Title: Mastocytoma in dogs

{{Short description|Cancer tumor in dogs}}
[[File:Mast cell tumor side.JPG|thumb|Mastocytoma of the skin of the lateral abdominal wall in a [[Boxer (dog)|German boxer]]]]
A '''mastocytoma in dogs''' (or '''mast cell tumor in dogs''') is a neoplasm ([[Neoplasm|neoplasia]]) originating from [[Mast cell|mast cells]] in the [[Dog|domestic dog]], which occurs mainly in the [[skin]] and [[Subcutaneous tissue|subcutis]]. Mastocytoma are not only extremely common in dogs, but also tend to be much more malignant in them than in other animal species. The average [[survival]] time for [[Malignancy|malignant]] tumors is only four months, whereas for [[Malignancy|benign]] tumors it is over two years.
[[File:Mast cell tumor of the toe.JPG|thumb|Mastocytoma on the paw in a [[Labrador Retriever]]]]
Mast cells are cells of the [[immune system]] that play a role in the [[Innate immune system|innate immune response]]. They produce a number of biologically active substances, including primarily [[histamine]]. Mastocytoma account for about one-fifth of all skin tumors in dogs. They present as nodules or raised patches, and about one-fifth of affected animals have ulcers and bleeding in the [[stomach]] and [[duodenum]]. [[Metastasis]] in malignant mastocytoma occur primarily in [[Lymph node|lymph nodes]], [[liver]], [[spleen]], and [[bone marrow]]. Any lump in the skin or subcutaneous tissue can be a mastocytoma. Detection is only possible by taking tissue with a fine needle ([[Fine-needle aspiration|fine needle biopsy]]) followed by staining and microscopic examination ([[cytopathology]]).

Although the classifications according to the clinical appearances and cell appearance in cytodiagnostics give indications of the biological behavior (benign or malignant) and thus the prospect of cure, this tumor disease is unpredictable and should be treated at an early stage. The treatment of choice is complete [[List of -ectomies|surgical removal]], possibly combined with [[Radiation therapy|radiotherapy]] or [[chemotherapy]]. Tumors for which surgical removal is not possible or only incompletely possible can also be treated with [[Tyrosine kinase inhibitor|tyrosine kinase inhibitors]].

Mastocytoma are also more common in [[Horse|domestic horses]], [[Ferret|ferrets]], and [[Cat|domestic cats]], but usually behave benignly in these species. In other animal species and in humans, mastocytomas are very rare.

== Mast cell ==
{{Main|Mast cell}}
[[File:SMCpolyhydroxysmall.jpg|thumb|Mast cells in [[cell culture]]]]
Mast cells (mastocytes) are [[Cell (biology)|cells]] of the [[immune system]] and represent an important link between the innate and acquired [[Innate immune system|immune response]]. They arise from precursor cells in the [[bone marrow]] and migrate as immature cells to many [[Tissue (biology)|tissues]], especially those in close contact with the outside world, where they [[Cellular differentiation|differentiate]].

Mature mast cells are roundish cells in [[connective tissue]] whose [[cytoplasm]] contains [[Granule (cell biology)|granules]] with deviating staining behavior ([[metachromasia]]). The granules are stored [[histamine]], [[heparin]] as well as [[Cytokine|cytokines]] such as [[Tumor necrosis factor|tumor necrosis factor-a]]. On the cell surface, mast cells bear binding sites ([[Receptor (biochemistry)|receptors]]), two of which are functionally most important: The stem cell factor receptor ([[tyrosine kinase KIT]]) regulates mast cell [[Cellular differentiation|differentiation]], [[Cell proliferation|proliferation]], activation and lifespan via [[stem cell factor]] binding. The [[Fc receptor|immunoglobulin receptor]] FcεRI (high-affinity IgE receptor) binds [[immunoglobulin E]] (IgE) with high binding strength ([[Affinity (Biologie)|affinity]]).&lt;ref name=&quot;Mayoral&quot;&gt;R. J. Mayoral et al.: ''MiR-221 influences effector functions and actin cytoskeleton in mast cells.'' In: ''PloS one.'' Band 6, Nummer 10, 2011, p.&amp;nbsp;e26133, {{ISSN|1932-6203}}. [[doi:10.1371/journal.pone.0026133]]. PMID 22022537. {{PMC|3192147}}.&lt;/ref&gt; Not only stem cell factor, but also a number of [[Interleukin|interleukins]]&lt;ref&gt;C. P. Shelburne und J. J. Ryan: ''The role of Th2 cytokines in mast cell homeostasis.'' In: ''[[Immunological Reviews]].'' Band 179, Februar 2001, pp.&amp;nbsp;82–93, {{ISSN|0105-2896}}. PMID 11292031. (Review).&lt;/ref&gt; and [[Ultraviolet|ultraviolet radiation]]&lt;ref name=&quot;Ch'ng&quot;&gt;S. Ch'ng et al.: ''Mast cells and cutaneous malignancies.'' In: ''[[Modern Pathology]].'' Band 19, Nummer 1, Januar 2006, pp.&amp;nbsp;149–159, {{ISSN|0893-3952}}. [[doi:10.1038/modpathol.3800474]]. PMID 16258517. (Review).&lt;/ref&gt; lead to activation and proliferation of mast cells. When mast cells are activated, they either release [[Inflammation|inflammatory mediators]], cytokines, and [[Protease|proteases]] from the granules or produce and release new ones in a short period of time.&lt;ref name=&quot;Mayoral&quot; /&gt;

The function of mast cells is best understood in [[Allergy|allergies]], and they are also involved in [[Autoimmune disease|autoimmune diseases]] and in enhancing [[Inflammation|inflammatory responses]] in [[Bacteria|bacterial]] [[Infection|infections]]. On the other hand, mast cells may also have anti-inflammatory effects by protecting against damaging factors such as bacteria and [[Parasitism|parasites]].&lt;ref&gt;S. J. Galli, M. Tsai: ''Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity.'' In: ''European Journal of Immunology.'' Band 40, Nummer 7, Juli 2010, pp.&amp;nbsp;1843–1851, {{ISSN|1521-4141}}. [[doi:10.1002/eji.201040559]]. PMID 20583030. (Review).&lt;/ref&gt; In addition, mast cells may contribute to the development and growth of other skin tumors due to their large repertoire of biologically active substances.&lt;ref name=&quot;Ch'ng&quot; /&gt;

