14.2.2.1 Melanoma

Melanocytic tumors have always been a challenge for canine patients, being one of the most common oral malignancies found, with a highly variable metastatic rate depending on the biological behavior (see Chapter 7 – Oral Maxillofacial Tumors, Cysts, and Tumor‐Like Lesions). Lymph node enlargement can be found, so full metastatic evaluation is recommended, as 70% of cases in one study had metastasis with lymphadenopathy, but 40% of metastatic patients had no lymph node enlargement [10]. Abdominal ultrasonography is recommended for patients [11]. Tumor size is an important prognostic factor, though relative size of tumor to patient size has not been standardized [11]. Incomplete margins have reported to be associated with a decreased prognostic outlook, but other studies have shown no significant decrease in ST and progression free intervals (PFIs) [12]. Patient age tends to have a negative impact on prognosis [13], but location, aside from contributing to tumor resection challenges, is not a prognostic factor [12].

Consideration of systemic treatment would be a likely choice for a metastatic disease, but melanomas in humans have been extremely chemoresistant [11]. The use of carboplatin has shown no significant difference in recurrence or survival time as compared to surgery alone [14, 15], and, in general, the inefficiency of chemotherapy is recognized [16]. Anecdotal results have been reported with complementary medicine efforts including hyperthermia and dendritic cell therapy [17]. Recent studies on canine melanoma cell lines that show apoptosis with high doses of celecoxib in Cox‐2 expressing cells continue to explore options [18].

Previous studies with external beam radiation therapy had shown some promise in local disease control, though earlier reports had not determined the optional fraction selection [16]. Studies include use of hypofraction protocols, including one in cats (without a durable response) [19] and one in dogs evaluating hypofraction with cisplatin in dogs, the majority with incompletely excised Stage 1 disease (but local control similar to other methods) [20]. The use of megavoltage versus orthovoltage to palliatively treat local disease unamenable to surgery (similar results, but some severe complications) has also been studied [21].

In 2007, a conditional license was granted for a DNA vaccine (xenogenic human tyrosinase) based on a Phase 1 clinical trial or proof of concept trial. A safety and efficacy study demonstrated a significantly improved survival time in treated patients, when achieving sufficient local control to allow the activation of a host response, in the absence of disseminated disease [22]. Two later retrospective studies did not show the benefits of the vaccine on survival time or PFIs [23, 24].

Therefore the concept that resection with wide margins and complete excision to improve survival time remains the optimal goal for managing melanocytic tumors [12, 13]. Any time a melanocytic mass, pigmented or not, is diagnosed, surgical attempts should be aggressive with full metastatic evaluation. The one exception, a benign variant called a melanocytoma, typically less than 1 cm and well circumscribed, can often be managed with wide excision [25].

14.2.2.2 Squamous Cell Carcinoma

As the second most common oral malignancy in dogs and by far the most common in cats, squamous cell carcinoma (SCC), is often seen characterized by aggressive local infiltration, especially in cats. As stated in Chapter 7, the metastatic rate in dogs is low for rostral tumors and high for lingual and tonsillar tumors. Recent studies show a higher metastatic rate (to the mandibular lymph node, often the only one checked) of near or greater than 30% [26, 27], which is higher than previously thought. Though location is not a definitive prognostic factor, a tumor that is inoperable, either due to its size or location (non‐maxillary), carries a poor to grave prognosis [27]. Truly resectable tumors followed by definitive radiation therapy carried the best prognosis in a small number of cats [28] and may also be true in dogs [9].

