Canine Cancer: Unmasking the “Great Pretender”

If you’ve read Siddhartha Mukherjee’s masterful “biography” of cancer, you understand why cancer is such a captivating, maddening, inspiring presence in medicine. Hope for a cure rises high and then crashes back to earth, even while progress in diagnosis and treatment lurches forward. Cancer claims so many victims but lets others live, sometimes for no reason but luck. It’s a testament to the breadth of the cancer saga that this Pulitzer-winning history is 600 pages long but doesn’t really have an ending. The cancer story isn’t likely to have an ending in our lifetimes, if that means it would go away or give up all its secrets.

But on the time scale of individual people and pets, cancer writes many endings. I think about my previous dog, Hula, and the aggressive mast-cell tumor that took her life just a few weeks after I discovered it. Mast-cell tumors (MCTs) are the most common type among dogs. They’re the “great pretenders,” with a wide repertoire of shapes, colors, textures, and locations. They get larger and smaller for no apparent reason; they may be painless or they may hurt. Hula’s primary tumor was only the size of a lentil, and I almost never saw it at all.

I was about to set off on a three-week RAVS trip when I found what looked to be a pimple on her side. I made a mental note to recheck it when I returned. When I did, the lesion hadn’t changed but the nearest lymph node was huge. Her biopsy told me what I already suspected: she had a grade 3 mast-cell tumor with the dreaded c-Kit mutation.

mast cellsMast cells are normal parts of the immune system. The dots you see in these mast cell are granules full of histamine. Mast cells have many functions in keeping bodies safe from invasions, but they’re best known for attaching to an antibody called IgE and releasing that histamine in allergic reactions. (That’s why doctors give antihistamines to counteract allergies and allergic responses like bee stings.) A flood of histamine, streaming from a mast-cell tumor brimming with this substance, can greatly damage a dog’s system. In cancer’s typically cryptic fashion, the actual cause of MCTs is unknown and probably depends on a number of things, but we commonly see it in dogs that have a history of allergic skin disease (Hula didn’t).

Eighty percent of mast-cell tumors in dogs are grade 2 on a three-point scale, with 3 the most aggressive. Grade 2 tumors often have a good chance of remission if they’re excised along with enough surrounding tissue. The problem is that to get those “clean margins” a surgeon needs to remove about an inch and a half of normal tissue around the tumor. This can be a significant problem if you’re a small dog or the tumor sits in a place without a lot of extra skin—like the leg or head. Besides the clean margins, the prognosis depends on where the tumor is located and to some extent on breed (pugs, for one, tend to have less-aggressive tumors). Sometimes radiation is called for.

Cancer really shows its genetic nature in dogs with aggressive grade 2 and 3 tumors that also have active mutations in an oncoprotein called c-Kit. This protein is involved with the proliferating and maturing of the cell. Clearly, a mutation in c-Kit that keeps it turned on all the time could set off an uncontrolled and abnormal growth of cells.

Seven years ago, when Hula was diagnosed with that potent mutation, there wasn’t much I could do. There was no specific chemotherapy available for grade 3 MCTs in dogs.

Recently, the first FDA-approved chemotherapy drug for dogs became available. Palladia belongs to a new class (new to veterinarians), tyrosine kinase inhibitors. These drugs target the Kit mutations in aggressive forms of grade 2 and 3 mast-cell disease. But even the less systemic, locally aggressive forms of MCT (with no Kit mutation) respond in some cases. This might help pups whose tumor isn’t very aggressive but is in a spot that doesn’t lend itself to surgery.

Everyone is aware of how grueling chemotherapy is. In veterinary medicine the patients don’t comprehend remission and can’t make the decision to endure severe side effects for the hope of living a bit longer. Many guardians find it agonizing to force their beloved pets to endure what we would endure for ourselves. So our job as guardians and veterinarians, as long as chemo comes with so many oppressive side effects—especially for the older animals who are more prone to tumors—also includes finding ways to maintain a pet’s quality of life. Meanwhile, let’s hope that researchers keep coming up with drugs that minimize side effects and maximize life.

Hula’s cancer was highly aggressive. A cure or remission wasn’t in the cards. But if today’s therapies had been available then, we might have had more than a few weeks to say goodbye.

Categories: Pet Wellness