I, Pires I, Canadas-Sousa A, Catarino J, Faísca P, Branco S, Peleteiro MC, Silva D, Severo M, Niza-Ribeiro J. Vet-OncoNet: Malignancy analysis of neoplasms in dogs and cats. Veterinary Sciences. 2022;9(10):535. https://doi.org/10.3390/vetsci9100535
).

The main mutation diagnosed was a duplication that causes constitutive phosphorylation of the receptor, without the need for binding to SCF. This finding may explain the exaggerated development of the tumors and the relationship between the duplication and the malignancy of the pathology. These cells exhibit varying degrees of differentiation, based on the presence and prominence of cytoplasmic granules. Furthermore, the mitotic indices of the cells are used to classify the disease with the aim of establishing a prognosis, into three different grades: I, II, and III (1515. Kim D, Dobromylskyj MJ, O'Neill D, Smith KC. Skin masses in dogs under one year of age. Journal of Small Animal Practice. 2022;63(1):10-15. https://doi.org/10.1111/jsap.13418
).

For histological grading, the methodology primarily considers the extent of the lesion, cellularity and cellular morphology, mitotic figures, and stromal reaction, classifying tumors into three grades: I. well-differentiated; II. intermediate differentiation and III, poorly differentiated or anaplastic. Based on this grading, dogs with grade I mast cell tumors rarely present with metastasis or complications and would have longer survival and, consequently, a better prognosis. Tumors classified as grade II exhibit variable biological behavior, with metastasis occurring in five % to 22 % of cases (1717. Juodžiukynienė N, Lasienė K, Savickienė N, Aniulienė A. Mast Cell Density in Squamous Cell Carcinoma of Skin in Dogs and Cats. Animals. 2025;15(3):316. https://doi.org/10.3390/ani15030316
). Grade III mast cell tumors exhibit aggressive behavior; more than 80 % would cause metastasis and death from related complications (1616. Larsen E, Watson AM, Muñoz-Gutiérrez JF. Intranasal mast cell tumors: clinical, immunohistochemical, and molecular features in 20 dogs. Veterinary pathology. 2022;59(6):915-921. https://doi.org/10.1177/03009858221109100
).

Grade II mast cell tumors, which are the predominant form, have a variation in biological behavior. It may present benign or more aggressive behavior, leading the clinician to underestimate the aggressiveness of the neoplasm or to perform potentially toxic and unnecessary aggressive treatments (1313. Engdahl K, Saellström S, Hedhammar AÅ, Dimopoulou M, Rönnberg H. The epidemiology of mast cell tumours in insured dogs in Sweden. Preventive Veterinary Medicine. 2025:242(1):106589. https://doi.org/10.1016/j.prevetmed.2025.106589
).

Most affected age group, races and genders

This neoplasm affects dogs aged between eight-nine years, with apparently no predilection between sexes. In general, these neoplasms tend to occur on a large scale in elderly canines and are 41 times more likely to develop the neoplasm than dogs younger than two years (1717. Juodžiukynienė N, Lasienė K, Savickienė N, Aniulienė A. Mast Cell Density in Squamous Cell Carcinoma of Skin in Dogs and Cats. Animals. 2025;15(3):316. https://doi.org/10.3390/ani15030316
).

A study like those of Patnaik et al. (88. Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Veterinary Pathology. 1984;21(5):469-474. https://doi.org/10.1177/030098588402100503
) and Shoop et al. (1818. Shoop SJ, Marlow S, Church DB, English K, McGreevy PD, Stell AJ, Thomson PC, O’Neill DG, Brodbelt DC. Prevalence and risk factors for mast cell tumours in dogs in England. Canine Genetics and Epidemiology. 2015;2(1):10. https://doi.org/10.1186/2052-6687-2-1
) describe that there is no predisposition for sex among dogs with cutaneous mast cell tumors. However, Mochizuki et al. (1919. Mochizuki H, Motsinger‐Reif A, Bettini C, Moroff S, Breen M. Association of breed and histopathological grade in canine mast cell tumours. Veterinary and Comparative Oncology. 2017;15(3):829-839. https://doi.org/10.1111/vco.12225
) indicate that the neoplasm has a higher occurrence in male dogs, while Śmiech et al. (2020. Śmiech A, Ślaska B, Łopuszyński W, Jasik A, Bochyńska D, Dąbrowski R. Epidemiological assessment of the risk of canine mast cell tumours based on the Kiupel two-grade malignancy classification. Acta Veterinaria Scandinavica. 2018;60(70):9. https://doi.org/10.1186/s13028-018-0424-2
) report a higher occurrence in females.