Few reports have shown significant improvement in therapy parameters when using chemotherapy for feline oral squamous cell carcinoma (FOSCC): cisplatin was shown to be ineffective [29] and carboplatin had one partial response of short duration [30]. However, an aggressive protocol using carboplatin and radiation therapy in cases of tonsillar FOSCC showed some long‐term survival rates [31]. Other therapies look at adjunctive therapy to slow the pathological bone changes and tumor growth with the use of bisphosphonates [32] and toceranib, especially when combined with non‐steroidal anti‐inflammatory drugs (NSAIDs) [33]. In particular, the Cox‐2 activity of some NSAIDs has been investigated, looking at the Cox‐2 expression of oral SCC cells and the impact of medication [34]. The co‐treatment of cells with masitinib and piroxicam significantly inhibited cell proliferation as compared to either drug alone [35]. Polyamine inhibitors that target a substance needed for cell proliferation have shown inhibited cell growth in mice [36], as well as tumor regression in 2 cats and stable disease in 6 cats out of 13 in one study [37].

While survival times may not change, such medications can provide clinical benefit and palliative treatment. Additional medications include analgesics (tramadol, gabapentin, amitryptillyine) to decrease inflammation and pain and oral prednisolone instead of NSAIDs to maintain appetite in the patient [28].

Radiation therapy has been considered as adjunctive therapy in FOSCC to reduce the tumor size prior to surgery [38] and as palliative therapy for non‐resectable tumors with varying responses [39, 40]. The previously noted responses for tonsillar SCC to radiation therapy and carboplatin [31], as well as an accelerated hypofraction protocol with 29% of cats lasting more than one year [41], show some promise, though tumor size is of a prognostic factor and most responses were of short duration [41].

As with melanocytic tumors, the standard of care remains early aggressive surgical removal of the entire mass, if possible, with adjunctive therapy in specific cases. Supportive care, particularly in cats, may include palliative medication and nutrition support.

14.2.2.3 Fibrosarcoma (FSA)

The third most common oral malignancy in dogs (and second in cats) is fibrosarcoma (FSA). FSA is known to be infiltrative and determining its full extent can be challenging (see Chapter 7 – Oral Maxillofacial Tumors, Cysts, and Tumor‐Like Lesions). While generally thought to have a low metastatic potential (12% pulmonary, 20% regional LN) [42], a higher metastatic rate can be seen in patients with longer survival times, probably due to the extended time to metastasize [43]. Another challenge with FSA is the discrepancy that can be seen with apparently low‐grade histological evaluation in a tumor with biologically high‐grade activity (“high–low FSA”) [42]. In this study of 25 dogs, 72% had bone lysis with aggressive infiltration of local tissues and local recurrence was the typical reason for euthanasia.

While surgical margin intent may be limited due to anatomical planes and anticipated post‐operative function, the widest margins should be the goal [43]. Even if 2 cm margins cannot be reached, surgery should still be considered, as even a narrow excision (<15 mm) can potentially provide dogs with a good long‐term outcome [43].

Adjunct treatment with radiation therapy has been proposed, with the optimal approach being aggressive surgery and definitive, rather than palliative, radiation therapy [41, 44]. Palliative RT alone in cases of non‐resectable tumors can help to reduce tumor size and improve the patient’s quality of life [41].

14.2.2.4 Osteosarcoma

Osteosarcoma (OSA) in the oral cavity tends to cause surrounding bone lysis rather than hard tissue proliferation (see Chapter 7), and low‐grade tumors, as well as benign osteomas, need to be differentiated from fibro‐osseous lesions by their clinical appearance, not just by histopathology [45]. While debulking an osteoma often results in minimal progression [46], OSA requires wide surgical margins of at least 1 cm, as incomplete resection will result in 100% recurrence [2].

While the roles of adjuvant therapy (radiation or chemo) have not been fully determined [2], with a reported 58% metastatic disease prevalence [47], further management needs to be addressed. Palliative radiation therapy for non‐resectable tumors may be considered. A recent study also investigated the effects of a selective inhibitor of nuclear export (SINE), where apoptosis of appendicular OSA cell lines was demonstrated [48]. Aggressive surgery remains the standard of care.

