Tips and Guides to Skin Mass Resection: PART 2, Emphasis on Mammary Gland Tumors (MGT) and Sarcomas
Catherine Reese DVM, DACVS
INCIDENCE: Mammary tumors in dogs have 50-50 odds of being benign or malignant. The benign ones are usually small, well circumscribed and firm, and the malignant ones are usually big, ulcerated, fixed and fast-growing.
Mammary Gland Tumor in a DOG
We all know the protective effects that early spaying has on the development of canine mammary tumors, but to review:
There is only a 0.5% risk of developing a mammary tumor if the dog is spayed before the first heat cycle. This risk increases to 8% after the 1st heat cycle, and jumps to 26% after the 2nd heat cycle. The risk for malignant tumor development does not change after a late spay, but the development of benign tumors does decrease after a late spay.
Tumors > 5 cm in diameter were more likely to have metastasized to regional LN. Tumors that have been present for > 6 months prior to Sx were more likely to have metastasized to a regional LN. SO OPERATE EARLY WHEN THE TUMOR IS SMALL!
PRE-OP WORK-UP: The pre-operative work-up for a canine mammary tumor includes standard blood work (CBC & Chem. Panel) and you might also add a coagulation panel if you suspect the tumor is an inflammatory carcinoma, as those often result in DIC development. Also chest x-rays are taken to look for lung metastasis and also to check the sternal lymph node for enlargement, which can also be a location for metastasis. A rectal exam is done to evaluate the sublumbar LN for enlargement, or an abdominal U/S can be done for this as well. Inguinal LN are palpated and aspirated (FNA) if enlarged. An abdominal and lung CT is the most accurate check for metastasis.
SURGICAL OPTIONS FOR MGT:
LUMPECTOMY: only for firm, superficial, mobile ( likely benign) masses < 0.5 cm.
MAMMECTOMY: (single mastectomy) - remove one gland. For masses > 1 cm, fixed to skin or deeper tissue.
REGIONAL MASTECTOMY: remove adjacent glands that have lymphatic drainage (1-3, 4-5 plus inguinal LN).
CHAIN MASTECTOMY: for simultaneous removal of tumors in multiple glands (faster than multiple lumpectomies, not for longer survival time).
We rarely do lumpectomy except for small, firm, mobile, superficial masses that are likely benign. Most of the time we do a single gland mastectomy. Occasionally we will remove the adjacent glands that share lymphatic drainage, which are glands 1-3, and glands 4-5. Rarely do we perform a full chain mastectomy unless there are tumors in multiple glands (for example a tumor on gland 1, 3 and 5 on the same side) - this saves time by making one long incision instead of 3.
SURGICAL MARGINS FOR MGT's: I usually try to do the least invasive and most efficient surgery that will remove all affected tissue - whether that is multiple single mastectomies or removing adjacent glands together as one excision. This depends on where the tumors are located and how big they are. I want to achieve 2-3 cm peripheral margins if possible,and also take a layer of abdominal fascia or muscle if possible. The inguinal LN is removed routinely if the 5th gland is removed, and it should be submitted in a separate jar so the histopathology technician doesn't overlook it when preparing the biopsies. I also recommend spaying the dog if she is not already spayed. The reports on whether spaying helps with longevity after malignant mammary tumor removal are mixed, but I recommend it anyway.
FELINE MGT's: Cats are a different story: most of the mammary tumors in cats are malignant. Spaying cats early helps prevent tumor development.1 At least 85% are malignant. Cats spayed prior to 6 months of age have a 91% reduction in risk of tumor development. Cats spayed prior to 1 year of age have an 86% reduction in risk. Feline mammary tumors are usually firm, and fixed and produce a yellowish discharge from the nipple. They are usually adenocarcinomas with lymphatic metastasis. The pre-op work- up is the same as dogs with routine CBC, chemistry panel, chest / abdominal-x-rays and LN evaluation via palpation or abdominal U/S. An entire body CT scan is the most accurate method to determine metastasis (not that much more cost than three chest / abdominal radiographs plus the ultrasound and radiologists reading).
