Partial Glossectomy in a Blue-Tongued Skink (Tiliqua scincoides) with Lingual Squamous Cell Carcinoma

A 16-year-old, male, intact blue-tongued skink (Tiliqua scincoides) was presented for reluctance to eat, deviation of the tongue, and a pink mass noted in the mouth. It was housed alone at the Micke Grove Zoo (Lodi, CA) with a temperature gradient maintained between 20–32°C (68–90°F) and a relative humidity of 35–45%. The diet consisted of vegetables, leafy greens, fruit, mealworms, and 1 pinky mouse per week. One year and 4 months prior to presentation, the patient had a 3 month history of anorexia and weight loss; this was most-likely associated with brumation during the winter months. No other significant abnormalities were noted on physical examination at that time, and appetite improved without intervention. One month prior to presentation, the patient experienced dysecdysis and a recommendation was made to increase humidity to 45%. A complete blood count (CBC) and plasma chemistry panel revealed no significant findings, and whole-body radiographs indicated six healed rib fractures along the mid thorax.

On presentation, the blue-tongued skink was reportedly reluctant to eat, although capable, and seemed to have lateral deviation of the tongue with a pink mass noted in the oral cavity. On examination it appeared alert, well hydrated, and was in good body condition, weighing 690 g. On assessment of the oropharyngeal cavity, there was a 2–3 cm long by 1 cm wide pink, well vascularized, irregular, friable, cobblestone-textured mass adhered to the median raphe on the ventral aspect of the tongue. The tongue deviated to the left when retracted into the mouth.

The decision was made to perform an incisional biopsy of the lingual mass. Anesthesia was induced with 5 mg/kg propofol IV in the ventral coccygeal vein (PropoFlo™, 10 mg/mL, Abbott, North Chicago, IL) and administration of isoflurane 2–4% delivered in oxygen via face-mask for full induction, followed by intubation with a 2.5-mm endotracheal tube. An incisional biopsy was taken of the lingual mass, which was then debulked by 60–70% using a sterile electrocautery pen (Pro Advantage® Sterile Cautery, National Distribution and Contracting, Inc., Nashville, TN). A sample of the mass was submitted for culture and sensitivity. The blue-tongued skink received 0.3 mg/kg of meloxicam (Metacam® 5 mg/mL, Boehringer Ingelheim Vetmedica, Inc., St. Joseph, MO) PO q24h for 5 days.

Histologically, the lingual tissue submitted was characterized by variably sized, irregularly shaped, anastomosing islands of neoplastic epithelium separated by dense fibrous tissue (desmoplasia). Neoplastic epithelial cells had marked anisokaryosis and anisocytosis, with coarsely stippled chromatin. Individual islands of epithelium infiltrated into and were entrapped within the glossal skeletal muscle. Neoplastic epithelial islands were bordered by a peripheral palisade of basaloid cells and exhibited progressive centripetal squamoid differentiation, often culminating in central keratin pearls or necrotic eosinophilic debris. The histological diagnosis of the lingual mass was squamous cell carcinoma (SCC). Very small numbers of mixed-growth bacteria were cultured, including Serratia liquifaciens and coagulase-negative Staphylococcus spp., as well as large numbers of fastidious, nonenteric species that were sensitive to multiple antibiotics. Toxic heterophils, monocytosis, and basophilia were noted on the CBC, but the total white blood cell count was not elevated.

The decision was made to perform a resection of the mass with partial glossectomy, as the patient was a good candidate for surgery and no metastases were seen on radiographs. The patient was premedicated with oxymorphone 0.1 mg/kg (Oxymorphone, 1 mg/mL, DSM Pharmaceuticals, Greenville, NC) IM prior to induction. An IV catheter was placed in the ventral coccygeal vein using the lateral approach. Anesthesia was induced with 5 mg/kg propofol (PropoFlo®, 10 mg/mL, Abbott) IV, followed by 4% sevoflurane in oxygen via face-mask for full anesthetic induction. The patient was then intubated using a 2.5-mm endotracheal tube and maintained on sevoflurane 3–4% with oxygen. Intravenous fluids (10 mL LRS) were delivered during the procedure, and 20 mg/kg ceftazidime (Cefepine 1 g, 100 mg/ml, Hospira Healthcare, India) was given IM. Heart rate was monitored with an electrocardiogram (LifeWindow Lite LW8, Digicare Biomedical Technology, Boyton Beach, FL) and a Doppler unit (Ultrasonic Doppler flow detector, model 811, Parks Medical Electronics, Inc., Aloha, OR) placed at the level of the pectoral girdle. To prepare for surgery, the oral cavity was flushed with sterile saline. Two stay sutures of 2-0 polydioxanone (PDS; Ethicon Inc., Johnson and Johnson, Somerville, NJ) were placed in the distolateral aspects of the tongue. A circumferential incision into the epithelial layer was made with a scalpel, excising approximately 40% of the distal tongue including the mass with 0.5–1 cm gross margins. The tongue musculature was then transected and the lingual artery ligated with 5-0 PDS (Ethicon Inc., Johnson and Johnson). The lingual epithelium was also closed with 5-0 PDS in a simple continuous pattern. The blue-tongued skink recovered well from anesthesia, with only a few ventricular premature contractions noted during recovery (Fig. 1).

