Abstract
Ectopic thyroid tissue was identified at the base of the tongue in a 9-year-old, euthyroid, domestic shorthair cat. The lingual submucosa and the muscles were replaced by thyroid tissue, which consisted of various-sized follicles each lined by a row of cuboidal epithelium. Many follicles contained eosinophilic, periodic acid Schiff-positive, colloid material. Imunohistochemically, the epithelial cells stained positive for AE1/AE3 and thyroglobulin. No calcitonin positive cells or parathyroid tissue was seen. The cat has been followed for 1018 days after surgery, is clinically well and remains euthyroid.
Ectopic thyroid is an embryologic aberration characterised by the presence of thyroid tissue at a site other than the normal pre-tracheal location. The thyroid gland arises from the fourth branchial pouch along with the thyroglossal duct. It migrates downward along the midline from the foramen caecum at the base of the primordial tongue to the base of the heart (Hamilton & Mossmann 1972, Titlbach et al 1987, Ohri et al 1994, Batsakis et al 1996, Arancibia et al 1998).
Aberrant migration of thyroid tissue along the midline from the neck to the diaphragm has been reported in various sites anterior to the diaphragm (Hamilton & Mossmann 1972, Titlbach et al 1987, Ohri et al 1994, Spinner et al 1994, Batsakis et al 1996, Lieberum & ten Cate 1996, Sambola-Cabrer et al 1996, Muysoms et al 1997, Arancibia et al 1998, See et al 1998, Tojo 1998, Kalan & Tariq 1999). Ectopic thyroid tissue might develop in the substance of the tongue at or near the point of attachment of the thyroglossal duct (Batsakis et al 1996, Lieberum & ten Cate 1996, Arancibia et al 1998). Rare cases of ectopic thyroid tissue have been reported in humans in the liver, pancreas and adrenal glands. The histogenesis of the post diaphragmatic sites is difficult to explain (Strohschneider et al 1993, Seelig & Schonleben 1997, Eyuboglu et al 1999, Shiraishi et al 1999). Also extremely rare is ectopic thyroid tissue giving rise to adenoma and adenocarcinoma, rarely with lymph node metastasis (Diaz-Arias et al 1992, See et al 1998, Hari et al 1999, Matsumoto et al 1999).
In dogs and cats, examination of anterior mediastinal tissue reveals persistent branchial cysts and rare groups of thyroid follicles. In dogs, thyroid and parathyroid adenocarcinoma have been occasionally reported in the mediastinum arising from ectopic tissue (Patnaik et al 1978, Stephens et al 1982, Constantino-Casas 1996). Mediastinal thyroid hyperplasia has been reported in cats undergoing bilateral thyroidectomy for the treatment of hyperthyroidism (Swalec & Birchard 1990). A functional adenoma from ectopic thyroid tissue has been reported in the thoracic inlet in a cat (Noxon et al 1983).
In humans, ectopic lingual thyroid tissue is uncommon, the estimated incidence being one case in 100 000. The lingual site is the most common, and the aberration develops mostly in paediatric patients and females (Batsakis et al 1996, Lieberum & ten Cate 1996, Kalan & Tariq 1999).
The purpose of this report is to describe ectopic lingual thyroid tissue in a cat and to review the literature.
Case Report
A 9-year-old spayed female domestic shorthair cat was given her annual physical examination. A 0.2×0.4 cm lesion resembling an eosinophilic granuloma was observed at the dorsal base of the tongue. Biopsy was performed and the results were adenocarcinoma. Re-examination 1 month later revealed a 0.8 × 0.2 cm, smooth, red, slightly raised, flat mass. The lesion was located on the left side of the base of the tongue. The serum thyroxine (T4) value, which was determined as part of the preoperative work-up, was 17 nmol/l (reference range, 10–50 nmol/l). The lesion was surgically resected and the cat recovered uneventfully. Histologic examination resulted in a preliminary diagnosis of adenocarcinoma or possibly thyroid carcinoma because of the presence of colloid-like material.
Paraffin blocks of formalin-fixed surgical tissue were sent to The Animal Medical Center for further evaluation. Prepared slides were stained with haematoxylin and eosin, periodic acid Schiff (PAS), and diastase periodic acid Schiff (DPAS). Other slides were immunohistochemically stained by a supersensitive multilink immunodetection system for antibodies against thyroglobulin, calcitonin, and AE1/AE3 (a marker for cytokeratin) following the instructions of the manufacturer (Biogenex, San Ramos, CA, USA).