== Occurrence and origin ==
Mastocytomas in dogs occur mainly in the skin and subcutaneous tissue. Very rarely, they are found in internal organs such as the small [[Gastrointestinal tract|intestine]],&lt;ref name=&quot;Dahme&quot;&gt;Erwin Dahme und Eugen Weiss: ''Grundriss der speziellen pathologischen Anatomie der Haustiere.'' 6. Auflage, Parey Verlag, Stuttgart 2007, {{ISBN|978-3-8304-1048-5}}, p.&amp;nbsp;143.&lt;/ref&gt; the [[mucosa of the mouth]],&lt;ref&gt;L. A. Hillman, et al.: ''Biological behavior of oral and perioral mast cell tumors in dogs: 44 cases (1996–2006).'' In: ''Journal of the American Veterinary Medical Association.'' Band 237, Nummer 8, Oktober 2010, pp.&amp;nbsp;936–942, {{ISSN|0003-1488}}. [[doi:10.2460/javma.237.8.936]]. PMID 20946081.&lt;/ref&gt; the [[nasal mucosa]]&lt;ref&gt;A. K. Patnaik et al.: ''Extracutaneous mast-cell tumor in the dog.'' In: ''Veterinary pathology.'' Band 19, Nummer 6, November 1982, pp.&amp;nbsp;608–615, {{ISSN|0300-9858}}. PMID 6815869.&lt;/ref&gt; or the [[conjunctiva]].&lt;ref&gt;M. Fife et al.: ''Canine conjunctival mast cell tumors: a retrospective study.'' In: ''Veterinary ophthalmology.'' Band 14, Nummer 3, Mai 2011, pp.&amp;nbsp;153–160, {{ISSN|1463-5224}}. [[doi:10.1111/j.1463-5224.2010.00857.x]]. PMID 21521438.&lt;/ref&gt; About 20% of all [[Neoplasm|skin tumors]]&lt;ref name=&quot;Hundeklinik&quot;&gt;Martin Kessler: ''Mastzelltumoren, Mastozytom (Mastzellsarkom).'' In: Hans Georg Niemand, Peter F. Suter (Hrsg.): ''Praktikum der Hundeklinik.'' 10. Auflage, Parey Verlag, Stuttgart 2006, {{ISBN|978-3-8304-1048-5}}, pp.&amp;nbsp;1135–1136.&lt;/ref&gt; and 6% of all tumors&lt;ref name=&quot;Stannard&quot;&gt;Anthony S. Stannard und L. Thoma Pulley: ''Mastocytoma of the dog''. In: Jack E. Moulton (Hrsg.): ''Tumors in domestic animals''. 2. Auflage, University of California Press, Berkeley [u. a.] 1978, {{ISBN|978-3-8304-1048-5}}, pp.&amp;nbsp;26–31.&lt;/ref&gt; in dogs are mastocytomas. They occur more frequently in some breeds: [[Boxer (dog)|German Boxer]] and related short-[[Breed|headed breeds]], [[Golden Retriever]], [[Beagle]], [[Irish Setter]], [[Dachshund]] and [[Bernese Mountain Dog]]. There is no dependence on the sex of the animal.&lt;ref name=&quot;Hundeklinik&quot; /&gt;&lt;ref name=&quot;Riva&quot;&gt;F. Riva et al.: ''A study of mutations in the c-kit gene of 32 dogs with mastocytoma.'' In: ''Journal of veterinary diagnostic investigation.'' Band 17, Nummer 4, Juli 2005, pp.&amp;nbsp;385–388, {{ISSN|1040-6387}}. PMID 16131001.&lt;/ref&gt; The median age of affected dogs is eight years, but a mastocytoma can develop in dogs as young as four months old or at a very advanced age.&lt;ref name=&quot;Stannard&quot; /&gt;
[[File:Kit ligand 2E9W.png|thumb|Surface model of stem cell factor receptor with bound stem cell factor (green).]]
In humans, a number of [[Mutation|mutations]] and [[chromosomal alterations]] are known to lead to pathological proliferation of mast cells ([[Mastocytosis|mastocytoses]]). Mutations of the gene for the [[KIT (gene)|stem cell factor receptor]] (c-KIT) lead to prolonged cell life and increased formation of new mast cells. The D816V mutation is the most common of these c-KIT mutations and occurs in 80% of patients with mastocytosis. However, there are also mastocytosis patients without alterations in the stem cell factor receptor. In total, there are over 20 known chromosomal alterations in humans that can lead to mastocytosis, with chromosomes 2, 7, 12, 13, 14, and X being most commonly affected.&lt;ref&gt;H. Sadrzadeh, O. Abdel-Wahab, A. T. Fathi: ''Molecular alterations underlying eosinophilic and mast cell malignancies.'' In: ''Discovery medicine.'' Band 12, Nummer 67, Dezember 2011, pp.&amp;nbsp;481–493, {{ISSN|1944-7930}}. PMID 22204765.&lt;/ref&gt;

In dogs, c-KIT alterations also appear to play a role. Both [[Protein production|increased gene expression]] and a mutation with [[phosphorylation]] of the stem cell factor receptor leading to activation without binding of the stem cell factor ([[ligand]]-independent) can occur. More than 30 such mutations are now known, the most common of which is a [[Gene duplication|duplication]] (tandem mutation) of [[exon]] 11, which [[Genetic code|encodes]] the portion of the stem cell factor receptor located directly on the inside of the [[cell membrane]] (juxtamembrane [[Protein domain|domain]]).&lt;ref name=&quot;Riva&quot; /&gt;&lt;ref&gt;Y. Takeuchi et al.: ''Aberrant autophosphorylation of c-Kit receptor in canine mast cell tumor cell lines.'' In: ''Veterinary immunology and immunopathology.'' Band 137, Nummer 3–4, Oktober 2010, pp.&amp;nbsp;208–216, {{ISSN|1873-2534}}. [[doi:10.1016/j.vetimm.2010.05.009]]. PMID 20591500.&lt;/ref&gt; However, mastocytomas without c-KIT mutations also occur in dogs;&lt;ref&gt;K. Ohmori et al.: ''Identification of c-kit mutations-independent neoplastic cell proliferation of canine mast cells.'' In: ''Veterinary immunology and immunopathology.'' Band 126, Nummer 1–2, November 2008, pp.&amp;nbsp;43–53, {{ISSN|0165-2427}}. [[doi:10.1016/j.vetimm.2008.06.014]]. PMID 18687474.&lt;/ref&gt; in contrast to US studies, almost no relevant c-KIT mutations were even detected in mastocytomas of German dogs. Whether this was coincidental or methodological or reflects genetic differences in breeding lines needs to be clarified by further investigations.&lt;ref name=&quot;Aupperle&quot;&gt;Heike Aupperle et al.: ''Neue diagnostische Aspekte bei kaninen Mastzelltumoren – Ein Überblick zur aktuellen Studienlage.'' In: ''kleintier konkret.'' S1 (2011), S.&amp;nbsp;44–48. ([https://web.archive.org/web/20120813153432/http://laboklin.com/pdf/de/fachbeitraege_online/2011_kleintier_konkret_14_mastzelltumor.pdf Complete text], memento from August 13, 2012)&lt;/ref&gt; The causes for the clustered occurrence of mastocytoma in dogs are so far unexplained, presumably there are several causes (multifactorial events).&lt;ref&gt;M. M. Welle et al.: ''Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment.'' In: ''Veterinary dermatology.'' Band 19, Nummer 6, Dezember 2008, pp.&amp;nbsp;321–339, {{ISSN|1365-3164}}. [[doi:10.1111/j.1365-3164.2008.00694.x]]. PMID 18980632. (Review).&lt;/ref&gt;

