• Mast cell tumors (MCTs) are a common and significant form of skin cancer in dogs. Their behavior can range from benign to highly aggressive, and therefore, effective treatment depends on accurate diagnosis, staging, and prognosis assessment. 

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Etiology

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• Genetic Factors:

  • Certain breeds are genetically predisposed to developing MCTs, including:

    • Boxers, Bulldogs, Boston Terriers, Shih Tzus, Pugs, and Shar Peis.

    • These breeds may have inherited genetic mutations that predispose them to mast cell proliferation.

  • c-kit Mutations: Mutations in the c-kit proto-oncogene, which encodes a receptor involved in mast cell development, have been implicated in MCT pathogenesis. Mutations often affect tumor behavior, as they lead to altered mast cell function and survival, influencing prognosis and treatment response.

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• Environmental Factors:

  • Chronic inflammation or trauma to the skin may contribute to the development of MCTs, but this is still under investigation. It is suggested that physical irritants, like insect bites or persistent skin infections, could act as promoting factors.

  • Exposure to toxic substances or carcinogens is theorized to play a role, but this connection remains largely unproven.

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Clinical Signs

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• Location: MCTs are most commonly found on the skin, but can also develop in other tissues such as the spleen, liver, bone marrow, and gastrointestinal tract.

  • They often present as solitary or multiple nodules on the skin, but they can occasionally affect internal organs, making them more challenging to diagnose early.

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• Skin Lesions:

  • Tumors appear as firm, raised masses that are typically pink, red, or tan in color. Some MCTs may ulcerate or become necrotic, which can lead to further complications like infection.

  • MCTs may be pruritic (itchy), and some dogs will repeatedly scratch, lick, or bite the tumor site.

  • The tumors can vary in size from small, well-circumscribed masses to larger, infiltrative lesions.

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• Systemic Signs (due to degranulation):

  • Histamine release from mast cells can lead to clinical signs of allergic reactions, such as:

    • Gastrointestinal signs: Vomiting, diarrhea, or melena (due to histamine-induced ulceration of the gastrointestinal tract).

    • Anaphylaxis: Severe allergic reactions like hypotension, tachycardia, shock, and respiratory distress may occur when tumors degranulate. This is a medical emergency and may be life-threatening.

  • Systemic Symptoms:

    • Lethargy, anorexia, and weight loss are common, particularly in cases with internal organ involvement or metastatic disease.

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Diagnosis

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• Cytology (Fine Needle Aspiration - FNA):

  • First-line diagnostic tool: Cytology is used to identify mast cells in aspirates from the mass. Mast cells typically appear as round cells with large cytoplasmic granules. The nucleus may appear centrally located and round or slightly indented.

  • Challenges: Other cell types like histiocytes or lymphocytes may be present, so distinguishing them from MCTs is crucial.

  • FNA may sometimes fail to provide sufficient information, especially if the tumor is poorly differentiated or if a significant inflammatory response is present.

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• Histopathology:

  • A more detailed evaluation of the tissue is performed to grade the tumor and assess its mitotic index (MI). This provides essential prognostic information.

  • Patnaik grading system (I–III) is commonly used:

    • Grade I: Well-differentiated, low metastatic potential.

    • Grade II: Intermediate differentiation, variable behavior.

    • Grade III: Poorly differentiated, high metastatic potential.

  • Mitotic Index (MI): The number of mitoses observed per high-power field is a significant prognostic indicator. Tumors with a higher MI (≥7) are more likely to be aggressive and have a worse prognosis.

  • Two-tier grading system has been proposed as a simplified method, classifying tumors into high-grade (MI ≥7) and low-grade (MI <7) categories to reduce subjectivity in grading.

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• Staging: Staging is critical for assessing the extent of the disease, which informs treatment decisions and prognosis.

  • Clinical Staging:

    • Primary Tumor: Assess the size and location for surgical planning. Complete excision with wide margins (2-3 cm) is preferred for low-grade tumors.

    • Lymph Node (LN) Aspiration:

    • Cytology of Regional Lymph Nodes: Fine needle aspiration (FNA) of prescapular, inguinal, popliteal, and other regional nodes is performed to check for metastasis, even if the nodes are of normal size.

    • Sensitivity of LN Palpation: Normal-sized lymph nodes can still harbor metastatic mast cells, so palpation alone is not enough to rule out metastasis.

  • Imaging:

    • Abdominal Ultrasound: Performed to check for metastasis to the liver and spleen. Mast cells may naturally be present in these organs, but increased mast cell numbers or atypical morphology suggest metastasis. Cytology (FNA) is essential to confirm metastasis.

    • Sublumbar LNs: If the tumor is located on the back half of the body, sublumbar lymph nodes should be evaluated with ultrasound and cytology.

    • Thoracic Radiographs: Typically used to assess the sternal lymph nodes for MCTs in the ventral abdomen, though pulmonary metastasis is rare.

    • Bone Marrow Aspiration: Only necessary in cases with suspected systemic disease or high-grade tumors.

  • Staging System:

    • Stage I: Localized tumor with no regional LN involvement or distant metastasis.

    • Stage II: Regional LN involvement but no distant metastasis.

    • Stage III: Distant metastasis to organs like the liver, spleen, or bone marrow.

Treatment

• Surgical Excision:

  • Wide excision with clean margins is the cornerstone of treatment for most localized MCTs. Tumors that are excised with negative margins typically have a high chance of curative surgery.

  • Recurrent tumors or those with positive surgical margins may require additional treatments, such as radiation or chemotherapy.

• Radiation Therapy:

  • Used in cases with positive surgical margins, non-resectable tumors, or high-grade MCTs.

  • Adjuvant therapy: Can also be employed after surgery if there is concern about residual disease.

• Chemotherapy:

  • Vinblastine and lomustine (CCNU) are commonly used for high-grade or metastatic MCTs.

  • Steroids (prednisone): Used to manage symptoms (e.g., gastrointestinal distress) and reduce the risk of mast cell degranulation.

  • Tyrosine Kinase Inhibitors (TKIs):

    • Toceranib (Palladia): A selective c-kit receptor inhibitor, used for high-grade or chemoresistant MCTs.

    • Masitinib: Another TKI with similar indications for advanced or metastatic MCTs.

• Supportive Care:

  • Medications to manage histamine release, including H1 and H2 blockers (antihistamines and antacids), can help control symptoms like vomiting, diarrhea, and gastric ulcers caused by mast cell degranulation.

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Prognosis

• Grade I (Low-grade):

  • Generally have an excellent prognosis with surgical excision. Median survival time (MST) can exceed 3 years, especially with complete surgical removal.

• Grade II (Intermediate-grade):

  • Variable prognosis. If surgically excised with wide margins, many dogs can be cured. However, some grade II tumors may recur or metastasize.

  • MST varies based on factors such as mitotic index (MI ≥7 indicates poorer prognosis).

• Grade III (High-grade):

  • Poorer prognosis. These tumors are more likely to metastasize and often require aggressive treatment (surgery, radiation, chemotherapy).

  • MST is typically <1 year, but some dogs can survive longer with appropriate therapy.

• Metastatic Disease:

  • If there is lymph node or internal organ involvement, the prognosis worsens, but dogs can still have extended survival with local and systemic therapy (e.g., surgery + chemotherapy or radiation).

• Anaphylaxis or Histamine Release:

  • Acute reactions to mast cell degranulation (e.g., shock, anaphylaxis) can be life-threatening and should be managed immediately with stabilization, antihistamines, and corticosteroids.

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