When in doubt, cut it out! But by how much?

Mast cell tumor on a three-year-old boxer. Photo: Creative Commons/Joel Mills Like any profession, veterinary medicine has its collection of common knowledge. These are “facts” nearly everyone knows, only hardly anyone can remember where they learned these facts or how they came to be facts in the first place. Even after 20 years in the profession, when much of what I was taught is no longer considered gospel, I often find veterinary students have somehow absorbed the same mysterious bits of conventional wisdom I did, usually without being able to trace their source or judge their reliability. One of my favorites is the optimal margins for excision of canine mast cell tumors (MCT). Everyone knows you should take out a MCT with 3-cm lateral margins and one fascial plane deep. Most early career veterinarians know this, but actually doing it is another thing altogether. A 3-cm margin is huge and technically challenging in many places on a dog’s body, and the potential for dehiscence and other complications is significant. But if I ever suggest a smaller margin might be acceptable in some cases, my students and new graduates are aghast at the idea of not offering the “gold-standard” treatment to their patients. Where did this magic number come from? Is it really magical? The first question is easier to answer: No one knows for sure! The earliest example of this claim I have found is from an oncology textbook published in 2001,1 and the introduction to the earliest clinical study examining the question, from 2004, indicates the authors failed to find the source of this recommendation despite “a thorough review of the veterinary medical literature.”2 This has all the hallmarks of something someone made up as a reasonable best guess that was magically transformed into a standard of care adopted widely throughout the profession. The carving into stone of such pragmatic guesses or preliminary research findings is all too common in veterinary medicine. Another perennial favorite is the precise percentage risk of mammary cancer development in dogs if spayed before the first (0.5%), second (8%) or third (26%) heat cycle. This is still memorized by the majority of the veterinary students I teach and quoted by reputable sources despite being derived from a relatively small, low-quality retrospective study in 19693, and despite significant doubt about the accuracy of these figures based on subsequent research.4,5 Regardless of its mysterious provenance, the 3-cm margin for MCT excision has been widely adopted. Given the technical difficulty of this practice and the risk of post-surgical complications, it is likely many patients have suffered such complications or even been denied treatment for their disease due to the lack of an available veterinarian comfortable performing such an aggressive surgical excision. The adoption of standards without strong evidence has real-world consequences for our patients. Fortunately, there has been a decent amount of research evaluating this practice and some alternatives, so we are in a better position to make evidence-based decisions about MCT excisions than we were when this idea popped up somewhere in the 1990s. As always, if we are to practice in a truly evidence-based manner, a simple, clear, universal recommendation must be replaced with a nuanced and probabilistic guidance adapted to the needs of individual patients. This is more work, and less satisfying psychologically, but it better reflects the inherent complexity of biology and the unavoidable uncertainties of medicine. A recent systematic review took a critical look at the studies that have evaluated the rate of marginal or incomplete excision and local recurrence of MCT following surgical removal with different margins.6 This review found four studies with sufficient information to allow an evaluation of the question whether “resection of canine cutaneous MCTs with lateral surgical margins <3-cm results in low rates of incomplete resection and local tumor recurrence.” Table 1 shows a simplified version of the data analysis in this paper. I have also added one study that was published after the review article. Table 1 Of course, this simplified presentation of the data leaves out much important information that would be necessary to produce guidelines readily adaptable to a broader range of patients. There are many limitations to these studies, none of which approaches the gold standard of a prospective randomized controlled study. Such a study is almost certainly unattainable, and is arguably unethical for this question since it would involve deliberately randomizing some patients to treatments considered likely to be inferior to the “standard,” however arbitrary that is. As always, we must make the best possible decision with the evidence we have, not the perfect evidence we wish we had. The appropriate surgical margins to minimize recurrence and to minimize surgical complications depends on the size, location, and grade of the tumor as well as many other factors. It is a moving target that is impossible to distil into a simple, one-size-fits-all recommendation. As with most clinical decisions, the “best” approach to the problem will depend on the unique circumstances of the individual case. However, the information provided by studies such as these can help us set reasonable limits within which to individualize our recommendations. In general, these results suggest recurrence rates for Kiupel low-grade or Patnaik grade one or grade two MCTs are very low, and there is no distinct advantage to a 3-cm margin over 2-cm or a margin equal to the diameter of the tumor. Large, high-grade tumors may be better treated with wider margins, though this is not a question directly answerable from these studies. There are not available studies comparing the surgical complication rates with different resection widths, but it is highly probable that wider excisions result in more complications. There is also a potential for owners to be more inclined to refuse surgical treatment for more aggressive surgery with greater risk. More conservative margins may also allow more MCTs to be treated by general practitioners, as opposed to surgical