Primary tracheal neoplasms are an uncommon malignancy in cats. Commonly reported tracheal tumors in cats including lymphoma, adenocarcinoma, and squamous cell carcinoma (5,12). Dyspnea is the most commonly reported clinical sign. Wheezing, coughing, and stridor may also be exhibited (4). The optimal treatment for tracheal cancer in humans is surgical resection and anastomosis (1). However, various treatment options can be administered depending on the location and size of the tumor, especially when surgery is neither feasible nor curative (9). Previous studies describing treatments for tracheal cancer have examined external radiation therapy, bronchoscopic debulking, tracheal stenting, and chemotherapy (2,16,17). The prognosis for cats with tracheal carcinomas is poor, with most cats surviving less than 1 month after diagnosis (11,17). Previous case reports have described tracheal carcinoma treated by bronchoscopic debulking using cup biopsy forceps, two wire snares, and a urinary catheter (16,17). The survival times were variable in the studies presented above, with the cats surviving 6 months, 6 weeks, 9 months, and 16 months, respectively (16,17). In the present case, the survival time after diagnosis was 10 months, during which time the cat underwent tracheostomy, debulking by endotracheal tube, and tracheal stent placement procedures in combination with toceranib chemotherapy. This case report describes the first documented use of multimodal palliative treatment of poorly differentiated tracheobronchial carcinoma with lung metastasis in a cat and long-term outcome.

A 14-year-old castrated male Persian cat (body weight: 2.8 kg) was referred to the Helix Veterinary Medical Center with a 2-week history of progressively increased respiratory effort and worsening wheeze. The cat had been vaccinated and dewormed regularly and was living indoors.

On physical examination, the patient showed a depressed body condition score of 3/9. An increased respiratory rate (60 breaths/min), labored breathing, and intermittent open-mouth breathing were also observed. Thoracic auscultation revealed wheezing.

Thoracic radiographs showed an irregularly narrowed tracheal lumen from the level of vertebra C7 through T1 and an increased opacity in the right caudal lung lobe (Fig. 1).

Figure 1. Thoracic radiographs at initial presentation (before treatment) showing an irregularly narrowed tracheal lumen (circle) from the level of vertebra C7 through T1 (A) and an increased opacity in the right caudal lung lobe (B). Thoracic radiograph following tracheal stenting documenting immediate and complete resolution of the tracheal narrowing after placement of the stent (after treatment) (C).

Computed tomography (CT, 80-row, 160-multi-slice, Aquilion Lightning, Canon Medical Systems Co., Otawara, Japan) and bronchoalveolar lavage (BAL) with a non-bronchoscopic method were performed under general anesthesia. Butorphanol (0.2 mg/kg, SC; Butophan Injection; Myungmoon Pharm Co., S. Korea) was administered as a premedication, and anesthesia was induced with propofol (5 mg/kg, IV; Provive Injection 1%; Baxter, India). General anesthesia was maintained using isoflurane (Ifran Liquid, Hana Pharm Co., S. Korea) via an endotracheal tube during the CT scan and BAL procedure. CT confirmed a mass occluding the lumen of the trachea at the level of vertebra C7 through T1, a mass causing right main bronchus stenosis, and a nodule on the right caudal lung lobe (Fig. 2). Cytological examination of BAL fluid tentatively diagnosed the mass as a carcinoma (Fig. 3).

Figure 2. CT scan at initial presentation showing a mass (arrow) that occludes the lumen of the trachea at the level of vertebra C7-T1 (A), showing a nodule (circle) on the right caudal lung lobe (B), and showing a mass (arrow) causing right main bronchus stenosis (C). Second CT scan showing a relapsed of the tumor at the trachea at the level of vertebra C7 (D) and a number of new tumors were further spreading to the lower trachea (E, F). A right main bronchus stenosis was observed more clearly and caused almost complete occlusion (G), a distinct increase in density in the middle and caudal lobes of the right lung is observed than before and density was increased throughout the left lung lobe (H), and multiple nodules were observed throughout the lung (I). Third CT scan showing a larger mass causing right main bronchus stenosis with complete occlusion (J, K) and multiple nodules in the lung (L). A relapse and further spreading of the tumors (arrow) in the trachea were observed (M).

Figure 3. Cytological smear. The slide consists of clustered hyperplastic epithelial cells with anisocytosis, anisokaryosis and coarse chromatin pattern (Diff-Quik stain, magnification : 1,000×).

