Take 5: Key points for managing cutaneous mast cell tumors in dogs
They're anything but predictable and unfortunately very common. Here's what veterinarians need to keep top of mind when managing this malignancy.
Do canine mast cell tumors drive you crazy? If so, I suspect that you probably aren't alone. The clinical behavior of these tumors runs the gamut from relatively benign to highly malignant, making it challenging to decide on the best treatment approach for an individual tumor. Surgical removal is the mainstay of treatment for most mast cell tumors, while chemotherapy and radiation therapy are valuable adjunctive treatments (or alternatives) to surgery in some cases. When deciding on which course of therapy is best for dogs with cutaneous mast cell tumors, here are five key points to keep in mind:
Introducing Take 5
This article is the first in a planned series by veterinary oncologist Dr. Michael Childress in which he will discuss five important facets of common types of tumors that general practice veterinarians should know.
1. The most important step in managing dogs with cutaneous mast cell tumor is determining whether the tumor is surgically curable.
This seems inherently logical, but rational thinking can be subverted by unreasonable expectations of surgical benefit harbored by pet owners and veterinarians alike. Most veterinarians are aware that histopathologic grade is the factor most associated with survival after surgical excision of a mast cell tumor. Unfortunately, this factor cannot be assessed until after the tumor is removed, so veterinarians must rely on other clinical features to decide whether to attempt surgery.
Small, solitary, slow-growing tumors on areas of the body amenable to wide surgical excision (such as the trunk) are usually excellent candidates for surgical removal. On the other hand, tumors that are large, rapidly growing or located at sites where wide excision is challenging may not be. These latter tumors are often high-grade cancers that cannot be cured with surgery.
Other clinical features that are more common in high-grade mast cell tumors include bleeding or ulceration of the tumor, regional lymph node enlargement and the presence of systemic signs of mast cell degranulation, such as vomiting, melena, hematemesis, coagulopathies, generalized pruritus, hypotension and anaphylaxis. Avoidance of surgery in these cases may be prudent because …
2. Surgery does more harm than good for some dogs with cutaneous mast cell tumors.
Approximately 40% of surgically resected high-grade mast cell tumors will recur locally even if “clean” margins are identified on the histopathology report. Managing locally recurrent mast cell tumors is extremely challenging, as these tumors often grow more rapidly and extensively than the original tumor. Heparin and tissue proteases released by neoplastic mast cells at the surgical site can cause hemorrhage, surgical wound dehiscence or both (see Figure 1).
Figure 1: Recurrent high-grade mast cell tumor in a dog. This tumor arose following incomplete excision of a high-grade tumor via midfemoral amputation. The amputation stump is largely replaced by tumor. Significant tumor-associated subcutaneous hemorrhage is readily apparent. Images courtesy of Dr. Michael Childress.
It's not clear whether dogs that undergo surgical removal of high-grade mast cell tumors experience a survival advantage compared with dogs treated palliatively with chemotherapy or radiation therapy. Therefore, the choice to pursue surgery in dogs with clinically aggressive mast cell tumors should be made carefully.
An incisional biopsy to confirm the tumor grade may be useful to plan surgery in these cases, as not all mast cell tumors with clinically aggressive features will be high-grade. Dogs with large but low-grade tumors may still benefit from carefully planned aggressive surgery.
3. The contemporary two-tiered histopathologic grading system for cutaneous mast cell tumors is probably more clinically useful than the previous three-tiered system.
The histopathologic grading system proposed by Patnaik in 1984 divided mast cell tumors into low (grade 1), intermediate (grade 2) and high (grade 3) grades, with increasing biological aggressiveness associated with increasing grade number.1 This system predicted the clinical behavior of grade 1 and grade 3 tumors very well, but it fared poorly with grade 2 tumors. The more recent two-tiered system proposed by Kiupel in 2011 circumvents this problem by classifying mast cell tumors as either low-grade (grade 1) or high-grade (grade 2), eliminating the intermediate-grade designation altogether.2 In the report initially describing this system, dogs with low-grade mast cell tumors survived more than two years after surgical tumor removal, while dogs with high-grade mast cell tumors survived less than four months.