SURGICAL RECOMMENDATIONS FOR MGT's IN THE CAT: Cats have 4 mammary glands and the cranial two share lymphatic drainage into the axillary LN, while the caudal 2 drain into the inguinal LN. The current recommendation for management of feline mammary tumors is to do either unilateral or bilateral full chain mastectomies (depending if the disease is unilateral or bilateral). Take out inguinal LN if removing gland 4. Take out axillary LN only if enlarged and FNA confirms metastasis (of questionable benefit). Recommend spay, however it may not help with recurrence but helps prevent recurrent ovarian/uterine disease, benign hyperplasia. Simultaneous bilateral full chain mastectomies can be difficult to do if there is inadequate skin available to close the resulting defect. Skin stretchers are a simple tool that is used to pre-operatively harvest skin for closure.
This is the skin stretcher kit that Dr. Pavletic developed, called the X-bander. It consists of wide adherent pads that are placed on the skin, attachable elastic cables, cyanoacrylate glue, and glue spreaders.
SKIN STRETCHERS - APPLICATION: The skin around the wound is clipped and scrubbed with surgical scrub, and then cleaned with alcohol. This helps reduce any skin oils that might prevent the pads from adhering to the skin. While the alcohol is allowed to dry, the glue is spread on the sticky surface of the pads and the pads are them placed on the dry and clean skin. The cables are placed on the pads and mild tension is applied. The tension on the cables is increased every 6-8 hr and you should see results within 48-72 hr. The skin stretcher is most effective on parts of the body where there is a large surface area of skin to mobilize, such as the trunk and neck and it can also be used to relieve tension on a closed incision.FELINE MGT's PROGNOSIS: Unfortunately, feline mammary cancer has a guarded to poor prognosis since most tumors have already invaded lymphatics at the time of surgery. Tumor size has been shown to correlate with survival time, with tumors less than 2 cm carrying the best prognosis and tumors greater than 3 cm having the worst. Feline mammary tumors need to be found at a small size to give us the best chance for helping the cat.
SOFT TISSUE SARCOMAS: (HEMANGIOPERICYTOMAS, PERIPHERAL NERVE SHEATH TUMORS, FIBROSARCOMAS, MYXOSARCOMAS, LIPOSARCOMAS, RHABDOMYOSARCOMAS, MALIGNANT FIBEROUS HISTIOCYTOMAS). Next we cover soft tissue sarcoma, not including feline vaccine-associated sarcoma, which we'll cover later...
Soft tissue sarcomas cover a wide range of histological diagnoses listed here, all of which are malignant tumors of mesenchymal tissue. They all behave similarly, in that they are locally aggressive and slow to metastasize. They are generally firm and fixed, but they can also be soft and lipoma-like. Cytology should be performed on these masses even though they don't tend to exfoliate well, so FNA may be inaccurate but the cytology can help rule out other benign tumors. To definitively diagnose these tumors, a tissue biopsy needs to be done. When taking a biopsy, the biopsy site should be located in an area that will be excised with the rest of the mass (if surgery is to be done) or in an area that will be in the radiation field.
 To obtain a biopsy sample, you can either just take a wedge of tissue, or use a punch biopsy or Tru-Cut biopsy needle to get a sample. In any case, make sure the sample is representative of the mass, and not just a piece of adjacent normal tissue. SURGICAL EXCISION: Soft tissue sarcomas usually have a pseudocapsule of compressed but viable tumor cells, so "shelling them out," does not obtain adequate margins. In these cases, you are simply debulking the tumor for future RT. Radiation therapy is more effective when there is minimal residual disease present. When removing a soft tissue sarcoma, you should try to obtain 3 cm margins in all directions, and a fascial plane deep (or 2-3 cm deep if there is available muscle/fat to remove). If you cannot get these wide margins, then excise all the gross disease and plan for RT. Sometimes an amputation is the only way to obtain the necessary margins. When doing surgery, you have to keep in mind the potential need for radiation therapy. If I think that I am not achieving adequate surgical margins, then I will place metallic clips in the tumor bed identifying the margins of the tumor bed. I use either Hemoclips or skin staples. These radio-opaque markers will show up when the radiation therapist is planning the RT field.
In addition, I am very careful to direct my incision away from regions of the body that don't tolerate radiation well, such as the spinal cord, eyes, heart, and lungs. Normally, I try to direct the incision parallel to the lines of tension on the body for ease of closure, but sometimes this will put the incision too close to one of these important structures. If you need to place a drain, then also keep in mind that the drain exit hole is considered "contaminated" with tumor cells (even if you change instruments, you are dragging a drain from the tumor bed to the exit hole). So the drain exit hole has to be included in the radiation therapy field. Either try to avoid using drains (close dead space in multiple layers) or make sure the drain exit hole is close to the incision so the RT field doesn't have to be excessively huge to include the drain site in the field.
