section name header

Basics ⬇

Basics

Definition

  • Malignant round cells derived of hematopoietic origin containing granules packed with many vasoactive substances including histamine, heparin, serotonin, dopamine, tryptase, and chymase.
  • Most common malignant skin tumor in the dog, representing approximately 7–21% of all canine skin tumors.
  • Second most common malignant skin tumor in the cat, representing approximately 20% of all feline skin tumors.
  • Tumors may affect dermis, subcutis, spleen, liver, and intestines.

Pathophysiology

  • Histamine release from MCTs affects a multitude of tissues.
  • Histamine (H2) receptors are primarily located within the stomach and histamine is thought to be one of the most significant stimulants of gastric acid secretion.
  • In extreme cases, perforation of the gastrointestinal tract may occur, leading to peritonitis.
  • Histamine release around a tumor leads to the production of wheals, hives, and erythema.
  • Local release of heparin is also common, resulting in bleeding and subsequent bruising, which can be seen around the tumor.

Systems Affected

  • Skin-MCTs are the most common malignant cutaneous tumor of the dog.
  • Gastrointestinal-on necropsy evaluation, 35–83% of dogs with MCTs have evidence of gastrointestinal ulceration.
  • Hemic/Lymph/Immune-lymph node metastasis is common in high-grade tumors. Bone marrow metastasis is rare but can occur.
  • Hepatobiliary-the liver and spleen are common distant sites of metastasis for high-grade MCTs.

Genetics

The specific breed predilections indicate that a genetic predisposition exists.

Incidence/Prevalence

  • Most common malignant skin tumor in the dog, representing approximately 7–21% of all canine skin tumors.
  • Primary visceral and intestinal MCTs are rare in the dog.
  • Second most common skin tumor in the cat, accounting for 20% of cutaneous tumors.
  • Most common splenic tumors of cats, comprising half of the MCTs diagnosed in cats.

Signalment

Species

Dog and cat

Breed Predilections

  • Dogs-brachycephalic breeds, as well as golden retriever, Labrador, Rhodesian ridgeback, beagle, Staffordshire terrier, Weimaraner, Shar-Pei, and Australian cattle dog.
  • Cats-Siamese.

Mean Age and Range

  • Dogs-middle-aged, range 4 months-18 years.
  • Cats-middle-aged (8–9 years for cutaneous mastocytic types) and older cats (intestinal and splenic); however, the histiocytic form of cutaneous MCTs affects young cats with a mean age of 2.4 years.

Predominant Sex

  • Dogs-no predilection
  • Cats-male Siamese

Signs

Dogs

  • Mass is found in the subcutis or on the skin and may also be present within lipomas.
  • Regional edema or a Darier's sign may be seen in the region around a tumor that has degranulated.
  • Lymphadenopathy of regional lymph nodes may be seen in dogs with metastatic disease.
  • History of intermittent progression and regression in size.
  • Systemic illness with advanced local or systemic disease; vomiting, anorexia, weight loss, and melena.

Cats

  • Visceral disease manifests as chronic weight loss, anorexia, diarrhea, and lethargy.
  • Focal mass lesion may be palpated with primary intestinal MCT.

Causes

  • Up to 30% of canine MCTs have been shown to contain a mutation in the c-kit oncogene, leading to constitutively activated receptor and unchecked cell division.
  • Up to 56% of feline MCTs have a c-kit mutation, though these mutations do not appear to have any bearing on prognosis nor on protein expression.

Risk Factors

See above under “Breed Predilections” and “Causes”

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Cutaneous forms-adenexal tumors, basal cell tumors, histiocytoma, lipoma, and soft tissue sarcoma.
  • Visceral forms-lymphoma, histiocytic tumors, malignant fibrous histiocytomas, multiple myeloma, hemangiosarcoma, hemangioma, and erythroid myeloid hyperplasia.
  • Intestinal forms-lymphoma, adenocarcinoma, leiomyoma, leiomyosarcoma, gastrointestinal stromal tumors, and fungal infections.

CBC/Biochemistry/Urinalysis

  • Anemia (regenerative secondary to gastrointestinal blood loss).
  • Eosinophilia, mastocytosis, and thrombocytopenia.
  • Identification of circulating mast cells is more common in the cat with visceral MCT than the dog.
  • Increased BUN secondary to gastrointestinal bleeding and increased liver values secondary to metastasis.

Other Laboratory Tests

  • Regional lymph node aspiration and cytology
  • Liver and splenic aspiration and cytology
  • Mast cell tumor prognostic panel
  • C-kit PCR and immunohistochemistry staining

Imaging

  • Thoracic radiographs-intrathoracic or sternal lymph node metastasis
  • Abdominal ultrasound-viscera assessment with emphasis on liver, spleen, and mesenteric lymph nodes

Diagnostic Procedures

  • Fine-needle aspirate and cytology for definitive diagnosis.
  • Biopsy (incisional or excisional) for definitive diagnosis and histologic grading.

Pathologic Findings

  • Dogs-Patnaik grading scale:
    • Grade I (low-grade) tumors have a mostly benign behavior and represent ∼36%.
    • Grade II (intermediate-grade) MCTs are the most common form and represent ∼43%.
    • Grade III (high-grade) MCTs are the most aggressive form, are metastatic, and represent ∼20%.
  • Cats-Histologic forms of cutaneous MCTs:
    • Mastocytic form-single tumor and is the most common (compact or diffuse). There are two histologic varieties of mastocytic MCTs in the cat, compact and diffuse: compact-more benign behavior; diffuse-more undifferentiated and aggressive.
    • Histiocytic form-multiple lesions on the head and neck with relatively benign behavior.