14.2.3.1 Surgical or Intraoperative Intent

With information gathered about the patient, the lesion, and the client’s goals for therapy, decisions can be made as to the extent of the surgical procedure to be performed. The ideal situation is detecting a small lesion early in the course of the disease with adequate excision and clean margins for curative surgical intent. Complete local disease control and no indication of metastasis provides the best scenario. If the intent is curative surgery, or eradication of the pathological condition [49], it is important to make every effort to completely excise the tumor the first time. If additional surgery is needed, the region now has a distorted anatomical structure and even more radical surgery would be required [5]. Unfortunately, many oral tumors are discovered later in their progression, with extensive local invasion and even indications of early metastasis. With these more advanced lesions, a balanced decision looking at the size of the lesion and the attainment of reasonable margins will be considered, taking into account the size of the patient and surrounding anatomical structures. This intraoperative intent – the gross margins the surgeon is attempting to obtain via excision – can be restricted by anatomical planes, the ability to reconstruct the defect, and maintenance of post‐operative functionality [43, 50]. If reconstruction is to be considered, a surgical plan for that reconstruction should occur prior to excision of the tumor [49].

On one extreme, removal of a cyst or cyst‐like lesion can be as simple as enucleation, the shelling‐out of the entire cystic lesion without rupture, including the entire epithelial lining. Often enucleation attempts are followed by curettage to remove 1–2 mm of bone around the entire periphery of the cyst to remove any remaining epithelial cells that could cause recurrence of the cyst [49]. Most tumors, however, require some degree of resection by incising through the uninvolved tissues around the tumor and delivering the tumor without direct contact during instrumentation (an en bloc resection) [49].

This determination of “involved” and “uninvolved” tissues can be described in the context of the zones around the tumor. The pseudocapsule is described as a grossly visible membrane consisting of normal and neoplastic cells, surrounded by a reactive zone of inflammatory cells [5]. An intracapsular excision (from within its pseudocapsule) would be a debulking of the tumor. This could be used for palliative therapy or for benign, well‐differentiated tumors such as odontomas [5, 51] (Figure 14.2a to d). In relation to the described zones, a marginal resection would be outside the pseudocapsule but still within the reactive zone, and may be appropriate for some well‐differentiated benign tumors. Another definition of marginal incision involves resection of a tumor without disruption of the continuity of the bone [49]. A wide excision would involve an en bloc resection of the tumor, pseudocapsule, reactive zone, and a wide margin of normal tissue [5]. The term “partial resection” parallels this description, with removal of a full‐thickness portion of the mandible or maxilla [49]. Relatively small to medium sized malignant tumors are likely to be treated with such procedures. Radical excision would involve removal of the entire involved bone or supporting tissue compartment (mandibulectomy). Ablative composite resection would extend the excision to include the bone, adjacent soft tissues, and contiguous lymph channels for malignant tumors [49].

For whatever reasons the client may have, sometimes providing palliative relief will be the limits of clinical efforts. Goals of such therapy would be to relieve clinical signs, restore or improve function, and to improve the quality of life of the patient, though not necessarily the life span [52]. Debulking or cytoreduction of the tumor is seldom recommended (see Chapter 7 – Oral Maxillofacial Tumors, Cysts, and Tumor‐Like Lesions), as recurrence would be likely, though may be utilized in conjunction with other treatments such as radiotherapy.

14.2.4.1 Access to Surgical Site

Positioning of the patient is critical for optimal access to the surgical site: for rostral procedures, dorsal recumbency has been described for working on the maxilla, and sternal recumbency for the mandible, with the opposite jaw suspended from a framework above. Dorsal recumbency or a “lazy lateral” position (mostly on their back but leaning to one side or the other) can work for most procedures, reserving ventral recumbency for nasal procedures. For central and caudal procedures, lateral recumbency affords good visualization of the buccal surfaces, though adjustment of the patient’s head would facilitate palatal and lingual access.

For caudal procedures, both maxillary and mandibular, commissurotomy can provide better access to the lesion and surrounding tissues. Some variations for maxillectomy will be discussed in that section. Closure of the lips further rostrally (to the first or second premolar), a commissuroplasty, can help post‐mandibulectomy to help prevent excessive drooling or tongue protrusion. This three‐layer closure will, however, minimize access to the caudal maxillary teeth, making home care, professional care, or any future extractions quite challenging.

