Primary Esophageal Squamous Cell Carcinoma in a Cat

Introduction

Tumors of the esophagus are rare and account for <0.5% of all cancers in the dog and cat.¹ Animals with an esophageal neoplasia most commonly are presented with clinical signs consistent with chronic esophageal obstruction including dysphagia, regurgitation, or signs associated with aspiration pneumonia.^1,2 More commonly diagnosed diseases of the esophagus in animals with these clinical signs include megaesophagus, esophagitis, esophageal granuloma, esophageal foreign body, esophageal diverticula, and esophageal stricture.³ These more common disease processes make neoplasia a less likely differential and demonstrate the importance of appropriate diagnostics such as endoscopy, histopathology, and computed tomography (CT) to make a definitive diagnosis.

Although rare, primary esophageal neoplasia has been reported in several cats, and the most common tumor type is squamous cell carcinoma (SCC).^4,5 Prognosis for esophageal neoplasia is poor and is dependant on how early in the disease process the neoplasia is diagnosed and the treatment option is initiated.⁵ This report describes a case of primary esophageal SCC in an 8-year-old cat. The tumor was identified via diagnostic imaging (radiography and CT) and was diagnosed via histopathology. The cat survived 16 weeks from the time of presentation and 4 weeks from the onset of treatment with piroxicam. This case illustrates the difficulty in making a definitive diagnosis of SCC based on endoscopic biopsies alone.

Case Report

An 8-year-old, castrated male domestic longhair cat was referred for evaluation of an esophageal stricture. The cat had a 3-month history of weight loss and regurgitation after every meal. Regurgitation of food and liquid had started approximately 1 week after an annual physical examination and vaccination.

On presentation, the cat was thin (body condition score of 2.5/5), weighed 4.46 kg, and was estimated to be 5% dehydrated. The cat was admitted to the hospital, and fluid therapy was initiated. A complete blood cell count revealed a normocytic normochromic nonregenerative anemia (hematocrit 26.0%, reference interval 30% to 45%), and serum biochemical analyses were unremarkable. Thoracic radiographs revealed slight ventral tracheal deviation, an enlarged air-filled esophagus extending to the base of the heart, and a subtle, soft-tissue opacity at the base of the heart at the site of the stricture [Figures 1, 2].

The following day, the cat was anesthetized with isoflurane gas, and endoscopy was performed. The area of esophageal stricture was identified at the base of the heart [Figure 3], and balloon dilatation was performed using a 12- and 14-mm balloon [Figure 4]. After dilatation, several biopsy samples were taken from the stricture site, the stomach, and the duodenum using a 2-mm biopsy instrument. A percutaneous gastrostomy tube was placed under endoscopic guidance at this time. The next day, endoscopic ballooning was again repeated, and the cat was discharged 2 days later. Histopathology revealed esophagitis, and samples obtained from the duodenum and stomach were normal. Over the next 2 weeks, the strictured area persisted, and the cat had two additional ballooning procedures.

Two weeks after initial presentation, the cat was presented on emergency after pulling out the gastrostomy tube. Abdominal radiographs revealed no abnormalities. The cat was again anesthetized with isoflurane gas, and endoscopy was repeated. The strictured area persisted, and esophageal ballooning was repeated. During this procedure, a total of 1 mg of triamcinolone was injected in four quadrants of the stricture in an attempt to decrease inflammation. The gastrostomy tube was replaced endoscopically, and the cat was discharged the following day.

Over a total of 2 months, the cat returned for a total of five esophageal ballooning procedures resulting in no change in the stricture. During the fifth ballooning procedure, four additional esophageal biopsies were collected using a larger, 3-mm biopsy instrument. Histopathology was consistent with a diagnosis of SCC. A CT scan was performed in helical mode with no slice overlap in 3-mm slices. Pre- and postcontrast studies were obtained. The primary alteration seen was a soft-tissue mass in the esophagus at the region of the heart base, causing constriction of the esophagus and mild compression of the airways distal to the carina [Figures 5A–5D].

After the diagnosis of SCC, no further ballooning procedures were performed. Nutritional support was continued by feeding through the gastrostomy tube to meet the cat’s energy requirements. During this time, the cat’s weight increased to 4.78 kg, and he was reportedly doing well at home. Treatment with piroxicam (0.3 mg/kg per os q 24 hours) for its antiinflammatory and antineoplastic effects was initiated and continued for a total of 1 month, at which time the owners elected euthanasia due to a decline in the cat’s quality of life. Necropsy confirmed a diagnosis of SCC of the esophagus. The tumor extended as an annular and stenosing mass from the esophageal mucosa and was approximately 2.5 × 3 × 2 cm in size, with thickening of the wall up to 1.5 cm [Figures 6, 7]. No metastatic lesions were noted. At the time of necropsy, the cat was in good body condition with adequate muscle mass and body fat.