BIOPSY RESULTS: The biopsy results will tell you the tumor type (which indicates it's tissue of origin, unless it's poorly differentiated, in which case they can't tell), and also give Grade for the tumor. 1-3 (low-high). Tumors that are Grade 1 and 2 have a low metastatic rate and Grade 3 tumors have a higher metastatic rate. Your treatment goals with surgery are a complete excision with wide margins, but if you cannot achieve wide margins, then RT has an 85% chance of long term tumor control. If the tumor comes back as a Grade 3, then chemo is recommended as well.
 In many cases, there is sufficient loose skin on the trunk to direct the incision perpendicular to the tension lines instead of parallel and still be able to remove all gross disease and close the wound bed. I usually pinch the skin around the tumor and see in which direction will I be able to close the wound, and then try to avoid making the incision near the RT.FELINE VACCINE-ASSOCIATED SARCOMAS (VAS): The last tumor type that I am going to discuss today is the vaccine associated sarcoma in cats. The best chance you have at eliminating this disease is with your first surgery, and it should be an aggressive one. If you cannot achieve wide margins with surgery, then RT is necessary for local tumor control. The median survival time after surgery and RT is 18 months. If the tumor is distal on the limb or tail, then amputation can be curative.There is a vaccine associated feline sarcoma task force that has designated some guidelines for treatment of these tumors. They recommend recording the location, shape and size of all masses that occur in the site of an injection. You should assume that the mass is malignant until proven otherwise. If the mass persists for longer than 3 months after an injection, or if the mass is greater than 2 cm in diameter, or if the mass is increasing in size one month after the injection, then you should treat these cats aggressively. If any of those criteria are met, then you should do a biopsy of the mass. Cytology is unrelable as these tumors do not exfoliate well. When doing the biopsy, make sure to choose a location that will not compromise future surgical excision, and that will be excised along with the mass during the definitive surgery. PRE-OP WORK-UP: It is no different from our previous cases, with routine blood and urine tests and chest films to check for mets. We also use CT pre-op to evaluate the extent of these masses like we do with the other soft tissue sarcomas. It would be wise to discuss your plan with an oncologist prior to doing any major surgery, to make sure it's in line with their current recommendations. SURGICAL RECOMMENDATIONS: Previous surgical recommendations were based on data derived from canine soft tissue sarcomas, and they were to remove the tumor with 3 cm peripheral margins and one fascial plane deep. A more recent paper has suggested better results with wider and deeper excision, specifically 5 cm peripheral margins and 2 fascial planes deep including bone if necessary (dorsal spinous processes, scapula, Iliac wing, ribs). They had 91 cats with VAS that underwent this type of surgery without pre-op CT or MRI planning and no adjuvant therapy. Previous recurrence rates for VAS with surgery alone were 35-59%, and 26%-52% with adjuvant therapies. With this surgical plan and no adjuvant therapy, their results were 14% recurrence. There was no difference in metastatic rate in this study as compared to past studies, which is about 20% with this type of cancer.
References:
1 JVIM 2005 Jul-Aug: 19(4): 560-3 Overley et al 2005
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NEVOG News Management of Veterinary Soft Tissue Sarcomas Andy Abbo DVM, MS, DACVIM (Oncology)
New England Veterinary Oncology Group
Soft tissue sarcomas (STS) are tumors originating from structural and connective tissues, they are diverse in histology but share a similar biological behavior and are therefore considered together. STS most often present as masses in the skin or subcutaneous tissues and their biological behavior is that of being locally invasive and that they readily invade adjacent normal tissues with finger-like projections/ tendrils that often extend far away from the primary tumor making complete resection challenging. The most important indicator of metastatic rate is grade ( i.e. degree of differentiation). STS's are graded as 1-3 with low grade (1) having a 10% metastatic rate while high grade tumors having a metastatic rate of ~40%. Examples of soft tissue sarcomas include fibrosarcoma, hemangiopericytoma, liposarcoma, nerve sheath tumor and leiomyosarcoma.
