Introduction

The list of differential diagnoses for cranial mediastinal masses in dogs is comparatively long, with thymoma and lymphoma as the most common ones.^1,2 Other differential diagnoses are osteosarcoma, fibrosarcoma, undifferentiated sarcoma, neuroendocrine tumors, mesothelioma, thymolipoma, histiocytic sarcoma, carcinoma, ectopic thyroid carcinoma, infectious granulomas, lymphosarcoma, branchial cyst, granulomatous disease, abscess, and heart-based tumors.^2–4 Before considering surgery as a treatment option, lymphoma should be ruled out as a possible differential, as the treatment of choice for this disease is chemotherapy.² Both thymoma and lymphoma or lymphosarcoma contain large numbers of lymphocytes, making it a challenge to differentiate these two by fine-needle aspirates alone. Flow cytometry may be helpful to distinguish these two in dogs.^1,5 Thymoma and lymphoma often cause paraneoplastic syndromes such as myasthenia gravis or hypercalcemia.⁶ Both of these syndromes can cause severe problems including megaesophagus, aspiration pneumonia, and weakness as well as polyuria and polydipsia.^2,6 Another possible symptom with cranial mediastinal masses is the so-called vena cava syndrome, with edema and swelling of the front limbs, neck, and head as a result of the compression of the cranial vena cava.²

Case Report

A 14 mo old female pug was presented for further work-up because of progressive breathing problems. The referring veterinarian had already performed chest radiographs, which were suggestive of an intrathoracic cystic structure or neoplasm. The dog was otherwise healthy, had no previous history of any other health issues, and was up to date on her vaccinations. At the time of presentation, she was bright and alert but somewhat subdued as a result of a moderate dyspnea with 60 breaths per min. There was an accentuated abdominal breathing pattern. The heart was hardly audible on the left side but clearly audible on the right side. Heart and pulse rate were 100 bpm, the pulses were strong and synchronous, and no pulse deficits were found. Mucous membranes were pink, and capillary refill time was one second. Abdominal palpation was unremarkable. All lymph nodes were <1 cm in size and not painful. A full orthopedic and neurological examination was not performed because, according to the owner, the dog did not show any other symptoms besides the dyspnea.

Chest radiographs at this time showed a large, ill-defined mass filling the left-to-mid cranial thoracic cavity with a clear mass effect visible. The latter was causing a dorsal- and right-sided displacement of the trachea and large bronchi. The trachea was compressed on the lateral projection. The caudal aspect of the heart silhouette was visible; however, the cranial, dorsal, and ventral aspects could not be defined. The aerated lung field was limited to a small area located caudodorsally and to the right. The lung vessels were superimposed over the mass and could therefore not be evaluated (Figures 1A, B).

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A differential blood count showed a mild leukocytosis with 23.1 × 10⁹/L (reference range 6–17 × 10⁹/L) and a moderate lymphocytosis of 11.4 × 10⁹/L (reference range 1–4.8 × 10⁹/L). All other parameters were within the reference intervals, including a biochemistry panel and C-reactive protein.

Four fine-needle aspirates were taken from the intrathoracal mass under visual guidance with ultrasound. The cell picture was the same for all four samples, showing 98% small mature lymphocytes. There were also some large activated lymphocytes and some macrophages. The conclusion was that this was the picture of a normal lymph node without any signs of neoplasia.

In addition, a computed tomography (CT) was performed for further work-up and to help in the process of decision making about whether surgery would be an option. The CT revealed a large soft-tissue mass within the thoracic cavity, occupying ∼80% of this cavity. The mass seemed to originate from the cranial and ventral mediastinum and was causing a severe mass effect on the trachea with dorsolateral displacement of the latter. The lung lobes and main bronchi seemed to be collapsed on the left side, and the heart was displaced caudally and towards the right side. No pleural effusion could be detected. After injecting 13 mL of iodinated contrast medium^a over 4 s, four additional sequences were performed: 7.0, 22.8, 44.3, and 120.0 s after injection of the contrast medium. There was a general mild contrast enhancement of the mass, and no ring enhancement could be seen. All tracheobronchial lymph nodes looked normal (Figures 1C–E). The most likely differentials were thymoma and lymphoma. Thymic hemorrhage, thymic cyst, a soft-tissue sarcoma, or abscess formation were considered less likely.

Subsequent to the CT, a sternotomy was performed. The mass could be removed in-toto by blunt dissection from the lung lobes, pericardium, phrenic nerves, and the adjacent vessels (Figure 2A). There was no grossly visible invasion into any of the adjacent tissues. The vessels running into the mass were sealed with the aid of a vessel-sealing device^b. After removing the mass, the lungs began to slowly reinflate. Before closure of the sternum with a 0 polydioxanone suture^c, a chest tube was placed under visual control. The muscles and subcutaneous tissues were closed with 3-0 polyglactone 25^d in a continuous fashion, and the skin with 3-0 Nylon^e with simple interrupted sutures. Postoperative radiographs revealed well-inflated lungs and an appropriate position of the chest tube. The dog recovered uneventfully in the intensive care unit, and the chest tube was removed 10 hr after surgery as it was not producing any air. Another 12 hr later, the dog was discharged to her owners. At the time of suture removal 10 days after surgery, the dog was completely normal, had no difficulties breathing, and follow-up radiographs revealed a normal lung field. At 9 mo after surgery, the dog was still doing well and not showing any signs of respiratory problems, according to the owners.