Since pulmonary metastasis was suspected, for palliative treatment, a tracheostomy was performed to remove the tracheal mass. Butorphanol (0.2 mg/kg, SC; Butophan Injection; Myungmoon Pharm Co., S. Korea) and midazolam (0.2 mg/kg, IV; Bukwang Midazolam Injection; Bukwang Pharm Co., S. Korea) were administered as a premedication, and anesthesia was induced using propofol (5 mg/kg, IV; Provive Injection 1%; Baxter, India). During surgery, general anesthesia was maintained using isoflurane via an endotracheal tube (armored type). An incision was made from the thoracic entrance toward the tracheal neck. The mass was extremely soft and friable, allowing it to be partially resected using cotton swabs and a surgical vacuum. Since no additional tumors were found in the surgical site, the tracheostomy was closed and the skin was sutured using a conventional method. The patient recovered from anesthesia and was discharged after 3 days with improved clinical symptoms. Amoxicillin-clavulanic acid (12.5 mg/kg, PO, q12h; Amocla Tab; Kuhnil Co., S. Korea), prednisolone (0.5 mg/kg PO, q12h; Solondo Tab; Yuhan, S. Korea), famotidine (0.5 mg/kg, PO, q12h; Famotidine Tab; Ilhwa Co., S. Korea), and theophylline (15 mg/kg, PO, q24h; Theolan-B; Alvogen, S. Korea) were prescribed to be taken at home.

Histopathological examination of the tracheal mass confirmed the presence of tracheobronchial carcinoma, poorly differentiated with necrosis and neutrophilic inflammation (Fig. 4). Aggressive chemotherapy was not performed due to the owner's refusal. Adjuvant chemotherapy using toceranib phosphate (10 mg/cat, PO, q48h; Palladia; Zoetis, Italy) commenced on day 14 and continued for approximately 9 months, except during periods of leukopenia (15). Thoracic radiographs and blood tests were repeated every 1-2 weeks during the first 2 months after toceranib phosphate administration, and then tests were performed every 2-4 weeks. The only abnormality noted by a complete blood count during therapy was mild leukopenia, which improved to normal following a temporary cessation of drug administration. Thoracic radiographs at 4 months showed worsening of the right caudal lung infiltration.

Figure 4. The slide shows proliferation of polygonal, round to ovoid cells arranged in cords, clusters and individual cells subdivided by a fine fibrovascular stroma. There is nuclear and cellular pleomorphism and mitotic figures. Numerous degenerated neutrophils and necrotic cellular debris are also evident.

The cat remained asymptomatic for 5 months following the operation, at which point the cat relapsed with the same symptoms that were exhibited during its first examination. Thoracic radiography was carried out and a narrowed tracheal lumen and an increased opacity in the caudal lung lobes were again present. The second CT showed a relapse of the tumor of the trachea at the level of vertebra C7 and several additional tumors that were further spreading to the lower trachea. The right main bronchus stenosis was observed more clearly, causing almost complete occlusion. A distinct increase in density in the middle and caudal lobes of the right lung was observed, density was increased throughout the left lung lobe, and multiple nodules were observed throughout the lung (Fig. 2). Since the previous tumor was found to be extremely friable, physical removal using tracheal tubes as a trial treatment was performed as further palliative treatment during anesthesia for a CT scan. Anesthesia was performed as previously described. The tracheal tube was inserted into the trachea as much as possible, the balloon was inflated manually without being tight, and the tracheal tube was then gently removed. The tracheal tube was covered with mucous substances and blood. No tracheal perforation was observed after the procedure. Cytological examination was performed, with exudate discovered in the tracheal tube, and several malignant epithelial-derived cells identified previously were observed. The patient recovered from anesthesia and was discharged the same day. Thoracic radiographs and blood tests were repeated every 2-4 weeks after the second CT scan. The abnormality noted by a complete blood count during therapy was mild leukopenia, which improved to normal following a temporary cessation of drug administration. Thoracic radiographs at 3 months after the second CT scan showed worsening of the right caudal lung infiltration and a small mass on the ventral upper tracheal lumen. Symptoms related to upper respiratory tract obstruction, such as wheezing, improved; however, tachypnea and dyspnea were observed, especially while running or moving.

After 4 months, the cat presented anew with severe respiratory distress. A relapse and further spreading of the tumors in the trachea were observed on the third CT scan (Fig. 2). Multiple nodules in the lung with pulmonary infiltration overall and a larger mass causing right main bronchus stenosis with complete occlusion were observed (Fig. 2). A tracheal stent (Hanarostent^® Trachea (NCN), M.I.Tech Co., Pyeongtaek, S. Korea) for the management of inoperable tumors was utilized for the lung metastases. Butorphanol (0.1 mg/kg, IV; Butophan Injection; Myungmoon Pharm Co., S. Korea) was administered as a premedication, and anesthesia was induced and maintained using propofol (5 mg/kg, CRI; Provive Injection 1%; Baxter, India). The stents were inserted under C-arm. After securing the tracheal airway, the stent delivery catheter was inserted into the lower end of the trachea. The stent was deployed by pulling the thread wrapping the stent from outside. After the stent was fully deployed, the delivery catheter was removed (Fig. 1). After adequate spontaneous ventilation was restored, the patient was awakened. Following the procedure, clinical signs associated with the upper respiratory tract gradually improved; however, the patient showed severe salivation and then died due to dyspnea on the second day of hospitalization.

