Endobronchial Polyp Derived From a Myxosarcoma in the Lung of a Dog

Introduction

Polyps are growths that protrude from a mucous membrane; they are usually benign. In humans, endobronchial polyps are uncommon. Nevertheless, isolated cases of single or multiple endobronchial polyps have been described. These endobronchial polyps have been associated with benign and malignant tumors such as hemangioma,¹ rhabdomyosarcoma,² squamous cell carcinoma,³ clear cell adenocarcinoma,⁴ non-Hodgkin’s lymphoma,⁵ malignant fibrous histiocytoma of the myxoid type,⁶ invasive thymoma,⁷ thyroid carcinoma,⁸ and carcinoma in situ.⁹ Polyps have also been associated with pulmonary inflammation (hypersensitivity pneumonitis,¹⁰ asthma,^11,12 chronic obstructive pulmonary disease,¹³ or secondary to inflammation in the lungs caused by trauma following mechanical ventilation,¹⁴ a foreign body,¹⁵ acute or chronic smoke injury,^16,17 titanium tetrachloride inhalation,¹⁸ actinomycosis,¹⁹ sarcoidosis,²⁰ or mycobacteriosis).^21–24 Polyps have also been reported to occur secondary to inflammation in the trachea of two cats and one dog;^25–27 but to date, the authors are unaware of any report of a polyp within the bronchus of a dog or cat. The following case report appears to be the first description of an endobronchial polyp and its management in a dog.

Case Report

An 11-year-old, 34-kg, castrated male, mixed-breed dog was presented for a persistent, soft, nonproductive gagging cough and slightly increased expiratory effort of 6 months’ duration. The cough occurred daily while at rest but was more frequent during exercise, and its overall frequency was increasing. The cough had not responded to treatment for a coincident allergic dermatitis and secondary superficial pyoderma (10 mg prednisone twice daily for 3 days, then tapered over 1 week; 250 mg cephalexin twice daily for 3 weeks; and 4 mL of 9.1% imidacloprid^a monthly). An enzyme-linked immunosorbent assay (ELISA) for heart-worm antigen had proved negative, and 23 mg milbemycin^b was being administered orally every month. No intestinal or lung parasites were detected on microscopic examination of the feces before or after a Baermann preparation.²⁸

On physical examination, the dog was found to be panting, but otherwise most parameters were normal. Several small subcutaneous masses of long-standing duration were seen on the ventrum. Examination of fine-needle aspirates of these masses suggested they were lipomas. Slight pain was detected on palpation of the right forelimb, which corresponded to a mild lameness of at least 2 weeks’ duration that had been treated intermittently with carprofen^c (120 mg daily by mouth [PO]).

A complete blood count and serum biochemical concentrations measured at the time of presentation and 2 months previously were unremarkable, except for a mild thrombocytopenia (111,000/μL). Measurements of arterial blood gas concentrations revealed mild metabolic acidosis (18 mM bicarbonate, pH 7.394) with respiratory compensation (partial pressure of carbon dioxide [pCO₂] 30 mm Hg). Mucosal bleeding time and activated clotting time were normal. A 2-cm diameter, well-demarcated, soft-tissue opacity was visible within the right caudal lung lobe on thoracic radiographs, which extended as an elongated soft-tissue projection into the right principal bronchus. This soft endobronchial opacity extended to the tracheal bifurcation [Figure 1].

Bronchoscopy was performed under general anesthesia, with the dog in sternal recumbency. The dog was premedicated with 1 mg acepromazine^d and 0.6 mg buprenorphine^e intramuscularly, and anesthesia was induced with 50 mg propofol^f and 7 mg diazepam^g administered intravenously. Anesthesia was maintained with propofol administered by continuous intravenous infusion (530 mg over 1 hour). The dog did not breathe voluntarily through much of the procedure and was ventilated with oxygen delivered through a 14-mm internal diameter endotracheal tube. This tube was attached to a circle rebreathing circuit by a right-angle connector, which allowed passage of the endoscope down the endotracheal tube with the rebreathing circuit still attached. Isoflurane^h was mixed with the oxygen initially, but not for most of the procedure.

Bronchoscopy was performed with a flexible 9.5-mm diameter gastroscopeⁱ with a 2.8-mm diameter biopsy channel connected to a video processor^j and xenon light source.^k A pale-red, polypoid mass was visible within the right principal bronchus [Figure 2]. No abnormalities other than a slight hyperemia were noted in other bronchi. A loop snare^l was passed around the polypoid mass, and the mass was removed by traction. The bulk of the mass was approximately 7 cm long and 1 cm in diameter in cross-section; but a thin, 2-mm diameter, 1.5-cm long tail extended from its caudal end [Figure 3]. After removal of the mass, a small amount of blood and mucus was noted in the caudal bronchus. A sample for bacterial and mycobacterial cultures was obtained by passing a sterile culture brush into the right caudal lung lobe bronchus. A bronchoalveolar lavage was performed of the right middle lung lobe. Of 30 mL 0.9% saline infused, 60% was recovered.