== Clinical image ==
[[File:Mast cell tumor on lip.JPG|thumb|Ulcerated disintegrating mastocytoma on the chaps of a [[Labrador Retriever|Labrador retriever]]]]
Mastocytomas of the skin present as [[Vocal cord nodule|nodules]] (papules), raised patches (plaques), or nodules (nodus), which may be superficially ulcerated. Their consistency ranges from soft to coarse-nodular. Locally, [[Red|redness]] and [[Itch|itching]] may occur ([[Darier's sign]]).&lt;ref name=&quot;Hundeklinik&quot; /&gt; Occasionally, satellite nodules occur, i.e., metastasis of the tumor via [[Lymphatic vessel|lymphatic vessels]] into neighboring skin areas;&lt;ref name=&quot;Warland&quot;&gt;James Warland und Jane Dobson: ''Hauttumore bei Hunden und Katzen.'' In: ''Veterinary Focus.'' Band 21, 2011, pp.&amp;nbsp;34–41.&lt;/ref&gt; in about 10% of cases, multiple mastocytomas are formed from the outset (primary multiplicity).&lt;ref name=&quot;Kessler2&quot;&gt;Martin Kessler: [http://www.tierklinik-hofheim.de/fileadmin/user_upload/Downloads_Tieraerzte/Merkblaetter/Der_Mastzelltumor_des_Hundes_2010.pdf ''Der Mastzelltumor des Hundes: ein Tumor mit vielen Gesichtern.'']&lt;/ref&gt;

Mastocytomas can form daughter tumors (metastases) to the (regional) lymph nodes responsible for the area as well as to other organs such as the [[liver]], [[spleen]], and [[bone marrow]]; other locations are very rare.[9] The metastasis rate for benign mastocytomas is less than 10%; for malignant tumors, it is more than 50%.&lt;ref name=&quot;Kessler2&quot; /&gt;
[[File:Mast cell tumor inner thigh.JPG|thumb|Mastocytoma on the inner thigh of a [[English Springer Spaniel|Springer Spaniel]]]]
Even without the formation of daughter tumors, a mastocytoma can trigger severe general disorders ([[paraneoplastic syndrome]]). These are triggered by the release of inflammatory mediators and cytokines. The production of [[heparin]] by the mast cells can lead to an increased tendency to bleed, and as a result of the production of fibroblast-inhibiting cytokines (especially FGF-2), to the disruption of [[wound healing processes]].&lt;ref name=&quot;Kessler2&quot; /&gt; In about one fifth of the dogs with a mastocytoma, feeding instability, [[vomiting]], [[tarry stools]] and [[anemia]] occur as a result of gastric or [[Peptic ulcer disease|duodenal ulcers]],&lt;ref name=&quot;Stannard&quot; /&gt; in [[Autopsy|autopsies]] such ulcers are even detected in more than 80% of patients.&lt;ref name=&quot;Kessler2&quot; /&gt; About 80% of the dogs with such ulcers are [[Animal euthanasia|euthanized]] due to poor general condition.&lt;ref name=&quot;Couto&quot;&gt;C. Guillermo Couto: ''Mast cell tumors in dogs and cats.'' In: Richard W. Nelson und C. Guillermo Couto (Hrsg.): ''Small animal internal medicine.'' 3. Auflage, Mosby, St. Louis 2003, {{ISBN|978-3-8304-1048-5}}, pp.&amp;nbsp;1146–1149.&lt;/ref&gt; In particularly severe cases, these ulcers can lead to a life-threatening gastric or [[Gastrointestinal perforation|intestinal rupture]].&lt;ref name=&quot;Warland&quot; /&gt; In addition, a clinical picture reminiscent of a malignant disease of the hematopoietic system can occur. This systemic mastocytosis is observed mainly in animals in which a mastocytoma has previously been removed. It is accompanied by lassitude, aversion to feeding, vomiting, weight loss, pallor, and enlargement of the [[liver]] and [[Splenomegaly|spleen]].&lt;ref name=&quot;Couto&quot; /&gt;

According to the clinical picture, mastocytomas are classified into four stages according to the criteria of the [[World Health Organization]]:&lt;ref name=&quot;Kessler3&quot;&gt;Martin Kessler: ''Kleintieronkologie: Diagnose und Therapie von Tumorerkrankungen bei Hunden und Katzen''. 2. Auflage, Parey Verlag, Stuttgart 2005, {{ISBN|978-3-8304-1048-5}}, pp.&amp;nbsp;210–215.&lt;/ref&gt;
{| class=&quot;wikitable&quot;
|+
|Stage 1
|a tumor confined to the skin without lymph node involvement
a) without general disturbances

b) with general disturbances
|-
|Stage 2
|a tumor confined to the skin with lymph node metastasis
a) without general disturbances

b) with general disturbances
|-
|Stage 3
|multiple tumors or [[Infiltration (medical)|infiltrative]] large single tumors with or without lymph node involvement
a) without general disturbances

b) with general disturbances
|-
|Stage 4
|Tumor with distant metastasis or [[Relapse|recurrence]] with metastasis
|}

== Diagnostics ==
A visual or palpatory diagnosis is not possible, since neither appearance nor consistency allow differentiation from other skin tumors.

The diagnostic tool of choice is [[Fine-needle aspiration|fine needle biopsy]], since sufficient cells can be obtained from mastocytomas. In the [[cytological preparation]], mast cells can be distinguished relatively easily from other cell types on the basis of their granules, although certain rapid staining solutions stain mast cell granules only unreliably, and cells of poorly differentiated mastocytomas may contain very few granules.&lt;ref&gt;Reinhard Mischke: ''Zytologisches Praktikum für die Veterinärmedizin''. Schlütersche, Hannover 2005, {{ISBN|978-3-8304-1048-5}}, S.&amp;nbsp;135.&lt;/ref&gt;

Changes are rarely observed in the [[Complete blood count|blood count]]; occasionally, an increase in a subtype of white blood cells ([[eosinophilia]]) may occur.&lt;ref name=&quot;Hundeklinik&quot; /&gt; In systemic mastocytosis, a decrease in white blood cells ([[leukopenia]]) often occurs. Circulating mast cells in the blood are usually not observed.&lt;ref name=&quot;Couto&quot; /&gt;

