Cystic Thyroid and Parathyroid Lesions in Cats
Reports of cystic thyroid and parathyroid masses in cats are uncommon. Herein, the authors describe a series of four cats with cystic ventral cervical lesions, among them thyroid cyst (n=1), thyroid cystadenoma (n=2), and parathyroid adenocarcinoma (n=1). Presentations ranged from completely asymptomatic cervical swellings to signs related to local compression of adjacent structures (e.g., trachea). Ultrasonographic evaluation was helpful in localization of the mass in two cases. Hormone analysis and concentration of cystic fluid were performed in one cat. Surgical excision was performed successfully in three cases. Histopathological examination was performed in all four cases. Long-term prognosis was excellent for those cases in which follow-up was available.
Case Reports
Case No. 1
A 16-year-old, neutered female domestic shorthair (DSH) cat was referred to the Kansas State University Veterinary Medical Teaching Hospital (KSU-VMTH) for evaluation of weight loss, inappetence, and lethargy of 1 month’s duration. Persistent hypercalcemia had been documented by the referring veterinarian. The only remarkable finding on physical examination was a firm, approximately 2.5 × 1.0-cm, non-painful subcutaneous (SC) mass in the left ventral cervical region. Results of a complete blood count (CBC) and complete serum biochemical analysis revealed a moderate hypercalcemia (total serum calcium, 14.3 mg/dL; reference range, 8.2 to 11.5 mg/dL; ionized calcium, 7.8 mg/dL; reference range, 4.37 to 5.87 mg/dL) and a mild azotemia (blood urea nitrogen [BUN], 37 mg/dL; reference range, 17 to 35 mg/dL; serum creatinine, 2.7 mg/dL; reference range, 0.8 to 2.3 mg/dL). Serum phosphorus was 3.1 mg/dL (reference range, 2.7 to 6.5 mg/dL). A urine sample collected by cystocentesis had a specific gravity (USG) of 1.014, with no other abnormalities. Serum total thyroxine (TT4) level was within the reference range (42.6 nmol/L; reference range, 10 to 45.5 nmol/L). Thoracic and abdominal radiography did not identify any abnormalities. Abdominal ultrasonography identified multiple, small, hypoechoic nodules within the liver. Cytopathological evaluation of fine-needle aspirates (FNA) of these hepatic nodules was consistent with extramedullary hematopoiesis. Cytopathological examination of a bone-marrow aspirate revealed no evidence of neoplasia or other abnormalities. Cervical ultrasonography identified a mass on the left side of the trachea at the level of the thoracic inlet [Figure 1]. The mass had a relatively anechoic central area, which was compressible and had a thick, irregular capsule. A small amount (1 to 2 mL) of clear fluid was aspirated from the mass using a 22-gauge needle. The parathyroid hormone (PTH) concentration within the cystic fluid was 107 pmol/L, nearly four times that of the serum PTH concentration (27.8 pmol/L; reference range, 0 to 4 pmol/L), which was also elevated. These results were consistent with primary hyperparathyroidism. On the basis of these findings, the cystic mass was diagnosed as parathyroid in origin, and parathyroidectomy was recommended.
Surgery was performed, identifying a left-sided solitary mass approximately 2.5 × 1.0 cm in diameter, which was excised using an extracapsular technique without incident. After surgery, the cat recovered well and showed no clinical signs of hypocalcemia. Within 12 hours, ionized calcium levels had decreased to within reference ranges (5.17 mg/dL). Upon reevaluation 1 week later, ionized calcium levels remained within reference range (ionized calcium, 4.48 mg/dL). Histopathological examination of the mass identified multiple clusters of neoplastic polygonal cells that appeared to invade adjacent normal thyroid gland. The tumor was classified as a parathyroid carcinoma. Six months after presentation, the cat had no evidence of either local recurrence or distant metastasis and remained normocalcemic. Radiography was not performed at this time.
Case No. 2
A 15-year-old, neutered male DSH cat was referred to the KSU-VMTH for intermittent dysphagia and regurgitation associated with a fluid-filled ventral cervical mass. Fine-needle aspiration of the mass by the referring veterinarian on three separate occasions had yielded 12, 20, and 50 mL of a brown, cloudy fluid. The cat was asymptomatic following fluid removal, but clinical signs would return with fluid reaccumulation. Cytopathological evaluation of the fluid was performed and was most consistent with a hematoma or seroma, with a specific gravity of 1.025, 6.9 g/dL of protein, and 1,100 white blood cells (WBC)/μL consisting mainly of lymphocytes (51%) and macrophages (38%). On physical examination, the cat had an approximately 6 × 2-cm, fluctuant, nonpainful, ventral cervical mass that deviated the trachea to the right. Results of a CBC and a complete serum biochemical analysis revealed a lymphopenia of 430/μL (reference range, 2 to 7 × 103/μL), consistent with a stress response. Total T4 levels were within reference ranges (21 nmol/L; reference range, 10 to 45.5 nmol/L). Radiographs of the thorax and neck demonstrated dorsolateral deviation of the cervical trachea to the right of midline by a soft-tissue density [Figure 2]. Cervical ultrasonography identified a large, cystic structure in the ventral cervical region, most likely associated with the left thyroid gland. The mass appeared well defined with thickening of the dorsal wall and evidence of septation within the mass. Surgical exploration of the ventral neck was performed. A ventral midline approach was made, and a well-encapsulated mass associated with the left thyroid and measuring 6 × 2 × 3 cm was excised. The cat recovered without incident and showed no signs of dysphagia, regurgitation, or stridor after surgery. The cat was discharged from the hospital 48 hours later. Histopathologically, the mass was comprised of fibrous connective tissue compartments interspersed by foci of glandular tissue. The glandular epithelium was arranged in dense sheets and packets of closely spaced polygonal cells, occasionally arranged around luminal structures. The mass was diagnosed morphologically as a thyroid cystadenoma. In the 10 months that followed surgery, the cat remained normal without recurrence of clinical signs.
Case No. 3
A 26-year-old, neutered female DSH cat was presented to the Atlantic Veterinary Collegea for anorexia, adipsia, lethargy, and vomiting of 3 to 4 days’ duration. The cat had been diagnosed with hyperthyroidism and mild hypertrophic cardiomyopathy 6 months prior and was currently being treated with methimazole (2.5 mg, per os [PO] q 12 hours). Physical examination revealed a thin cat (body condition score, 1.5/5) with small, irregular kidneys present on abdominal palpation. An approximately 2-cm, nonpainful, SC mass was present in the region of the right thyroid gland. Other findings included dehydration (estimated at 7%), pale mucous membranes, weakness, and depression. Results of a CBC and a complete serum biochemical analysis identified a mild normocytic, normochromic anemia (hematocrit, 25.8%; reference range, 30% to 45%); hypernatremia (174 mmol/L; reference range, 150 to 165 mmol/L); hypokalemia (2.9 mmol/L; reference range, 4.0 to 5.8 mmol/L); hypercalcemia (total calcium, 19.1 mg/dL; reference range, 8.9 to 11.2 mg/dL; ionized calcium, 7.8 mg/dL; reference range, 4.0 to 5.6 mg/dL); hyperphosphatemia (7.7 mg/dL; reference range, 3.2 to 5.9 mg/dL); and azotemia (BUN, 60.5 mg/dL; reference range, 14.0 to 30.8 mg/dL; serum creatinine, 4.3 mg/dL; reference range, 1.01 to 2.03 mg/dL). A voided urine sample identified a USG of 1.022, with no other abnormalities. The azotemia was attributed to chronic renal failure, although a prerenal component was likely also present. The hypernatremia and hyperphosphatemia were thought to be due to dehydration and decreased glomerular filtration rate. The hypokalemia could be explained by decreased intake as well as increased renal losses. The anemia was considered secondary to decreased production of erythropoietin by the kidneys as well as anemia of chronic disease. Neoplasia (i.e., lymphosarcoma), primary hyperparathyroidism, and chronic renal failure were considerations for the hypercalcemia. Serum TT4 level measured 2 months prior to presentation was within the reference range (33.46 nmol/L; reference range, 16 to 47 nmol/L). Serum PTH level was significantly elevated at 84.0 pmol/L (reference range, 0 to 4 pmol/L), and in the face of the hypercalcemia was consistent with a diagnosis of primary hyperparathyroidism. Radiographs of the cervical region and thorax revealed an irregular, multi-lobulated mass deviating the cervical trachea ventrally. Abdominal radiographs demonstrated mineralization of the gastric wall and renal parenchyma. Abdominal ultrasonography revealed small, irregular kidneys with diffuse mineralization bilaterally. Echocardiography confirmed the presence of left ventricular hypertrophy. Initial treatment consisted of correction of dehydration and electrolyte imbalances using saline solution with 5% dextrose/L (7.5 mL/kg body weight per hour, intravenously [IV]) and supplemental potassium chloride (20 mEq/L).
