The current case report describes the presence of an uncommon tumour, thyroid cystadenoma, in three boxer dogs. Although this tumour type has been previously reported in dogs, detailed clinical features are lacking [1, 5, 7, 18]. Greater detail is provided in two case reports, but the clinical appearance differed substantially from the current cases because of the presence of hyperthyroidism [19, 20]. In the current study, investigation was prompted by identification of a mass, or clinical signs secondary to a mass, rather than the consequences of hyperthyroidism. In addition, the presence of this tumour type in three dogs of the same breed may suggest a possible breed predisposition; a finding that is further supported by the identification of this tumour type mainly in boxer dogs in the database review.
Non-functional benign thyroid masses can cause clinical signs because of their size and localisation. Dysphagia, dyspnoea, cough or regurgitation can occur because of compression of surrounding tissues such as the trachea and oesophagus. In case 1, regurgitation and increased respiratory effort after strenuous exercise and excitement were reported. In this case, the CT of the neck and chest showed that the mass was causing intermittent partial obstruction of the tracheal lumen by compression of the tracheal membrane. Case 3 was reported to drool excessively. Although potentially related to the thyroid masses, the subsequent discovery of a rapidly growing oral neoplasm was considered a more likely cause.
None of the dogs had overt clinical signs of hypothyroidism at the time of diagnosis. This is not unexpected with unilateral lesions. However, information on thyroid function was not available for Case 1 and thyroid dysfunction could not be definitively ruled out. Case 2 had a low total T4 with upper reference interval cTSH concentration. This may suggest subclinical thyroid dysfunction given that primary hypothyroidism was subsequently definitively diagnosed six weeks after removal of the thyroid cystadenoma. Neoplasia within, and subsequent removal of, the first lobe may have contributed to decreased functional thyroid reserve and the development of overt hypothyroidism. In this case, the T4 concentration of the cystic fluid was lower compared to cases 1 and 3. This raises the possibility that the T4 concentration in the cystic fluid may provide some information on thyroid function that warrants further investigation. In humans, post-operative hypothyroidism has been reported in up to one third of patients following hemithyroidectomy because of suspected neoplasia [21,22,23]. In these cases, lymphocytic infiltration was identified within the resected tissue, but it is unclear if the tumour itself acts as a trigger for autoimmune thyroiditis [21] or if this represents concurrent but unrelated immune-mediated disease [22]. Lymphocytic infiltration was not apparent histologically in the resected tissue of any of the current cases, but thyroglobulin autoantibodies were not assessed. Therefore, the cause of hypothyroidism in case 2 remains unclear as the contralateral thyroid lobe was not removed or sampled.
It has been proven that fine needle aspiration (FNA) of solid cervical masses has a good diagnostic accuracy in humans [24]. In dogs, one study showed that correlation between cytological results and histopathological findings for thyroid carcinomas was only fair and the aspiration technique resulted in excessive contamination with blood in one third of cases [25]. Cytology was performed in all cases and only the FNA results in case 3 were consistent with the histopathologic diagnosis of adenoma. It is believed that this sample included tissue from the solid part of the thyroid tumour, as the enlargement was not confined to a single cyst in this case. In cases 1 and 2, cytologic evaluation was made from the aspirated fluid and was not diagnostic. This supports previous reports in which cytology of cystic fluid has rarely offered evidence of a particular tumour type or origin due to the paucity of cellular material and lack of pathognomonic cytological features, revealing only cell necrosis and blood cells [19, 20].
In adult humans presenting with a solitary cystic mass in the lateral neck, measurement of thyroglobulin concentration in the cystic fluid is advised as an initial step to confirm the thyroidal origin [26,27,, 28]. Canine thyroglobulin assays are not commercially available. However, a similar approach was taken by measurement of cystic T4 concentrations, and the increased values rapidly confirmed thyroidal origin in all three cases. This appears to be a useful diagnostic procedure in dogs but has only been reported once before [19].
Although long-term effects of thyroid cysts are not known, drainage was only temporarily beneficial. Without treatment, thyroid cysts could continue to grow with progressive compression of adjacent structures, or malignant transformation from adenoma to carcinoma could occur. Although only suspected in dogs, this has been suggested to occur in cats with hyperthyroidism [29]. Also, one study suggested that in theory, TSH may contribute to further growth of primary thyroid carcinomas in dogs [30]. Surgical excision was therefore recommended and curative in the two cases in which it was performed. In humans, thyroidectomy is recommended for all patients with thyroid cysts who have a history of prior neck irradiation, abnormal FNA cytology results, recurrence of the cyst despite two or more needle aspirations and compressive clinical signs despite draining the cystic fluid [31].
In small animals, thyroid cystadenomas are described as follicular cell adenomas with one or two large cavities filled with proteinaceous fluid, necrotic debris and erythrocytes [7, 15, 17]. Cysts develop due to follicular distension and degeneration within thyroid tumours [17]. Further enlargement occurs due to frequent haemorrhage and desquamation of the follicular cells into the cystic lumen [15]. Follicular cysts have also been described in which the fluid filled cavities are lined by a dense fibrous capsule from which fronds of uniform cells arranged in follicular and/or compact cellular patterns project [8]. In these cases, neoplastic tissue is not identified. However, follicular cysts show similar morphological features to cystadenomas, and the differentiation can be somewhat arbitrary and dependent upon whether or not solid adenomatous tissue is present within the section examined [17, 24, 32]. Indeed, adenomatous change was not initially observed in case 2, and was only identified after preparation and examination of additional histopathologic sections.
Interestingly, all three dogs in the present study were boxers; a breed in which thyroid tumours have been reported with increased frequency in some [2, 7, 8] but not all [1] previous studies. The UCD Veterinary Diagnostic Laboratory database search of all internal and external samples over a 12-year period revealed the presence of this tumour type in only six cases (including the three dogs included in this case report), and five of these were boxer dogs. Whether boxers are truly predisposed to this particular condition warrants further investigation.
To the authors’ knowledge, this is the first report of non-functional thyroid cystadenomas in dogs. The cystic thyroid structures were detectable clinically because of their large volume but were not associated with clinical signs related to thyroid dysfunction. Measurement of T4 concentration in the cystic fluid was supportive of thyroidal origin and should be considered as a simple, relatively inexpensive first line diagnostic tool. Despite their apparent rarity, thyroid cystadenoma should be considered a differential for dogs presenting with cervical masses. Surgical excision is recommended as it is curative and because it provides tissue samples to investigate the underlying thyroid lesion.