Treatment ⬆ ⬇

Treatment

Activity

Limit for animals with heavy tumor burdens (such as cats with visceral MCTs or dogs with large tumors) until the mass has been treated appropriately.

Diet

N/A

Client Education

Owners of dogs with MCTs should be informed that 14–17% of dogs will develop additional MCTs. All new masses should be evaluated by a veterinarian.

Surgical Considerations

  • Conventional recommendations (dogs)-2–3 cm margins and one fascial plane deep, maybe unnecessary with grade II MCTs in dogs as majority (70%) of “dirty” margins fail to locally regrow.
  • Narrow margins (cats)-majority of tumors will not regrow following narrow surgical margins.
  • Splenectomy (cats)-recommended in cats with massive visceral tumor burden despite the presence of metastases.

Radiation Therapy

  • For incompletely excised mast cell tumors in locations that are not amenable to surgical re-excision or in cases where another surgery is not possible (dogs).
  • Can be used in a gross disease setting, but severe systemic reactions (including death) are possible.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Dogs

  • Vinblastine (2.0 mg/m2 IV q7 days × 4, then q14 days × 4) and prednisone (1 mg/kg PO q24h).
  • Vinblastine only (3.5 mg/m2 IV q14 days).
  • Lomustine (50–70 mg/m2 PO q 21 days).
  • Torcerinib (2.75 mg/kg PO MWF).
  • Masitinib (12.5 mg/kg PO q24h).

Cats

  • Lomustine (32–60 mg/m2 PO q4–6 weeks).
  • Vinblastine (2 mg/m2 IV q7 days × 4, then q14 days × 4) and prednisone (1 mg/kg PO q24h).

Contraindications and Precautions

  • Vinblastine-use with caution in animals with liver disease; drug is also myelosuppressive and possesses vesicant properties.
  • Lomustine is hepatotoxic and should be avoided in dogs with underlying liver disease; drug is extremely myelosuppressive and associated with refractory thrombocytopenia. Administer with Denamarin.
  • Torcerinib and masitinib can cause gastrointestinal ulcers, myelosuppression, muscle pain, hypertension, proteinuria and gastrointestinal upset.

Possible Interactions

  • Torcerinib and masitinib should be used with caution with other drugs that induce gastric ulcers such as prednisone or NSAIDs, or in patients with gastric ulceration secondary to mast cell tumor.
  • Lomustine should be used with caution with other hepatotoxic drugs such as NSAIDs.

Alternative Drug(s)

Symptomatic treatment-benadryl, prednisone, famotidine or other H2 inhibitors, omeprazole, and sucralfate should be considered for any dog or cat with gross mast cell disease.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

Dogs

  • Grade I or II-complete surgical resection should be curative in the majority of patients.
  • Grade II (high)-complete surgical resection evaluated every 3 months for 1 year with physical examination, abdominal ultrasound, and lymph node assessment.
  • High-grade tumors (grade III or those in a location associated with a negative prognosis)-physical examination, blood work, and abdominal ultrasound every 3 months for 1 year and then every 6 months for an additional 2 years.

Cats

Visceral or intestinal-abdominal ultrasound every 3 months for 1 year.

Prevention/Avoidance

N/A

Possible Complications

Chemotherapy-related myelotoxicity or hepatotoxicity

Expected Course and Prognosis

  • Complete excision of low-grade mast cell tumors in most locations is curative.
  • Complete excision of high-grade mast cell tumors or those located in areas associated with a poor prognosis (mucocutaneous junctions, ± inguinal regions) often require adjuvant therapy with chemotherapy. Median survival times average approximately 11–12 months.
  • Incomplete excision of a low-grade mast cell tumor may require additional local therapy with another surgery (often cured) or radiation therapy (93% disease-free at 3 years).
  • Incomplete excision of a high-grade mast cell tumor requires additional local therapy in addition to systemic chemotherapy. Median survival times range from 6 to 12 months.
  • Regional metastasis to a lymph node should be treated with surgical excision at the time of the primary tumor removal. Systemic chemotherapy is necessary. Median survival times are typically less than 9 months.
  • Evidence of distant metastasis is often treated with systemic chemotherapy or ancillary therapies alone with a median survival of 4 months or less.

Miscellaneous ⬆

Miscellaneous

Associated Conditions

Progressive and metastatic disease has the potential to cause excessive parietal cell production of hydrochloric acid with associated gastric ulceration, melena, and iron-deficiency anemia and gastric perforation.

Age-Related Factors

N/A

Zoonotic Potential

N/A

Pregnancy/Fertility/Breeding

While on chemotherapy dogs should not be bred. There are no long-term studies regarding fertility in dogs or cats previously treated with lomustine, vinblastine, or RTKIs.

Synonyms

  • Mastocytoma
  • Systemic mastocytosis

Abbreviations

  • MCT = mast cell tumor
  • NSAID = nonsteroidal anti-inflammatory drug
  • RTK = receptor tyrosine kinase
  • RTKI = receptor tyrosine kinase inhibitor

Client Education Handout Available Online

Suggested Reading

London CA, Kisseberth WC, Galli SJ, et al. Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumours. J Comp Pathol 1996, 115(4):399–414.

London CA, Seguin B. MCTs in the dog. Vet Clin North Am Small Anim Pract 2003, 33(3):473–489, v.

Ogilvie GK, Moore AS, eds. Feline Oncology. Yardley, PA: Veterinary Learning Systems, 2001.

Wilcock BP, Yager JA, Zink MC. The morphology and behavior of feline cutaneous mastocytomas. Vet Pathol 1986, 23(3):320–324.

Withrow SJ, Vail DM, eds. Small Animal Clinical Oncology, 5th ed. Philadelphia: Saunders, 2013.