Discussion

Esophageal carcinomas start at the squamous cell mucosa layer and eventually infiltrate the tunica muscularis and then the esophageal lumen.⁶ In cats, SCC of the esophagus may occur anywhere along the length of the esophagus, but the most common location is the middle and distal thirds of the esophagus, as was seen in this case.³ Tumors resulting in a decreased esophageal lumen diameter do not always originate from the esophageal tissue itself. Paraesophageal tumors such as thymic, heart base, or thyroid tumors may also invade the mediastinum and cause esophageal stricture.⁶ As evidenced by this case, the presenting clinical signs are usually the result of the effects of the mass on the luminal diameter and function of the esophagus. This is important, because successful treatment is limited if the disease is advanced at the time of presentation.⁵

Diagnosis of an esophageal mass is made by evaluation of thoracic radiographs, positive-contrast esophagram, endoscopy, CT, and biopsy. As was demonstrated in this case, thoracic radiographs may show abnormalities such as retention of gas, soft-tissue opacity within the mediastinum, and/or dilatation of the esophagus proximal to the tumor.⁶ Positive-contrast studies may also show segmental dilatation of the esophagus, and they are helpful in localizing the disease process and indicating an esophageal stricture.⁶ Although helpful, these diagnostic modalities often do not allow for a specific diagnosis of neoplasia. Endoscopy is the diagnostic procedure of choice in diagnosing an esophageal stricture or neoplasia.⁷ Endoscopy allows the clinician to visualize the affected area of the esophagus and to take samples for histopathology, cytology, culture, or other diagnostic testing.⁷ As illustrated in this case, the size and quality of the biopsy sample are very important in obtaining a diagnosis. The diagnosis of SCC in this case was only made when a larger, 3-mm biopsy instrument was utilized.

Endoscopic biopsies of the affected area may or may not allow a definitive diagnosis to be made. When obtaining esophageal samples, many deep biopsies should be taken, because necrosis and inflammation⁶ may obscure the underlying disease process. Most studies investigating endoscopy have evaluated the use of endoscopic biopsies of various segments of the gastrointestinal (GI) tract to make a diagnosis of lymphoma. These investigations indicate that multiple samples are necessary and that the diagnostic accuracies of endoscopic samples differ depending upon the segment of the GI tract that is sampled.^8,9 No studies investigating esophageal biopsies are available at this time; however, after extrapolating from studies of other areas of the GI tract, it seems likely that a definitive diagnosis is difficult to obtain from such small samples. As illustrated by the case reported here, endoscopic biopsy samples often yield conflicting results; thus, larger and deeper biopsies may be necessary.

After diagnosis, the treatment of choice for esophageal SCC is surgical resection and anastomosis of the normal segments of esophagus. The feasibility of resection and anastomosis is directly limited by the length of esophagus with neoplastic involvement. Primary surgical resection and anastomosis of the esophagus is only an option if <5 cm of the esophagus is affected, because a length >5 cm significantly increases the risk of dehiscence of the surgical site.¹⁰ Problems associated with this procedure include poor esophageal healing, leakage, and restricture of the esophagus at the site of repair.¹ In this case, histopathology at necropsy was used to make the final diagnosis. Advanced imaging (CT) of the thorax was helpful in making the initial diagnosis of an esophageal mass, in determining the extent and invasiveness of the mass, and in determining if surgical resection was an option.

Although chemotherapy is useful in the treatment of many neoplastic conditions in pets today, its role and efficacy in the treatment of esophageal carcinomas in cats are not known. Esophageal SCC is a very rare disease, and this may contribute to the lack of case reports describing the use of chemotherapy for treatment. Cyclooxygenase-2 (COX-2) inhibitors, such as piroxicam, have shown some promise in the treatment of oral SCCs in dogs.^11,12 Recent studies have shown that oral SCCs in the cat have COX-2 expression and that the use of piroxicam in these cases may be of benefit.¹³ Although piroxicam treatment of esophageal SCC in cats has not been evaluated, it was used in this case because the owners declined aggressive chemotherapeutic options.

Radiation therapy has also been used as either a curative or palliative treatment option in many types of neoplasia. Unfortunately, the use of radiation therapy on intrathoracic segments of the esophagus is of limited value because of the poor tolerance of the heart and lungs to radiation.⁶ One study investigating the use of radiation as a palliative therapy for feline oral SCC in seven cats showed poor efficacy of treatment. The most common reason for discontinuing treatment was a lack of palliation.¹⁴ It is possible that different radiation therapy protocols for SCC may be more effective than what has been reported thus far. To the authors’ knowledge, no reports have investigated the use of radiation therapy in esophageal SCC.

Photodynamic therapy is also showing promise in the treatment of esophageal SCC, including those tumors located in the intrathoracic segment.¹⁵ This therapy involves the systemic administration of a photosensitizing dye that preferentially binds to tumor cells and then exposes the animal to a specific wavelength of light, administered via a laser.¹⁵ The interaction of the photosensitizing dye with light in the presence of oxygen results in the formation of oxygen anions that cause tissue necrosis of the surrounding tissue.¹⁵ Although a promising treatment option, photodynamic therapy is limited by the depth of penetration of light and involvement of the esophageal wall, limiting its use to tumors confined to the mucosal layer.¹⁵ Treatment with photodynamic therapy in cases where the tumor is trans-mural carries a high risk of esophageal perforation and therefore limits its use for treatment of more invasive tumors.¹⁵

Conclusion

Although rare, primary tumors of the esophagus are an important cause of esophageal stricture in cats. The prognosis is usually poor, although management by esophageal dilatation and nutritional support can be palliative. Due to the infrequency of esophageal SCC, conclusions regarding treatment options and their success are difficult and often inferred from studies investigating treatment of SCC in other areas of the body. The main treatment options available at this time include surgical resection and anastomosis of the esophagus, use of COX-2 inhibitors, and photodynamic therapy. These treatment options have been successful, but their success and availability are directly related to the size of the tumor. At this time, early diagnosis of esophageal neoplasia, when the size of the mass is relatively small, seems to hold the most promise for long-term treatment. Early endoscopy, multiple deep biopsy samples of the lesion, and early CT imaging hold the most promise for the early diagnosis and treatment of esophageal neoplasia.