Survey radiography is the diagnostic procedure of choice for the visualization of a mass. Soft tissue opacities revealed on cervical radiographs are significant indicators of a neoplasm (4,6). In previous studies of tracheal masses, radiographic findings showed no correlation with specific tumors (4,6). Direct tracheobronchial examination or advanced imaging such as CT may be useful for further investigation of the mass or if an abnormal-looking lesion is identified. Either cytology or histology can be used to diagnose the type of tumor or lesion. In a previous report, five cases of misdiagnosis followed fine-needle aspiration cytology of tracheal masses that were subsequently identified as neoplasia upon further histological testing (12). In the present case, the cat was able to confirm a mass in the main bronchus other than a mass in the upper airway by performing a CT scan, providing the information for setting the treatment plan. Since the upper airway mass was surgically accessible, a biopsy was planned, but because the main bronchus mass was surgically inaccessible, a cytological examination was planned. BAL cytology and histopathological examination were performed. The cytological diagnosis was consistent with the histological diagnosis in identifying a carcinoma.

In humans, the optimal treatment for tracheal neoplasia, excluding lymphoma, involves surgical resection and anastomosis (1,14). In a previous report, multimodal non-surgical treatment (radiotherapy, chemotherapy, and cyclooxygenase-2 inhibitors) was described as leading to a long-term outcome for feline tracheal adenocarcinoma (2). In the present case, surgical resection and anastomosis or radiotherapy were impossible due to the wide extent of the tumors and pulmonary metastasis. A tumor in the lower respiratory tract was also confirmed, but the clinical symptoms and development were found to be related to the tumor in the upper respiratory tract. On the second CT scan, it was confirmed that the existing tracheal tumors were seeded in the direction of the trachea bifurcation. It is possible that they were seeded during endotracheal tube intubation for anesthesia or BAL procedures. If extensive tracheal resection and anastomosis were performed during the initial tracheostomy, quality of life improvement and further metastasis prevention could have been realized. In another study, cats undergoing a tube tracheostomy without any other treatment were found to have a median survival time of 3 days (mean 3.3 days, range 1-6 days) (17). Another case report described a cat still being alive at 12 months after surgery (8). Non-invasive and effective bronchoscopic interventions have replaced surgical resection for the treatment of symptomatic upper respiratory airway obstructions in human medicine (3). Several techniques have been developed such as laser therapy, brachytherapy, phototherapy, cryotherapy, electrocautery, balloon dilation, and airway stent placement (3). In veterinary medicine, these interventions are in the initial stage; previous case reports have described tracheal carcinoma treated by bronchoscopic debulking using cup biopsy forceps, two wire snares, and a urinary catheter (16,17). The survival times were variable in the studies presented above, with the cats surviving 6 months, 6 weeks, 9 months, and 16 months, respectively (16,17). There has been one report of a cat with tracheal carcinoma being treated by tracheal stenting (7). The survival time of the cat after the procedure was 6 weeks (7).

The prognosis for cats with tracheal carcinomas is poor, with most cats surviving less than 1 month after beginning treatment (11,17). In previous case reports, the survival times of most tracheal carcinomas treated with solely with either, bronchoscopic debulking or tracheal stenting were less than 6 months. In the present case, the survival time after diagnosis was 10 months, during which time the cat received multimodal treatment including tracheostomy, debulking by endotracheal tube, and tracheal stent placement procedures to improve respiratory obstruction despite the presence of metastasis.

Toceranib phosphate is a multi-target small molecule inhibitor approved for use in the treatment of canine mast cell tumors (10). It has also been used to treat other solid neoplasms in dogs (13). In a recent report on multimodal non-surgical treatment, including administration of toceranib phosphate in feline tracheal adenocarcinoma, the survival period was 755 days (2,14). However, since the main treatment for the cat is radiation therapy and chemotherapy, it is not appropriate to evaluate the effect of toceranib phosphate administration. In the present case, administration of toceranib phosphate had no effect on tumor size reduction and prevention of metastasis. Evaluation of the effect of the drug is necessary to evaluate the effective dose of toceranib phosphate. However, the dose of toceranib phosphate was not adjusted because the adverse effect of leukopenia was observed in the cat. Further studies are necessary to confirm the efficacy of toceranib phosphate for the treatment of feline tracheobronchial carcinoma.

In cases of poorly differentiated obstructive tracheobronchial carcinoma with pulmonary metastasis, palliative multimodal therapy for central airway obstructions could be an alternative option, improving the quality of life and life expectancy even if the pulmonary metastasis is uncontrolled.

The authors have no conflicting interests.