JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2025

I-N21D

SLIDE A:

Signalment (JPC # 1957907): Age and breed unspecified dog

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: Expanding the dermis and subcutis, elevating the overlying epidermis, separating and surrounding adnexa, skeletal muscle fibers, and collagen bundles, and extending to the margins of the submitted tissue is an unencapsulated, poorly-circumscribed neoplasm composed of sheets of neoplastic round cells (mast cells) on a preexisting fibrovascular stroma. Neoplastic cells have distinct cell borders, moderate amounts of amphophilic cytoplasm that occasionally contains fine basophilic granules, a centrally located, round nucleus with coarsely stippled chromatin and 1-2 distinct nucleoli. Anisocytosis and anisokaryosis are mild, there is 1 mitotic figure per 2.37 mm² and no trinucleated cells are observed. Scattered throughout the neoplasm are moderate to high numbers of eosinophils and fewer lymphocytes, plasma cells, and hemosiderin-laden macrophages. The overlying epidermis has mild orthokeratosis. Within the dermis, there is increased clear space (edema), and mild dilation of lymphatics.

SLIDE B: Luna mast cell stain: Neoplastic cells contain numerous intracytoplasmic metachromatic granules.

MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis: Mast cell tumor, low grade, breed unspecified, canine

SLIDE C:

Signalment (JPC # 2924576): 13-year-old Standardbred gelding

HISTORY: A subcutaneous mass on the right flank

HISTOPATHOLOGIC DESCRIPTION: Subcutis (per contributor): Infiltrating, separating, and surrounding collagen bundles is an unencapsulated, paucicellular, poorly demarcated neoplasm composed of sheets of neoplastic round cells (mast cells) on a preexisting dense collagenous stroma. Neoplastic cells have distinct cell borders, moderate amounts of amphophilic cytoplasm that often contain fine basophilic granules, a centrally located, round to oval nucleus with coarsely stippled chromatin and an indistinct nucleolus. Anisocytosis and anisokaryosis are mild and there is 1 mitotic figure per 2.37 mm². There are multiple large, irregular, up to 5 mm diameter areas of lytic necrosis composed of brightly eosinophilic cellular and basophilic karyorrhectic debris, degenerate mast cells, and multifocal brightly eosinophilic, thick bands of collagen that are bordered by deeply basophilic fragmented mineral (collagen flame figures). Throught the stroma there are macrophages containing intracytoplasmic brown globules (hemosiderin), few multinucleated giant cells (foreign body and Langhans type), and occasional eosinophils, foci of pale basophilic material (mucin), hemorrhage, fibrin, and edema.

MORPHOLOGIC DIAGNOSIS: Subcutis (per contributor): Mast cell tumor, Standardbred, equine

SLIDE D:

Signalment (JPC #4014162-02): 13 year old, spayed female domestic shorthair cat

HISTORY: Several cutaneous masses; this mass on the left shoulder

HISTOPATHOLOGIC DESCRIPTION (Slide D): Haired skin and subcutis: Expanding the dermis and subcutis, elevating the overlying epidermis, and separating adnexa is an unencapsulated, well-demarcated, densely cellular neoplasm composed of round cells (mast cells) arranged in sheets on a moderate preexisting fibrovascular stroma. Neoplastic cells are separated from the overlying epidermis by a narrow zone of dermal collagen devoid of neoplastic cells (Grenz zone). Neoplastic cells have distinct cell borders, a moderate amount of eosinophilic cytoplasm, and a centrally located, round to oval nucleus with coarsely clumped chromatin and 1-2 prominent nucleoli. Anisocytosis and anisokaryosis are marked with frequent karyomegalic and pleomorphic cells and 1 mitotic figure per 2.37 mm². Entrapped collagen fibers are brightly eosinophilic and hyalinized. There are multifocal dense perivascular lymphocytic infiltrates.

MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis: Mast cell tumor, mastocytic type, domestic shorthair, feline.

