A 4-year-old spayed female mixed-breed dog was referred with a 1-month history of regurgitation and progressive generalized weakness. At the time of presentation, the general physical examination was unremarkable. The neurologic examination revealed exercise intolerance, with the development of weakness beginning in the hindlimbs and progressing into a non-ambulatory flaccid tetraparesis with neck ventroflection, which was alleviated by rest and bilateral symmetrical reduction of patellar, tibialis cranialis, and withdrawal of reflexes. The dog showed mild dysphagia characterized by reduced and difficult swallowing and hypersalivation. The neurologic exam was indicative of a generalized lesion of the low motor neuron system. The neurologic examination was followed by an extended laboratory analysis, including blood counts, serum biochemical profile, coagulation and urinary analysis, and chest radiographs. The haematological abnormalities were a mild increase of WBC (13.1; reference ranges (RR): 5.37–12.39 × 103/mcl) characterized by neutrophilia (11,135; RR: 2,778–8,220 × 103/mcl), lymphocytosis (1,179; 1,009–3,471 × 103/mcl), and monocytosis (655; RR: 155–537 × 103/mcl). Biochemistry revealed significant increase in creatine kinase (CK) (7,934; 39–168 U/l) with a less severe increase of aspartate aminotransferase (AST) (389; 16–39 U/l) and alanine aminotransferase (ALT) (302; 15–79 U/l), moderately elevated C reactive protein (4.54; RR: 0.01–0.41 mg/dl), and hyperferritinemia (776; RR: 38–272 ng/ml). Urinalysis was within normal limits. The thoracic radiographs showed a diffusely dilated esophagus and soft tissue opacity in the cranial mediastinum. The diagnostic suspicion was a form of acquired MG associated with a cranial mediastinal mass although clinically polymyositis could not be completely excluded. A 0.05 mg/kg (0.02 mg/lb) of neostigmine (Prostigmina®) was administered intramuscularly to support our first suspicion. After few minutes, the dog showed a positive result, with increased muscular strength. A computed tomographic (CT) scan examination showed a rounded cranial mediastinal neoformation, characterized by heterogeneous appearance due to the presence of cystic intraparenchymal areas and associated with normal cranial sternal and mediastinal lymph nodes. The CT scan also showed an expansion of the entire esophagus and stomach, mainly due to gas. These findings confirmed a moderate megaesophagus and the presence of a cranial mediastinal mass. A cytological examination and, subsequently, a tru-cut biopsy of the mediastinal mass was performed both with non-diagnostic results. Serum antibodies against ACHRs were highly supportive of MG (5.23 nmol/l; normal in dogs < 0.6 nmol/l). The dog was treated with neostigmine therapy (Prostigmina®) at 0.01 mg/kg (0.004 mg/lb) IM q8h, showing mild improvement of muscular weakness. The cranial mediastinal mass was surgically excised by a median sternotomy. Histology of the formalin-fixed specimen revealed a capsulated, well demarcated, not infiltrative neoplasm, composed of sheets and cords of mildly pleomorphic, spindle to oval cells, multifocally lining variably sized cystic spaces, often filled with eosinophilic secretory material. Neoplastic cells were associated with a moderate number of lymphocytes, forming small multifocal aggregates (). To further characterize the neoplasm, immunohistochemistry was performed using the automated immunostainer Bond RX (Leica Biosystem, Nussloch GmbH; Nusloch, Germany). Antibodies manufacturer, source, clone and dilution are listed in. The antigen unmasking technique was performed as indicated by the manufacturer. Neoplastic cells were found to express cytokeratin, which exhibited strong cytoplasmatic staining within neoplastic cells lining the cysts, while having a weak to moderate intensity in solid areas. Rare aggregates of desmin and muscle actin expressing cells, interpreted as myoid cells, were also detected. According to the WHO classification, based on anatomic location and on morphologic and phenotypic features, a diagnosis of type A thymoma was made. The day after the surgery, dysphagia progressively worsened, and clinical respiratory signs with tachypnea, dyspnea and cough appeared. The patient was hyperthermic [40°C (104°F)]. Reassessment of blood tests showed a worsening of the inflammatory parameters. The blood count showed a severe increase in leukocytes (38; 5.37–12.39 × 103/mcl) characterized by neutrophilia (33,820; 2,778–8,220 × 103/mcl) with the presence of banded neutrophils (1,140 × 103/mcl) and by toxic neutrophils and cytoplasmic foaming detected by blood smear analysis. The serum chemistry profile showed a severe increase of C reactive protein (15.88; 0.01–0.41 mg/dl). An alveolar pattern consistent with aspiration pneumonia was apparent on thoracic radiographs. Oxygen therapy by nasal tube and four quadrant antibiotic therapy with amoxicillin- clavulanic acid [22 mg/kg (10 mg/lb) IV q12h) and enrofloxacin [10 mg/kg (4.5 mg/lb) IV q24h] was promptly started. A few hours later, a third-degree atrioventricular block was observed, and dysphagia and respiratory signs worsened, leading to induction of general anaesthesia to protect the lower airway tracts and to maintain the patient under mechanical ventilation. The appearance of a severe arrhythmia suggested the onset of myocarditis, and the increase in serum troponins (1.34 ng/ml, 0.05–0.24 ng/ml) supported this diagnostic hypothesis. During mechanical ventilation, arrhythmia worsened dramatically up to cardiopulmonary arrest on the second post-surgical day. A necropsy was performed. The main macroscopic finding consisted of a diffused megaesophagus. Low numbers of white, small-sized spots were also visible on the myocardial surface, with random distribution. The subsequent histology of the heart showed that myocardium was infiltrated by a severe multifocal to coalescing inflammatory process, mainly composed of lymphocytes, admixed with a lower number of macrophages, plasma cells and neutrophils, and rare giant multinucleated cells, with up to five haphazardly arranged nuclei. Inflammatory infiltrate was associated with small foci of necrotic cardiomyocytes with hypereosinophilic cytoplasm, loss of cross striations and pyknotic nuclei (). A similar inflammatory process consisting of multiple, variably sized foci of necrotizing myositis also involved esophageal and diaphragmatic skeletal muscle. Immunohistochemistry (IHC) was performed to characterize the inflammation involving the myocardium, esophagus and diaphragmatic skeletal muscle: the inflammatory cell population infiltrating the myocardium was mainly composed of CD3+ lymphocytes (T cells), admixed with a lower number of Iba1 positive macrophages, most of them being MHC-II positive. Rare, scattered B lymphocytes expressed CD20. Interestingly, a low proportion of cardiomyocytes expressed MHC-II in the cytoplasm or on the sarcolemma. Esophageal and diaphragmatic skeletal muscles were also characterized by an infiltration of T lymphocytes and macrophages. The histopathological picture was consistent with lymphocytic and necrotizing myocarditis and polymyositis. Based on this evidence, to exclude possible infectious causes, PCR for the detection of Toxoplasma gondii and Neospora caninum was carried out on myocardial samples and results came out negative.