Most affected breeds

Several dog breeds have a predilection for developing this neoplasm, among which the following stand out: Boxer, Boston Terrier, Bull Terrier, Labrador Retriever, Fox Terrier, Beagle, Weimaraner, Staffordshire Bull Terrier, Schnauzer, and Pug (1818. Shoop SJ, Marlow S, Church DB, English K, McGreevy PD, Stell AJ, Thomson PC, O’Neill DG, Brodbelt DC. Prevalence and risk factors for mast cell tumours in dogs in England. Canine Genetics and Epidemiology. 2015;2(1):10. https://doi.org/10.1186/2052-6687-2-1
-2020. Śmiech A, Ślaska B, Łopuszyński W, Jasik A, Bochyńska D, Dąbrowski R. Epidemiological assessment of the risk of canine mast cell tumours based on the Kiupel two-grade malignancy classification. Acta Veterinaria Scandinavica. 2018;60(70):9. https://doi.org/10.1186/s13028-018-0424-2
). Various studies show that mixed-breed dogs, Cocker Spaniels, Pit Bull Terriers and Shar-Peis, also have a predilection for developing mast cell tumors (1515. Kim D, Dobromylskyj MJ, O'Neill D, Smith KC. Skin masses in dogs under one year of age. Journal of Small Animal Practice. 2022;63(1):10-15. https://doi.org/10.1111/jsap.13418
).

Affected organs

The skin is the organ most affected by the tumor, although different organs or body areas can be involved. Among the most commonly affected areas, the following stand out: the trunk, accounting for approximately 50 to 60 % of cases; the extremities, comprising 25 to 40 %; and finally, the head and neck region, at 10 % (2020. Śmiech A, Ślaska B, Łopuszyński W, Jasik A, Bochyńska D, Dąbrowski R. Epidemiological assessment of the risk of canine mast cell tumours based on the Kiupel two-grade malignancy classification. Acta Veterinaria Scandinavica. 2018;60(70):9. https://doi.org/10.1186/s13028-018-0424-2
).

Mastocytoma is a neoplasm of mast cell origin, immunocompetent cells that play a relevant role in hypersensitivity reactions and inflammatory processes. Although its cutaneous manifestation is predominantly observed in canines, the visceral presentation in dogs has a considerably lower incidence when compared to the feline population. In cats, visceral mass cell tumors classically affect organs such as the spleen, liver and gastrointestinal tract, causing non-specific clinical symptoms including emesis, cachexia and lethargy. On the other hand, in canines, the visceral form occurs less infrequently; however, when it does occur, it can affect abdominal organs, notably the spleen and gastrointestinal tract, and it is commonly associated with an unfavorable prognosis (2020. Śmiech A, Ślaska B, Łopuszyński W, Jasik A, Bochyńska D, Dąbrowski R. Epidemiological assessment of the risk of canine mast cell tumours based on the Kiupel two-grade malignancy classification. Acta Veterinaria Scandinavica. 2018;60(70):9. https://doi.org/10.1186/s13028-018-0424-2
).

It is noteworthy that the perineum, scrotum, dorsum, and tail are affected, but less frequently ³3. Pinello K, Amorim I, Pires I, Canadas-Sousa A, Catarino J, Faísca P, Branco S, Peleteiro MC, Silva D, Severo M, Niza-Ribeiro J. Vet-OncoNet: Malignancy analysis of neoplasms in dogs and cats. Veterinary Sciences. 2022;9(10):535. https://doi.org/10.3390/vetsci9100535
. A point to be taken into account is the way in which the mast cell tumor is characterized, since this tumor can be confused with other neoplasms, thus, this disease should be adopted as a differential diagnosis ¹⁷17. Juodžiukynienė N, Lasienė K, Savickienė N, Aniulienė A. Mast Cell Density in Squamous Cell Carcinoma of Skin in Dogs and Cats. Animals. 2025;15(3):316. https://doi.org/10.3390/ani15030316
.