SYNONYMS: Mastocytoma, cutaneous mastocytosis

GENERAL DISCUSSION:

• Cutaneous mast cell tumor (MCT):
  • Single or multiple nodular dermal proliferations of mast cells
  • Most common in dogs, but occur in other domestic species
    • Dog: 15-20% of skin tumors are MCTs; the most frequent malignant or potentially malignant skin tumor; wide range of biologic behavior; histological grading, staging, growth rate (via proliferation factor assessment), and c-KIT protooncogene mutation status, are used to determine biological behavior
    • Cat: 12-20% of skin tumors are MCTs (second most common); less aggressive, low metastatic potential; those with multiple MCT are often FIV positive; common tumor in the eyelid
    • Horse: Growth is like in other species but are called cutaneous mastocytosis rather than MCT; metastasis unreported
• Subcutaneous MCT:
  • Less common; possibly more favorable outcome (less aggressive), but data lacking and no validated grading system currently

PATHOGENESIS:

• Proto-oncogene c-kit (C117, encodes for tyrosine kinase receptor “KIT protein”) and KIT ligand (mast cell growth factor) involved in MCT tumerogenesis; mutations in KIT or aberrant c-kit expression present in 15-40% of MCT
  • Internal tandem duplications (ITD) in the juxtamembrane domain result in constitutive activation of KIT; the most commonly detected c-KIT mutation is an ITD on exon 11 (45%), exon 8 (33%), and exon 9
  • Canine MCT with an activating point mutation in exon 11 have a poorer prognosis and are associated with higher histologic grades and proliferation markers than those without a c-kit mutation or with an exon 8 mutation
  • Canine MCT with mutations in exon 8 or exon 11 have increased therapeutic success with tyrosine kinase inhibitors
• DNA mismatch repair (MMR) system (including repair proteins MSH2, MSH6, MLH1) is responsible for preserving genomic stability; when dysfunctional (mismatch repair deficiency [dMMR]), it has been linked to multiple neoplasms, including mast cell tumor (Inanaga, Vet Pathol 2021)
• Inflammation and erythema due to mast cell degranulation and release of inflammatory mediators (e.g. histamine, eosinophil/neutrophil chemotactic factors, prostaglandins, serine esterases, and TNF-a)
• Gastroduodenal ulceration occurs secondary to excessive histamine release > local ischemia and stimulation of H2 gastric parietal cells > increase acid secretion; seen in dogs and cats; occurs in 35-83% of cases of dogs with disseminated disease; may lead to severe exsanguination
• Massive synchronous degranulation may also result in hypotensive shock (rare)

TYPICAL CLINICAL FINDINGS:

• Dogs:
  • Average age 9 years old (range 3 weeks to 19 years); Boxer, bulldog, pug, retrievers, terriers, beagles, Shar Pei, and Schnauzers are predisposed; Shar Peis develop lesions at a younger age and are more likely to develop multiple lesions
• Horses:
  • No reports of metastasis
• Cats:
  • Typically, older cats (9-11 years); Siamese cats predisposed

TYPICAL GROSS FINDINGS:

• Dog: Varies widely; 1-4cm irregular, nodular, rubbery to firm, erythematous, variably alopecic mass(es) on the skin, mouth, conjunctiva, and ear; less often found in the inguinal area, perineum, scrotum, prepuce, and digits
  • Poorly differentiated tumors grow rapidly, are less circumscribed, and often associated with inflammation and edema, +/- satellite lesions
  • With metastasis, may see lymphadenomegally, splenomegaly, splenic nodules, hepatomegaly, kidney nodules, epicardial nodules
  • May develop gastroduodenal ulceration with disseminated disease
• Cat: One to several firm, raised, pink, alopecic papules ranging from millimeters to several centimeters on the head, neck, or eyelid; less often may be a poorly defined swollen area
• Horse: Solitary nodule on the head, trunk, neck, or limbs; may be hyperpigmented, alopecic or ulcerated