Recommended Diagnostic Testing for STS (Staging)
Staging tests recommended include baseline CBC/ CHEM/ UA, regional lymph node evaluation, three view thoracic radiographs, and abdominal ultrasound if the tumor involves the caudal portion of the trunk or pelvic limbs, sonogram may also be indicated as a general geriatric screen to evaluate for other tumors or co-morbid conditions prior to surgical intervention. In addition, a CT scan of the lesion is recommended for surgical planning to best determine the extent of disease PRIOR to surgical excision as it is well established in the literature (both human and veterinary) that the first surgery is the best chance for local control/ cure, therefore surgery and biopsies must be PLANNED carefully so that the mass and biopsy tracts are excised completely at the time of surgery. Surgical planning depends on the knowledge of tumor type, clinical stage/ extent of local disease and expected biological behavior. Excisional biopsy though tempting is generally NOT recommended as a source of initial diagnosis/histopathology and the importance of pre-surgical planning so that adequate local control is achieved at the time of the first surgery can not be stressed enough.
Treatment Options:
There are several treatment options for soft tissue sarcomas and the initial surgery is the best chance for cure/ long term control. Ultimately, the decision to pursue a particular treatment modality is based on the tumor location, histologic grade, stage, clients' wishes and consultation with a veterinary oncologist or surgical oncologist. There are four levels of "surgical dose" that are applied to resection: 1.) radical, 2.) wide, 3.) marginal, 4.) and debulking. It is important to remember that incompletely excised malignant tumors WILL recur and that recurrent tumors are typically more locally invasive due to altered vascularity and tissue planes which makes subsequent surgeries more extensive and as well as adding additional cost to the client in the form of additional surgeries or necessity of radiation therapy for local control.
It is important to discuss clients that there often is an opportunity for cure in locally confined disease with aggressive surgical intervention, when aggressive surgical intervention is not feasible then marginal or debulking surgery may be indicated especially when clients are willing to pursue adjunct radiation therapy. Many clients approach veterinarians with the mind set that they just "want the tumor off" but do not wish to be aggressive, again, it is important to educate these clients that while marginal or debulking surgeries may be palliative in the short term there are significant risks and implications associated with local recurrence in this situation.
Margin evaluation is extremely important and we recommend that margins are inked with india ink or hemoclips for orientation purposes. It is also important to remember that margins are three-dimensional, therefore lateral and deep margins must be considered when planning resections, lateral margins are determined by tumor type and biological behavior (i.e 1cm margins recommended for benign tumors and 3cm or larger are recommended for malignant tumors). Deep Tissue margins are determined by natural tissue barriers; fat, SQ tissue, muscle and parenchyml tissue does not provide a barrier to tumor invasion while muscle fascia and bone are resistant to neoplastic invasion and provide a good natural tissue barrier.
Treatment options:
Surgery
Complete excision with adequately wide margins generally involves resection of approximately 3cm margins laterally and removal of one intact fascial plane deep to the tumor. When these margins can be achieved, surgery is generally considered the treatment of choice and can be curative in some cases.
Surgery + radiation therapy
This involves a combination of surgery to remove the bulk of the tumor (macroscopic disease) and subsequent radiation therapy to destroy residual microscopic disease. This combination treatment generally provides a 70-80% chance of controlling the tumor long term (3-5 years). Definitive radiation therapy is offered at our Waltham facility with our linear accelerator, in addition to photon therapy we also have electron capabilities, which allows us to treat more superficial tumors and spare deeper tissues. Most initial radiation therapy consults and follow up can be performed at our satellite facilities. Definitive radiation therapy consists of ~15-20 treatments/ fractions given on a Mon-Friday schedule. This fractionation schedule (small daily doses) helps to reduce the risk for long term side effects in normal tissues. Potential side effects of radiation include an early, reversible reaction to rapidly dividing tissues (skin, hair) that develops midway through treatment and lasts 2-4 weeks before healing. Most side effects that occur during radiation therapy, although unpleasant, are usually not serious, and are almost always limited to the area being treated. Side effects may consist of alopecia, moist desquamation and leukotrichia. I f any side effects are noted, patients are treated with anti-inflammatories, analgesic medications and topical medications as needed. There is also the potential, although unlikely, for late irreversible side effects to slowly dividing tissues (bone, muscle, nerves) which would include risk for stricture and fibrosis, nerve dysfunction or rarely secondary sarcomas in the treatment field ( < 5% risk).
Radiation treatment planning consists of a CT scan and computer calculated dose which allows the radiation oncologist to optimize the effects against the tumor and minimize the impact on adjacent normal tissues. A common concern amongst clients is the necessity of general anesthesia for radiation therapy, it is important to know that anesthesia is only utilized to immobilize the patient long enough to receive the calulated radiation dose. Anesthesia times are very short and the agents used are ultra short acting with limited to no residual effects.