Clinical Appearance

The clinical appearance of mast cell tumors is variable (1818. Shoop SJ, Marlow S, Church DB, English K, McGreevy PD, Stell AJ, Thomson PC, O’Neill DG, Brodbelt DC. Prevalence and risk factors for mast cell tumours in dogs in England. Canine Genetics and Epidemiology. 2015;2(1):10. https://doi.org/10.1186/2052-6687-2-1
). Lesions can be firm or friable, well or poorly circumscribed, nodular or pedunculated, and hyper-pigmented in color; the diameter also varies (2020. Śmiech A, Ślaska B, Łopuszyński W, Jasik A, Bochyńska D, Dąbrowski R. Epidemiological assessment of the risk of canine mast cell tumours based on the Kiupel two-grade malignancy classification. Acta Veterinaria Scandinavica. 2018;60(70):9. https://doi.org/10.1186/s13028-018-0424-2
). Its behavior within the biological system has varied and unpredictable characteristics. They can be benign, acting in multiple tissues with a metastatic appearance, or extremely aggressive in their malignant form, being fatal and leading to death (99. Kiupel M, Webster JD, Bailey KL, Best S, DeLay J, Detrisac CJ, Fitzgerald SD, Gamble D, Ginn PE, Goldschmidt MH, Hendrick MJ, Howerth EW, Janovitz EB, Langohr I, Lenz SD, Lipscomb TP, Miller MA, Misdorp W, Moroff S, Mullaney TP, Neyens I, O’Toole D, Ramos-Vara J, Scase TJ, Schulman FY, Sledge D, Smedley RC, Smith K, Snyder PW, Southorn E, Stedman NL, Steficek BA, Stromberg PC, Valli VE, Weisbrode SE, Yager J, Heller J, Miller R. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Veterinary Pathology. 2011;48(1):147-155. https://doi.org/10.1177/0300985810386469
).

Diagnosis and Prognosis

Although in most cases, the diagnosis of cutaneous mastocytoma in dogs is easy to detect, it normally occurs between seven and 18 years of age, except in atypical cases. This neoplasm has a biological behavior and, in most cases, pathologists seek to identify the most serious cases in a cured way (1717. Juodžiukynienė N, Lasienė K, Savickienė N, Aniulienė A. Mast Cell Density in Squamous Cell Carcinoma of Skin in Dogs and Cats. Animals. 2025;15(3):316. https://doi.org/10.3390/ani15030316
).

Regarding clinical terms, canine MCTs can manifest in different forms with different sizes and aspects, with variable presentations, such as in the femoral anatomical region (Figure 2).

Several complementary tests are indicated to enhance the research and increase the probability of diagnosing various neoplasms: ultrasonography, for the evaluation of visceral metastases in dogs with preputial tumors; and thoracic radiography, which may reveal potential pulmonary metastases. Computed tomography has proven to be a promising tool for diagnosing several types of neoplasms, such as hepatic lesions (2121. Contel IJ, Fonseca-Alves CE, Ferrari HF, Laufer-Amorim R, Xavier-Júnior JC. Review of the comparative pathological and immunohistochemical features of human and canine cutaneous melanocytic neoplasms. Journal of Comparative Pathology. 2024;211(1):26-35. https://doi.org/10.1016/j.jcpa.2024.04.001
-2222. Marouda C, Anagnostou T, Brunetti B, Savvas I, Papazoglou LG, Psalla D. Cutaneous canine mast cell tumor: The use of proliferative markers (Ki-67 and Ki-67× AgNOR) in cytological samples for diagnosis and prognosis. Veterinary Sciences. 2024;11(1):23. https://doi.org/10.3390/vetsci11010023
).

Biopsy is established as a standard sampling method, with high consistency of cytology and histopathology (1010. Biase DD, Leo MD, Piegari G, D’Aquino I, Napoli ED, Mercogliano C, Calabria A, Pula A, Navas L, Russo V, Paciello O. Investigation of the Theragnostic Role of KIT Expression for the Treatment of Canine Mast Cell Tumors with Tyrosine Kinase Inhibitors. Veterinary Sciences. 2024;11(10):492. https://doi.org/10.3390/vetsci11100492
-1111. Sabattini S, Faroni E, Renzi A, Ghisoni G, Rigillo A, Bettini G, Pasquini A, Zanardi S, Guerra D, Marconato L. Longitudinal lymph node step-sectioning for the identification of metastatic disease in canine mast cell tumor. Veterinary Pathology. 2022;59(5):768-772. https://doi.org/10.1177/03009858221088780
). However, histological evaluation is prone to operator subjectivity, leading to extremely variable grading results for the same tumor among different pathologists.