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Dog
  • Unencapsulated, variably circumscribed dermal to subcutaneous neoplasm composed of diffuse loose sheets or densely packed cords, separating collagen bundles, of well- to poorly-differentiated round cells (mast cells) with distinct cell border, abundant eosinophilic cytoplasm containing variable numbers of gray to blue fine metachromatic granules and central round nucleus; mitotic index and pleomorphism vary
  • Mature eosinophils are often diffusely scattered among neoplastic cells
  • The infiltrative border of the tumor frequently contains cords of neoplastic cells alternating with collagen bundles, even in the solid type
  • Grenz zone is typically present, separating the mast cells from an intact epidermis
  • +/- collagen flame figures: degenerate collagen with deposition of irregular, amorphous, sometimes radiating eosinophilic material with an infiltrate of eosinophils; results from metalloproteinases released from neoplastic cells
  • +/- ulceration, edema, tumor necrosis, eosinophilic or mononuclear leukocytic vasculitis, vascular necrosis, mineralization, mucinous extracellular matrix, collagen degeneration with secondary granulomatous inflammation
• Cat
  • Mastocytic type: Looks similar to a classic mast cell tumor
  • Histiocytic (atypical) type: multiple, simultaneous, or sequential tumors located at the junction of the dermis and subcutis; tumor mast cells resemble histiocytes
  • Feline MCT are often poorly granular or have poorly staining granules that may be detectable with TEM; eosinophils are rare
• Horse 
  • Generally similar to dogs histologically, but with prominent collagen degeneration, large aggregates of eosinophils, necrosis, and focal mineralization

GRADING SYSTEMS

• Dog (cutaneous only; conjunctival MCT correlates well); note that grading is only considered one prognostic factor and should be used in conjunction with clinical picture (age, clinical progression, site, stage, completeness of surgical margins) and other prognostic markers (e.g. proliferation markers, KIT expression, c-KIT mutation)
  • Two-tiered Grading System - more commonly used due to more objectivity in its criteria; grade is low or high grade based mitotic index (7 or greater); karyomegaly (nuclear diameter of at least 10% of neoplastic cells vary by at least 2-fold), and multinucleation (3 or more cells with 3 or more nuclei); mitotic index appears to be a distinct indicator of clinical behavior
    • Low grade: does not possess any of the features of malignancy listed above; MST >2 years; rarely metastasizes
    • High grade: possesses any of the following features: 7+ mitotic figures per 10 consecutive HPF’s, 3+ multinucleated cells with 3+ nuclei, 3+ bizarre nuclei in 10 HPF, karyomegally in at least 10% of the neoplastic cells (variation by at least 2-fold); MST <4 months
  • Three-tiered grading system: Not widely used due to subjectivity and variability in grading; grade I, II, or III based on the extent of tissue involvement, cellularity, nuclear/cellular morphology, granularity, mitoses, and stromal reaction (hyalinization, necrosis, and hemorrhage)
    • Grade I: well differentiated cells, confined to dermis, no mitoses or necrosis; excellent long-term prognosis
    • Grade II: moderately to highly cellular, extends into lower dermis or subcutis, 0-2 mitotic figures per HPF, stromal reaction present; difficult to predict behavior (majority benign, but around 20% are aggressive); discordance on prognostication
    • Grade III: poorly differentiated, densely cellular, pleomorphic cells with vesicular nuclei and prominent nucleoli, 3-6 mitotic figures per HPF, subcutaneous involvement, stromal reaction present; guarded to poor prognosis (high recurrence and metastatic rate)
  • Grading systems can be combined, creating 4 categories with different prognoses (the recommended method per OPWG Canine Cutaneous Mast Cell Tumor Subgroup on Grading, Berlato et al, Vet Pathol 2021)
    • Grade I/low grade: excellent prognosis with no MCT related deaths and low risk of lymph node (6%) and distant (2%) metastasis
    • Grade I/low grade: good prognosis with 3-17% rate of MCT related deaths and moderate risk of lymph node (16%) and distant (2%) metastasis; MST >96 months
    • Grade II/high grade: fair to guarded prognosis with 14-56% of MCT related deaths and moderate risk of lymph node (15%) and distant (2%) metastasis: MST 7.5-23.3 months
    • Grade III/high grade: guarded to poor prognosis with 67-75% MCT related deaths and high risk of lymph node (46%) and distant (21%) metastasis; MST 3.6-6.8 months
  • Sterology is highly accurate and can be used to help remove inter- and intraobserver variability when assessing nuclear pleomorphism (Casanova, Vet Pathol 2021)
• Cat
  • No widely accepted grading system due to the need to validate on various feline MCT subtypes
• Metastasis
  • Touldine blue is particularly helpful in highlighting lymph node metastasis, but it must be kept in mind that lymph nodes will normally have low numbers of mast cells present in them and not all lymph nodes with metastasis will be grossly enlarged (Sabattini, Vet Pathol 2022)
  • Bisecting a lymph node at the hilum (directly in the middle) is reliable for detection of metastasis, although additional step-sections will increase accuracy (Sabattini, Vet Pathol 2022)

