Introduction

The most common cranial mediastinal masses (CMMs) in the dog and cat are lymphoma and thymoma.^1,2 Other malignancies, such as sarcomas and ectopic thyroid carcinomas, have been reported and are much less common.² This is the first reported case of a thyroglossal duct adenocarcinoma presenting as a CMM in a dog.

Diagnostic imaging (i.e., thoracic radiography, computed tomography [CT]) is useful for evaluation of involvement of surrounding structures and for surgical planning.¹ Definitive diagnosis of a CMM is important because it may affect whether it is managed medically or surgically.² This requires a fine-needle aspirate (FNA) or biopsy of the mass for cytology or histopathology.^1,2 Surgical excision can be pursued if clinical signs from the CMM are present, and/or previous diagnostics yield inconclusive results.

Case Report

A 7 yr old female spayed Canaan dog weighing 16.2 kg was initially presented to the primary care veterinarian for a persistent mass on the dorsal aspect of digit four on the left pelvic limb and a polyp-like lingual mass. The patient’s medical history included a urinary tract infection 1 mo before that resolved with medical management. Physical examination did not reveal any abnormalities other than the digit and lingual masses. A compete blood count, urinalysis, and biochemistry panel were unremarkable. An FNA of the digit mass was concerning for a possible soft-tissue sarcoma. Thoracic radiographs revealed a possible mass in the cranial mediastinum or left cranial lung lobe with suspected sternal lymphadenopathy.

The patient was referred to an oncologist for further diagnostic evaluation. A thoracic ultrasound examination revealed a larger cavitated mass, ∼ 6.0 × 5.5 cm, in contact with the left thoracic wall and a single nodule measuring 0.5 cm in diameter in the right cranial lung lobe. The ultrasound was not able to determine whether the mass originated from the mediastinal or lung tissue. A fluid sample from within the mass was obtained with ultrasound guidance and was noted to be iridescent brown in color. FNA was completed of the solid portions of the mass in two separate areas. The samples were submitted for fluid analysis, bacterial culture, and cytology. Bacterial culture was negative for growth, and analysis reported a turbid fluid with a specific gravity of 1.034 and a protein level of 5.2 g/dL. Cytologic evaluation was consistent with a cyst with evidence of mild previous hemorrhage and neutrophilic inflammation.

An abdominal ultrasound revealed a 1.3 × 1.0 cm hyperechoic nodule within the body of the spleen. An FNA was performed of the splenic nodule, and cytologic evaluation was consistent with mild lymphoid hyperplasia. A prothrombin time and activated partial thromboplastic time were completed before aspiration and were normal. FNAs of the left and right mandibular lymph nodes were obtained and returned as mild lymphoid hyperplasia. A coccidioidomycosis Immunoglobulin G and Immunoglobulin M antibody panel were negative. A fungal serology was also negative for Histoplasma, Blastomyces, and Aspergillus antibodies. Radiographs of the left pelvic limb revealed no osseous changes around the fourth digit.

The patient was then referred to a tertiary hospital for evaluation by a soft-tissue surgeon. On physical exam, the dog was bright, alert, and responsive, with normal vital parameters. She had a normal respiratory rate and effort with clear lung sounds bilaterally. A contrast-enhanced CT scan of the thorax showed that the mass was in the cranial mediastinum (Figure 1). The mass was described as 8.8 × 4.1 × 4.6 cm and septated, with mixed fluid and soft-tissue structures with no evidence of vascular invasion. There was no evidence of pulmonary nodules, metastatic disease, or intrathoracic lymphadenopathy. There were reported multiple pulmonary bullae in the right cranial, right caudal, and left caudal lung lobe with no evidence of a pneumothorax. An incisional biopsy of the digit mass, an excisional biopsy of the lingual mass, and removal of the popliteal lymph node were performed. Histopathologic analysis of these tissues revealed benign masses with inflammatory changes in both the digit and lingual mass and no evidence of neoplasia in the popliteal lymph node.

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The patient underwent surgery for removal of the CMM 6 days later. With the patient in dorsal recumbency, thoracoscopy was attempted in an effort to remove the mass minimally invasively. A 15 mm diaphragmatic thoracoscopic portal was placed, followed by a 12 mm instrument portal in the right lateral thorax at the ventral fifth intercostal space. The mass was identified in the cranial thorax extending further cranially into the thoracic inlet than reported on CT scan, and internal thoracic vessels were extending into the mass. Using blunt dissection and a bipolar vessel sealing device^a for hemostasis, the mass was dissected from the caudal soft tissues including the pericardium. Numerous adhesions to the vena cava, phrenic nerve, and the left cranial lung lobe were identified. Because of these adhesions, the procedure was converted to a median sternotomy. The thoracic portals were removed, and the sites were closed in routine fashion.