On day 2, the cat remained very depressed but appeared adequately hydrated. Results of a second serum biochemical analysis revealed resolution of the hypernatremia (sodium concentration, 146 mmol/L) and hypokalemia (potassium concentration, 4.2 mmol/L) and improvement of the hypercalcemia (total calcium concentration, 15 mg/dL), hyperphosphatemia (serum phosphorus concentration, 5.4 mg/dL), and azotemia (BUN concentration, 42.8 mg/dL; serum creatinine concentration, 3.4 mg/dL). The serum glucose concentration had increased to 258 mg/dL (reference range, 60 to 102 mmol/L). The rate of fluid administration was decreased (5 mL/kg body weight per hour, IV), and the dextrose administration was discontinued. The cat was also treated with furosemide (5 mg/kg body weight, IV, q 12 hours for the first 12 hours, then 0.4 mg/kg body weight per hour, IV, in saline solution) for the hypercalcemia. Ranitidine (1 mg/kg body weight, IV, q 12 hours) was given to reduce gastric acidity.
On day 3, the cat appeared stronger and was drinking on its own. Treatment was initiated with prednisone (3.75 mg, PO, q 12 hours) for a presumptive diagnosis of lymphosarcoma, and nutritional support was provided via a naso-esophageal tube. Over the following 24-hour period, the cat had multiple episodes of vomiting, and on day 4, therapy with metoclopramide (0.3 mg/kg body weight, SC, q 8 hours) was initiated. Throughout the day, the cat appeared quiet and depressed, and that evening she died. Necropsy identified a large, approximately 2-cm thyroid cyst with multiple adenomatous nodules. Histopathological examination revealed that one of the adenomas was parathyroid in origin, consisting of closely packed narrow cords of cuboidal cells contained in a fine fibrous stroma. The 1-cm parathyroid adenoma was adjacent to the larger thyroid cyst. Other findings included end-stage renal disease with significant nephrocalcinosis and pancreatic acinar nodular hyperplasia. At the owner’s request, the necropsy was limited to the abdomen and cervical region. With these limitations, no definitive cause of death was determined.
Case No. 4
A 15-year-old, neutered female DSH cat was referred for a swelling in the ventral cervical region of approximately 3 months’ duration. The cat was reported as otherwise normal. Upon physical examination, a large, nonpainful, fluctuant, SC mass was present over the ventral to cervical trachea. No other significant abnormalities were noted. Results of a CBC and a complete serum biochemical analysis did not reveal any abnormalities. Serum TT4 level was normal on referral blood work. Fine-needle aspiration of the mass identified a small amount of brown, slightly cloudy fluid. Cytopathological evaluation of the fluid was consistent with a hematoma or seroma. Surgical exploration of the ventral neck was performed, identifying a well-circumscribed mass, approximately 3 cm in diameter, in the region of the left thyroid gland. The mass was excised without incident, and the cat recovered uneventfully following surgery. Results of the histopathological examination were consistent with a thyroid cyst. Follow-up information was not available.
Discussion
Cystic masses arising from the cervical region are uncommon. In cats, salivary mucoceles,1 branchial cysts,2 and thyroglossal cysts3 have been reported. Branchial cysts, derived from the remnants of the second pharyngeal pouch, are located lateral to the parathyroid-thyroid area and attached deeply to cervical structures; thyroglossal duct cysts, derived from the embryonic thyroglossal duct, tend to be located near midline. In dogs, ultimobrachial duct cysts have also been reported.4 These cysts, derived from the embryonic fifth pharyngeal pouch, are often present in the parenchyma of the thyroid. Reports of cats with cystic nodules arising primarily from the thyroid or parathyroid glands, or both, are uncommon.
The term “cyst” is used to describe any fluid-filled space that is lined by epithelial cells, either benign or malignant.5 The pathogenesis of cystic lesions of the thyroid and parathyroid glands is not uniform. Benign thyroid cysts, lined by a thyroidal epithelium, may arise from a degenerated adenoma or nodule. Many so-called thyroid and parathyroid cysts are actually pseudocysts, that is, fluid-filled spaces not demarcated by an epithelium, but rather by granulation or fibrous connective tissue.5 Many malignant cysts lack a true epithelial lining, representing a cyst-like lesion that forms as the tumor outgrows its own blood supply. Thyroid and parathyroid cysts can be broadly classified as functional or nonfunctional based on the presence or absence of concomitant hyperthyroidism and hyperparathyroidism, respectively.
