Feline Anaplastic Giant Cell Adenocarcinoma of the Thyroid

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1 Vet. Pathol. 16: (1979) Feline Anaplastic Giant Cell Adenocarcinoma of the Thyroid A. K. PATNAIK and P. H. LIEBERMAN Departments of Pathology, The Animal Medical Center and Memorial Sloan-Kettering Cancer Center, New York, N.Y. Abstract. An 8-year-old castrated, male, domestic short-haired cat had anaplastic giant cell adenocarcinoma in the thyroid gland. The cat had difficulty in breathing and swallowing because of a rapidly growing mass in the left thyroid region that partially enclosed the trachea and esophagus and had evidence of diffuse discrete interstitial pulmonary metastases. The neoplasm, which was locally invasive, was formed by groups of pleomorphic cells arranged in an endocrine-like pattern. The cells were round, spindle, fusiform or irregular; some were large and multinucleated with up to 50 nuclei. Metastases were in the lungs, pleura and regional lymph nodes. Microscopically, both thyroid glands were involved; areas of transition from a well differentiated papillary adenocarcinoma to an anaplastic form were seen. Anaplastic giant cell tumors of the thyroid in man are a distinct clinicopathologic entity [ 1, 2, 11, 15, 16, 181. These pleomorphic neoplasms occur in late adulthood, have a rapid growth rate, and are invariably fatal. They differ from the well differentiated thyroid adenocarcinomas common in younger people in that they have slower evolution, well defined treatment and better prognosis. Foci of well differentiated thyroid adenocarcinomas frequently are seen in these anaplastic tumors [ 1, 2, 7-12]. Dogs have more malignant than benign thyroid tumors, and more of these tumors are follicular than papillary. Anaplastic neoplasms have been described [3, 4, 121. In a recent study, only two of the 94 malignant thyroid neoplasms were considered to be giant cell carcinomas [ 131. A survey of the literature on feline thyroid neoplasms showed that the malignant neoplasms are less common than the benign ones and that no anaplastic or giant cell adenocarcinomas have been described [4-6, 13, 14, 171. In a survey of feline nonhematopoietic neoplasms [ 171, however, two of the seven thyroid adenocarcinomas were considered anaplastic. Case Report An 8-year-old castrated, male, domestic short-haired cat that had progressive difficulty in breathing and swallowing had a rapidly growing palpable mass surrounding the larynx, and greatly reduced mobility of the larynx and epiglottis. Radiographs 687

2 688 Patnaik and Lieberman indicated a soft tissue mass surrounding the larynx and upper trachea. A month earlier, the lungs had no apparent lesions but now had diffusely distributed, discrete interstitial nodules. The only other significant change was an eosinophil count of 12/ 100 white blood cells. The cat was killed and necropsied. Materiais and Methods Tissues taken at necropsy were fixed in 10% buffered formalin, embedded in paraffin, sectioned at 6 micrometers, and stained with hematoxylin and eosin (HE). Selected sections of the primary and metastatic tumors were stained also with mucicarmine. Necropsy findings Results The left thyroid lobe was normal size but looked pale gray and round. The right thyroid lobe was replaced by a 42-cm3 mass opposite the cricoid cartilage and the first 10 tracheal rings. The mass extended dorsally between the trachea and the esophagus to which it was attached. The esophageal mumsa was intact. Ventrally, the mass encircled the trachea beyond the midline and extended anteriorly into the space between the cricoid and the thyroid cartilages, partially distorting the tracheal passage. It did not infiltrate the laryngeal and tracheal mucosa but had infiltrated adjoining skeletal muscles. The cut surface of the mass was pale brown and had small cystic and darkened areas. The lymph nodes around the thyroid, the jugular vein and in the anterior mediastinum were normal. The pleural cavities were filled with a thin pink-white fluid. Numerous discrete (4 to 8 millimeters) and confluent gray nodules were diffusely distributed in all lung lobes. There were more nodules in the diaphragmatic lobe than in the others and the nodules were more evident on cut than pleural surfaces. The heart had left ventricular hypertrophy. Microscopic findings The mass was composed of densely packed pleomorphic cells with areas of necrosis and severe desmoplasia. The desmoplasia was more common at the periphery. The pleomorphic cells were arranged in various sized groups, surrounded by a thin fibrovascular stroma, producing an endocrine pattern. The capillaries in the stroma were lined with prominent endothelial cells (fig. 1). Most pleomorphic cells were large with single nuclei or were multinucleate with up to 50 nuclei. There were occasional spindle and small round cells. The large cells were round, fusiform or irregular and had abundant pale eosinophilic and granular cytoplasm. The nuclei, which were large and vesicular with scattered chromatin, occasionally had prominent nucleoli. The nuclei in the multinucleated cells had the same characteristics as the nuclei of the large cells and were randomly arranged. In some cells the nuclei occupied most of the cytoplasm; in others they were at one end of the cell, which had