Histologically, the lesion in the tongue had mostly intact mucosa. The submucosa and the adjoining skeletal muscle were replaced by thyroid tissue. The thyroid tissue consisted of various-sized follicles, each lined by a row of cuboidal epithelium. Many follicles contained eosinophilic colloid material (Fig 1). This colloid material stained with PAS, and the stain remained after treatment with the enzyme diastase. A few areas of solid groups of cells were seen; the cells had vesiculated nuclei and small nucleoli. The cytoplasm of both the follicular and solid groups of cells was mostly eosinophilic, but some cells had clear cytoplasm. None of the cells were seen in blood vessels, and the lesion was not encapsulated. Parathyroid tissue was not seen. Immunohistochemically, thyroglobulin stained both the cytoplasm of the cells and the colloid (Fig 2). The epithelial cell cytoplasm stained with AE1/AE3 (Fig 3). There were no calcitonin-stained cells.
Photomicrograph of the lingual submucosa, which is replaced by multiple follicular structures with colloid. Clear cells can be seen in some areas. Haematoxylin and eosin, original magnification ×200.
Photomicrograph of ectopic follicular tissue stained with thyroglobulin antibody showing both intracytoplasmic and colloid positivity Stain: supersensitive multilink immunodection system (Biogenex, San Ramos, CA, USA) and Gill III counterstaining, original magnification ×400.
Photomicrograph of ectopic follicular tissue stained against AE1/AE3 showing intracytoplasmic staining. Stain: supersensitive multilink immunodection system (Biogenex, San Ramos, CA, USA) and Gill III counterstaining, original magnification ×400.
At 1018 days after surgery, the cat was doing well, exhibiting no clinical signs relating to the tongue or signs of hyperthyroidism. A second serum T4 determination revealed a concentration of 21 nmol/l.
Discussion
Ectopia of the thyroid has been reported in various sites in humans, lingual being the most common (Chanin & Greenberg 1988, Batsakis et al 1996, Muysoms et al 1997, Arancibia et al 1998, Hazarika et al 1998, See et al 1998, Eyuboglu et al 1999, Kalan & Tariq 1999, Shiraishi et al 1999). Ectopia arise from the failure of descent of the median analogue of the thyroid gland and incomplete obliteration of its vertical tract during embryologic development of the thyroid (Hamilton & Mossmann 1972, Titlbach et al 1987, Batsakis et al 1996, Kalan & Tariq 1999).
The single lesion located at the base of the tongue, containing thyroid follicles, which were immunohistochemically positive for thyroglobulin, established the diagnosis of lingual ectopia of the thyroid in this cat. A primary thyroid carcinoma arising from ectopic thyroid or metastatic carcinoma from the thyroid gland itself is morphologically difficult to differentiate from a benign lesion, especially on the basis of examination of small biopsy specimens. In this cat, lack of follicular cell proliferation and the absence of cellular and nuclear atypia suggested the benign nature of the lesion (Stephens et al 1982, Noxon et al 1983, Constantino-Casas et al 1996, Kakudo et al 1998). The benign nature was established by the long (1018 days), uneventful follow-up.
Ectopic lingual thyroid tissue in humans occurs at the junction of the anterior two-thirds and posterior one-third of the tongue; symptoms develop from childhood to adult life and correlate to the size of the lesion and functional status of the thyroid tissue (Chanin & Greenberg 1988, Batsakis et al 1996, Lieberum & ten Cate 1996, Hazasrika et al 1998, Tojo 1998, Kalan & Tariq 1999). Most ectopic thyroid tissue is considered to be non-functional in humans (Sambola-Cabrer et al 1996, Muysoms et al 1997, Kalan & Tariq 1999). In this cat, the location of the lesion at the base of the tongue was similar to that seen in humans and the tissue was not hyperfunctional (ie, did not lead to hyperthyroidism).
The morphologic and immunohistochemical findings of this study are similar to those in humans with ectopic thyroid tissue (Titlbach et al 1987, Kakudo et al 1998). The follicular cells and the colloid in this cat stained with thyroglobulin. The epithelial cells stained with the epithelial marker AE1/AE3, but there were no calcitonin positive cells in the lesion. In cats, the C-cells containing calcitonin appear at 38 days of gestation as single scattered cells and migrate into interfollicular spaces from the 50th day of gestation (Titlbach et al 1987). The absence of C-cells in the lesion of this cat indicated that the ectopia might have occurred before the 38th day of gestation (Titlbach et al 1987). Similar observations have been made in humans with ectopic thyroid tissue (Hamilton & Mossmann 1972, Batsakis et al 1996). The absence of parathyroid tissue indicates a different embryogenesis for the parathyroid glands (Batsakis et al 1996).
Clinically, surgical resection of ectopic thyroid tissue in the tongue is considered to be an effective treatment in humans. Surgery also seemed to be effective in this cat (Chanin & Greenberg 1988, Lieberum & ten Cate 1996, Kalan & Tariq 1999).