According to the [[Histopathology|histopathological]] cellular pattern, mastocytomas in dogs are classified into different grades. The most widely used classification of mastocytomas is based on the scheme of Patnaik and coworkers from 1984:&lt;ref&gt;A. K. Patnaik, W. J. Ehler, E. G. MacEwen: ''Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs.'' In: ''Veterinary pathology.'' Band 21, Nummer 5, September 1984, S.&amp;nbsp;469–474, {{ISSN|0300-9858}}. PMID 6435301.&lt;/ref&gt;
{| class=&quot;wikitable&quot;
|+
|Tumor grade 1 (well differentiated)
|
* well defined cell borders
* round to oval, uniform [[Cell nucleus|cell nuclei]]
* hardly any [[Mitosis|mitoses]]
* granules numerous, large and well stained
|-
|Tumor grade 2 (moderately differentiated)
|
* unclear cell boundaries
* few mitoses
* granules reduced in number, size and staining
|-
|Tumor grade 3 ([[Anaplasia|anaplastic]])
|
* cell boundaries hardly recognizable
* cell size and nuclear-[[Cytoplasm|cytoplasmic]] ratio strongly varying
* many mitoses
* few, small, poorly stained granules
|}
However, a 2011 study challenges this classification. Identical specimens of 95 mastocytomas, of which the [[outcome of the disease]] was also known, were sent to 28 pathologists in 16 different institutions. While the agreement between the different investigators was 75% for grade 3 tumors, it was less than 63% for grades 1 and 2, and the predictions derived from them also showed little agreement with the outcome of the disease. Kiupel and coworkers therefore proposed a new system with only two grades: low-grade and high-grade. Tumors are judged to be high-grade (high grade, malignant) if one or more of the following criteria are met in ten fields of view at high magnification ([[Objective (optics)|objective]] 40x):&lt;ref name=&quot;Kiupel&quot;&gt;M. Kiupel et al.: ''Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior.'' In: ''Veterinary pathology.'' Band 48, Nummer 1, Januar 2011, S.&amp;nbsp;147–155, {{ISSN|1544-2217}}. [[doi:10.1177/0300985810386469]]. PMID 21062911.&lt;/ref&gt;

* at least seven [[Mitosis|mitoses]]
* at least three multinucleated cells (three or more nuclei)
* at least three abnormal nuclei (retractions, segmentation, irregular shape)
* Nucleus enlargement (karyomegaly, the nucleus diameters of 10% of mast cells vary at least twofold).

The median survival time was four months in animals with high-grade mastocytomas, whereas it was over two years in animals with low-grade mastocytomas. In addition, [[Recurrence relation|recurrences]] and metastases were significantly more frequent in high-grade mastocytomas.&lt;ref name=&quot;Kiupel&quot; /&gt; Furthermore, there seems to be a correlation between the type of c-KIT mutation on the one hand and the biological behavior or tumor grade on the other hand. &lt;ref name=&quot;Riva&quot; /&gt;&lt;ref&gt;R. M. Gil da Costa et al.: ''CD117 immunoexpression in canine mast cell tumours: correlations with pathological variables and proliferation markers.'' In: ''BMC veterinary research.'' Band 3, 2007, S.&amp;nbsp;19, {{ISSN|1746-6148}}. [[doi:10.1186/1746-6148-3-19]]. PMID 17711582. {{PMC|2077863}}.&lt;/ref&gt;&lt;ref&gt;D. Zemke, B. Yamini, V. Yuzbasiyan-Gurkan: ''Mutations in the juxtamembrane domain of c-KIT are associated with higher grade mast cell tumors in dogs.'' In: ''Veterinary pathology.'' Band 39, Nummer 5, September 2002, S.&amp;nbsp;529–535, {{ISSN|0300-9858}}. PMID 12243462.&lt;/ref&gt; Immunohistochemical detection of cell division markers such as [[Ki-67 (protein)|Ki-67]] or the [[Tauopathy|argyrophilic]] [[nucleolus organizer region]] (AgNOR) also shows correlations with the biological behavior of mastocytomas.&lt;ref name=&quot;Thompson&quot;&gt;J. J. Thompson et al.: ''Canine subcutaneous mast cell tumors: cellular proliferation and KIT expression as prognostic indices.'' In: ''Veterinary pathology.'' Band 48, Nummer 1, Januar 2011, S.&amp;nbsp;169–181, {{ISSN|1544-2217}}. [[doi:10.1177/0300985810390716]]. PMID 21160022.&lt;/ref&gt; More than 23 Ki-67-positive cells per cm2 or more than four AgNOR per nucleus are considered to be prognostically unfavorable.&lt;ref name=&quot;Aupperle&quot; /&gt;

Thus, the biological behavior of mastocytomas in dogs is highly variable and only predictable to a limited extent, which is why the term mastocytoma is preferable to the terms mastocytoma (benign) and mastosarcoma (malignant) in dogs.&lt;ref name=&quot;Couto&quot; /&gt; The clinical stage, histopathological grade, c-KIT expression pattern, and cell division markers provide clues but do not allow precise conclusions. Apparently, mastocytomas in dogs are molecularly heterogeneous neoplasms.&lt;ref name=&quot;Riva&quot; /&gt; Mastocytomas  in the German Boxer, one of the most commonly affected breeds, usually show a benign course.&lt;ref name=&quot;Mayer&quot;&gt;M. N. Mayer: ''Radiation therapy for canine mast cell tumors.'' In: ''The Canadian veterinary journal. La revue vétérinaire canadienne.'' Band 47, Nummer 3, März 2006, S.&amp;nbsp;263–265, {{ISSN|0008-5286}}. PMID 16604985. {{PMC|2823470}}. (Review).&lt;/ref&gt; The localization of the tumor also seems to play a role. For example, mastocytomas of the toes, perineum, groin, and mucous membranes are more prone to metastasis than those of other regions.&lt;ref name=&quot;Couto&quot; /&gt; In contrast, mastocytomas of the [[conjunctiva]] are rarely prone to recurrence or metastasis, regardless of grade.&lt;ref&gt;M. Fife et al.: ''Canine conjunctival mast cell tumors: a retrospective study.'' In: ''Veterinary ophthalmology.'' Band 14, Nummer 3, Mai 2011, S.&amp;nbsp;153–160, [[doi:10.1111/j.1463-5224.2010.00857.x]], PMID 21521438.&lt;/ref&gt; Apparently, [[Epigenetics|epigenetic factors]], immediate environmental conditions (microenvironment), [[Angiogenesis|vascularization]], and [[Growth factor|growth factors]] may influence biological behavior.&lt;ref name=&quot;Thompson&quot; /&gt;