3 Feline Thyroid Giant Cell Adenocarcinoma 689 Fig. 1: Cellular areas with endocrine pattern and giant cells. HE. tapering cytoplasm. The spindle cells had elongated nuclei with prominent nucleoli. The small round cells were similar to the normal cuboidal cells lining the follicles. Mitoses and abnormal mitotic figures occasionally were seen. Rarely, large irregular follicles were seen lined with cuboidal or low columnar epithelium as well as with large cells. Normal acini also rarely were seen. The tissue with these pleomorphic features merged with fairly well differentiated papillary structures with fibrovascular stalks projecting into cystic spaces lined with single or multiple layers of columnar and cuboidal cells, with large vesicular nuclei and prominent nucleoli (fig. 2). Mitoses were common in this segment of the neoplasm. The transition from papillary adenocarcinoma to giant cell neoplasm was more obvious in the left thyroid lobe, which had multiple areas of typical papillary adenocarcinoma with occasional psammoma bodies and transition from acini. Some of these papillary structures had anaplastic large cells. Multinucleated cells were not seen in these areas. Mitosis and invasion of the lymphatics were common. Occasional acini close to the papillary structures were large and filled with actively dividing atypical epithelial cells. Skeletal muscles and outer layers of the esophagus and trachea adjoining the mass showed severe desmoplasia, degeneration, necrosis, regeneration of the skeletal muscles, and occasional areas of highly cellular stroma containing spindle cells with hyperchromatic nuclei and prominent nucleoli and cells similar to those seen in the mass. Invasion into the vessels, mostly lymphatics, consisted of papillary as well as giant cell parts. Neoplastic cells also were seen in the subcapsular sinusoids of the draining lymph nodes.

4 690 Patnaik and Lieberman Fig. 2 Papillary and anaplastic areas with transition from papillary to giant cells. Fig. 3: Lungs with papillary, spindle and giant cells. The alveolar spaces of the lungs were replaced with discrete and confluent lesions containing predominantly papillary structures similar to the well differentiated areas of the neck mass. Areas with large and multinucleated cells were seen in and around the papillary structures. Also rarely seen were the cellular areas, as in the primary tumor that had spindle cells mixed with distinct glandular elements (fig. 3). Occasional mitoses were seen among all these different cell types in the lungs. The pulmonary pleura was thick with active fibrosis and metastatic neoplastic cells. The mucicarmine stain did not indicate that any of the neoplastic cells at the primary site or in the lungs contained m u c h Other changes were focal necrosis and mineralization in the adrenal cortex and hypertrophic cardiomyopathy with diffuse myocardial changes. Discussion Anaplastic thyroid adenocarcinomas in man are divided into three types: I ) small round cell, 2) spindle cell and 3) giant cell [9]. All three, which are becoming rarer, are highly malignant and have a rapid course with short survival time [2, 11, 161. The clinical course and histologic features we describe are similar to those of the giant cell anaplastic adenocarcinoma of the thyroid in man. In the cat, only follicular and papillary adenocarcinomas have been described [4, 13, 141.