Subsequent reports have confirmed the prognostic relevance of the two-tiered system, although it does fail to predict outcome for about 5% to 10% of dogs with low-grade mast cell tumors that ultimately succumb to tumor-related death.2,3 Importantly, the two-tiered system is applied consistently by pathologists, who agree on tumor grade in more than 95% of cases when using it.2 This compares with rates of agreement of approximately 60% to 70% when using the three-tiered system.2,4
4. Dogs with multiple cutaneous mast cell tumors usually have a good prognosis.
One of the most frustrating syndromes in dogs with mast cell tumors is that of multiple cutaneous tumors. This syndrome vexes pet owners and veterinarians alike, who may worry that the presence of multiple mast cell tumors implies a systemic, life-threatening disease. However, many-if not most-of these dogs appear to have a favorable prognosis. Veterinarians do still need to be mindful of the clinical features associated with aggressive tumors (see point 1) when assessing dogs with multiple cutaneous mast cell tumors, as dogs with multiple large, rapidly growing, ulcerated tumors probably do have a life-threatening disease (see Figure 2).
Figure 2: Dog with multiple aggressive mast cell tumors.
Most dogs with multiple cutaneous mast cell tumors have an indolent disease characterized by the sporadic appearance of small, slow-growing dermal tumors over many months to years. This condition is a cosmetic nuisance but essentially harmless. However, some dogs with multiple cutaneous tumors, such as the one in this photograph, have a life-threatening disease. This dog has numerous rapidly growing, ulcerated or discolored cutaneous tumors. Note also the preputial swelling, which was associated with metastatic mast cell tumor in the superficial inguinal lymph nodes.
But most dogs with multiple mast cell tumors tend to present with small, slow-growing tumors. In such cases, surgical removal of one or two representative tumors is recommended to establish their histopathologic grade (they are almost always low-grade). If a low histopathologic grade is confirmed, watchful waiting is prudent for these cases, accompanied by batched surgical removal of several tumors at a time if new tumors continue to form (and they often do).
There is no evidence that any medical therapy prevents new tumors from forming in these cases, which can be upsetting to pet owners. However, reassuring these owners that the disease is not life-threatening (think of it as “mast cell acne”) can help to ease their concerns.
5. The most useful chemotherapy drugs for cutaneous mast cell tumors are toceranib (Palladia-Zoetis), vinblastine and prednisone.
Chemotherapy is indicated for dogs with mast cell tumors that cannot be removed surgically or dogs that have undergone successful surgical removal of high-grade tumors, which carry a significant risk for metastasis. In the first of these settings, chemotherapy is given with palliative intent, with the goal of temporarily shrinking the tumor and improving the dog's quality of life. In the second, chemotherapy is given to prevent or delay metastasis, thereby extending survival. Toceranib, vinblastine and prednisone are the drugs that most reliably achieve either one of these outcomes.
Because its spectrum of side effects does not overlap with that of toceranib or vinblastine, prednisone can be combined with either drug, which may result in additive or synergistic anti-tumor activity. Combinations of toceranib and vinblastine, however, have proven too toxic to recommend their use at this time. Other drugs whose use for treating mast cell tumors is reported include lomustine (CCNU), cyclophosphamide and chlorambucil. However, these drugs appear to be less effective than the aforementioned three, and they probably should not be used in the first-line treatment setting.
References
1. Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet Pathol 1984;21(5):469-474.
2. Kiupel M, Webster JD, Bailey KL, et al. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Vet Pathol 2011;48(1):147-155.
3. Berlato D, Murphy S, Laberke S, et al. Comparison of minichromosome maintenance protein 7, Ki67, and mitotic index in the prognosis of intermediate Patnaik grade cutaneous mast cell tumors in dogs. Vet Comp Oncol 2018;16(4):535-543.
4. Northrup NC, Howerth EW, Harmon BG, et al. Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference. J Vet Diagn Invest 2005;17(6):552-555.
Dr. Michael O. Childress is associate professor of comparative oncology at Purdue College of Veterinary Medicine.