Histopathology (Figure 3), as reported in several studies (2323. Guerra D, Faroni E, Sabattini S, Agnoli C, Chalfon C, Stefanello D, Magno SD, Cola V, Grieco V, Marconato L. 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. Veterinary and comparative oncology. 2022;20(3):551-558. https://doi.org/10.1111/vco.12806"
-2424. Cruz VS, Borges JCA, Nepomuceno LL, Gonçalves PAM, Prado YCL, Bianchi C, Fioravanti, MCS, Araújo EG. Histological classification and expression of markers of canine mast cell tumors. Veterinary World. 2020;13(8):1627-1634. https://doi.org/10.14202/vetworld.2020.1627-1634"
), is essential for determining the histological grade of the neoplasm.

Patnaik et al. (88. Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Veterinary Pathology. 1984;21(5):469-474. https://doi.org/10.1177/030098588402100503
) proposed a three-grade classification, namely: well-differentiated tumors (Grade I - low grade), with an excellent prognosis and no reported deaths; intermediately differentiated tumors (Grade II - low and high grade), with a prognosis ranging from good to fair and a mortality rate of three to 56 %; and, lastly, poorly differentiated tumors (Grade III - high grade), with high mortality of up to 75 % (2323. Guerra D, Faroni E, Sabattini S, Agnoli C, Chalfon C, Stefanello D, Magno SD, Cola V, Grieco V, Marconato L. 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. Veterinary and comparative oncology. 2022;20(3):551-558. https://doi.org/10.1111/vco.12806"
). This classification has been routinely used for surgical biopsies and, consequently, for designing appropriate treatment (2121. Contel IJ, Fonseca-Alves CE, Ferrari HF, Laufer-Amorim R, Xavier-Júnior JC. Review of the comparative pathological and immunohistochemical features of human and canine cutaneous melanocytic neoplasms. Journal of Comparative Pathology. 2024;211(1):26-35. https://doi.org/10.1016/j.jcpa.2024.04.001
).

Considering the heterogeneous nature of moderately differentiated neoplasms and their unpredictable clinical course, Kiupel et al. (99. Kiupel M, Webster JD, Bailey KL, Best S, DeLay J, Detrisac CJ, Fitzgerald SD, Gamble D, Ginn PE, Goldschmidt MH, Hendrick MJ, Howerth EW, Janovitz EB, Langohr I, Lenz SD, Lipscomb TP, Miller MA, Misdorp W, Moroff S, Mullaney TP, Neyens I, O’Toole D, Ramos-Vara J, Scase TJ, Schulman FY, Sledge D, Smedley RC, Smith K, Snyder PW, Southorn E, Stedman NL, Steficek BA, Stromberg PC, Valli VE, Weisbrode SE, Yager J, Heller J, Miller R. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Veterinary Pathology. 2011;48(1):147-155. https://doi.org/10.1177/0300985810386469
) proposed a new classification with only two grades of malignancy: low grade and high grade. This classification was based on nuclear morphology and the number of mitotic figures. Thus, tumors presenting features involving at least seven mitotic figures, three multinucleated cells, three cells with bizarre nuclei per 10 high-power fields (HPF), and karyomegaly in 10 % of cells were classified as high-grade mast cell tumors (Figure 4. a, b). All other tumors not meeting these criteria are classified as low-grade mast cell tumors (44. Zmorzynski S, Kimicka-Szajwaj A, Szajwaj A, Czerwik-Marcinkowska J, Wojcierowski J. Genetic changes in mastocytes and their significance in mast cell tumor prognosis and treatment. Genes. 2024;15(1):137. https://doi.org/10.3390/genes15010137
, 99. Kiupel M, Webster JD, Bailey KL, Best S, DeLay J, Detrisac CJ, Fitzgerald SD, Gamble D, Ginn PE, Goldschmidt MH, Hendrick MJ, Howerth EW, Janovitz EB, Langohr I, Lenz SD, Lipscomb TP, Miller MA, Misdorp W, Moroff S, Mullaney TP, Neyens I, O’Toole D, Ramos-Vara J, Scase TJ, Schulman FY, Sledge D, Smedley RC, Smith K, Snyder PW, Southorn E, Stedman NL, Steficek BA, Stromberg PC, Valli VE, Weisbrode SE, Yager J, Heller J, Miller R. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Veterinary Pathology. 2011;48(1):147-155. https://doi.org/10.1177/0300985810386469
, 2020. Śmiech A, Ślaska B, Łopuszyński W, Jasik A, Bochyńska D, Dąbrowski R. Epidemiological assessment of the risk of canine mast cell tumours based on the Kiupel two-grade malignancy classification. Acta Veterinaria Scandinavica. 2018;60(70):9. https://doi.org/10.1186/s13028-018-0424-2
).