Cystic thyroid nodules have been associated with thyroid carcinoma in dogs67 as well as thyroid adenomas or adenomatous hyperplasia in cats.8–11 Most of these cats also exhibited hyperthyroidism. The authors are aware of two reports in the literature of apparently nonfunctional cystic thyroid adenomas in cats.1213
Reports of cystic cervical masses arising from the parathyroid gland in cats are even less common. There is a single report of parathyroid cysts in a cat associated with bilateral adenomas;3 however, the masses were not palpable, and surgical excision was required for diagnosis. More recently, two cats with cystic functional parathyroid adenomas were identified using ultrasonography.14 This case series represents one of three reports of parathyroid carcinoma in a cat,314 and it is the only case in which a cystic mass was identified.
The distinction of a cystic parathyroid mass from a cystic thyroid mass is important in terms of perioperative and potential therapeutic considerations. Hyperfunctioning parathyroid lesions require early surgical intervention, while some functional cystic thyroid lesions could be managed with methimazole or other medical therapies. Both may present as asymptomatic cervical swellings or masses, or occasionally (as in case no. 2) with local signs related to compression of adjacent structures, including dysphagia, regurgitation, pain, and laryngeal nerve palsy.1215 In humans, FNA of cystic fluid is often used to differentiate thyroid from parathyroid cysts. Thyroid cysts usually contain blood-tinged, brown-colored material and may have elevated levels of thyroid hormones as well as other biochemical analytes such as acid phosphatase, aspartate aminotransferase, amylase, lactate dehydrogenase, and total bilirubin.5 Cytopathological findings may include the presence of colloid or bare follicular-type nuclei, or both.16 Parathyroid cysts often contain a clear, watery fluid. Analysis of cystic fluid for the presence of PTH is considered diagnostic for a cystic parathyroid mass.16 Fine-needle aspiration also allows for microscopic examination of cells for malignancy. In the four cases described here, evaluation of the cystic fluid for the presence of thyroid and parathyroid hormone levels was performed only in case no. 1. In this case, the elevation of parathyroid hormone levels in both serum and cystic fluid was consistent with a diagnosis of a functional parathyroid cyst. This information allowed the authors to alter the perioperative treatment plan for this patient to include periodic measurement of serum total calcium and monitoring for clinical signs of hypocalcemia. Unfortunately, insufficient or unrepresentative material limited the ability to perform hormonal level analyses and cytopathological evaluation of cystic fluid in all of these cases. Ideally, thyroid and parathyroid hormone levels should be measured from the cystic fluid of all suspected thyroid and parathyroid masses.
Ultrasonographic evaluation of cystic neck lesions is useful in the identification of the anatomical site of the lesion, lesion tissue characteristics, invasion into nearby vessels and lymph nodes, as well as to assist in FNA or biopsy of the cyst or cyst wall. Ultrasonographic characteristics of adenomatous thyroid glands in hyperthyroid cats have been described,8 as have carcinoma, adenoma, and hyperplasia of the parathyroid gland of dogs.1718 In a recent study of dogs, ultrasonography was found to be accurate in localizing parathyroid lesions presurgically and in differentiating neoplastic from hyperplastic lesions based on size criteria.17 Cervical ultrasonography was performed on two of the cases presented (case nos. 1, 2). An ultrasound-guided FNA of cystic fluid contained within the masses was performed in both cats. In case no. 1, hormonal analysis performed on the cystic fluid led to a preoperative diagnosis of a parathyroid cystic lesion. In case no. 2, ultrasound examination enabled localization of the mass to the region of the thyroid gland.
Radionuclide imaging has been utilized in humans in the localization of adenomas and hyperplastic parathyroid and thyroid glands. Technetium-99m (99mTc) sestamibi has commonly been used to identify parathyroid masses in humans and, more recently, has been evaluated in dogs.1920 In the two dogs reported, scintigraphical images identified persistent focal uptake of 99mTc-sestamibi in the region of the parathyroid gland. The use of sestamibi radionuclide imaging for parathyroid cysts has not been formally evaluated in cats, but it may be valuable in distinguishing parathyroid from thyroid cysts.