ULTRASTRUCTURAL FINDINGS:

• Resemble normal mast cells
• Cytoplasm contains many membrane-bound granules, which appear as single or fused vesicles that lack microvilli; fine fibrillar material forms a loose network within these vesicles

ADDITIONAL DIAGNOSTIC TESTS:

• Cytology:
  • Highly cellular samples with individualized, round cells with variable numbers of purple cytoplasmic granules (may not stain well with Diff-Quik; stain well with May-Grunwald-Giemsa or Wright’s stain, but may cause granules to obscure the nuclear features); the background often contains granules from ruptured cells or degranulation, variable numbers of eosinophils (sometimes out-numbering the mast cells; greater in dogs than cats), fibroblasts (reactive fibroplasia), collagen strands (collagenolysis)
  • Degranulation may be associated with hemorrhage, vascular necrosis, edema, and collagenolysis
  • Anaplastic (poorly differentiated) mast cells may be devoid of granules because the cells have not differentiated sufficiently to produce them
  • Cytological features indicative of a poorly differentiated, high-grade tumor include binucleation, multinucleation, mitotic figures, anisocytosis, and anisokaryosis
  • Using stereologic tools (2D-nucleator method) or morphometry (image analysis) can assist with prognostication (i.e. assessing nuclear areas) and are highly accurate (Marcos, J Vet Diagn Invest 2022)
• Histochemistry to highlight metachromatic granules (absence of granules does not exclude a MCT): Giemsa, toluidine blue
• Electron microscopy: can confirm presence of mast cell granules that are otherwise unable to be visualized with histochemistry (e.g. feline MCT’s)
• Immunohistochemistry for mast cells (neoplastic or normal):
  • c-KIT (CD117) positive (most commonly used)
    • Note that c-KIT is also expressed on some hematopoietic stem cells, gastrointestinal interstitial cells of Cajal, melanocytes, and others
  • Carboxypeptidase A3 (CPA3) positive and similar staining patters as with c-KIT (Hamalainen, Vet Pathol 2022)
  • Trypase or chymase positive (Hamalainen, Vet Pathol 2022): Enzymes within mast cell granules that can be used to identify mast cells and their subpopulations; connective tissue mast cells (the primary type in the body) contain both; [gastrointestinal] mucosal mast cells only contain tryptase
• Prognostic tests:
  • Ki-67, AgNOR (agryrophilic nuclear organizing region), proliferating cell nuclear antigen (PCNA), mitotic count: high proliferation indices are associated with a worse prognosis and shorter MST; higher Ki-67 is associated with MCT size and age of the patient (Firsching, J Comp Pathol, 2022); mitotic count is most accurate when using computer assisted algorithms (Bertram, Vet Pathol, 2022)
  • c-KIT (CD117) PCR: mutations in c-KIT have a worse prognosis (especially exon 11)
  • Kit staining pattern and protein location: pattern I – perimembrane, pattern II – focal or stippled cytoplasmic staining, pattern III – diffuse cytoplasmic staining; increased cytoplasmic staining indicates a poorer prognosis due to increase recurrence and shorter MST
  • Beclin-1 immunohistochemistry: Beclin-1 is an autophagy protein; while not prognostic, it is predictive for MST after adjunctive treatment; dogs with high beclin-1 expression had shorter survival times (Knight, Vet Pathol 2022)
• Hematology
  • Mast cells are normally not found in the blood, mastocytemia may be reactive (nonneoplastic) or neoplastic; when neoplastic, it is usually associated with solid tissue mast cell tumors

DIFFERENTIAL DIAGNOSIS:

• Accumulations of mast cells
  • Abundant mast cells may be seen with parasitic, mycotic, allergic, and idiopathic inflammatory syndromes, but these will not have sheets of mast cells
  • Urticaria pigmentosa: diffuse, dermal and subcutaneous infiltrates of well differentiated mast cells over large areas of the body in cats, dogs, and foals
  • Mast cell hyperplasia: Multiple, spontaneously regressing aggregates of mast cells in young dogs, cats, pigs, calves, and foals
• High eosinophils, low mast cells: insect bite hypersensitivity
• Other round cell neoplasms (for poorly granular mast cell tumors):
  • Lymphoma
  • Plasmacytoma
  • Histiocytoma
  • Transmissible venereal tumor
• Horse (for eosinophilic/mastocytic inflammation): Can differentiate from these by morphological presence of sheets of mast cells
  • Cutaneous habronemiasis
  • Cutaneous onchocerciasis
  • Eosinophilic granuloma
• Dogs and cats (more common) can also develop systemic and visceral mastocytosis
• Peripheral blood smears, bone marrow aspirates, and aspirates of any enlarged lymph nodes or abdominal organs (particularly liver and spleen) can be useful in detecting systemic spread of the mast cell tumor

COMPARATIVE PATHOLOGY:

• Mast cell tumors occur throughout the alimentary tract (D-N04)
• Ferrets: Similar in morphology and behavior to well-differentiated feline MCTs
• Cattle: Rare primary cutaneous tumors (more common to have visceral MCT that metastasizes to the skin); usually multiple cutaneous masses with associated with visceral mast cell aggregates; morphologically similar to dog well-differentiated tumors; congenital cutaneous MCT has been reported with well-circumscribed 1-7cm nodules all over the body; report of a calf with congenital diffuse cutaneous mastocytosis.
• Swine: Mast cell nodules have been described as tumors and as inflammatory aggregates, perhaps in response to Eperythrozoon; may be single or multiple masses with similar morphology to well-differentiated feline MCTs; visceral mast cell aggregates found in animals with multiple cutaneous masses; metastasis rare; intracytoplasmic granules often faint and need toluidine blue to visualize; KIT is a promising diagnostic marker (Rasche, J Vet Diagn Invest, 2022)
• Reptiles: MCT has been rarely reported in lizards, turtles, and snakes
• Non-human primate: MCT has been rarely reported
• Avian: Reported in chickens, owls, and rarely psittacines; special stains may be needed to highlight the granules
  • Systemic mastocytosis reported in a lovebird; reported in chickens and owls; rarely in psittacines
• Malayan Tiger: developed cutaneous and splenic mastocytosis at 1 week old; started as well-circumscribed, erythematous lesions on the face, torso, and paws which either regressed (face, torso) by 1 year old or developed into pendulous masses up to 6.5cm (paws) which were removed without recurrence; somatic mutation in exon 8 of c-KIT (Smedley, J Vet Diagn Invest, 2022)
• Goats: sheets of large round cells with finely vacuolated cytoplasm that lacks visible granules with frequent interspersed eosinophils; often no granules visible with metachromatic stains, but will be positive for CD117 immunolabeling (O’Neill, Vet Pathol 2021)
• Seals: Poorly granulated CMCT are suspected to behave benign; majority of tumors found occurred near mucocutaneous junctions (eyelid, lip, or anus). (Miller, Vet Pathol 2025)
• Puerto Rican crested toads: Most common neoplasm reported is mast cell tumor (Imanse, Vet Pathol, 2024)
• Hedgehog: Reported subcutaneous mast cell tumor
• Llama: Mast cell tumor reported
• Bats: One case reported, aggressive; may be malignant in these species. (Terrade, JVDI, 2025)
• Mice: Mice normally have mast cells in the spleen.

REFERENCES:

1. Aceino A, Jeffery U, Piccione J, Hodo CL. Systemic mastocytosis with subcutaneous hemorrhage and edema in a Greyhound dog: case report and review of diagnostic criteria. J Vet Diagn Invest. 2021;33(1):95-100.
2. Agnew D. Camelidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:193.
3. Avallone G, Rasotto R, Chambers JK, et al. Review of histological grading systems in veterinary medicine. Vet Pathol. 2021;58(5):809-828.
4. Aupperle-Lellbach H, Grassinger JM, Floren A, et al. Tumour Incidence in Dogs in Germany: a Retrospective Analysis of 109,616 Histopathological Diagnoses (2014-2019). J Comp Pathol. 2022;198:33-55
5. Barnes HJ, Fletcher OJ. Chapter 1: Hemic System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016:10.
6. Berlato D, Bulman-Fleming J, Clifford CA, et al. Value, limitations, and recommendations for grading canine cutaneous mast cell tumors: A consensus of the oncology-pathology working group. Vet Pathol. 2021;58(5):858-863.
7. Bertola L, Pellizzoni B, Giudice C, et al. Tumor-associated macrophages and tumor-infiltrating lymphocytes in canine cutaneous and subcutaneous mast cell tumors. Vet Pathol. 2024;61(6):882-895.
8. Bertram CA, Aubreville M, Donovan TA. Computer-assisted mitotic count using a deep learning-based algorithm improves interoserver reproducibility and accuracy. Vet Pathol. 2022;59(2):211-226.
9. Brannick EM, Newkirk KM, Schaefer DMW. Neoplasia and Tumor Biology. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:374, 383.
10. Brocks BA, Bertram CA, Bartel A, et al. Internal tandem duplication of exon 8 of c-KIT is associated with longer total survival in canine cutaneous mast cells tumors. Vet Pathol. 2021;58(2):315-324.
11. Casanova M, Branco S, Veiga IB, et al. Stereology in grading and prognosis of canine cutaneous mast cell tumors. Vet Pathol. 2021;58(3):483-490.
12. Catarino J, Macara A, Barros A, et al. Stereological estimation of mean nuclear volume as a prognostic factor in canine subcutaneous mast cell tumors. Vet Pathol. 2025;62(3):284-292.
13. Davidson GA, Smith SH, Dobromylskyj MJ. Differentiation of feline cutaneous round cell tumours using immunohistochemistry. J Comp Pathol. 2025;219:41-47. 
14. Durham AC, Boes KM. Bone marrow, blood cells, and lymphoid/lymphatic system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:840-841.
15. Firsching TC, Dietert K, Bartel A, et al. Dependence of the Ki67 labeling index of selected canine tumors on patient age, sex and tumour size. J Comp Pathol. 2022;193:1-8.
16. Fragoso-Garcia M, Wilm F, Bertram CA, et al. Automated diagnosis of 7 canine skin tumors using machine learning on H&E-stained whole slide images. Vet Pathol. 2023;60(6):865-875.
17. Hamalainen S, Kareinen L, Sukura A, et al. Carboxypeptidase A3 expression in canine mast cell tumors and tissue-resident mast cells. Vet Pathol. 2022;59(2):236-243.
18. Imanse SM, Burrell CE, Cannizzo SA, Reilly TS, Rainwater KL, Delaney MA. Neoplasia in an assurance population of Puerto Rican crested toads (Peltophryne lemur). Vet Pathol. 2024;61(3):482-487.
19. Inanaga S, Igase M, Sakai Y, et al. Mismatch repair deficiency in canine neoplasms. Vet Pathol. 2021;58(6):1058-1063.
20. Jacocks K, Hoepp N, DeNicola DB. Round cells. In: Valenciano AC, Cowell RL, eds. Cowell and Tyler’s Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St Louis, MO: Elsevier; 2020: 65-67.
21. Knight BJ, Wood GA, Foster RA, et al. Beclin-1 is a novel predictive biomarker for canine cutaneous and subcutaneous mast cells tumors. Vet Pathol. 2022;59(1):46-56.
22. Kramer JA, Bielitzki J. Integumentary system diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, et al, eds. Nonhuman Primates in Biomedical Research. Vol 2. 2nd ed. San Diego, CA: Academic Press; 2012:580.
23. Labelle P. The eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1411.
24. Larsen E, Watson AM, Muñoz Gutiérrez JF. Intranasal mast cell tumors: Clinical, immunohistochemical, and molecular features in 20 dogs. Vet Pathol. 2022;59(6):915-921.