specialists, which also increases the availability and affordability of treatment for many dog owners. A balancing act The potential increase in risk of recurrence with more conservative excision must be balanced against these advantages, and the data available so far suggests the scales likely tip in favor of less-aggressive excision in many cases. Certainly, wider excision is still reasonable where anatomic location and surgical ability allow, but veterinarians should not feel they are lowering their standard of care or putting their patients at great risk when choosing more conservative approaches to MCT. The literature concerning excisional margins for MCT provides additional interesting facts. One is surgical margins differ from margins assessed histologically, and the former are more relevant to the clinician when making decisions about treatment and offering a prognosis. I have been shocked and dismayed in the past to receive a pathology report indicating margins of less than 1 or 2 cm when I carefully measured and laboriously performed a 3-cm wide excision. I was relieved, then to find a study in 2015 that compared surgical and histologic margins and concluded, “Surgical and histologic margins may differ significantly for canine cutaneous and subcutaneous MCTs. This may be a result of tissue shrinkage following excision and fixation, extension of the MCT beyond palpable margins, or both. Histologic measurements may significantly underestimate the tumor-free margins in dogs with cutaneous and subcutaneous MCTs.”11[emphasis added] Another important point, notable in the results of the studies reviewed above, is narrow or incomplete margins appear to be a poor predictor of local recurrence for Patnaik grades one or two or Kiupel low-grade MCTs.10 This should be reassuring to the surgeon and the owner, especially given histologic margins are often narrower than surgical margins. Decisions about additional surgery or adjunctive therapy need to thoughtfully balance the potential benefits in terms of long-term recurrence with the risk to the patient and the burden on the owner of additional treatment aimed at reducing recurrence. It is important to understand I am not declaring the death of the 3-cm MCT excisional margin and replacing it with 2-cm, 1-cm, or proportional margins. Such a declaration would be as unsophisticated and nearly as arbitrary as the time-honored practice it was intended to overthrow. We rarely have the luxury of robust, high-quality evidence indicating a single universal approach as the optimal choice. Evidence-based medicine involves making clinical decisions that integrate the best available scientific research evidence with the unique context of each decision, including our own knowledge and abilities, the overall status and needs of the patient, and the goals and resources of the owner. There are still circumstances in which I aim for 3-cm margins when I remove a MCT. But there are plenty of circumstances in which the optimal approach for the individual patient is something more conservative, and I make frequent use of other approaches, from referral to oncology and surgery specialists to proportional-margin excision, to palliative therapy alone. In making these decisions, I always have thorough conversations with the owners of the patient so that they understand the potential risks and benefits of each option and the degree of the uncertainty. The key point is I do not rely blindly on an arbitrary practice that emerged from the mysterious mists of time and somehow became a de facto standard of care from which vets are ashamed to deviate. Evidence is often seen as limiting our choices, but it more often frees us from the strictures of habit and individual opinion to tailor our care to the needs of each patient and their owners. Brennen McKenzie, MA, MSc, VMD, cVMA, discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists’ opinions do not necessarily reflect those of VPN Plus+. References Thamm D, Vail D. Mast cell tumors. In: Small Animal Clinical Oncology. 3rd ed. Philadelphia, PA: WB Saunders Co; 2001:261-282. Simpson AM, Ludwig LL, Newman SJ, Bergman PJ, Hottinger HA, Patnaik AK. Evaluation of surgical margins required for complete excision of cutaneous mast cell tumors in dogs. J Am Vet Med Assoc. 2004;224(2):236-240. doi:10.2460/javma.2004.224.236 Schneider R, Dorn CR, Taylor DON. Factors Influencing Canine Mammary Cancer Development and Postsurgical Survival&lt;xref ref-type=&quot;fn&quot; rid=&quot;FN2&quot;&gt;2&lt;/xref&gt; JNCI J Natl Cancer Inst. 1969;43(6):1249-1261. doi:10.1093/jnci/43.6.1249 Beauvais W, Cardwell JM, Brodbelt DC. The effect of neutering on the risk of mammary tumours in dogs - a systematic review. J Small Anim Pract. 2012;53(6):314-322. doi:10.1111/j.1748-5827.2011.01220.x Mckenzie B. Evaluating the benefits and risks of neutering dogs and cats. doi:10.1079/PAVSNNR20105045 Selmic LE, Ruple A. A systematic review of surgical margins utilized for removal of cutaneous mast cell tumors in dogs. doi:10.1186/s12917-019-2227-8 Séguin B, Leibman NF, Bregazzi VS, et al. Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996-1999). J Am Vet Med Assoc. 2001;218(7):1120-1123. doi:10.2460/javma.2001.218.1120 Fulcher RP, Ludwig LL, Bergman PJ, Newman SJ, Simpson AM, Patnaik AK. Evaluation of a two-centimeter lateral surgical margin for excision of grade I and grade II cutaneous mast cell tumors in dogs. J Am Vet Med Assoc. 2006;228(2):210-215. doi:10.2460/javma.228.2.210 Pratschke KM, Atherton MJ, Sillito JA, Lamm CG. Evaluation of a modified proportional margins approach for surgical resection of mast cell tumors in dogs: 40 cases (2008-2012). J Am Vet Med Assoc. 2013;243(10):1436-1441. doi:10.2460/javma.243.10.1436 Itoh T, Kojimoto A, Uchida K, Chambers J, Shii H. Long-term postsurgical outcomes of mast cell tumors resected with a margin proportional to the tumor diameter in 23 dogs. J Vet Med Sci. 2021;83(2):230-233. doi:10.1292/jvms.20-0281 Risselada M, Mathews KG, Griffith E. Surgically planned versus histologically measured lateral tumor margins for resection of cutaneous and subcutaneous mast cell tumors in dogs: 46 cases (2010-2013). J Am Vet Med Assoc. 2015;247(2):184-189. doi:10.2460/javma.247.2.184