Several authors state that one of the best diagnostic approaches is through aspiration cytology, a safe and relevant method, especially in the preoperative period. It aids in establishing a definitive disease diagnosis and can support decision-making regarding the type and extent of the procedure, enabling the performance of surgical resection with a high safety margin (2525. Lopes NL, Peixoto AP, Costa TS, Silva MA, Araújo DCC, Antonioli T, Mascarenhas MB, Fernandes JI. Mastocitoma cutâneo em felino: Relato de caso. Veterinária Notícias. 2017;23(1):9. http://dx.doi.org/10.010101/XXXXX2017"
).

According to Vail (2626. Vail DM. Cancer clinical trials: development and implementation. Veterinary Clinics of North America: Small Animal Practice. 2007;37(6):1033-1057. https://doi.org/10.1016/j.cvsm.2007.06.007"
), up to 96 % of mast cell tumor cases are diagnosed by cytological examination (Figure 5 a,b), using slides prepared from fine-needle aspiration material, with sequential confirmation through histological analysis. This is because the cytoplasmic granules present in mast cells are easier to observe in cytology compared to histology, due to the larger cell size and the use of metachromatic stains such as Giemsa (2727. Gobbo F, Sarli G, Silva MD, Galiazzo G, Chiocchetti R, Morini M. A double histochemical/immunohistochemical staining for the identification of canine mast cells in light microscopy. Veterinary Sciences. 2021;8(10):229. https://doi.org/10.3390/vetsci8100229"
).

Regarding prognosis, clinical signs and the location of the anatomical site where the tumor is located should be considered, along with the growth rate, size, general appearance, clinical stage, recurrences, metastases, and immunohistochemical and molecular markers (1616. Larsen E, Watson AM, Muñoz-Gutiérrez JF. Intranasal mast cell tumors: clinical, immunohistochemical, and molecular features in 20 dogs. Veterinary pathology. 2022;59(6):915-921. https://doi.org/10.1177/03009858221109100
, 2424. Cruz VS, Borges JCA, Nepomuceno LL, Gonçalves PAM, Prado YCL, Bianchi C, Fioravanti, MCS, Araújo EG. Histological classification and expression of markers of canine mast cell tumors. Veterinary World. 2020;13(8):1627-1634. https://doi.org/10.14202/vetworld.2020.1627-1634"
).

Treatment

According to Daleck et al. (2929. Daleck CR, Nardi AB. Oncologia em cães e gatos. Roca. 2016;2(50):649-660. ISBN: 978-85-277-2991-8
), treatment will depend on the animal's clinical condition, based on tumor staging and its histological classification. The treatment of choice is aggressive surgical excision, aiming to reduce the chances of tumor recurrence (2727. Gobbo F, Sarli G, Silva MD, Galiazzo G, Chiocchetti R, Morini M. A double histochemical/immunohistochemical staining for the identification of canine mast cells in light microscopy. Veterinary Sciences. 2021;8(10):229. https://doi.org/10.3390/vetsci8100229"
). When complete margins are achieved and there is no evidence of metastasis, the surgical technique becomes curative. However, recurrence is possible; for example, approximately 27 % of dogs with grade II mast cell tumors experienced tumor recurrence after the surgical procedure (3030. Catarino J, Pinello K, Niza-Ribeiro J, Santos J, Payan-Carreira R, Reis J, Faísca P. Exploring canine mast cell tumors: An investigation into demographic characteristics, and grading system analysis from a pathology lab data (2019-2021). Preventive Veterinary Medicine. 2025;236(1):106416. https://doi.org/10.1016/j.prevetmed.2025.106416"
).