Only a low number (10 colonies/mL) of a nonpathogenic Staphylococcus species grew on aerobic culture. Culture for mycobacteria was negative. The bronchoalveolar lavage fluid contained only a small number of cells (15/μL, mostly nucleated cells and nondegenerate neutrophils), which suggested a mild nonseptic inflammation. Microscopic examination of a touch preparation of the mass showed normal respiratory epithelial cells, as well as many nucleated cells that were too necrotic to identify. On histological examination, the mass had an undulant surface lined by ciliated, pseudostratified, columnar epithelium that varied in thickness from one to 10 cells. The submucosal region was comprised of a lowly cellular population of spindle-shaped mesenchymal cells arranged in loose whorls and clusters within abundant, lightly basophilic, Alcian Blue-positive matrix. The mesenchymal cells were more dense in the immediate submucosal zone. An occasional cell was bi- or multinucleated. A rare mitotic figure was found. The mass was interpreted to be an endobronchial, polypoid, myxomatous fibroma [Figure 4].

Recovery from the procedure was uneventful. After recovery, the same mass was visible in the caudal lung lobe on thoracic radiographs, but air was now visible in the caudal lung lobe bronchus where the polyp had previously been. The cough had almost completely resolved, and the owner decided to monitor progress of the remaining mass rather than pursue further diagnostic tests or treatment.

Three months later, the dog was coughing once weekly. The dog was still being treated for atopic dermatitis with diphenhydramine^m (50 mg daily PO) and was being fed a chicken and rice-based commercial food free choice. Also, carprofen (120 mg daily PO) was still being given for degenerative joint disease. Thoracic radiographs showed that the soft-tissue opacity in the caudal lung lobe had increased in size, and a slight opacity was seen within the caudal bronchus.

After another 3 months, the cough was again more frequent. The owner elected further diagnostic tests to evaluate the extent of the disease and the potential benefit of a right caudal lung lobectomy. Physical examination was unremarkable. Complete blood count and serum biochemical analysis results were normal. Thoracic radiographs showed further enlargement of the soft-tissue opacity in the right caudal lung lobe, but a second soft-tissue opacity (6 mm in diameter) was also visible in the left caudal lung field. An ultrasound examination of the abdomen was unremarkable.

After premedication with 1.8 mg acepromazine, 0.4 mg glycopyrrolate,ⁿ and 5.5 mg hydromorphone,^o general anesthesia was induced with 7.5 mg midazolam^p and 20 mg propofol; anesthesia was maintained with isoflurane in oxygen. A computed tomography scan with 5-mm slices showed that a 3-cm diameter spherical soft-tissue mass was present in the middle of the right caudal lung lobe, and that the adjacent bronchus was filled with a 3-cm long mass. A second soft-tissue mass (6 mm in diameter) was also visible in the periphery of the left caudal lung lobe. After infusion of 60 mL of contrast agent (diatrizoate meglumine and diatrizoate sodium injection),^q a patchy central and moderate rim enhancement of the right caudal mass was seen, as well as homogenous enhancement of the left caudal mass. A fluoroscopic-guided fine-needle aspiration of the right caudal lung mass was performed, and cytological examination of the sample revealed mild neutrophilic inflammation. However, a firm diagnosis was not possible, because the mass did not exfoliate well and few cells were present.

A polypoid mass was again visible with a bronchoscope within the right principal bronchus, but it was smaller than it had been 6 months previously. The bulk of the polyp within the bronchus was once again removed by traction with a loop snare. The polypoid mass had a similar appearance histologically to that of the first mass removed, and it was again interpreted to be a polypoid myxomatous fibroma. After the mass was removed, the cough was much improved.

After an additional 6 months, the dog was presented once again with persistent gagging and retching. Physical examination was otherwise unremarkable, except that the tongue was slightly cyanotic. Thoracic radiographs showed the right caudal lung mass had increased to 4 cm in diameter, that the left caudal lung mass had increased to 2 cm in diameter, and that a third soft-tissue mass (3 to 4 mm in diameter) was visible just caudal to the first mass. General anesthesia was induced and maintained as for the first bronchoscopy, except that 0.8 mg glycopyrrolate was administered before induction. Ventricular premature contractions were observed on the electrocardiogram during anesthesia; they were treated with lidocaine^r (3.3 mL bolus, then 0.2 mL per minute as continuous infusion intravenously). Bradycardia during recovery was treated with 0.3 mg atropine^s intravenously.

A polypoid mass was again visible with a bronchoscope within the right principal bronchus. This mass proved to be multilobulated and more difficult to remove by traction. A small section of the mass appeared to be attached to the bronchial wall, and more hemorrhage occurred after the polyp was removed. Diphenoxylate (7.5 mg) and atropine (0.075 mg)^t were recommended to be given twice daily PO to suppress the cough if the cough persisted.

Euthanasia was performed 2 months later, because the cough was becoming worse despite treatment. A cosmetic necropsy showed three masses within the lungs. In the right caudal lung lobe, a 6-cm diameter mass was seen that on cut cross-section had a cauliflower-like appearance, with 3- to 13-mm diameter, irregular, finger-like nodules extending out from 1- to 2-cm diameter cystic structures filled with clear mucus [Figure 5]. A red, gelatinous mass extended from this area through the bronchi up to the principal bronchus and into the carina, filling the lumen of the airway. The mass was firmly attached to the branching bronchi, but it was not attached to the principal bronchus. The right caudal lung lobe was not collapsed. In addition, a 2-cm diameter mass was in the left caudal lung lobe, and a 2-mm diameter mass was on the dorsal aspect of the right lung.

Histologically, the gelatinous mass from the right caudal lung lobe was similar to the original mass, in that it was lined by columnar to stratified epithelium; but the epithelium was often thrown into numerous, undulant folds and papillary projections. The core of the mass was much more cellular and comprised of neoplastic spindle- to stellate-shaped cells arranged in tight bundles and streams within a loose fibrovascular to myxoid stroma [Figure 6]. The cells had vesicular nuclei, each with a prominent nucleolus. Moderate anisocytosis and anisokaryosis were seen. Mitotic figures numbered zero to two per 40× field [Figure 7]. The tumor cells extended through the airway and into the adjacent alveoli in a few areas. The high cellularity, cellular pleomorphism, and invasive nature of the neoplasm led to the diagnosis of a myxosarcoma.

The 2-cm diameter mass in the left caudal lung lobe consisted of an expansile, well-demarcated, moderately cellular neoplasm formed by neoplastic epithelial cells lining papillary projections supported by a loose fibrovascular stroma. The tumor cells were cuboidal to low columnar, with oval vesicular nuclei having one to two visible nucleoli. Mitotic figures numbered zero to one per 40× field [Figure 8]. This neoplasm was interpreted as a bronchioloalveolar carcinoma.

Histologically, the 2-mm diameter mass on the dorsal aspect of the right lung was comprised of solid nests and broad papillary projections of polygonal to cuboidal epithelial cells that filled alveoli [Figure 9]. The tumor cells had variably distinct borders and scant to moderate amounts of eosinophilic, homogenous to vacuolated cytoplasm. Nuclei were round to oval with stippled chromatin and one to two visible nucleoli. Mitotic figures were not detected. This neoplasm was interpreted to be a carcinoma of unknown origin. As predicted from radiographs, scattered throughout the lungs were multiple, 1- to 2-mm diameter, firm gritty nodules (i.e., heterotopic bone).

Discussion

This case is unusual for two reasons: first, a polypoid mass has not been described previously within the lumen of the bronchus of a dog; and second, three morphologically distinct malignant tumors developed coincidentally in the same dog. Masses within the lumen of the airways of dogs and cats may be neoplastic or inflammatory in origin, but primary tumors of the trachea are uncommon,²⁹ and inflammatory polyps are even more rare.²⁶

One report describes a nodule of the midtrachea of a dog, which was removed surgically via thoracoscopy.²⁷ This proved to be an inflammatory polyp associated with chronic ulcerative, eosinophilic, and proliferative tracheitis. The authors of that study stated that the polyp was visible endoscopically, but because it was submucosal in origin, it could not be removed using laser surgery or loop snare. Two reports describe inflammatory polyps in the feline trachea that were removed endoscopically—one just caudal to the larynx and the other just cranial to the carina.^25,26 In the latter case, a snare was looped around the stalk of the polyp, and the stalk was cut with electrocautery. In the present case, the polyp was removed easily by simple traction of the polyp itself. Electrocautery was not used, because the stalk was too distal to visualize. Fortunately, hemorrhage after traction was minimal.

