A Canine Case of Complex Carcinoma of the Mammary Gland with Metastasis to the Axillary Lymph Node

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1 A Canine Case of Complex Carcinoma of the Mammary Gland with Metastasis to the Axillary Lymph Node Kenjiro Hashimoto 1), Atsushi Kawabata 1), Tamio Ohmuro 2), Kinji Shirota 1, 3) * 1) Research Institute of Bioscience, Azabu University, 2) Ohmuro Veterinary Clinic, 3) Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University Abstract: A 10-year-old, female Labrador Retriever had a well-circumscribed mass beneath the third nipple of right mammary gland. Histologically, the tumor was composed of multiple lobules and consisted of both neoplastic epithelial cells forming tubulo-acinar structures and myoepithelial cells arranged in solid nests. These neoplastic cells rarely showed nuclear atypia, mitotic activity without evidences of vascular invasion. However, multifocal metastatic foci were detected in the axillary lymph node. Therefore, the tumor was diagnosed as complex carcinoma of the mammary gland. In the present case, differential diagnosis between benign tumor (complex adenoma) and malignant one (complex carcinoma) was challenging on the basis of histopathological findings on routine hematoxylin and eosin-stained sections of the primary tumor. Therefore, we compared the expression of proliferating cell nuclear antigen (PCNA) in the neoplastic cells between 3 complex carcinomas including the present case and 9 complex adenomas of canine mammary gland. The PCNA-positive rate among the neoplastic cells was significantly higher in complex carcinomas than in complex adenomas. These results indicate the importance of histopathological evaluation of the regional lymph nodes, and PCNA may be a useful parameter for the differential diagnosis in canine complex type mammary tumors. Key words: dog, mammary tumor, complex carcinoma (Jpn J Vet Dermatol 2009, 15 (1): 33 37) *Correspondence to: Kinji Shirota (Laboratory of Veteriary Pathology, School of Veterinary Medicine, Azabu University) Fuchinobe, Sagamihara, Kanagawa , Japan

2 34 Fig. 1a. Neoplastic mass in the right mammary gland. Fig. 1b. The right axillary lymph node with multiple metastatic lesions (arrows). α α

3 35 Table 1. Profile of the cases with complex adenoma or complex carcinoma of mammary gland Case No. Mammary tumor Breed Age (year) 1 Complex adenoma Shih Tzu 1 2 Complex adenoma Mix 10 3 Complex adenoma Mix 13 4 Complex adenoma West highland white terrier 9 5 Complex adenoma Shepherd 8 6 Complex adenoma Miniature dachshund 8 7 Complex adenoma Maltese 18 8 Complex adenoma Miniature dachshund 9 9 Complex adenoma Shih Tzu (present case) Complex carcinoma Labrador retriever Complex carcinoma Shih Tzu Complex carcinoma Shih Tzu 10 Fig. 2. Multilobular structure of the tumor. HE stain. Bar=500 µm. U Fig. 3. Each lobule was consisted of the neoplastic epithelial cells forming tubulo-acinar structures (arrows) and the myoepithelial cells arranged in solid sheet. The tumor cells rarely showed nuclear atypia and mitotic activity. HE stain. Bar=50 µm. α

4 36 Table 2. PCNA expression in canine complex adenoma and complex carcinoma Mammary tumor No. of cases PCNA-positive rate (%)* Complex adenoma ± Complex carcinoma ± ** *Ratio of PCNA-positive cells among epithelial neoplastic cells in 10 high-power fields (mean ± SD). **Mann Whitney test, P<0.05. Fig. 4. PCNA/CK8 double immunostaining. Most nuclei of neoplastic epithelial cells were intensely positive for PCNA (deep purple, arrows). CK8 was stained as brown color. Bar=50 µm. Fig. 5. PCNA-positive rate of the neoplastic cells. PCNA-positive rate of the neoplastic epithelial cells of complex carcinoma including the present case was significantly higher than that of complex adenoma (*Mann-Whitney U test, P<0.05).

5 37 Fig. 6. Metastasis of the tumor in the axillary lymph node. Fig. 7. PCNA/CK8 double immunostaining of the metastatic The structure of the metastatic tumor (*) was same as tumor. Most of the neoplastic epithelial cells were that in the primary mammary tumor. HE stain. intensely positive for PCNA (deep purple). Bar=50 Bar=500 µm. µm. 1) Chrisp, C.E. and Spangler, W.L pp In: The Canine as a Biomedical Research Model: Immunological, Hematological and Oncological Aspects, 17. U.S. Department of Energy, Washington, D.C. 2) Funakoshi, Y., Nakayama, H., Uetsuka, K., Nishimura, R., Sasaki, N. and Doi, K Vet. Pathol. 37: ) Hellmen, E J. Dairy. Res. 72: ) Karayannopoulou, M., Kaldrymidou, E., Constantinidis, T.C. and Dessiris, A J. Comp. Path. 133: ) Lohr, C.V., Teifke, J.P., Failing, K. and Weiss, E Vet. Pathol. 34: ) Meuten, D.J pp In: Tumors in Domestic Animals, 4th ed, Iowa State Press, Ames. 7) Misdorp, W., Else, R.W., Hellmen, E. and Lipscomb, T.P pp In: Histological Classification of Mammary Tumors of the Dog and the Cat, 2nd ed, Armed Forces Institute of Pathology American Registry of Pathology, Washington, D.C. 8) Preziosi, R., Sarli, G., Benazzi, C. and Marcato, P. S J. Comp. Path. 113: ) Woosley, J.T Arch. Pathol. Lab. Med. 115: ) Yamagami, T., Kobayashi, T., Takahashi, K. and Sugiyama, M J. Vet. Med. Sci. 58: