Mast Cell Dilemma

(published in Spaniels In The Field – summer 2003 )

A recent communication from a SITF reader concerned a tragic loss he had suffered with a young spaniel. In response to his request, I’d like to discuss a problem we see in daily veterinary practice. This is the mast cell tumor, the most common skin mass that we see in the dog. Various sources quote the incidence of mast cell tumors, among all skin tumors that we handle, as being anywhere from 16-27%. They have been reported in dogs as young as 3 weeks and as old as 19 years. The mean age of diagnosis is about 9 years, so we definitely see more of them in the older patient. There is no sex predilection. They are seen more commonly in a few breeds such as Boxers, but spaniels are not over represented. Although there is significant study underway, we currently have no known cause for mast cell tumors.
These tumors arise from tissue mast cells in the dermis (the layer just below the skin.) In dogs, approximately 50% of these mast cell tumors show malignant behavior. The mast cell is a normal part of the immune system and constitutes a part of the tissue reaction to trauma. The cells contain granules that are very characteristic. When the cells are better differentiated they contain more granules. The types of granules also differ. This will become important when we discuss the grading of the tumors.

Most mast cell tumors in the dog are solitary. They are well-defined, raised masses, hairless, ulcerated and sometimes erythematous (reddened.) A key fact to remember here as that they can look surprisingly harmless, often being mistaken for a lipoma, or fatty tumor. About 50% are found in the skin of the trunk and perineum, 40% on the extremities and 10% on the head and neck. The location of the tumor and its rate of growth help to predict its future behavior. As would be expected, slow growing masses have a better prognosis than a more aggressive tumor that is growing quickly. The worst locations for long-term survival are the oral, preputial, inguinal and perineal area as well as the nailbeds. These tumors involving the nail often first appear as an injury but quickly grow, deforming the toe and quickly spreading. In my experience these have the worst prognosis as they are usually not detected until they are fairly extensive. When the tumor metastasizes, it usually goes to the associated lymph nodes and less often the spleen, liver and bone marrow. Spread to the lungs is uncommon. When the tumors involve internal organs and/or bone marrow, the prognosis is grave.

Mechanical manipulation of the tumor causes the cells to degranulate causing localized redness and possibly an area of swelling. The granules contain several substances. One is histamine2 (H2) that results in gastrointestinal ulceration. This release is manifested over the long term by loss of appetite, vomiting and possibly diarrhea, both with the presence of blood. Another substance released is histamine1 (H1) that causes the blood vessels to dilate throughout the body leading to a drop in blood pressure, weakness and possible collapse. The last substance released is heparin that impairs blood clotting and causes increased hemorrhage locally. This is important for those of us who will be dealing with the removal of such tumors. The presence of systemic signs such as those just described are associated with more aggressive forms of this tumor.

Presented with a dog that has developed a “lump”, we have several steps we use to determine if the lump may be a mast cell tumor. As always, we need an accurate history, a thorough physical examination, some laboratory analysis and cytology and may even request x-rays or ultrasound exams. The most important part of the history is the length of time that the mass has been present and its rate of growth. The presence of blood in stool or vomit should also be noted. During our examination, along with palpation of the area in question, we check other lymph nodes for enlargement and palpate the abdomen to evaluate the liver and spleen. Blood may be drawn to check for anemia and examination of the “buffy coat”. The blood is separated into its components and the buffy coat is the portion composed of the white blood cells. The presence of mast cells in circulating blood is a key indicator of disease. Probably the most useful and easiest procedure is the fine needle aspirate. Depending on the location and nature of the patient, this may be done in the office without sedation in many cases. A needle approximately the diameter of that used to vaccinate the dog, is inserted into the suspect mass and a sample of cells is withdrawn, stained and examined under the microscope. This is an easy procedure that will usually quickly categorize the mass as a fatty tumor or something more serious. It is not a foolproof test as the actual sampling process can sometimes be tricky, but it is an excellent screening test. Mast cells have a very characteristic appearance due to their very large granules. In my opinion all masses should be examined this way prior to considering surgery so that the surgeon will have an idea of how aggressive they need to be. If mast cells are found on the fine needle aspirate, the owner, patient and surgeon are prepared for what may appear to the owner to be an excessively large excision but can anticipate better out-comes. Depending on the initial findings, further aspirates may be recommended from the regional lymph nodes or even bone marrow. These usually require sedation or light general anesthesia. The bone marrow exam is usually reserved for patients with a high degree of suspicion of metastasis or if additional assurance for thera-peutic decision making is necessary.

The treatment of choice for mast cell tumors of the skin is surgery. In spite of surgical excision, approximately 50% will recur. The treatment of small, localized, and well to intermediately differentiated tumors is usually successful and rewarding. Although they appear as discrete masses, they usually extend deep into surrounding tissue, requiring wide surgical margins and possibly the removal of regional lymph nodes. It is critically important to have all samples evaluated by a pathologist following surgery. The edges will be checked to see if they are “clean.” In other words, was the surgery successful in eliminating all questionable tissue, even microscopically? This is shown by the presence of completely normal tissue around all boundaries of the surgical specimen. The other part of the exam is the pathologist’s grading of the degree of differentiation of the tumor cells. Low grade tumor cells are less likely to recur or metastasize and the patients survival time is apt to be longer than one having a less differentiated tumor. This information is vital for prognosis and for formulating a treatment plan. If the margins are not clean, further treatment is based on the histological grade, clinical stage of the tumor, and its location. Preservation of limb or other organ function may become an issue.

Other modalities some-times used in conjunction with surgery are radiation and chemotherapy. Radiation may be used in cases where excision is not complete or in non-responsive mast cell tumors. The same is true for chemotherapy but also includes masses that cannot be removed surgically. In some cases the mass is “debulked” or partially removed surgically and palliative radiation is used as a follow-up. The most common chemotherapeutic agent used is prednisone. This is relatively inexpensive, can be given by mouth under the care of the owner and the side effects are all those seen in any form of cortisone therapy. When this fails, various combinations of drugs have been used but results are usually disappointing.

The treatment of mast cell tumors extends beyond the tumor. In animals that suffer from systemic mastocytosis, it is necessary to treat the gastrointestinal hemorrhage caused by the histamine release. We commonly use H2 agonists that most humans associate with treatment of gastric ulcers. Tagamet (Smith Kline Beecham) Zantac (Glaxo Wellcome) and Pepcid (Johnson and Johnson) are commonly prescribed. In addition, an H1 blockade prevents the dilation of blood vessels and collapse symptoms previously described. This is usually done by administration of diphenhydramine (Benedryl.)

Mast cell tumors are biologically complex. As they are quite rare in humans, comparative studies are not available and research proceeds primarily in the veterinary field. Current studies are being done on the molecular mechanism that is responsible for tumor formation. It is hoped that more effective therapies will be discovered soon. In the meantime, it is important to be vigilant for any lump or swelling and have it checked soon.
– Robin T. Stronk D.V.M.

Robin T. Stronk D.V.M. attended Cornell University. She is a member of the American Canine Sports Medicine Association. She and her husband, John, own two small animal practices in Brattleboro, VT and Hinsdale, NH. They enjoy hunting and the outdoors and own two English Springer Spaniels. “Chip” has proved to be an able assistant in the clinic.