Canine mast cell tumor, a prevalent cutaneous neoplasm, originates from mast cells and exhibits heterogeneous biological behavior. Its histopathological stratification is commonly performed using the Patnaik classification, which grades them as I, II, and III, and the Kiupel classification, which categorizes them into low- and high-grade malignancy. Low-grade neoplasms are typically characterized by indolent growth, marked cellular differentiation and low metastatic propensity; whereas high-grade neoplasms display aggressiveness, poor cellular differentiation and high metastatic potential. Clinical staging of the disease is conducted using the TNM (Tumor, Lymph Nodes, Metastasis) system, and the assessment of pathological extent is supported by complementary diagnostic methods such as fine-needle aspiration cytology, abdominal ultrasonography and thoracic radiography (88. Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Veterinary Pathology. 1984;21(5):469-474. https://doi.org/10.1177/030098588402100503
-99. Kiupel M, Webster JD, Bailey KL, Best S, DeLay J, Detrisac CJ, Fitzgerald SD, Gamble D, Ginn PE, Goldschmidt MH, Hendrick MJ, Howerth EW, Janovitz EB, Langohr I, Lenz SD, Lipscomb TP, Miller MA, Misdorp W, Moroff S, Mullaney TP, Neyens I, O’Toole D, Ramos-Vara J, Scase TJ, Schulman FY, Sledge D, Smedley RC, Smith K, Snyder PW, Southorn E, Stedman NL, Steficek BA, Stromberg PC, Valli VE, Weisbrode SE, Yager J, Heller J, Miller R. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Veterinary Pathology. 2011;48(1):147-155. https://doi.org/10.1177/0300985810386469
).

In cases where surgical intervention is not feasible, combination therapy with prednisone, cyclophosphamide, and vinblastine, in addition to cryosurgery, has been reported (2121. Contel IJ, Fonseca-Alves CE, Ferrari HF, Laufer-Amorim R, Xavier-Júnior JC. Review of the comparative pathological and immunohistochemical features of human and canine cutaneous melanocytic neoplasms. Journal of Comparative Pathology. 2024;211(1):26-35. https://doi.org/10.1016/j.jcpa.2024.04.001
). Similarly, radiotherapy is a viable treatment option for skin tumors in locations that preclude surgical excision. However, it should be noted that these therapeutic options are uncommon and not always accessible for dogs in remote regions (3030. Catarino J, Pinello K, Niza-Ribeiro J, Santos J, Payan-Carreira R, Reis J, Faísca P. Exploring canine mast cell tumors: An investigation into demographic characteristics, and grading system analysis from a pathology lab data (2019-2021). Preventive Veterinary Medicine. 2025;236(1):106416. https://doi.org/10.1016/j.prevetmed.2025.106416"
).

Various therapeutic methods are documented in the literature, such as the use of tigilanol tiglate for the treatment of cutaneous mast cell tumors in dogs, as it does not require anesthesia or sedation for administration-a relevant parameter given the age and nature of the disease across different breeds and age groups. Typically, antibiotic therapy or wound dressings are not required, and healing is rapid, and curation is achieved within one month, as described by Boyle et al. (3131. Boyle GM, D'Souza MM, Pierce CJ, Adams RA, Cantor AS, Johns JP, Maslovskaya L, Gordon VA, Reddell PW, Parsons PG. Intra-lesional injection of the novel PKC activator EBC-46 rapidly ablates tumors in mouse models. PloS On. 2014;9(10):e108887. https://doi.org/10.1371/journal.pone.0108887"
) and Campbell et al. (3232. Campbell J, Poulos C, Lowden S. Using triamcinolone in combination with the investigational anticancer agent EBC-46 (tigilanol tiglate) in the local treatment of a canine subcutaneous mast cell tumour. CVE Control Ther Ser. 2017;46(286):11-17.
) in studies involving rats and mice. In dogs, using a concentration of 1 mg/mL dosed at 0.5 mL per cm³ of tumor volume (50 % v/v of tumor), a high cure rate is observed (2727. Gobbo F, Sarli G, Silva MD, Galiazzo G, Chiocchetti R, Morini M. A double histochemical/immunohistochemical staining for the identification of canine mast cells in light microscopy. Veterinary Sciences. 2021;8(10):229. https://doi.org/10.3390/vetsci8100229"
).