14.2.4.2 Surgical Preparation

In determining the intraoperative intent, evaluation of the tissues external to the oral cavity should also be evaluated. If any portion of the lips should be incorporated into the resection, a broad area around that region should receive complete surgical preparation, with isolation of the area with surgical draping. Likewise, if a section of skin needs to be excised to obtain margins or to facilitate esthetic closure, the area should be prepped and marked prior to the start of surgery, keeping final closure in mind before starting [53].

The oral cavity should be rinsed with dilute chlorhexidine solution and the pharynx can be packed with gauze sponges, which will be removed at the end of the procedure. The endotracheal tube should be secured in a position that will not allow it to interfere with the procedure (see options for transmylohyoid and pharyngeal intubation in Chapter 13 – Oral Surgery – Fracture and Trauma Repair). Appropriate soft mouth gags (wedge, not spring‐loaded) can be placed to position the opposite jaw if other suspension devices are not used. Pharyngeal packs or suctioning in the back of the mouth should be provided.

14.2.4.3 Intraoperative Intent

In conjunction with the pre‐operative evaluation of the tumor to be excised, the marking of the planned incisions should allow for adequate margins and retain sufficient tissue for complete, tension‐free closure, hopefully with the possibility of harvesting large mucosal flaps to minimize tension. Tissues should be gently handled to minimize any trauma to the tissue to be closed and to minimize handling of tissues of the tumor to be removed. Visualization and identification of exposed neurovascular bundles will help to preserve the local blood supply and minimize damage to associated nerves. Minimize the use of electrocautery, using pressure and ligation of blood vessels where possible.

14.2.4.4 Mucosal and/or Skin Incision

Following the marked intended incisions, lightly score the mucosa, producing a bleeding line that will not be distorted when the time comes to make the incision deeper. When incising the mucosa, sharp dissection rather than electrocautery is preferred to minimize post‐surgical dehiscence [54]. Carefully dissect through the soft tissue down to the bone, preserving neurovascular bundles as they are encountered, or ligating when necessary [51]. A periosteal elevator can be used to elevate the soft tissues with the periosteum of the bone to either side of the planned ostectomy line. Stay sutures may be used to retract these soft tissue layers with care. Protective gauze may be used over the tumor segment itself to minimize handling or potential dissemination of cells [51].

14.2.4.5 Osteotomy – Ostectomy

While an osteotome and mallet can be used, following pinpoint holes initially drilled into the line of the ostectomy, more precise cutting can be made with burs and power equipment. Ideally, a surgical handpiece with no air‐insufflation and built‐in sterile irrigation can be used for a precision ostectomy. A standard high‐speed handpiece with cutting burs and irrigation certainly can also be used, adding the risk of compressed air being introduced into the surgical site. Carbide burs are commonly used for cutting teeth and bone, but will produce a rougher cut edge. Diamond burs with medium grit can be used for a smoother cut or for osteoplasty to smooth the sharp bone edges.

The potential risk of thermal injury using any rotating cutting instruments should be minimized with careful use and appropriate irrigation. This thermal injury can be avoided if ultrasonic piezoelectric units are utilized, with better protection of adjacent soft tissue and a lack of coagulative necrosis [55]. Surgical time can be increased with these piezoelectric units as they are less effective than mechanical saws, and it is said they have a learning curve, but the benefits should be considered [55]. In most resections, a 90° sharp‐angled cut should be avoided, as a curvilinear ostectomy has been shown to have higher resistance to occlusal forces [56].

14.2.4.6 Closure Concepts

Once the mass is removed, general principles of closure are followed, including lavage of the area with dilute (0.12%) chlorhexidine or sterile saline. With certain tumors, changing gloves, instruments, and drapes may be warranted [5]

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