25. Marcos R, Almeida J, Marques J, et al. Canine mast cell tumors: utility of stereologic tools in cytology. J Vet Diagn Invest. 2022;34(2):263-276.
26. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Saunders Elsevier; 2016: 519, 730-732.
27. Meinkoth JH, Cowell RL, Tyler RD. Cell types and criteria for malignancy. In: Valenciano AC, Cowell RL, eds. Cowell and Tyler’s Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St Louis, MO: Elsevier; 2020:25-26.
28. Miller AD. Neoplasia and proliferative disorders of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, et al, eds. Nonhuman Primates in Biomedical Research. Vol 2. 2nd ed. San Diego, CA: Academic Press; 2012: 341.
29. Miller BM, Stacy NI, Iredale M, et al. Cutaneous mast cell tumors in California sea lions (Zalophus californianus). Vet Pathol. Published online September 20, 2025.
30. Njaa BL. The ear. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1362.
31. O’Neill TW, Lohr CV. Mast cell tumors and histiocytomas in domestic goats and diagnostic utility of CD117/c-KIT and IBA1 immunohistochemistry. Vet Pathol. 2021;58(3):508-515.
32. Ossiboff RJ. Serpentes. In: Terio, KA, McAloose, D, St. Leger, J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press Elsevier; 2018:905.
33. Puget C, Ganz J, Ostermaier J, et al. Artificial intelligence can be trained to predict c-KIT-11 mutational status of canine mast cell tumors from hematoxylin and eosin-stained histological slides. Vet Pathol. 2025;62(2):152-160.
34. Rasche BL, Mozzachio K, Linder KE. Cutaneous mast cell tumors in 11 miniature pigs: a retrospective study. J Vet Diagn Invest. 2022;34(3):523-527.
35. Raskin RE, Conrado FO. Integumentary system. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023: 102-108.
36. Ribeiro PR, Branchi MV, Bandinelli MB, et al. Pathologic aspects of cutaneous mast cell tumors with metastasis in 49 dogs. Vet Pathol. 2022; 59(6):922-930.
37. Rodriguez CE, Duque AMH, Steinberg J, et al. Chelonia. In: Terio, KA, McAloose, D, St. Leger, J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press Elsevier; 2018:837.
38. Sabattini S, Brocanelli A, Zaccone R, et al. The 2-tier grading system identifies canine cutaneous and/or subcutaneous mast cell tumors with aggressive biological behavior regardless of growth model. Vet Pathol. 2024;61(6):874-881
39. Sabattini S, Faroni E, Renzi A, et al. Longitudinal lymph node step-sectioning for the identification of metastatic disease in canine mast cell tumor. Vet Pathol. 2022;59(5):768-772.
40. Schmidt RE, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: Wiley and Sons, Inc; 2015: 143, 256, 259-260.
41. Schlein LJ, Thamm DH. Immunohistochemical evidence of NF-kB activation in canine lymphomas, histiocytic sarcomas, hemangiosarcomas, and mast cell tumors. Vet Pathol. 2024;61(1):20-31.
42. Spagnoli ST, Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:436.
43. Smedley RC, Stedman NL, Kiupel M. Cutaneous and splenic mastocytosis in a juvenile Malayan tiger. J Vet Diagn Invest. 2022;34(2):288-291.
44. Stacy NI, Hollinger C. Introduction to Comparative Clinical Pathology. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:109.
45. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Ames, IA: Blackwell Publishing; 2008:351.
46. Terrade G, Muller V, Berthévas G, Huet H, Reyes-Gomez E. Subcutaneous mast cell tumor with nodal metastasis in a serotine bat. J Vet Diagn Invest. 2025;37(4):630-634
47. Welle MM, Linder KE. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1214.
48. Wilcock BP, Njaa. Special senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Saunders Elsevier; 2016:482.
49. Williams BH, Burek-Huntington KA, Miller M. Mustelids. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:294.
50. Zamarian V, Stefanello D, Ferrari R, et al. Salivary miR-21 is a potential biomarker for canine mast cell tumors. Vet Pathol. 2023;60(1):47-51.

Click the slide to view.

---