Canine Mast Cell Tumors (MCTs)

Canine MCTs

• Mast cells are the cell of origin for canine MCTs.
• Mast cell function includes wound healing and induction of innate immune response
• Mast cell function involves antiparasite activity, and modulation of the reaction to insect and spider venoms
• Mast cells contain granules, including heparin, histamine, eosinophil chemotactic factor, and proteases (chymase, tryptase).
• Heparin in mast cells functions as an anticoagulant but causes bleeding when aspirated.

Canine MCTs: Typical Presentation

• MCTs typically present as a cutaneous mass exhibiting a variety of clinical appearances, from slow-growing and non-ulcerated to rapidly growing, large, and ulcerated masses.
• The size of MCTs may wax and wane due to histamine release, causing inflammation and swelling
• Ulceration, erythema, and pruritus may be present
• Masses will bleed or enlarge when aspirated due to histamine or heparin release (degranulation):
• MCTs can occur in any breed, but are common in Bulldog descent, Labs, Goldens, Cockers, Schnauzers, Pits, Beagles, and Shar-Peis, which are brachycephalic breeds
• 10-15% of MCTs are present as multiple cutaneous lesions
• MCTs can occur in the conjunctiva, nasopharynx, larynx, or oral cavity
• They can also occur in visceral or disseminated form

Canine MCTs: Testing

• Fine needle aspiration (FNA) of a mass is usually diagnostic and shows many purple (metachromatic) granules, but granules may be poorly granulated or may not show up well with Diff-Quik
• Granules contain histamine and can be released (degranulation)
• CBC/Chem/UA does not usually pick up cancer
• There may be no significant changes, but May see eosinophilia
• The cells of less granules are more aggressive
• Abdominal ultrasounds may reveal hepatomegaly or splenomegaly.
• Enlarged lumbar lymph nodes can be apparent for MCT of the hind limbs.
• Thoracic radiographs could show rare pulmonary parenchymal involvement or enlarged sternal lymph nodes.

Canine MCTs: Lymph Node Evaluation

• Evaluating regional lymph Nodes is important
• Mast cells are normally found in lymph nodes, so definitive criteria for metastatic disease can be challenging if mast cells are present in low numbers, additionally their numbers can be increased in the presence of infection and ulceration
• Occasional, solitary mast cells may be present but are not indicative of metastasis
• Clustering, aggregates, and abnormal morphology are more cause for concern
• Poorly granulated cells indicate that metastasis is likely, nodes may need to be removed for histologic confirmation
• The Weishaar Nodal Classification System aids in determining if it's a true metastasis, using HN0, HN1, HN2, and HN3 classifications
• Ultrasound guided aspiration of the liver and spleen is not recommended, unless it's a very aggressive MCT, or the doctor is in Japan, this is because GI Mast Cell Tumors occurs in smaller japanese dogs

Canine MCTs: Biopsy

• Biopsy of the mass is part of testing
• Generally a post-surgery step.
• Degranulation from incisional biopsy can occur.
• Surgical margins tend to be invasive which can make achievement of wide margins difficult
• There are dendritric like lines going down, so you will need wide margins
• Tumour grade can be a testing method
• The Old grading system (Patnaik) has three grades, with Grade 1-3
• Grade is defined by Subjective criteria for pathologists
• Most come back as grade 2
• There is a High grade 2 and low grade 2
• Mitotic index: <= 5 is good
• Can use Prognostic panels (several variables)

Canine MCTs: Grading Systems

• Kiupel system : a New grading system that uses a "Two-tier” grading system
• Using More objective histologic criteria
• Mitotic figures, multinucleation, and “bizarre" nuclei, specifically karyomegaly, are able to identify and count
• The tumour is classified as Low grade or High grade, with 2 possible opinions, which is helpful for client understanding
• Median survival : > 2 years for low grade and< 4 months for high grade
• Skeptical at first, but now a two-tier grading system is useful as it allows for More agreement among pathologists
• This system Seems to be accurate and Easy for clients to understand
• It is Reasonable to use as the sole predictor of metastatic potential, although, Nothing's 100%

Canine MCTs: Cytologic and Staining Properties

• Cytologic grading involves Grading to determine degree of granulation and cell morphology

• It has Pretty good correlation with histologic grading.

• It might recommend staging more strongly prior to surgery

• In the case of normal tumour, there is normal size, alot of granules and is low grade

• With tumours of madly different sizes; there is little granule present

• Attempt to gain more insight into tumors of borderline grade using an MCT prognostic panel

• Evaluate Proteins/Genes, such as:

  • Ki67 where if levels GO UP, there is Cells about to divide
  • AgNORS
  • c-Kit protein (KIT) staining pattern

• c-kit mutational status (PCR) which determines Tyrosine Kinase Receptor and whether it is MONE AGGRESSIVE, could help in determining treatment decisions

• Opinions vary on the usefulness of the above information.