In humans, treatment of polyps usually involves removal of the polyp and/or treatment of the underlying cause of inflammation. In the dog presented here, the parenchymal mass was considered to be the source of the polypoid mass, and effort was directed at establishing the nature and cause of the parenchymal mass. Solitary pulmonary masses may be inflammatory or neoplastic, and tumors may be benign or malignant, primary or metastatic.³⁰ Metastatic tumors are more common than primary tumors in the lungs of dogs,³⁰ but no extrapulmonary primary site of malignancy was detected on physical or ultrasonographic examination. Primary lung tumors are uncommon, but most primary lung tumors are of bronchioloalveolar origin such as the one found in this dog.³⁰ Anaplastic carcinomas, such as the third tumor in this dog, are also common forms of primary pulmonary tumor, but primary sarcomas of the lung are rare.³⁰

Myxomas and myxosarcomas are benign and malignant tumors, respectively, that are rare and most commonly arise within the skin and subcutis.³¹ They are tumors of fibroblast or other mesenchymal cell origin that produce and are resident within an extracellular myxoid matrix that is rich in mucin rather than collagen.³² Myxoid tumors have also been described in dogs at sites other than skin, including within the heart,³³ spleen,³⁴ spine,³⁵ and synovium.³⁶ Both myxomas and myxosarcomas are infiltrative tumors with poorly defined margins. They frequently recur following excision, but they rarely metastasize to distant sites. The lung has been reported as the most common metastatic site.³⁷ The histological appearance of both tumors can be similar, and distinguishing features are subtle. Both comprise a proliferation of stellate to spindle-shaped fibroblasts loosely embedded within mucinous matrix. A diagnosis of malignancy is made when cellular density is increased, the nuclear to cytoplasmic ratio is increased, and nuclear pleomorphism and atypical mitotic figures are present.³¹

The behavior and prognosis of primary lung myxoid tumors and other primary lung mesenchymal tumors vary with the tumor type and differentiation state, presence of histological indicators of malignancy, location, surgical resectability, and whether spread to adjacent tissue has occurred. Primary lung carcinomas in dogs exhibit variable behaviors, including intrapulmonary metastasis, transcoelomic spread, and spread by local invasion of lymphatics and vessels. In general, tumors that are less differentiated are more malignant, but all carcinomas retain a strong predilection for vascular spread. Prognosis for long-term survival is best predicted by evaluating lymph node metastasis and the differentiation state of the tumor.³⁸ Histopathological examination of the polypoid mass initially suggested a benign mass, and removal of the lung lobe containing the mass was contemplated subject to finances becoming available. This option was discarded, however, when additional masses appeared within the lung, making malignancy more likely. Alas, the masses did not exfoliate well with fine-needle aspiration, which precluded a definitive diagnosis prior to euthanasia.

It is unusual that three distinct tumors should appear independently in the lung of this dog. Multiple endocrine neoplasia is a recognized syndrome in humans. It is characterized by the independent appearance of benign or malignant changes in several endocrine organs. These changes are occasionally combined with similar changes in neural, muscular, or connective tissue, but typically the lung is not involved.³⁹ This syndrome is transmitted as an autosomally dominant trait with a high degree of penetrance; but other factors probably contribute, because neoplastic changes appear in different organs independently at different times, with different causes. No evidence of endocrine disease or multiple endocrine tumors was seen in this dog.

The appearance of three tumors independently in the lung of this dog also suggests a genetic component to the etiology of the cancers,⁴⁰ but the fate of this dog’s siblings is unknown. Environmental factors may also have played an inciting role, but this dog was not exposed to any potential causes of lung injury (such as smoke, dust, or chemicals) and had no known exposure to radiation other than for diagnostic purposes. Dermatitis consistent with allergic inflammatory disease was present, but at necropsy, histological examination of lung tissue unaffected by neoplasia did not show evidence of chronic or acute inflammation. This dog was of advanced age, however, when the tumors appeared. Oxidant damage to deoxyribonucleic acid appears to increase while repair mechanisms appear to decline with age in dogs and other mammals.⁴¹ Antioxidant deficiency is unlikely to have contributed to this process, however, because the dog was being fed a complete and balanced commercial food.

Conclusion

Cough due to an endobronchial polyp associated with a myxomatous sarcoma was managed successfully for 15 months by intermittent removal of the polyp with the aid of bronchoscopy. Multiple masses within the lung of a dog may be of more than one tumor type.

Acknowledgments

This dog could not have been managed without the assistance of Betsy Uhl, DVM, PhD, Diplomate ACVP; Carol J. Detrisac, DVM, PhD, Diplomate ACVP; and many others at the University of Florida College of Veterinary Medicine.