Histopathology showed complete excision of the mass; however, the margins were narrow, leading to the concern of possible tumor recurrence and subsequent metastasis. The histopathology of the completely excised mass was consistent with the findings on incisional biopsy (Figs. 2, 3).

Postoperatively the patient was given 1 mg/kg morphine (Morphine, 15 mg/mL, West-Ward, Eatontown, NJ) IM q24h for 3 days, 0.3 mg/kg meloxicam PO q24hr for 9 days, and was continued on 20 mg/kg ceftazidime IM q72h for 1 month. The blue-tongued skink was kept in the hospital for 1 wk following surgery to allow for postoperative monitoring and to provide enteral support. Because the patient lost weight daily for a period of 1 wk, it was assist-fed using standard dietary items (king worms and a mixed fruit–vegetable puree) added to a recovery food designed for carnivores (Carnivore Care™, Oxbow Animal Health, Murdock, NE). Two days after discharge to the zoo, the patient began eating normal prey items independently. Weekly recheck appointments revealed the tongue was healing without complication and the patient was eating on its own, had good activity, and was doing well. At 2.5 yr postsurgery, no tumor recurrence was noted during weekly veterinary visits to this zoological institution. Additionally, the skink was able to adequately locate and prehend food and was maintaining its weight and normal body condition.

Squamous cell carcinomas are malignant tumors of squamous epithelial cells (Meuten, 2008). These tumors are common in many mammalian and avian species, and there are several reports in reptiles (Ratcliffe, 1993; Roe et al., 2002; Garner et al., 2004; Meuten, 2008; von Deetzen et al., 2012; Steeil, 2013). In some mammals, a link has been made between SCC development and excessive exposure to ultraviolet light, chronic inflammation, and carcinogens (Withrow et al., 2006). In reptiles, an exact cause has not yet been implicated, but previous case reports have suggested a correlation between environmental factors or the ingestion of bracken fern leading to SCC formation (El Mofty et al., 1980; Frye, 1994).

In reptiles, cutaneous SCC has been described in squamates, rhyncocephalians, and chelonians, while oral SCC has been reported in several species of snakes, monitors, skinks, and tegus (Garner et al., 2004). In one retrospective study on reptile neoplasia, SCC had a prevalence of 5.5% in lizards, making it the third most common tumor type diagnosed and the most common tumor type described in skinks (Garner et al., 2004). Squamous cell carcinomas have been diagnosed in multiple locations including the epidermis, digestive tract, lungs, periorbital tissue, oral cavity, urinary bladder, prostate, vagina–cervix–cloaca, and pericloacal scent glands. A retrospective study suggested that SCC may have a predilection for the mucocutaneous junction in bearded dragons, particularly the periocular tissues (Abou-Madi and Kern, 2002; Hannon et al., 2011). Squamous cell carcinomas commonly metastasize in some mammals, whereas metastatic disease is uncommonly reported in reptiles (Garner et al., 2004, von Deetzen et al., 2012).

The clinical signs in reptiles and other animals with oral SCC may include anorexia, dysphagia, weight loss, lethargy, oral hemorrhage, dyspnea, and ptyalism, although some animals may be asymptomatic and a mass may be found incidentally (Syrcle et al., 2008; Hannon et al., 2011). The skink in this case report presented with oral aversion to food, weight loss of 5%, deviation of the tongue, and a pink mass noted within the oral cavity.