Cookie	Duration	Description
cookielawinfo-checkbox-analytics	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Analytics".
cookielawinfo-checkbox-functional	11 months	The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
cookielawinfo-checkbox-necessary	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
cookielawinfo-checkbox-others	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other.
cookielawinfo-checkbox-performance	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Performance".
JSESSIONID	session	The JSESSIONID cookie is used by New Relic to store a session identifier so that New Relic can monitor session counts for an application.
viewed_cookie_policy	11 months	The cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. It does not store any personal data.

Cookie	Duration	Description
vuid	2 years	Vimeo installs this cookie to collect tracking information by setting a unique ID to embed videos to the website.
_ga	2 years	The _ga cookie, installed by Google Analytics, calculates visitor, session and campaign data and also keeps track of site usage for the site's analytics report. The cookie stores information anonymously and assigns a randomly generated number to recognize unique visitors.
_gat	1 minute	This cookie is installed by Google Universal Analytics to restrain request rate and thus limit the collection of data on high traffic sites.
_gat_UA-	1 minute	A variation of the _gat cookie set by Google Analytics and Google Tag Manager to allow website owners to track visitor behaviour and measure site performance. The pattern element in the name contains the unique identity number of the account or website it relates to.
_gid	1 day	Installed by Google Analytics, _gid cookie stores information on how visitors use a website, while also creating an analytics report of the website's performance. Some of the data that are collected include the number of visitors, their source, and the pages they visit anonymously.
__gads	1 year 24 days	The __gads cookie, set by Google, is stored under DoubleClick domain and tracks the number of times users see an advert, measures the success of the campaign and calculates its revenue. This cookie can only be read from the domain they are set on and will not track any data while browsing through other sites.

Cookie	Duration	Description
ADV_u_id	3 months 8 days	Unique customer identifier used to track unique ad views and interactions with some ads.
anj	3 months	AppNexus sets the anj cookie that contains data stating whether a cookie ID is synced with partners.
fr	3 months	Facebook sets this cookie to show relevant advertisements to users by tracking user behaviour across the web, on sites that have Facebook pixel or Facebook social plugin.
IDE	1 year 24 days	Google DoubleClick IDE cookies are used to store information about how the user uses the website to present them with relevant ads and according to the user profile.
loc	never	AddThis sets this geolocation cookie to help understand the location of users who share the information.
OAGEO	session	OpenX sets this cookie to avoid the repeated display of the same ad.
OAID	1 year	Cookie set to record whether the user has opted out of the collection of information by the AdsWizz Service Cookies.
test_cookie	15 minutes	The test_cookie is set by doubleclick.net and is used to determine if the user's browser supports cookies.
uuid2	3 months	The uuid2 cookie is set by AppNexus and records information that helps in differentiating between devices and browsers. This information is used to pick out ads delivered by the platform and assess the ad performance and its attribute payment.
_fbp	3 months	This cookie is set by Facebook to display advertisements when either on Facebook or on a digital platform powered by Facebook advertising, after visiting the website.

When in doubt, cut it out! But by how much?

A look at margins for mast cell tumor excision

Membership Required