Spontaneous bilateral thyroid follicular cell carcinoma (subtype: compact cellular carcinoma) with C-cell complexes in a male beagle

Abstract

We report the features of spontaneous bilateral thyroid follicular cell carcinoma in a 10-year-old male beagle. Necropsy revealed bilateral masses on the trachea, corresponding to the left and right sides of the thyroid gland. The masses were elastic, encapsulated, and distinct, with no connecting tumor tissues between them. Histologically, the tumor cells exhibited a predominant sheet-like growth pattern in both masses, and small follicular structures containing colloids were observed. Immunohistochemically, >50% of the tumor cells were positive for thyroglobulin. In the sheet-like growth area, all tumor cells were positive for cytokeratin and approximately 50% of them were positive for vimentin. The tumor cells were negative for calcitonin and parathormone. Electron microscopy of the tumor cells revealed colloid droplets and lysosomes in the cytoplasm, which are characteristics of follicular cells of the thyroid gland, although they were abnormally shaped and smaller in size compared to the normal cells. Many calcitonin-positive C cells were observed in the nodule area without a capsule in the left mass and were scattered within the tumor in the right mass. C cells were found individually and were negative for Ki-67 expression. Therefore, each of these cells was deemed to be derived from an individual C-cell complex. Based on these morphological features, the tumor was diagnosed as spontaneous bilateral thyroid follicular cell carcinoma of the compact cellular carcinoma subtype. This is the first report of electron microscopic findings and co-expression of cytokeratin and vimentin in thyroid follicular cell carcinoma in beagles.

Keywords: C-cell complex; beagles; compact cellular carcinoma; follicular cell carcinoma; thyroid glands.

Fig. 1.

Cross-sectional gross appearance of the formalin-fixed grayish-white to yellowish-brown masses in the left (L) and right (R) lobes of the thyroid gland in a male beagle.

Fig. 2.

Histological appearance of the left tumor. a) Loupe image of the left tumor. The left mass was covered with a thick fibrous capsule. However, no capsule was observed in the nodule area indicated by the arrow. In the parathyroid gland indicated by the arrowhead, the tumor cells had infiltrated and proliferated in the center, and the normal parathyroid cells were compressed at the periphery. b) Sheet-like growth area. c) Follicular growth area. d) C cells in a sheet-like growth area surrounded by the square indicated in (a). HE staining. Bars=2 mm (a) and 25 µm (b, c, and d).

Fig. 3.

Histological appearance of the right tumor. a) Loupe image of the right tumor. The right mass was covered with a thick fibrous capsule. b and c) Follicular and island-like growth areas with abundant weak eosinophilic fibers or mucus-like materials. d) Sheet-like growth area. The tumor cells are large and have partially clear cytoplasm. e) C cells in a sheet-like growth area surrounded by the square indicated in (a). They were scattered over a wide area. HE staining. Bars=3 mm (a) and 25 µm (b, c, d, and e).

Fig. 4.

Immunohistochemical staining for thyroglobulin (a–c) and MT (d) staining. a and c) Left tumor. b and d) Right tumor. Tumor cells were positive for thyroglobulin in the follicular (a) and island-like (b) growth areas, but were negative in the central sheet-like growth area (c). d) MT staining showed blue to red colloids in the follicular growth area and pale blue fibrous or plasma components in the stroma. Bars=100 µm (a) and 50 µm (b, c, and d).

Fig. 5.

Immunohistochemical staining for cytokeratin AE1/AE3 (a and b) and vimentin (c and d). a and c) Left tumor. Tumor cells in the sheet-like growth area were positive for both cytokeratin AE1/AE3 and vimentin. b and d) Right tumor. Tumor cells in the follicular growth area were positive for cytokeratin AE1/AE3 but negative for vimentin. Stromal microvessels were positive for vimentin. Bars=100 µm (a and c) and 50 µm (b and d).

Fig. 6.

Immunohistochemical staining for calcitonin. a and b) Loupe image of the left and right tumors. c and d) High magnification of the areas surrounded by squares in (a) and (b). C cells were positive for calcitonin and each C cell existed singly without forming clusters in both tumors. Bars=3 mm (a and b) and 50 µm (c and d).

Fig. 7.

Ultrastructural appearance of thyroid follicular cells. a and b) Thyroid follicular cells of a normal male 4-year-old beagle. c and d) Tumor cells in the sheet-like growth area. e and f) Tumor cells in the right tumor were large and had partially clear cytoplasm observed using the HE staining technique. b, d, and f) High magnification of (a), (c), and (e), respectively. Colloid droplets (arrowheads) and lysosomes (arrows), which are characteristic of thyroid follicular cells, were also seen in the tumor cells, although they were irregularly shaped or small compared with those in normal cells. Bars=2 µm (a, c, and e) and 500 nm (b, d, and f).