Diagnosis of SCC is based on medical and husbandry history, physical examination findings, and an incisional or excisional biopsy and histopathology. In this case, the biopsy interpretation revealed islands of neoplastic epithelium surrounded by stromal desmoplasia, with keratin pearls and necrotic eosinophilic debris. These findings are pathognomonic for the diagnosis of SCC in reptiles (Roe et al., 2002; Garner et al., 2004). Additionally, blood biochemistry testing may be helpful to assess for humoral hypercalcemia of malignancy (HHM), as has been reported in mammals and a single Hermann's tortoise (Testudo hermanni) with SCC of the plastron and carapace (von Deetzen et al., 2012). Humoral hypercalcemia of malignancy with SCC can occur through either increased production of Parathyroid hormone-related protein (or PTHrP) by tumor cells or tumor-induced osteolysis (von Deetzen et al., 2012). Radiographic imaging may show a soft-tissue opacity in the region of the neoplasia, but is less likely to reveal metastases in reptiles, as SCC has proven to be infrequently metastatic with the exception of a few case reports in loggerhead sea turtles (Caretta caretta) and an eastern diamondback rattlesnake (Crotalus adamanteus) (Garner et al., 2004; Oros et al., 2004; Anderson et al., 2010; von Deetzen et al., 2012).

Treatment options for lingual SCC in human and veterinary medicine typically involve surgical excision, radiotherapy, or various treatment combinations in more-advanced stages of the cancer (Al-Rajhi et al., 2000; Bettendorf et al., 2004; Gorsky et al., 2004; Culp et al., 2013). In humans, dogs, and cats there are limited but promising reports of intralesional chemotherapy used to treat SCC of the mouth and skin (Kitchell et al., 1995; Theon et al., 1996; Iwanaga et al., 2007). Systemic chemotherapy has also been used as an adjunctive treatment, but in humans and dogs SCC tends to be poorly responsive to both radiation and systemic chemotherapy (Dvorak et al., 2004; Culp et al., 2013). These adjunctive therapies are occasionally pursued due to the risk of metastasis seen in humans and other mammals (von Deetzen et al., 2012). In reptiles, systemic chemotherapy may be unnecessary due to the rare incidence of metastatic SCC (Garner et al., 2004). Radiation therapy was shown to be unsuccessful at treating pharyngeal SCC in a case report of a Madagascar ground boa (Acrantophis madagascariensis); however, given a lack of published reports, radiation therapy may still prove useful in cases where complete surgical excision cannot be achieved or where tumor location does not allow for surgical removal (Steeil et al., 2013). In a single case report of a yellow-bellied slider (Trachemys scripta scripta), intralesional electrochemotherapy was used to successfully treat a cutaneous SCC, indicating the need for further investigation of this modality (Lanza et al., 2015).

Regarding surgical intervention, there are several categories of glossectomy described in humans, classified according to the anatomic location and amount of lingual tissue removed. A partial glossectomy is defined as amputation of the tongue rostral to the frenulum, the attachment to the floor of the mouth. A subtotal glossectomy is removal of the entire freely moveable tongue and a portion of the muscles required for lingual movement and coordination. A near-total glossectomy is amputation of >75% of the tongue, and a total glossectomy is removal of the entire tongue (Dvorak et al., 2004; Culp et al., 2013). Because the patient in this case report developed neoplasia of the ventral lingua, cranial to the frenulum, the decision was made to pursue surgical excision via partial glossectomy.

Because SCC is typically locally invasive and not metastatic in reptiles, surgical excision in similar cases may prove curative as long as adequate surgical margins are obtained. Although no literature exists regarding the appropriate surgical margins for this tumor in reptiles, literature on lingual SCC in mammals recommends 1-cm margins (Withrow et al., 2006). Therefore, 0.5–1-cm margins were obtained in this case; unfortunately, further excision was limited based on the amount of tongue that remained.

Some uncommon, possibly short-term surgical complications related to glossectomy in humans and dogs include intraoperative hemorrhage, postsurgical bleeding, pain, partial tongue paralysis, local tumor recurrence, surgical dehiscence, and ptyalism, which is usually self-limiting (Dvorak et al., 2004; Syrcle et al., 2008; Culp et al., 2013). Aspiration pneumonia is one of the most-common postsurgical complications in humans but has not been reported as a complication in animals (Razack et al., 1983; Weber et al., 1991; Dvorak et al., 2004). It should be assumed that the surgical and postsurgical complications associated with glossectomy could also occur in reptile patients as well. In this current case, the patient did not experience any of these aforementioned complications, although the patient's postsurgical oral aversion to food may have been caused by dysphagia or pain. The only postsurgical complication noted was a small focal region of necrosis on the right aspect of the remaining tongue, which resolved with time.