Differentially, any other skin tumor of the dog can be considered: In the skin especially [[Histiocytoma (dog)|histiocytomas]], [[Basal-cell carcinoma|basaliomas]], [[Melanoma|melanomas]] and [[T-cell lymphoma|T-cell lymphomas]], in the subcutis especially [[Lipoma|lipomas]], [[Hemangiopericytoma|hemangiopericytomas]] and [[Hemangiosarcoma|hemangiosarcomas]]. However, the differentiation of these tumors hardly causes any problems in cytodiagnostics.&lt;ref name=&quot;Kessler3&quot; /&gt;&lt;gallery&gt;
File:Canine histiocytoma.jpg|Histiocytoma
File:Canine malignant melanoma.JPG|Malignant melanoma
File:Canine cutaneous T-cell lymphoma.jpg|T-cell lymphoma
File:Hemangiosarcoma of skin.JPG|Hemangiosarcoma
&lt;/gallery&gt;

== Treatment ==
Although the classifications based on clinical appearances and cellular appearance in cytodiagnostics provide clues to the biological behavior, a mastocytoma remains unpredictable and is potentially to be considered malignant. The [[first-line treatment method]] is surgical removal of the tumor at the earliest possible stage. Concomitant chemotherapy and radiation may be necessary, especially if complete removal is not possible or unsafe for anatomic reasons.&lt;ref name=&quot;Kessler3&quot; /&gt; For inoperable tumors, treatment with tyrosine kinase inhibitors may be attempted. In general, the prospect of cure is best in well-differentiated mastocytomas (low-grade or grade 1) and in animals without general signs (substages a).&lt;ref name=&quot;Kessler2&quot; /&gt; Young dogs (&lt;1 year of age) also have a better prognosis than older dogs.&lt;ref&gt;K. Rigas et al.: ''Mast cell tumours in dogs less than 12 months of age: a multi-institutional retrospective study.'' In: ''J. Small Anim. Pract.'' Band 61, 2020, Heft 7, S. 449–457.&lt;/ref&gt;

=== Surgery ===
Surgical removal ([[Resection margin|resection]]) should be performed as early as possible, i.e. before lymph nodes or even other organs are affected (stage 1). Mastocytomas have a pseudocapsule of compressed tumor cells and usually fine extensions into the surrounding tissue that extend beyond the palpable tumor tissue. For this reason, a safe distance of about 3 cm beyond the palpable margin is recommended. Removal is performed, even in the case of mastocytomas in the subcutaneous tissue, with the entire skin and in depth, including the subcutaneous [[fascia]]. On the limbs, it can be difficult to close the resulting skin defect, so [[skin grafting]] may also be necessary. [[Biopsy|Biopsies]] should be taken from the margins and the remaining tissue in depth (tumor bed) to check for the presence of residual tumor tissue.&lt;ref name=&quot;Kessler3&quot; /&gt;&lt;ref name=&quot;Warland&quot; /&gt;

Particularly on the limbs, these basic tumor surgery rules cannot always be fully implemented because this would result in the loss of [[Nerve|nerves]], [[Vessels (Starset album)|vessels]] and [[Tendon|tendons]], so that [[amputation]] must also be considered. In some circumstances, the use of [[Antihistamine|H₁]]- and [[H2 receptor antagonist|H₂-receptor antagonists]] prior to surgery may attempt to reduce tumor size. The administration of these agents is also indicated in cases of incomplete excision to reduce the number of tumor cells (cytoreductive resection), as the procedure may lead to degranulation of mast cells and consequent release of inflammatory factors.&lt;ref name=&quot;Kessler3&quot; /&gt;

For well-differentiated mastocytomas smaller than 5 cm, the prospect of cure ([[prognosis]]) is very good with proper surgical excision, but poor for recurrence. Therefore, planning the surgical approach at the time of initial surgery is crucial.&lt;ref name=&quot;Warland&quot; /&gt; For tumors smaller than 2.5 cm, survival is very high, even for high-grade tumors.&lt;ref&gt;A.S. Mooreet al.: ''Retrospective outcome evaluation for dogs with surgically excised, solitary Kiupel high-grade, cutaneous mast cell tumours.'' In: ''Vet. Comp. Oncol.'' 2020. [[doi:10.1111/vco.12565]]&lt;/ref&gt;

=== Radiotherapy ===
[[Radiation therapy]] is mainly used as an adjuvant therapy for mastocytomas that cannot be completely removed and is considered the treatment of choice. Mast cells are very sensitive to [[ionizing radiation]]. For grade 2 mastocytomas, various studies show freedom from disease after one year in about 95% of patients, and between the second and fifth year after treatment in about 90% of patients. For grade 3 tumors without lymph node involvement, the one-year [[survival rate]] in one study was 71%. Radiation therapy can also be used as a [[Neoadjuvant therapy|neoadjuvant]] or [[Palliative care|palliative treatment]], as it usually leads to significant shrinkage of the tumor.&lt;ref name=&quot;Mayer&quot; /&gt; A study of [[brachytherapy]] for grade 2 and 3 tumors after surgical excision also showed good success and good tolerability.&lt;ref&gt;N. C. Northrup, R. E. Roberts, T. W. Harrell, K. L. Allen, E. W. Howerth, T. L. Gieger: ''Iridium-192 interstitial brachytherapy as adjunctive treatment for canine cutaneous mast cell tumors.'' In: ''Journal of the American Animal Hospital Association.'' Band 40, Nummer 4, 2004 Jul–Aug, pp.&amp;nbsp;309–315, {{ISSN|1547-3317}}. PMID 15238561.&lt;/ref&gt;

=== Chemotherapy ===
Various agents are used for [[chemotherapy]]. [[Glucocorticoid|Glucocorticoids]] have a direct inhibitory effect on the proliferation of mast cells. Direct injection into the tumor is no longer recommended, but [[systemic administration]] is often combined with the administration of [[Cytostasis|cytostatic drugs]]. The cytostatic agents used are [[Vinca alkaloid|vinca alkaloids]] such as [[vinblastine]], [[cyclophosphamide]], [[hydroxycarbamide]], [[doxorubicin]], [[mitoxantrone]], and [[Asparaginase|L-asparaginase]], although combinations of different agents are more promising.&lt;ref name=&quot;Kessler3&quot; /&gt;&lt;ref&gt;S. M. Govier: ''Principles of treatment for mast cell tumors.'' In: ''Clinical techniques in small animal practice.'' Band 18, Nummer 2, Mai 2003, pp.&amp;nbsp;103–106, {{ISSN|1096-2867}}. [[doi:10.1053/svms.2003.36624]]. PMID 12831070. (Review).&lt;/ref&gt; According to the 2012 European consensus paper, chemotherapy is always indicated when the tumor has already spread throughout the body or when neither reoperation nor radiation are possible in cases of incomplete surgical removal.&lt;ref&gt;L. Blackwood et al.: ''European consensus document on mast cell tumours in dogs and cats.'' In: ''Veterinary and comparative oncology.'' Band 10, Nummer 3, September 2012, pp.&amp;nbsp;e1–e29, [[doi:10.1111/j.1476-5829.2012.00341.x]], PMID 22882486 (Review)&lt;/ref&gt;