During the median sternotomy, the CMM was noted to be closely adherent to multiple structures including the fat within the mediastinum, pericardium, internal thoracic arteries, and phrenic nerve. It was carefully dissected with the use of the bipolar vessel sealing device,^a blunt dissection, and bipolar electrocautery for hemostasis. The apex of the left cranial lung lobe was adhered to the mass, and a partial left cranial lung lobectomy of the apical region was performed to ensure complete resection of the mass. The remainder of the lungs appeared normal on evaluation with no evidence of bullae or blebs. A 14 Fr thoracostomy tube^b was placed in the left lateral thorax and secured using 2-0 nylon in a purse string and finger trap suture pattern. The sternotomy incision was closed routinely. The muscle and subcutaneous layer were injected with a bupivacaine liposome suspension^c (5.3 mg/kg) upon closure.

The patient had no perioperative anesthetic complications and recovered uneventfully from anesthesia. The patient received cefazolin^d (22 mg/kg IV) every 90 min perioperatively, which was continued postoperatively every 8 hr for three doses. The patient was continued on Normosol R^e with potassium chloride supplementation^f (20 mEq/L) at a maintenance rate and was started on hydromorphone^g (0.05 mg/kg IV q 6 hr) and meloxicam^h (0.1 mg/kg subcutaneously q 24 hr). The patient was recovered with oxygen supplementation and subsequently tapered to room air over the following 6 hr. The chest tube had minimal fluid and air production and was removed 20 hr after the operation. The patient was discharged from the hospital 2 days after the procedure with codeineⁱ (15 mg per os q 8–12 hr for 5 days) and meloxicam (0.1 mg/kg per os q 24 hr for 14 days).

Histopathology of the mass revealed a cyst adenocarcinoma arising from the thyroglossal ducts or ultimobranchial origin. The tumor appeared to be well differentiated. It consisted of multiple large cystic structures filled with proteinaceous rich fluid and lined by cuboidal to columnar epithelium, which was somewhat ciliated. In some areas, the cells formed more solid sheets of cells with clumps. The nuclei were mildly pleomorphic, round to oval, and had small nucleoli. Mitoses were ∼1 per high-powered field. The tumor was multicystic, partially well demarcated, and surrounded by some normal thymic and lymphoid tissue. The tumor compressed and formed adhesions to the lung parenchyma but did not appear invasive. There were some areas of inflammation throughout with lymphocytes and plasma cells. The tumor was suspected to have been completely removed based on the thin margins around the sample.

The patient continued follow-up and management with the oncology service. She received intensity-modulated radiation therapy 1 mo after the operation (51 Gy over 20 fractions), and carboplatin^j monthly for 4 doses total (160 to 200 mg/m² per dose). She has not received any additional treatments for the last 22 mo. At the time of writing this report, the patient was doing well at home. Most recent thoracic radiographs (25 mo after the operation) revealed no evidence of pulmonary metastasis and static mild focal fibrosis within the left lungs, likely associated with thoracic surgery. Abdominal ultrasound findings showed no growth of the splenic nodule and no new evidence of masses or lymphadenopathy.

Discussion

The thyroglossal duct develops as the embryonic thyroid gland descends from the foramen cecum at the base of the tongue to the final location in the pretracheal inferior midline of the neck.^3–5 The thyroid gland is the first endocrine gland to develop, and the duct will involute, but persistence may give rise to a thyroglossal duct cyst (TDC).^5,6

TDCs are one of the most common neck masses diagnosed in humans, clinically making up 70% of all congenital neck lesions.⁷ It is predominantly seen in males among pediatric patients and females in adulthood.^5,8 Malignancy in a TDC is rare (around 260 cases have been described) and typically presents later in life.⁹ The majority of thyroid tumors that arise in TDCs are papillary tumors with 1–5% of cases being of squamous cell–type.^5,6 TDCs can be found anywhere between the base of the tongue to the level of the suprasternal notch. There have been a small number of case reports in the human literature that report a TDC that reaches or extends beyond the suprasternal notch, including a case report describing extension into the superior mediastinum toward the aortic arch.³

In animals, TDCs are rarely reported, and current literature shows individual case reports in cats, horses, three dogs, and one calf.^4,10,11 They are mainly reported as ventral cervical swellings but have been observed in the caudal mediastinum of a cat and the subepiglottic area of a dog.^4,10 There have been three isolated case reports of malignancy of the thyroglossal duct in the veterinary literature, all detailing a well-described swelling in the ventral cervical region.^11,12 This is the first case report of a TDC adenocarcinoma located in the cranial mediastinum of a dog.