Prior to pursuing surgical removal of lingual neoplasia, the functions of the tongue as well as the general risks and species-specific consequences of lingual surgery must be considered. Functionally, the tongue is important in feeding due to its role in food prehension, bolus formation, and maneuvering the food bolus for proper chewing and swallowing. Additionally, the tongue is the organ responsible for taste and it assists with grooming, thermoregulation, and vocalization in some animal species (Dvorak et al., 2004; Syrcle et al., 2008). Because glossectomy involves amputation of part of or all of the tongue, it stands to reason that important functions may be lost.

A major concern with performing glossectomies in mammals is loss of the ability to properly thermoregulate, prehend food, and drink water via lapping with the tongue. However, three different studies performed since 2004 revealed that partial and subtotal glossectomy was well-tolerated in dogs, and prehension and thermoregulation were not affected. Even in cases of near-total and total glossectomy, dogs were able to adapt to their disability, eat and drink on their own, and live good-quality lives (Dvorak et al., 2004; Syrcle et al., 2008; Culp et al., 2013).

In squamates, as in humans and dogs, the tongue is important in deglutition, gustation, and drinking. Unique to snakes and lizards is the role the tongue plays in chemosensation and smell through its interaction with the vomeronasal organ (Burghardt, 1970; Schwenk, 1988, 1993; Rehorek et al., 2000). This chemosensation is involved in many predatory, environmental, social, and mating behaviors. Squamates use their tongue to chemically sample the environment by tongue-flicking, and these chemicals then reach the vomeronasal organ via the interaction between the tongue and vomeronasal ducts located on the oral palate (Cooper and Alberts, 1991; Filoramo and Schwenk, 2009). One study assessing the effects of glossectomy on garter snakes (Thamnophis sirtalis) found that despite removal of the tongue, snakes were able to transport a low level of radiolabeled chemicals to the vomeronasal organ by touching their nose directly to the material of interest (Halpern and Kubie, 1980). A similar study conducted on ocellated skinks (Chalcides ocellatus) revealed vomeronasal labeling was equivalent when the snout made contact with the target substance, regardless of whether or not the lizards had intact tongues (Graves and Halpern, 1989). Tongueless animals in both studies that did not directly contact the material with their nose showed no radiolabeling present in the vomeronasal organ. These experiments indicated that the tongue is not required to bring chemosensory molecules into the vomeronasal organs, as long as the snout is able to make contact with the substance or food. It also appears that the tongue is less necessary for chemosensory transfer to the vomeronasal organ in certain lizards as compared to snakes. This likely indicates that glossectomy in some lizard species may be more well tolerated than in snakes (Halpern and Klubie, 1980; Graves and Halpern, 1989). In fact, the patient in this case report was able to successfully locate and consume enough food on its own that it is not only still alive today but has been able to maintain weight and normal body condition for 2.5 yr after surgery.

It is recommended that patients be kept in hospital for at least 1 wk following surgery to monitor for postoperative complications, appropriate food prehension, and normal behavior. Opioid drugs may be administered to control pain for 3–5 days and non-steroidal anti-inflammatories, such as meloxicam, may aid in managing pain and inflammation for the first 7–10 days. Antibiotics, such as ceftazidime, can be administered prophylactically to help prevent secondary infection of intraoral incisions. In this case, antibiotics were administered due to an active infection of the tongue that required treatment. The clinician should be prepared to intervene with enteral support if needed until feeding behavior is observed and the animal is able to maintain weight and normal body condition. Dogs undergoing major glossectomies in one study required esophagostomy or gastrostomy tubes for several weeks to months to provide sustenance and assist in feeding (Dvorak et al., 2004). The patient in this case was nutritionally supported via intermittent gavage feedings with mealworms, kingworms, and a liquid diet because it was anorectic and losing weight postoperatively. An esophagostomy or gastrostomy tube was not required in this case. Recheck examinations were performed and are recommended every 2–6 months following surgery to assess for tumor recurrence.

In summary, partial glossectomy was a curative and viable option for treatment of lingual SCC in this blue-tongued skink. There was no tumor recurrence 2.5 yr postsurgery and the patient was doing well, able to adequately locate and prehend food, and was maintaining its weight. Based on the locally invasive nature and low metastatic risk associated with SCC in reptiles, surgical excision with adequate margins should be considered as a treatment option with a good prognosis.