Tips and Guides to Skin Mass Resection: Part One, Emphasis on Mast Cell Tumors

Catherine Reese DVM, DACVS

 

I chose this topic because skin and subcutaneous tumors occur very frequently in our patients and can be benign or malignant. I consider these cases part of our everyday surgical schedule. My goal is to provide you with useful information that you can use in your everyday practice. I will discuss my general principles of mass removal including my approach to surgical management of several specific types of tumors. We will review how to obtain good margins for mass removal and define what really is a "good margin".  And lastly, our Tech Tips  subject this month will be a link to videos on the use of tissue inks to assist your pathologist in determining if your surgical margins are "clean". I feel tissue marking of your excised tumors is important in our prognosis and subsequent treatment recommendations.    

 

  

The Davidson marking system has 5 colors that allow you to identify the anatomical orientation of the excised tissue. The set is $160.00, but it lasts for years since you only use a drop or so each time. You should allow the ink to dry prior to placing the tissue in formalin, otherwise the formalin gets very murky and some of the ink might wash away. I usually just blot the inked edges with gauze to help expedite drying. You should write on the path form what directions the colors refer to... see Tech Tips.  

  

GENERAL PRINCIPLES: When a patient is brought to me for mass removal, I start with the basics, including a full history and physical exam. Specifically, I want to know about any other health problems or medications that might affect anesthesia or wound healing, and I want to ask specific Qs about the mass itself. How long has it been there?  Has it changed in color or size? Does it seem to bother the pet - does he lick or scratch at it? And have they tried any medications (oral or topical) for the mass.

 

PHYSICAL EXAM: I do a thorough physical exam to check for any conditions that might preclude anesthesia, like heart or lung problems. Then palpate the abdomen for masses or other problems. I palpate peripheral lymph nodes for enlargement. Then I focus on the mass itself, measuring its size with a ruler or calipers. I describe the mass as accurately as I can in the medical record (MR): dermal or SQ, fixed or mobile, ulcerated, red, white, pigmented, fluid filled, etc. Often I will draw a picture in the MR or use a skin chart:

 

 

  

 

These are especially helpful for patients with multiple masses that you chart over years and years. You can write the description and FNA results of each mass using whatever system to track them: numbering them, etc.

Tyrosine Kinase Inhibitors (TKI's) and Steven Jobs's Pancreatic Cancer: This was the lead article in the Janurary 2012 Harvard Health Letter that I receive monthly. Since it pertains to our discussion as an alternate treatment for aggressive mast cell tumors I thought I would share an excerpted portion of Dr. Mathew H. Kulke's comments regarding Steve Jobs's treatment. Dr. Kulke is a physician at the Harvard affiliated Dana Farber Cancer Institute. He specializes in neuroendocrine pancreatic tumors that arise from the Islet cells. He stated that in metastatic neuroendocrine liver disease surgery is seldom recommended. As we do in the dog, primary tumors he states, even as large as 10 cm, without metastasis have "done great following surgery". Dr.Kulke stated the liver transplant for metastatic pancreatic neuroendocrine tumors "as highly investigational". He stated that the response to TKI's for this kind of cancer have been dramatic and would have been his primary recommendation for Steven Job's metastatic liver disease. This is a new era in cancer treatment called "targeted therapy". Based on the early research being published there may be a number of aggressive cancers that respond to this therapy. Certainly the photographs of the mast cell tumor response provided by a veterinarian, Dr. Albert Ahn, are dramatic. Dr. Andy Abbo will expand on TKI's mechanism of action and the NEVOG experience with TKI's in this months NEVOG newsletter contribution.

- W. B. Henry DVM, DACVS   

 

NEVOG News  

 

Tyrosine Kinase Inhibitors in Veterinary Medicine

Andy Abbo DVM, MS, DACVIM (Oncology)

 

Receptor Tyrosine Kinases (RTK's) work via phosphorylation which is that they bind ATP and use this to add phosphate groups to key residues both on themselves (autophosphorylation) as well as other molecules. This phosphorylation ultimately results in downstream signaling inside the cell which results in a signaling cascade leading to alterations in gene transcription influencing cell proliferation, differentiation and survival, therefore it stands to reason that dysregulation of this pathway provides a potential survival advantage to the cell.  In addition to regulating cell function, certain RTK's play a critical role in the process of tumor angiogenesis. Tyrosine kinase inhibitor (TKI's) therapy work by inhibiting these pathways as well as angiogensis and is the rationale behind their use.