Clinical signs of a TDC in the mediastinum in animals include those associated with a space-occupying intrathoracic mass, such as abnormal breathing, respiratory distress, and exercise intolerance.² Pleural effusion was reported in a cat with a caudal mediastinal TDC.¹⁰ The dog in this current case report did not show any signs of a ventral cervical swelling and was subclinical for an intrathoracic mass.

TDCs have been correlated to clinical signs of hypothyroidism in humans with elevated thyroid-stimulating hormone (TSH) levels. TDCs may contain ectopic thyroid tissue that is the only functional thyroid tissue, leading to an inadequate production of thyroxine.⁴ This patient did not have any signs of hypothyroidism but did not have a T4 or TSH level measured before surgery. A total T4 was documented 25 mo after the operation and was within normal limits. In a 2014 retrospective study on thyroid carcinoma in dogs, patient thyroid function and tumor scintigraphic uptake were not found to have a significant effect on outcome.¹³ Hypothyroidism, high TSH, or low T4 in dogs and cats with TDC or TDC malignancy has not been documented.

A CT scan is the preferred imaging modality in both humans and dogs for the diagnosis, local staging, and evaluation of lung metastasis.² Definitive diagnosis of a thyroglossal duct adenocarcinoma is with histopathology after complete surgical excision. The Windstrom criteria have been referenced in the human literature for a definitive diagnosis. These include (1) carcinoma should be in the wall of the thyroglossal duct remnant, (2) carcinoma must be differentiated from a cystic lymph node metastasis by histologic demonstration of a squamous or columnar epithelium lining and normal thyroid follicles in the wall of the thyroglossal duct remnant, and (3) there should be no malignancy in the thyroid gland or any other possible primary site. However, these criteria are still debated.^12,14 Incisional biopsy is not recommended as part of a diagnostic workup for a suspected TDC because there is an increased recurrence rate following biopsy in humans.⁴ In two case reports of TDC in a dog and cat, incisional biopsies were performed as part of the diagnostic plan before definitive surgery, and no recurrence of disease was revealed.^4,10 The CT scan for this patient did not report any abnormalities of the ventral cervical neck region, the thyroid, or parathyroid glands, and histopathologic findings were consistent with a TDC adenocarcinoma based on the Windstrom criteria.

Additional diagnostic considerations that were not performed in this patient include immunohistochemistry to definitively rule out an ectopic thyroid carcinoma as well as to further gauge risks of metastasis. Immunohistochemistry can be performed for thyroglobulin, calcitonin, Ki-67, and E-cadherin. Ki-67 labeling was found to be negatively associated with time to distant metastasis in dogs with thyroid carcinoma.¹³

The definitive treatment for TDCs and thyroglossal duct malignancies in dogs may not be known. In previous case reports, there was no recurrence or evidence of metastasis described for a canine patient with a subepiglottic TDC and for a feline patient with a cervical TDC evaluated 14 mo after surgical excision.^4,12 This patient did not show any evidence of metastasis or recurrence 25 mo after operation. As adjunctive therapies were administered, it cannot be concluded whether surgical resection alone may have reduced recurrence or metastasis.

Similarly, in humans, there is still no clear consensus to the optimal treatment and further management of TDCs and TDC malignancies.⁹ The Sistrunk procedure is the standard treatment for TDCs located in the ventral neck^5–7 with a recurrence rate up to 5% in cases with no evidence of metastasis.^9,12 Case reports of a mediastinal TDC and a ventral neck TDC papillary carcinoma showed no recurrence 22 and 12 mo, respectively, following complete surgical excision with no adjunctive therapies.^3,7

Conclusion

This is the first reported case of a dog with a TDC adenocarcinoma that presented in the cranial mediastinum. It should be considered as a differential, albeit less likely, for cranial mediastinal masses. Further diagnostics, including a CT scan, of the cervical region and thorax are recommended to evaluate mediastinal masses and are helpful to determine other structural associations. A TSH and T4 level should be considered to evaluate for hypothyroidism. Definitive diagnosis is made postoperatively with histopathology of the mass. No evidence of recurrence or metastasis was noted 25 mo following complete excision of the mass with adjunctive intensity-modulated radiation therapy and chemotherapy.