Surgical exploration of the thyroid/parathyroid regions was performed in three of the four cases presented. In these cases, surgical excision of the masses with histopathological evaluation proved to be both diagnostic and therapeutic. Complications related to the surgical procedures were not seen. None of the cats in this report developed hypocalcemia following surgery or problems referable to hypocalcemia. Postsurgical recovery in the three surviving cats was excellent. Case no. 1 developed chronic renal failure 2 months following surgical resection of its parathyroid carcinoma, perhaps secondary to prolonged hypercalcemia and secondary nephrocalcinosis or chronic interstitial nephritis, or both. The diagnosis of carcinoma was based on the histopathological finding of extracapsular invasion by neoplastic cells, which were seen extending into the adjacent normal thyroid gland. No evidence of metastasis was seen during 6 months of follow-up. Only two reports of a parathyroid carcinoma have been documented in the literature; metastasis was not identified in either case.314 In case no. 2, removal of the thyroid cyst adenoma resulted in immediate resolution of the clinical signs of dysphagia and regurgitation. Case no. 3 had a thyroid cystadenoma diagnosed only at necropsy. The mass was likely the cause of the cat’s hyperthyroidism that had been diagnosed 6 months prior to presentation. The finding of a parathyroid adenoma might explain the cat’s chronic hypercalcemia or worsening of preexisting renal disease, or both. The thyroid cyst diagnosed in case no. 4 was not associated with any overt clinical signs and, therefore, was not considered to be functional.
In humans, nonfunctional thyroid and parathyroid cysts have been successfully treated with FNA and drainage.2122 A recent study in dogs23 investigated the use of chemical ablation of functional parathyroid masses, by injection of ethanol into the parathyroid under ultrasonographic guidance. Chemical ablation was successful in seven of the eight dogs in this study. Hypocalcemia developed in four dogs, with one dog developing hypocalcemic tetany after treatment. Two dogs developed transient changes in their bark. Several recent studies in cats have investigated percutaneous ethanol injection for the treatment of hyperplastic thyroid nodules.1024 In four cats where a single thyroid nodule was injected, all cats became euthyroid after treatment, and adverse effects were considered mild (i.e., two developed dysphonia). In cats that were injected multiple times or that had both thyroid lobes injected,2425 long-term return to euthyroidism was not achieved, and multiple adverse effects were noted, including one fatality from bilateral laryngeal paralysis. Due to the adverse effects reported following this treatment as well as the potential concern for malignancy in these cases, the authors currently advocate surgical excision of thyroid and parathyroid cysts in cats. The recurrent laryngeal nerves should be identified and protected to avoid the complication of laryngeal paralysis.
Conclusion
Cystic thyroid and parathyroid masses are uncommon lesions of the neck found mainly in older cats. The differential diagnoses for a cat presenting with a cystic ventral cervical mass should include branchial cyst, thyroglossal cyst, thyroid cyst, thyroid cyst adenoma, parathyroid cyst, parathyroid cyst adenoma, parathyroid carcinoma, thyroid carcinoma, salivary mucocele, and abscess. The initial diagnostic workup of a cat presenting with a cystic cervical mass should include ultrasonographic examination, which can aid in the localization of the tissue of origin as well as provide assistance in FNA of any cystic fluid. Cytopathological evaluation and selective hormonal analyses of cystic fluid should be performed whenever possible and may occasionally provide a preoperative diagnosis. In most cases, surgical exploration of the cervical region is necessary for diagnosis. In three of the four cases presented here, surgical excision of the cystic thyroid and parathyroid masses resulted in resolution of all referable clinical signs. Complications including postoperative hypocalcemia were not seen in any of the cases. Long-term prognosis was excellent for those cases in which follow-up was available.
Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PEI, Canada.
Citation: Journal of the American Animal Hospital Association 39, 4; 10.5326/0390349
Citation: Journal of the American Animal Hospital Association 39, 4; 10.5326/0390349
Ultrasonographic image of a cystic parathyroid mass in a 16-year-old cat with a parathyroid carcinoma (case no. 1). The mass has a hypoechoic central area with a thick, irregular wall.
Ventrodorsal radiographic view of a cystic thyroid mass in a 15-year-old cat with a thyroid cystadenoma (case no. 2). The large mass deviates the trachea to the right.
