Monday, February 17, 2014

Things I learned: mast cell tumours

A mast cell tumour, clipped prior to surgical resection.

Mast cell tumours (aka mastocytomas, histocytic mastocytomas or mast cell sarcomas, we call them MCTs) are commonly seen in companion animal practice. Recently I attended a webinar by oncologist Dr Sandra Nguyen about MCTS, which provided a fantastic review. Veterinarians can log in to the Vet's Australia website to view the whole thing.

MCTs occur in all breeds, but boxers, pugs, bulldogs, bull terriers, Labradors and Shar-Peis are over-represented (most vets who attended agreed that in Australia at least, Staffordshire terriers are commonly affected although this predisposition isn't documented in the published literature). Boxers and pugs tend to have lower grade MCTs while Shar-Peis have the more biologically high-grade types.

MCTs are very common. Between 6 and 21% of skin tumours in dogs are MCTs, and these account for 25 per cent of malignant skin tumours. On presentation, 14 per cent of affected dogs have more than 1. Most occur in dogs over the age of 8 but some recorded in dogs as early as three weeks old!
MCTs located on the prepuce, perineum, inguinal region and muzzle tend to be more malignant.

Chronic inflammatory skin disease may predispose dogs. A mutation of c-KIT, a receptor for stem cell factor, is present in around 40 per cent of MCTs and is therefore a potential therapeutic target (a test for c-KIT mutation is available through Colorado State University).

The most common location for MCTs in the dog is the skin (in the cat it’s the spleen).

Mast cells contain heparin, histamine, eosinophilic chemotactic factor, proteolytic enzymes and serotonin. Thus for example heparin causes local haemorrhage at the tumour removal site, histamine release causes inflammation, proteolytic enzymes may be responsible for the “squooshy” feel of MCTs (often leading them to be mistaken for lipomas) etc.

FNA is highly sensitive (although can be misleading or non-diagnostic), but biopsy is needed to grade the tumour which is helpful for prognostication and treatment planning. Additionally, Diffquick stains may not show intracytoplasmic granules so while you may be able to get to diagnosis of a round cell tumour on cytology you might need to send out slides for a Giemsa stain.

Staging is recommended for Grade II MCTS and above. This involves aspiration of regional lymph nodes (MCTs usually metastasize to the lymph nodes first); abdominal ultrasound (especially focusing on the spleen, liver and lymph nodes); complete blood count; thoracic radiographs and, in dogs with an abnormal haemogram – eg neutrophilia, monocytosis, eosinophilia, basophilia, anaemia or thromocytopaenia) – bone marrow aspirate may be performed.
MCTs rarely metastasize to the lung.

Treatment usually involves radiotherapy or chemotherapy (prednisolone with vinblastine or CCNU +/- tyrosine kinase inhibitors). Prednisolone has been used for pallation as a monotherapy.

Tyrosine kinase inhibitors inhibit c-KIT, the stem cell factor that is overexpressed in MCTs. They can also inhibit angiogenesis by targeting vascular endothelial growth factor (VEGF) and platelet-derived growth factor.
According to Dr Nguyen, these are indicated with grade III or higher MCTs with a mitotic index of over 5, or metastatic low grade tumours.

Her protocol involves administration three times a week (eg Monday, Wednesday and Friday) at a dose of 2.5mg/kg. Steroids or NSAIDs can be used on the off-day.

Complications of treatment with tyrosine kinase inhibitors include GI ulceration (treat with sucralfate), diarrhoea (use metronidazole), proteinuria or hypertension (use benazepril or enalapril), neutropaenia or hepatoxocity (a break from the drug is usually enough).

1 comment:

  1. Do you use prophylactic sulcralfate when having the tyrosine kinase chemo?

    ReplyDelete

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