5 Feline Thyroid Giant Cell Adenocarcinoma 69 1 With light microscopy alone it is often difficult to differentiate the spindle and giant cell carcinomas from mesenchymal neoplasms such as fibrosarcoma, leiomyosarcoma and rhabdomyosarcoma. These occur rarely in the thyroid of man [7, 9, 161. Adenocarcinomas have a more polymorphous cell population and an epitheliallike pattern in contrast to the monomorphous and sarcomatoid pattern of sarcomas. Differentiation is easier with electron microscopy [7-9, 121. In our cat there was a polymorphous cell population, epithelial-like pattern and transition from a well differentiated papillary adenocarcinoma in the thyroid. The clinically rapid course also aided the diagnosis. Anaplastic thyroid adenocarcinomas in man often are seen with well differentiated adenocarcinomas, particularly the follicular and papillary types, and accumulated data suggest that spindle and giant cell carcinomas arise from the transformation of differentiated carcinoma of the thyroid [ 1, 7, 1 I, 121. Ultrastructural studies have shown that spindle and giant cells in thyroid anaplastic carcinomas are of epithelial cell origin [I, 7, 9, 121. These studies also have shown the neoplastic cells to range from well differentiated to highly anaplastic spindle and giant cells. This supports the contention that these spindle and giant cells arise from the well differentiated neoplastic cells [7, 161. This also has been demonstrated by serial transplantation studies in mice in which well differentiated follicular and papillary adenocarcinomas were transformed to spindle and giant cell carcinomas [ 191. Similar transformation has been seen in spontaneous differentiated thyroidal carcinomas [lo] and in vifro cultures of neoplastic cells [7]. In our cat we found not only an associated papillary adenocarcinoma but also areas of transition from it to the anaplastic form, both in the primary and metastatic sites. Acknowledgements We thank The Bodman Foundation for support and Cynthia J. Fazzini for editorial assistance. References I ALDINGER, K.A.; SAMAAN, N.A.; IBANEZ, M.; HILL, C.S., JR.: Anaplastic carcinoma of the thyroid. A review of spindle and giant cell carcinoma of the thyroid. Cancer 41: BEEMER, R.K.; BAKER, H.W.: Anaplastic cancer of the thyroid. Northwest Med , BRODEY, R.S.; KELLY, D.F.: Thyroid neoplasms in the dog: clinicopathologic study of 57 cases. Cancer , CLARK, S.T.; MEIER, H.: A clinicopathological study of thyroid disease in the dog and cat. I. Thyroid pathology. Zentralbl Veterinarmed A , COTCHIN, E.: Neoplasia in the cat. Vet Rec , ENGLE, G. C.; BRODEY, R.S.: A retrospective study of 395 feline neoplasms. J Am Anim HOSP ASOC , FISHER, E.R.; GREGORIO, R.; SHOEMAKER, R.; HORVAT, B.; HUBAY, C.: The derivation of so-called giant cell and spindle cell undifferentiated thyroidal neoplasms. Am J Clin Pathol61: , GAAL, J.M.; HORVATH, E.; KOVACS, K.: Ultrastructure of two cases of anaplastic giant cell tumor of the human thyroid gland. Cancer , 1975

6 692 Patnaik and Lieberman 9 GRAHAM, H.; DANIEL, C.: Ultrastructure of an anaplastic carcinoma of the thyroid. Am J Clin Pathol61: , HUTTER, R.V.; TOLLEFSEN, H.R.; DECOSSE, J.J.; FOOTE, F.W.; FRAZELL, E.L.: Spindle and giant cell metaplasia in papillary carcinoma of the thyroid. Am J Surg , 1965 I I IBANEZ, M.L.; RUSSELL, W.P.; ALBORES-SAAVEDRA, J.; LAMPERTICO, P.; WHITE, E.C.; CLARK, R.L.: Thyroid carcinoma: biologic behavior and mortality. Cancer 19: , I JAO, W.; GOULD, V.E.: Ultrastructure of anaplastic (spindle and giant cell) carcinoma of the thyroid. Cancer , LEAV, I.; SCHILLER, A.L.; RIINBERK, A.; LEGG, MA.; DERKINDEREN, P.J.: Adenomas and carcinomas of the canine and feline thyroid. Am J Pathol B61-93, LUCKE, V.M.: A histological study of thyroid abnormalities in the domestic cat. J Small Anim Pract , MEISSNER, W.A.; WARREN, S.: Tumors of the thyroid gland in Atlas of Tumor Pathology, pp ; 2nd ser, fasc. 4, Armed Forces Institute of Pathology, Washington, D.C., NISHIYAMA, R.M.; DUNN, E.L.; THOMPSON, N.W.: Anaplastic spindle cell and giant cell tumors of the thyroid gland. Cancer N , PATNAIK, A.K.; LIU, S.-K.; HURVITZ, A.I.; MCCLELLAND, A.J.: Non-hematopoietic neoplasms in cats. J Natl Cancer Inst W , SCHOUMACHER, P.; METZ, R.; BEY, P.; CHESNEAU, A.M.: Anaplastic carcinoma of the thyroid gland. Eur J Cancer , UEDA, G.; FURTH, J.: Sarcomatoid transformation of transplanted thyroid carcinoma: similarity to anaplastic human thyroid carcinoma. Arch Pathol B3-12, 1967 Request reprints from Dr. Amiya K. Patnaik, The Animal Medical Center, 510 East 62nd Street, New York, NY (USA).