Palliative radiation therapy
If a tumor cannot be removed surgically, cannot be treated with the combination of surgery + radiation therapy, or if distant metastasis is identified, palliative radiation therapy can be considered. Palliative radiation therapy consists of once weekly radiation therapy for three weeks. The goal of this type of radiation therapy is aimed at alleviating pain, inflammation, and swelling associated with the tumor. Even when long-term control is not possible, radiation therapy may improve a patient's quality of life. This protocol consists of 3-5 large fractions of radiation given on a weekly, daily or every other day protocol depending on the cancer. The side effects with this protocol are mild as it is designed to improve the patient's comfort and quality of life while minimizing the negative impact.
Chemotherapy
Traditional intravenous chemotherapy is recommended for dogs with high-grade tumors, given the increased likelihood of metastasis. It may also be considered for patients with incompletely-excised tumors and for whom radiation therapy is not an option or for patients with non-resectable tumors. The drug of choice for treating soft tissue sarcomas is doxorubicin as a sole agent or in combination with cyclophosphamide. The protocol is administered at 3-week intervals for a total of 4-6 treatment cycles. Another option for chemotherapy is metronomic chemotherapy. This form of chemotherapy utilizes constant exposure to very low dosages of chemotherapy in combination with non-steroidal anti-inflammatory drugs. The goal of this approach to therapy is to inhibit the formation of new blood vessels (i.e. anti-angiogenesis). Cancer cells have a higher metabolic rate than ordinary cells and require a continuous supply of oxygen and nutrients. The tumor must build a network of new blood vessels in order to obtain the necessary nutrients and oxygen it needs to survive. In human medical research, a lot of emphasis has been placed on the study of angiogenesis and novel therapies to target it. In a recent veterinary study, canine patients with incompletely excised STS's were treated with metronomic therapy alone showed significantly improved survival and disease free intervals when compared to patients that received no further treatment after surgery. Therefore, the use of metronomic therapy alone or in combination with other forms of therapy may gain more popularity in the future.
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CT Corner
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 With the CT availability in veterinary medicine, we now realize a myelogram alone is not as accurate as a CT or CT/myelogram combined. (Comparison of CT and Myelography to a Reference Standard of CT Myelography for Dogs with IVD: Newcomb B. et al Veterinary Surgery 41 2012 207-214) In that study, using a 4 slice helical CT alone or combined with a myelogram was more accurate than myelography alone. This months CT demonstrates how a helical CT, like ours at CCVS, clarifies what clinically appears to be an inoperable cancer. It was actually a soft tissue sarcoma amenable to radiation therapy (RT) resulting in a long term survival.
CT Video:
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Continuing Education Opportunies
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Drs. Henry, Briere and Reese lead CE courses throughout the year for practicing veterinarians on a wide range of topics in veterinary surgery.
Register online!
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Tech Tip
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We often deal with dogs who have the following problems; neurologic disease resulting in compromised motor function and/or conscious proprioceptive deficits; bilateral ACL injuries; bilateral MPL instability; combination of ACL/MPL instability; severe spinal OA. Often these dogs are over weight which adds to the difficulty of helping them to get up, navigate slippery floors, stairs, and getting in and out of the car. The improvised beach towel support slings are hard to grasp and control especially for women with small hands. Going down stairs with hind leg only slings, either towels or professionally made (Quick Lift) are not ideal because one can not safely control the dogs descent. We are often concerned for the safety of the owner on stairs as they assist their dog. Lifting dogs using ones legs and back can cause injury more often than lifting and guiding the dog with your arms while standing erect. Our TECH TIP this month is the use of SupportRx a total body support system. They were developed by a veterinarian, Dr. James St. Clair. They come in multiple sizes (S, M, L, XL, XXL, XXXL) from S for dogs 15#'s or less to dogs XXXL 85-110#'s. They are moderately priced ranging from $25.00 to $57.00 based on the dogs size. The dog can comfortable wear them all the time so it is easy to help them ambulate quickly. Often their use is temporary for post-op assistance following limb surgery with either unilateral or bilateral injuries. For those older dogs with chronic disease (lumbo-sacral instability, severe spinal OA, demyelinating disease) these support harnesses are very helpful. See video.
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