Complete cure of the animals can be observed in cases of less severe tumors (Grade I) and in some Grade II cases, combining surgical excision (3333. Iodence AE, Wallace ML, Grimes JA, Schmiedt CW. Dogs undergoing surgical excision of mast cell tumors are not at increased risk of incisional complications. Journal of the American Veterinary Medical Association. 2022;260(S1):S88-S95. https://doi.org/10.2460/javma.20.09.0488.
-3434. Gill V, Leibman N, Monette S, Craft DM, Bergman PJ. Prognostic Indicators and Clinical Outcome in Dogs with Subcutaneous Mast Cell Tumors Treated with Surgery Alone: 43 Cases. Journal of the American Animal Hospital Association. 2020;56(4):215-225. https://doi.org/10.5326/JAAHA-MS-6960"
) with radiotherapy, chemotherapy, or other complementary therapies, as described by Michels et al. (3535. 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. Journal of the American Animal Hospital Association. 2022;38(5):458-466. https://doi.org/10.5326/0380458"
), Mullins et al. (3636. 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). Journal of the American Veterinary Medical Association. 2006;228(1):91-95. https://doi.org/10.2460/javma.228.1.91"
), Mendez et al. (3737. 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 highgrade mast cell tumours. Veterinary and Comparative Oncology. 2020;18(2):239-246. https://doi.org/10.1111/vco.12541"
), Moore et al. (3838. Moore AS, Frimberger AE, Taylor D, Sullivan N. Retrospective outcome evaluation for dogs with surgically excised, solitary Kiupel high-grade, cutaneous mast cell tumours. Veterinary and Comparative Oncology. 2020;18(3):402-408. https://doi.org/10.1111/vco.12565"
), and Cruz et al. (2424. Cruz VS, Borges JCA, Nepomuceno LL, Gonçalves PAM, Prado YCL, Bianchi C, Fioravanti, MCS, Araújo EG. Histological classification and expression of markers of canine mast cell tumors. Veterinary World. 2020;13(8):1627-1634. https://doi.org/10.14202/vetworld.2020.1627-1634"
).

Conventional chemotherapy protocols and complementary therapies are well-established for the treatment of canine mast cell tumors, particularly in high-grade cases with incomplete surgical margins or the presence of metastasis. Systemic chemotherapy drugs include prednisolone, due to its specific cytotoxicity against mast cells; vinblastine, used alone or in combination with prednisolone; lomustine (CCNU), effective in cases of therapeutic resistance or as monotherapy; and tyrosine kinase inhibitors, such as masitinib and toceranib (Palladia), whose efficacy in high-grade or metastatic tumors stems from their modulation of molecular pathways linked to mast cell proliferation, such as c-KIT mutations. In addition to systemic chemotherapy, localized approaches include intralesional injection of chemotherapeutic agents (e.g., tigilanol tiglate, corticosteroids) for smaller or surgically inaccessible lesions, and electrochemotherapy, which enhances the intracellular penetration of chemotherapeutic drugs through electrical impulses, demonstrating favorable outcomes in cutaneous and subcutaneous lesions (3939. Horta RS, Lavalle GE, Costa MP, Moura LL, Marcinowska A, Araújo RB. Outcome of adjuvant chemotherapy with lomustine, vinblastine and chlorambucil on management of canine mast cell tumour of high to intermediate risk. Arquivo Brasileiro de Medicina Veterinária e Zootecnia. 2017;69(6):1426-1436. https://doi.org/10.1590/1678-4162-9172"
). Radiotherapy is indicated as an adjuvant modality for local control, especially when re-excision of incomplete surgical margins is not feasible, or as a palliative treatment for inoperable tumors. The selection of the therapeutic regimen must carefully consider the histological grade, disease extent, the patient's clinical status, and resource availability (3737. 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 highgrade mast cell tumours. Veterinary and Comparative Oncology. 2020;18(2):239-246. https://doi.org/10.1111/vco.12541"
-3838. Moore AS, Frimberger AE, Taylor D, Sullivan N. Retrospective outcome evaluation for dogs with surgically excised, solitary Kiupel high-grade, cutaneous mast cell tumours. Veterinary and Comparative Oncology. 2020;18(3):402-408. https://doi.org/10.1111/vco.12565"
, 4040. Ercolin ACM, Uchôa AS, Aires LPN, Gomes DR, Tinto ST, Feliciano GSM, Feliciano MR. Use of new ultrasonography methods for detecting neoplasms in dogs and cats: a review. Animals. 2024;14(2):312. https://doi.org/10.3390/ani14020312.
).