Hydroxycarbamide responded in 28% of treated dogs in one study, and 4% (two animals) showed complete cure ([[Cure|complete remission]]). Side effects were primarily blood count changes such as [[anemia]] and [[neutropenia]].&lt;ref&gt;K. M. Rassnick et al.: ''Phase II open-label study of single-agent hydroxyurea for treatment of mast cell tumours in dogs.'' In: ''Veterinary and comparative oncology.'' Band 8, Nummer 2, Juni 2010, pp.&amp;nbsp;103–111, {{ISSN|1476-5829}}. [[doi:10.1111/j.1476-5829.2010.00211.x]]. PMID 20579323.&lt;/ref&gt; The combination of hydroxycarbamide with [[prednisolone]] in incompletely removed grade 2 tumors resulted in death from [[liver failure]] in two cases; of the remaining dogs, all survived the first year and 77% survived the second year.&lt;ref&gt;K. Hosoya et al.: ''Adjuvant CCNU (lomustine) and prednisone chemotherapy for dogs with incompletely excised grade 2 mast cell tumors.'' In: ''Journal of the American Animal Hospital Association.'' Band 45, Nummer 1, 2009 Jan–Feb, pp.&amp;nbsp;14–18, {{ISSN|1547-3317}}. PMID 19122059.&lt;/ref&gt; With the combination of hydroxycarbamide, vinblastine, and prednisolone, a response rate of 65% was achieved in unremovable or incompletely removable mastocytomas, and the median survival time was significantly higher in grade 2 than in grade 3 tumors (954 versus 190 days). Side effects (neutropenia, increase in [[Liver function tests|liver enzymes]]) were moderate.&lt;ref&gt;K. M. Rassnick 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.'' In: ''Veterinary and comparative oncology.'' Band 8, Nummer 2, Juni 2010, pp.&amp;nbsp;138–152, {{ISSN|1476-5829}}. [[doi:10.1111/j.1476-5829.2010.00217.x]]. PMID 20579327.&lt;/ref&gt;

=== Tyrosine kinase inhibitors ===
In the meantime, with the [[Tyrosine kinase inhibitor|tyrosine kinase inhibitors]], there are active substances that act specifically on the [[stem cell receptor]] of the mast cells. Since 2009, two tyrosine kinase inhibitors - [[masitinib]] (trade name Masivet) and [[toceranib]] (trade name Palladia) - have been [[Regulatory affairs|approved]] for the treatment of mastocytomas in dogs in the EU.&lt;ref name=&quot;Warland&quot; /&gt;&lt;ref&gt;Österreichische Apotheker-Verlagsgesellschaft m.b.H.: ''Austria-Codex Schnellhilfe 2016/17''. Hrsg.: Österreichische Apotheker-Verlagsgesellschaft m.b.H. Wien 2016, {{ISBN|978-3-85200-244-6}}, p. 1015.&lt;/ref&gt;&lt;ref&gt;{{cite web|access-date=2017-01-02|language=de|title=Fachinformation für Palladia Filmtabletten für Hunde|url=http://www.pharmazie.com/graphic/A/88/8-90188.pdf}}&lt;!-- auto-translated by Module:CS1 translator --&gt;&lt;/ref&gt;

Masitinib is approved for the treatment of unresectable grade 2 and 3 (or high-grade) mastocytomas with c-KIT mutation. Side effects are primarily vomiting, diarrhea, [[neutropenia]], [[anemia]], and [[proteinuria]], but most are mild. Median survival increased from 75 to 118 days in a study of dogs with grade 2 and 3 tumors without metastases, and to 253 days when the agent was used for initial treatment.&lt;ref&gt;K. A. Hahn et al.: ''Masitinib is safe and effective for the treatment of canine mast cell tumors.'' In: ''Journal of veterinary internal medicine'' Band 22, Nummer 6, 2008 Nov–Dec, S.&amp;nbsp;1301–1309, {{ISSN|0891-6640}}. [[doi:10.1111/j.1939-1676.2008.0190.x]]. PMID 18823406.&lt;/ref&gt;

Toceranib has multiple targets (multitarget drug): It acts not only at the stem cell receptor but also at the [[Blood vessel|vascular]] (VEGF) and [[platelet-derived growth factor]] (PDGF) receptors, making it applicable to mastocytomas without a c-KIT mutation. Side effects are similar to those of masitinib, but occur very frequently and are severe in over one-third of animals.&lt;ref&gt;Eintrag zu ''[https://www.vetpharm.uzh.ch/Wirkstoffe/000000035606/8945_01.html Toceranib]'' bei Vetpharm, retrieved July 29, 2012.&lt;/ref&gt;

There is also positive experience with the tyrosine kinase inhibitor [[imatinib]], which is approved for human medicine.&lt;ref&gt;O. Yamada et al.: ''Imatinib elicited a favorable response in a dog with a mast cell tumor carrying a c-kit c.1523A&gt;T mutation via suppression of constitutive KIT activation.'' In: ''Veterinary immunology and immunopathology.'' Band 142, Nummer 1–2, Juli 2011, pp.&amp;nbsp;101–106, {{ISSN|1873-2534}}. [[doi:10.1016/j.vetimm.2011.04.002]]. PMID 21561667.&lt;/ref&gt;

=== Stelfonta (tigilanol tiglate injection) ===
In 2020, [https://web.archive.org/web/20201116182038/https://www.fda.gov/news-events/press-announcements/fda-approves-first-intratumoral-injection-treat-non-metastatic-mast-cell-tumors-dogs FDA] approved a non-surgical treatment called [https://stelfonta.com/ STELFONTA (tigilanol tiglate injection)] for the treatment of all grades of non-metastatic mast cell tumors.  Injected directly into the tumor, Stelfonta has a targeted mode of action to destroy mast cell tumors, evident within hours. Stelfonta activates [[protein kinase C]] and causes [[necrosis]] of tumor cells by damaging blood vessels.&lt;ref name=&quot;Devillers&quot;&gt;Isabelle Devillers und Laura Meyer: ''Therapie von Mastzelltumoren beim Hund mit Tigilanoltiglat – Erfahrungen mit besonderen Fällen.'' In: ''Kleintiermedizin'' Band 24, 2021, Nummer 3, pp. 1–7.&lt;/ref&gt; 

