COMPREHENSIVE MANAGEMENT OF A PITUITARY ADENOMA WITH MALIGNANT FEATURES IN A MALTESE DOG

AIM OF THE STUDY: The aim of the study is to describe the long-term survival of a dog affected by an ACTH producing-pituitary adenoma treated by surgery, medication and radiation therapy. MATERIAL AND METHODS: A 7-yr-old old male Maltese dog w as referred to DIMEVET for epileptic seizures, polyuria, polydipsia, polyphagia and symmetrical alopecia. Pituitary-dependent hypercortisolism w as diagnosed by endocrine tests. Computed tomography (CT) revealed a pituitary mass w ith a P/B ratio 0.75, reference <0.311 that w as treated w ith transsphenoidal hypophysectomy; Immunohistochemistry of the surgical specimen confirmed an ACTH-producing adenoma. Hypercortisolism w ent into remission for three years but then polyuria/polydipsia and alopecia reappeared and CT scan revealed a small sellar abnormal structure (interpreted as pituitary tissue regrow th). Hypercortisolism w as confirmed by endocrine tests and medical treatment w ith trilostane w as started, w ith good control of the clinical signs for one year, until the occurrence of obtundation, seizures and stupor. CT scan show ed a sellar mass and radiation therapy w as performed w ith a protocol of 20 fractions of 2.25 Gy. Neurological signs regressed and trilostane treatment w as continued w ith good control of the disease. Six years after the first admission, the dog developed lumbosacral pain and inability to w alk and w as euthanatized for animal w elfare reasons. Histological sections w ere stained w ith H&E and PAS and immunostained w ith antibodies against ACTH, MSH, GH, C-erb-B2 and Ki67. RESULTS: Macroscopically the formalin fixed brain revealed grey tissue in the pituitary region extending caudally to the mesencephalon. Histologically, unencapsulated neoplastic tissue in contiguity w ith the meninges and infiltrating the neuropil w as detected; neoplastic cells arranged in islands and cords w ere embedded in a rich amorphous eosinophilic extracellular matrix; neoplastic cells show ed an intensely eosinophilic cytoplasm. The nucleus w as vesicular, often tw o or three nuclei w ere seen, w ith chromatin margination and a prominent nucleolus. Anisocytosis and anisokaryosis w ere moderate. Mitotic figures w ere three in ten random selected fields at 400x magnification. A diagnosis of a recurring infiltrative ACTH-adenoma w as made; Ki67 labelling index w as 4,8%. CONCLUSIONS: Pituitary tumors that recur or progress despite resection and radiotherapy are often termed “atypical” adenomas, as they do not appear overtly malignant by histological criteria, but exhibit aggressive biologic behavior, have a Ki67 labelling index >3%, p53 immunoreactivity.2 Reports of invasive canine pituitary tumors are rare; this is the first report of a long-term survival of a dog affected by this type of tumor that w as treated by surgery and subsequently by radiation therapy. Comprehensive management of pituitary adenomas using the various treatment modalities may significantly prolong the dog’s life. BIBLIOGRAPHY: 1Kooistra et al., 1997; 2Mamelak et al., 2011.