 

Tyrosine kinase inhibitors that have been utilized most frequently in veterinary medicine include: Tocerinib (Palladia, Pfizer), and Masitinib (Kinavet, AB- Science) - both Palladia and Kinavet have been approved for use in dogs with mast cell neoplasia. A recent study by Hahn et al., (Journal Vet Intern Med 2008) evaluating the outcome of dogs with grade II/III recurrent or non resectable, non metastatic cutaneous mast cell tumors reported that masitinib significantly delayed time to tumor progression (TTP) compared to placebo control, this effect was noted when masitinib was used as first line therapy regardless of mutant vs. wild type kit status. In addition, the data supported that 62% of masitinib treated dogs were alive12 months compared to 36% of placebo control. In this trial, masitinib was generally well tolerated, with mild- moderate diarrhea or vomiting as the most common adverse events.

  

Toceranib (Palladia) for the treatment of dogs with measurable Grade II or III mast cell tumors has also been evaluated via a Phase III trial by  London et al, (Clinical Cancer Research, 2009). Dogs were randomized to receive either Palladia or a placebo. In those dogs that received Palladia, the combined response rate (complete and partial response rates) was 37.2%. Dogs that had progressive disease on the placebo were then allowed to receive Palladia and when this group of dogs was included, the overall combined response rate was 42.8%. Dogs with c-kit mutations and no lymph node metastasis were more likely to have a response to Palladia. Dogs with Grade II mast cell tumors were more likely to have a longer response. It was also found that about 12% of the dogs had stable disease. When combined with the objective response rate, it means that Palladia has almost a 60% overall biologic response rate. In this study, Palladia-treated responders scored higher on health-related quality of life versus Palladia-treated non responders. This study also supported that Palladia was reasonably well tolerated with manageable side effects.

There are currently no head to head trials that evaluate Kinavet vs. Palladia and it remains unknown if one agent is superior to the other. It is important to remember that while both of these agents are for oral administration, both can be associated with significant side effects.  Side effects reported for both agents include vomiting, diarrhea, muscle cramping, hematachezia, inappetance, hypoproteinemia, renal dysfunction and weight loss. I strongly recommend that practitioners become well versed in the side effects and management of side effects related to these agents prior to instituting their use in practice. Neither Palladia nor Kinavet are recommended as a substitute for wide surgical excision or radiation therapy for local disease control, instead these agents are best suited to be used in patients with either non-resectable mast cell tumors, metastatic disease or when other negative prognostic factors are present (high mitotic rate, c-kit mutation +, high mitotic index, large tumors with rapid growth rates or located in areas traditionally thought of as high risk for metastasis   (oral, mucocutaneous junctions, inguinal etc.).

 

Much debate and varying opinions exist in the oncology community regarding the use of these agents as front line therapy as opposed to traditional chemotherapeutic approaches in the management of mast cell disease exist, as I previously mentioned these agents do not take the place of surgery and/ or radiation therapy for those tumors that are low to intermediate grade where excision and local control is possible. I generally recommend the use of either traditional chemotherapy (Vinblastine/ Prednisone or Vinblastine/ Lomustine/ Prednisone) as my front line therapy in cases of metastatic disease or patients with large tumor burdens that we are attempting to "down stage" prior to surgery or instituting TKI therapy, The premise of which being that dogs treated with TKI's whom are already sick or have large tumor burdens  will typically become sicker when these drugs are administered. In addition, because these drugs are pathway inhibitors they do not generally lead to rapid responses and in theory require life long therapy. TKI's can become cost prohibitive over time, therefore I reserve their use for refractory non surgical disease or dogs with metastatic disease that are feeling well at the time of diagnosis.