Canine Thymoma Associated to Myasthenia Gravis

Background: Thymomas are epithelial neoplasms of the thymus, although lymphocyte infiltration is common. Histological features are not sufficient to define its biological behaviour, which is dependent of clinical criteria of invasiveness and resectability. Myasthenia gravis may happen as a paraneoplastic syndrome in up to 47% of canine thymomas. This article aims at reporting a case of thymoma associated with myasthenia gravis in a dog, emphasizing the morphological, phenotypical and therapeutical aspects. Case: A 7-year-old, male Labrador, was presented with a history of acute dyspnea and exercise intolerance. The physical examination revealed a “red-brick” mucousa, tachycardia and cardiac and pulmonar hypofonese. Chest radiographs revealed an area of increased radiopacity in the cranial mediastinum without a plane of separation to the heart. The eccodopplercardiogram exam identified a poorly delimited mass adjacent to the base of the heart, measuring 9.5x6.8cm. Computed tomography demonstrated it as an expansive neoformation (9.5x6.5x7.8cm). Mass was removed through intercostal thoracotomy and the removed tissue was submitted to histopathology with a diagnosis compatible with type AB thymoma (mixed). Immunohistochemistry was positive for AE1/AE3 citokeratin in 90% of epithelial cells, confirming tumour origin. Tumour infiltrating lymphocytes were positive for CD79a (70%) and CD3 (20%). The proliferation index (Ki-67 imunolabeling) was 60%. About 45 days after surgery the patient was presented with generalized muscle weakness and regurgitation, with confirmed megaesophagus on chest X-ray. Treatment with pyridostigmine was initiated because of suspected myasthenia gravis, and complete remission of the neurological signs occurred within a month. A chemotherapeutic protocol with carboplatin was then instituted. After four sessions, a new thoracic radiograph revealed tumour recurrence in the cranial mediastinum. Therefore, metronomic chemotherapy was started sequentially with oral chlorambucil and firocoxib. Patient remained well for nine months when regurgitation and muscle weakness re-initiated, even with pyridostigmine treatment. New chest X-ray demonstrated increased tumour mass and the owner decided for euthanasia, resulting in a survival time of 368 days. Discussion: The prognosis of the thymoma depends on the histological type, clinical staging and presence of paraneoplastic syndromes. Due to the heterogeneity of the cases, there are not enough studies available to compare the animals submitted to different therapeutic modalities. In humans, when possible, and in the absence of metastases, complete surgical resection is the standard treatment followed by chemotherapy and/or adjuvant radiotherapy. In dogs, surgical resection of thymomas should be considered, despite the invasiveness detected in imaging studies. The presence of paraneoplastic syndromes, such as myasthenia gravis, are commonly associated with worse prognosis, however, as evidenced in this case, pyridostigmine was useful in maintaining the neuromuscular function and patient´s quality of life, along with surgery and adjuvant chemotherapy, which probably contributed to the increase of the expectation of life. Further studies are necessary to evaluate the efficacy of adjuvant chemotherapy in maximum tolerated and metronomic dosage, for thymic neoplasms in dogs. Keywords: thymus, neoplasia, paraneoplastic syndrome, carboplatin, cyclophosphamide.