Post marketing data mirrors the pivotal study, achieving a 75% complete response rate with a single injection, or 88% with up to two injections.&lt;ref&gt;T.T. De Ridder et al.: ''Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canina mast cell tumors with Tigilanol tiglate (EBC-46).'' In: ''J. Vet. Intern. Med.''  2020, [[doi:10.1111/jvim.15806]].&lt;/ref&gt;  89% of dogs have no tumor recurrence at the site of Stelfonta treatment at 12 months.&lt;ref&gt;{{Cite journal |last=Jones |first=P. D. |date=2021 |title=Recurrence-free interval 12 months after local treatment of mast cell tumors in dogs using intratumoral injection of tigilanol tiglate. |url=https://doi.org/10.1111/jvim.16018 |journal=Journal of Veterinary Internal Medicine |volume=35 |issue=1 |pages=451–455|doi=10.1111/jvim.16018 |pmid=33350511 |pmc=7848364 }}&lt;/ref&gt;  

Stelfonta is also approved for treatment of canine mast cell tumors by the EMA, VMD, APVMA and Swissmedic.  The treatment is accompanied by the administration of an [[antihistamine]], a corticosteroid, and an analgesic.&lt;ref name=&quot;Devillers&quot; /&gt;

== Mastocytomas of other species ==

=== Mastocytomas in humans ===
{{Main|Mastocytosis}}
An abnormal proliferation of mast cells is called mastocytosis in human medicine. The increased storage of 
{| class=&quot;wikitable&quot;
|+
| colspan=&quot;2&quot; |Classification according to ICD-10
|-
|C94.3
|Mast cell leukemia
|-
|C96.2
|Malignant mastocytomas
Malignant mastocytosis
|-
|Q82.2
|congenital mastocytosis
Urticaria pigmentosa
|-
| colspan=&quot;2&quot; |[https://www.dimdi.de/static/de/klassifikationen/icd/icd-10-who/kode-suche/htmlamtl2019/ ICD-10 online (WHO version 2019)]
|}
mast cells in the skin (cutaneous mastocytosis) is a rare disease with an [[Incidence (epidemiology)|incidence]] of less than ten new cases per 1 million population.&lt;ref&gt;[http://www.mastozytose.net/fileadmin/documents/013-058l_S1_Mastozytose.pdf ''Leitlinie Mastozytose''] (PDF; 313&amp;nbsp;kB) der [[Deutsche Dermatologische Gesellschaft|Deutschen Dermatologischen Gesellschaft]]&lt;/ref&gt; The most common form of these skin mastocytoses is the benign [[urticaria pigmentosa]] (&quot;pigmented nettle rash&quot;).&lt;ref&gt;Heiko Traupe, Henning Hamm: ''Pädiatrische Dermatologie''. 2. Auflage, Springer, Heidelberg 2005, {{ISBN|978-3-540-25646-5}}, pp.&amp;nbsp;215–223.&lt;/ref&gt; In about 20% of young children, other organs are also affected, and in adults, the figures vary between 40% and 90%.&lt;ref name=&quot;Plewig&quot;&gt;Gerd Plewig, P. Thomas: ''Fortschritte der praktischen Dermatologie und Venerologie 2006''. Band 20 von ''Fortschritte Der Praktischen Dermatologie und Venerologie''. Springer, Heidelberg 2007, {{ISBN|3-540-30514-9}}, p.&amp;nbsp;391.&lt;/ref&gt;

Isolated mastocytomas as in dogs, on the other hand, are very rare in humans. Benign mastocytomas (mastocytoma, mast cell [[nevus]]) usually develop in young children under two years of age and appear as single or multiple, reddish or reddish-brown raised spots or nodules of the skin. In response to mechanical stimuli or spontaneously, they may swell like [[hives]] (Darier's sign) and cause [[Itch|itching]]. There is no tendency for degeneration or involvement of other organs. Mastocytomas usually regress without treatment, but this may take years.&lt;ref&gt;Otto Braun-Falco et al.: ''Dermatologie und Venerologie''. 5. Auflage, Springer, Heidelberg 2005, {{ISBN|978-3-540-40525-2}}, p.&amp;nbsp;1396.&lt;/ref&gt; Malignant mastocytomas (mast cell [[Sarcoma|sarcomas]]) are extremely rare in humans[46] and are controversial as a disease entity in their own right.&lt;ref&gt;Wolfgang Remmele: ''Pathologie. 1. Rechtsfragen in der Pathologie; Einführung in die bioptische Diagnostik; Herz und Gefäßsystem; Hämatologie; Milz; Thymus''. 2. Auflage, Springer, Berlin 1999, {{ISBN|3-540-61095-2}}, pp.&amp;nbsp;507–508.&lt;/ref&gt;

=== Mastocytomas in other animal species ===
Mastocytomas are also relatively common in horses, cats, and ferrets, although less so than in dogs. In the [[Horse|domestic horse]], they occur primarily in older animals in the head and neck region and lower limb sections. The recurrence rate is low with proper surgical removal.&lt;ref&gt;Hanns-Jürgen Wintzer: ''Krankheiten des Pferdes: ein Leitfaden für Studium und Praxis.'' 3. Auflage, Parey, Berlin 1999, {{ISBN|3-8263-3280-6}}, p.&amp;nbsp;483.&lt;/ref&gt; In the [[Cat|domestic cat]], mastocytomas of the skin are mostly benign. Histologic grading, as in the dog, has not been shown to be useful. Surgical excision is also the treatment of choice in the cat, in combination with radiation if resection is incomplete. If numerous mastocytomas occur, [[Palliative care|palliative treatment]] with [[Glucocorticoid|glucocorticoids]] may also be attempted. A special form of mastocytoma occurs in [[Siamese cat|Siamese cats]]. Here, the mast cells resemble [[Histiocyte|histiocytes]] and collections of [[Lymphocyte|lymphocytes]] and [[Eosinophil|eosinophilic granulocytes]] are interspersed in the tumor.&lt;ref name=&quot;Warland&quot; /&gt; In older cats, mastocytomas occasionally occur in the small intestine and can lead to [[Intussusception (medical disorder)|intestinal intussusception]] or perforation and exhibit aggressive biological behavior.&lt;ref&gt;Laura Marconato und Giuliano Bettini: ''Darmtumoren bei der Katze.'' In: ''Veterinary Focus'' 23 (2013), pp. 39–45.&lt;/ref&gt; In [[Ferret|ferrets]], mastocytomas account for approximately 16% of skin tumors, but also usually behave benignly.&lt;ref&gt;G. A. Parker, C. A. Picut: ''Histopathologic features and post-surgical sequelae of 57 cutaneous neoplasms in ferrets (Mustela putorius furo L.).'' In: ''Veterinary pathology.'' Band 30, Nummer 6, November 1993, pp.&amp;nbsp;499–504, {{ISSN|0300-9858}}. PMID 8116142. (Review).&lt;/ref&gt;