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Histopathology of the tissue samples showed a moderately cellular, poorly demarcated, infiltrative, unencapsulated neoplasm composed of neoplastic cells in small nests and trabecules within abundant pale eosinophilic cytoplasm, obscuring and effacing the normal thymic tissue (Figure 2B). Neoplastic cells were surrounded and often obscured by numerous lymphocytes. The neoplastic cells were polygonal with indistinct cell borders and variable amounts of pale eosinophilic to fibrillar cytoplasm. Nuclei were round-to-oval with finely stippled chromatin and variably distinct nucleoli. There was moderate anisocytosis and anisokaryosis, and mitotic rate was <1 per high-power field. Centrally within the neoplasm was a large clear cystic space lined by a multilayered epithelium (Figure 2C). Epithelial cells of the cystic space and within the neoplasm stained deeply positive with an antibody against cytokeratin^f (Figure 2D).

Discussion

The thymus is located within the cranial mediastinum and responsible for the development of cell-mediated immunity. It usually continues to grow until 45 mo of age and then begins to involute. During the process of involution, its lymphoid structure gradually disappears and is replaced by fat. There is a very close relationship among the pericardial sac, phrenic nerves, cranial vena cava, and trachea. The blood supply comes from the internal thoracic arteries and sometimes also from the brachiocephalic or left subclavian artery. Lymphatic drainage goes to the sternal lymph node. Histologically normal thymus tissue consists of small lymphocytes, similar to the lymphocytes found in other lymphoid tissue. These are interspersed with spherical or oval corpuscles, so-called Hassall bodies.² During advanced imaging studies, many of the thymic masses are associated with cystic areas.² In the pug of this report, almost all of the differentials listed above could be excluded with the help of CT in combination with cytology. The tissue was less dense compared with soft tissue structures, was relatively homogeneous, and did not take up contrast medium. The samples from the fine-needle aspirate showed almost exclusively small mature lymphocytes, leading to the conclusion that the tissue must be of thymic origin. The histopathologic findings of the presented case are consistent with normal thymic tissue, aside from the formation of the cystic lobes separated by fibrous tissue. Therefore, the diagnosis of a thymoma with central benign cystic lesions was made.

At presentation, the dog did not show any signs of paraneoplastic syndrome and had relatively normal blood work, diagnostic imaging did not show invasion into any important anatomical structures, there were no signs of malignancy in the cytology, and all intrathoracic lymph nodes were of normal size. Therefore, surgery was considered the treatment of choice. One study in cats has shown that there is still a high risk of invasion into local structures, even if CT does not show invasion into adjacent structures.⁷ Consequently, sternotomy is the preferred approach to gain sufficient access to the mass and avoid important anatomical structures. Alternatively, a thoracoscopic-assisted approach has been described, dependent on the size of the mass, but was not an option in this case. The survival rate with thymoma in dogs is reported to be 73% and 49% for 1 and 3 yr after surgery, respectively.⁵ Thymomas typically occur in older medium-to-large–breed dogs, with an average age at the time of presentation of dogs with thymoma of 10.5 yr.^2,6,8 In contrast, lymphoma is more commonly diagnosed in younger dogs, with a mean age of 5.8 yr.⁶ The median survival time with lymphoma in dogs is comparatively short: 248 days⁹.

In the study from Day, the median age for thymic cysts at the time of presentation was 10 yr, similar to the age of dogs presenting with thymomas.⁶ In general, cystic lesions within the mediastinal region are comparatively rare and may originate from the pleural, branchial, thyroglossal, lymphatic, bronchogenic, or thymic tissue.^6,10 These lesions are usually lined by epithelium, include eosinophilic fluid, and are low in protein and cellular content.^6,11,12 The most common clinical signs are related to compression of adjacent structures or are a result of paraneoplastic syndrome.^6,11 Because of the rarity of this disease, there are no reports in the literature regarding prognosis and survival times.

Conclusion

This case report describes the unusual appearance of a large thymoma with central cystic lesions in a 1 yr old pug, with successful surgical resection of the diseased tissue. Therefore, thymoma should be included in the differential list of cranial mediastinal masses, especially in young dogs without any signs of paraneoplastic syndrome. Because of the short follow-up time, it is not possible to comment on the prognosis and possible survival times, but surgery seems to have at least an excellent short-term prognosis.