• C-Kit Gene Mutations on exon 11 indicates poor prognosis, but respond well to tyrosine kinase inhibitors like, Palladia and Kinavet-CA1:

• Staining Pattern I of C-Kit proteins indicates good prognosis

• Staining Patterns II and III of C-Kit proteins indicate decreased survival

• Ki67 and AgNOR counts determine proliferative index and complement mitotic index for low grade tumors only

Canine MCTs: Prognosis and Potential Outcomes

• Wide range of potential outcomes can be expected if tumour is not treated
• Low grade MCTs will often live for years, even with no removal of tumour
• High grade MCTs will sometimes metastasize in weeks.
• MCTs are notoriously unpredictable and Tumor grade is recognised as most important factor
• Mitotic count (<=5 in one study, <=7 in another) and cell morphology are factored into grade
• Other prognostic factors exist that can influence treatment decisions
• Presence of metastasis
• c-Kit mutation
• Tumor size/growth rate
• the Location/location (can be superseded by grade if on muzzle or genital) and May not be easy to remove at time of even if low grade
• Higher grade /more aggressive

Canine MCTs: Treatments

• Surgery is for curative purposes only
• MCTs are invasive; the consensus is to take wide, deep margins.
• Many studies have discussed margins.
• A surgeon should try to get 2 cm laterally and 1 fascial plane deep (1cm)
• Microscopic margin is usually 10 mml lateral and 5mm deep.
• Can be difficult to achieve wide margins in distal limbs and the muzzle
• Local tumor regrowth happens, but Low grade MCTs often do not recur, even if they are incompletely resected
• Just watch to see if grows back to
• Local therapy in the way of radiation can be applicable for local disease.
• Is a Definitive therapy for incompletely resected tumors if there is no distant metastasis
• 95% 5-year survival (Grade II). High grade tumours are not considered for radiation as standard
• Now, many patients do well with no therapy.
• Palliative therapy may be necessary for large, non-resectable masses which Allows Some Shrinkage
• 8 Gy x 4 doses delivered in cutaneous regions and lymph nodes.
• Systemic therapy, given after resection for high grade tumors or if metastasis is present for non-resectable & multiple cutaneous tumors

Canine MCTs: Treatment - Types of Therapies

• Prednisone, Diphenhydramine, and Famotidine are options for therapeutics
• Gross disease indicates that therapy should involve chemotherapeutics:
  • CCNU
  • Vinblastine
  • Chlorambucil for low grade tumors
• Tyrosine Kinase Inhibitor Therapy (Palladia) blocks dividing signals.
• Intended for the treatment of canine MCTs due to the presence of c-Kit mutations
• Consider using in cases with known c-Kit mutation (prognostic panel)? It is a good choice since given at home
• Monitor for GI toxicity
• Gilvetmab is New therapy Conditionally licensed for dogs with mast cell tumors (stage 1,2,3) and also for dogs with melanoma (stages 2,3)
• It is an Immune checkpoint inhibitor and a Monoclonal antibody against PD-1
• Intratumoral injection of Triamcinolone
• Many MCTs appear larger due to degranulation if the tumour is "squishy, can be a good option- degranulated, puffy
• An Injection of Stelfonta can be given, which causes the tumor to sloughs off

Feline MCTs - Cutaneous and Visceral

• The majority of cutaneous mast cell tumors in cats are benign

• Surgery is the treatment of choice

• There is No established histologic grading system -

• Tumors can can be classified as Well-differentiated vs. anaplastic

• Grade May have prognostics significance

• Chemotherapy/Palladia if anaplastic

• Evaluate for other cutaneous tumors

• Staging with abdominal ultrasound +/- thoracic radiographs

• Multiple cutaneous mast cell tumors can be treated with Chemotherapy/Palladia

• Most cats have other organ involvement and surgery, even in the face of disseminated disease-

• Median survival times 1-1.5 years with Chemotherapy/Palladia are to be expected.

• Splenic Visceral form is the most common differential for splenic disease in cats

• Most cats do not have concurrent cutaneous involvement

• In Gastrointestinal mast cell tumor, the Prognosis is generally considered poor due to high metastatic rate at the time of diagnosis

• One study of intestinal sclerosing mast cell tumor found a greater than 80% metastatic rate with survival times around 2 months.

• In more recent study found median survival time of 1.5 years

• treatment of with Surgery, if no disseminated metastasis, plus adjuvant post-op chemotherapy/targeted therapy or If disseminated disease thenchemotherapy/Palladia

Questions about the prognosis, treatment, and management of canine mast cell tumors (MCTs). Explores radiation therapy, systemic therapy, and surgical considerations for different grades and presentations.