In other mammals, mastocytomas are very rare. There are single case reports in [[Cattle|domestic cattle]],&lt;ref&gt;B. I. Smith und L. A. Phillips: ''Congenital mastocytomas in a Holstein calf.'' In: ''The Canadian veterinary journal.'' Band 42, Nummer 8, August 2001, pp.&amp;nbsp;635–637, {{ISSN|0008-5286}}. PMID 11519274. {{PMC|1476568}}.&lt;/ref&gt; [[Donkey|domestic donkeys]],&lt;ref&gt;G. Kay et al.: ''Grade III mastocytoma in a donkey.'' In: ''The Veterinary record.'' Band 152, Nummer 9, März 2003, pp.&amp;nbsp;266–267, {{ISSN|0042-4900}}. PMID 12638914.&lt;/ref&gt; [[Pig|domestic pigs]],&lt;ref&gt;G. Migaki, K. A. Langheinrich: ''Mastocytoma in a pig.'' In: ''Pathologia veterinaria.'' Band 7, Nummer 4, 1970, pp.&amp;nbsp;353–355, {{ISSN|0031-2975}}. PMID 4998946.&lt;/ref&gt; [[Llama|llamas]],&lt;ref&gt;T. Y. Lin et al.: ''Mast cell tumors in a llama (Lama glama).'' In: ''Journal of veterinary diagnostic investigation.'' Band 22, Nummer 5, September 2010, pp.&amp;nbsp;808–811, {{ISSN|1040-6387}}. PMID 20807950.&lt;/ref&gt; [[Richardson's ground squirrel|Richardson's gopher]],&lt;ref&gt;X. J. He et al.: ''Spontaneous cutaneous mast cell tumor with lymph node metastasis in a Richardson's ground squirrel (Spermophilus richardsonii).'' In: ''Journal of veterinary diagnostic investigation.'' Band 21, Nummer 1, Januar 2009, pp.&amp;nbsp;156–159, {{ISSN|1040-6387}}. PMID 19139521.&lt;/ref&gt; [[Hamster|hamsters]]&lt;ref&gt;K. Nishizumi, K. Fujiwara, A. Hasegawa: ''Cutaneous mastocytomas in Djungarian hamsters.'' In: ''Experimental animals.'' Band 49, Nummer 2, April 2000, pp.&amp;nbsp;127–130, {{ISSN|1341-1357}}. PMID 10889951.&lt;/ref&gt; and [[Atelerix|African hedgehogs]].&lt;ref&gt;J. T. Raymond, M. R. White, E. B. Janovitz: ''Malignant mast cell tumor in an African hedgehog (Atelerix albiventris).'' In: ''Journal of wildlife diseases.'' Band 33, Nummer 1, Januar 1997, pp.&amp;nbsp;140–142, {{ISSN|0090-3558}}. PMID 9027702.&lt;/ref&gt; In [[Mouse|mice]], spontaneous mastocytomas are very rare,&lt;ref&gt;D. J. Lewis, J. M. Offer: ''Malignant mastocytoma in mice.'' In: ''Journal of comparative pathology.'' Band 94, Nummer 4, Oktober 1984, pp.&amp;nbsp;615–620, {{ISSN|0021-9975}}. PMID 6439762.&lt;/ref&gt; but the mouse mast tumor [[Immortalised cell line|cell line]] P 815 is widely used in research.

In birds and reptiles, mastocytomas are very rare; isolated cases have been described in the [[Chicken|domestic chicken]],&lt;ref&gt;G. M. Patnaik, D. Mohanty: ''A case of avian mastocytoma.'' In: ''The Indian veterinary journal.'' Band 47, Nummer 4, April 1970, pp.&amp;nbsp;298–300, {{ISSN|0019-6479}}. PMID 4987390.&lt;/ref&gt; the [[Lampropeltis getula|chain snake]],&lt;ref&gt;J. Schumacher, R. A. Bennett, L. E. Fox, S. L. Deem, L. Neuwirth, J. H. Fox: ''Mast cell tumor in an eastern kingsnake (Lampropeltis getulus getulus).'' In: ''Journal of veterinary diagnostic investigation.'' Band 10, Nummer 1, Januar 1998, pp.&amp;nbsp;101–104, {{ISSN|1040-6387}}. PMID 9526872.&lt;/ref&gt; and a [[Galápagos tortoise|Galápagos giant tortoise]].&lt;ref&gt;M. Santoro et al.: ''Mast cell tumour in a giant Galapagos tortoise (Geochelone nigra vicina).'' In: ''Journal of comparative pathology.'' Band 138, Nummer 2–3, 2008 Feb–Apr, pp.&amp;nbsp;156–159, {{ISSN|0021-9975}}. [[doi:10.1016/j.jcpa.2007.11.004]]. PMID 18308330.&lt;/ref&gt;

== References ==
&lt;references /&gt;

== Bibliography ==

* [[:de:Martin_Kessler_(Tiermediziner)|Martin Kessler]]: ''Kleintieronkologie: Diagnose und Therapie von Tumorerkrankungen bei Hunden und Katzen''. 2. Auflage, Parey Verlag, Stuttgart 2005, {{ISBN|978-3-8304-4103-8}}, pp.&amp;nbsp;210–215.
* Martin Kessler: ''Mastzelltumoren, Mastozytom (Mastzellsarkom).'' In: Hans Georg Niemand, Peter F. Suter (Hrsg.): ''Praktikum der Hundeklinik.'' 10. Auflage, Parey Verlag, Stuttgart 2006, {{ISBN|978-3-8304-4141-0}}, pp.&amp;nbsp;1135–1136.
* Anthony S. Stannard und L. Thoma Pulley: ''Mastocytoma of the dog''. In: Jack E. Moulton (Hrsg.): ''Tumors in domestic animals''. 2. Auflage, University of California Press, Berkeley [u. a.] 1978, {{ISBN|0-520-02386-2}}, pp.&amp;nbsp;26–31.
* C. Guillermo Couto: ''Mast cell tumors in dogs and cats.'' In: Richard W. Nelson und C. Guillermo Couto (Hrsg.): ''Small animal internal medicine.'' 3. Auflage, Mosby, St. Louis 2003, {{ISBN|0-323-01724-X}}, pp.&amp;nbsp;1146–1149.
* 55. Österreichische Apotheker-Verlagsgesellschaft m.b.H: [[:de:Austria-Codex|Austria-Codex]] Schnellhilfe 2016/17. Druckerei Berger, Horn 2016, p. 1015, {{ISBN|978-3-85200-244-6}}

== External links ==

* [http://www.tierklinik-hofheim.com/chameleon//outbox//public/4/download_8.pdf Martin Kessler: Mastocytomas in dogs: a tumor with many faces.]
* [https://www.med.vetmed.uni-muenchen.de/einrichtungen/onko/krank/mastzell/index.html Mastocytomas] - Information from the University of Munich

[[Category:Dog anatomy]]
[[Category:Dog diseases]]
[[Category:Tumors]]