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Objective: Thymoma-associated paraneoplastic syndromes in dogs and cats include myasthenia gravis, hypercalcemia, exfoliative dermatitis, erythema multiforme, T-cell lymphocytosis, myocarditis, anemia, and polymyositis. Paraneoplastic myasthenia gravis (MG) is the most commonly reported paraneoplastic syndrome in dogs with thymic epithelial tumors. The objective of this study was to examine cases of canine thymic-associated MG treated surgically, with the specific objective of providing an updated clinical picture of the preoperative management, postoperative complications, and outcomes of these cases., Animals: Nine dogs with paraneoplastic MG underwent surgical removal of a thymic epithelial tumor., Procedure: Medical records of dogs with MG that received surgical treatment of a thymic epithelial tumor between January 1, 2012 and October 1, 2022 were obtained from 4 veterinary teaching hospitals. Descriptions of perioperative MG management, complications, and outcomes were reported., Results: Six of the 9 dogs received medical therapy for MG, with either a cholinesterase inhibitor (4 dogs) or a cholinesterase inhibitor and immunosuppressive agent (2 dogs), before surgery. The median duration of medical therapy for MG before surgery was 7.5 d (range: 2 to 60 d). Three of 9 dogs experienced immediate postoperative complications and were euthanized. Six of 9 dogs (66.6%) survived to discharge and 3 of 6 dogs that survived to discharge were alive at the time of writing. At the time of writing, 3 of 6 dogs had complete resolution of clinical signs attributable to MG and 2 of 6 had partial resolution. The median time from surgery to resolution of clinical signs of MG in these dogs was 63 d (range: 2 to 515 d)., Conclusion: Dogs with thymic epithelial tumors and paraneoplastic MG are at a high risk for perioperative complications., Clinical Relevance: The findings of this study corroborate previous literature stating that paraneoplastic MG is a poor prognostic indicator for dogs with thymic epithelial tumors, while also highlighting the variation in approaches to clinical management of thymic-associated MG in veterinary medicine and the lack of established protocols guiding perioperative management., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: Canine thymomas are associated with multiple paraneoplastic syndromes, among which myasthenia gravis (MG) is the most common. Acquired MG is an autoimmune disease characterized by the presence of antibodies against acetylcholine receptors (ACHRs). ACHRs antibodies are the most commonly formed, but the production of antistriational antibodies binding to skeletal and cardiac muscle proteins has also been recorded both in humans and dogs. An association between the occurrence of antistriational antibodies and a severe form of myocarditis, giant cell myocarditis, has been described in humans., Case Description: A 4-year-old mixed-breed dog was referred because of 1 month history of exercise-induced weakness, hypersalivation, and regurgitation. The neurologic examination was indicative of a neuromuscular junction disease, and MG was suspected. A computed tomographic scan examination showed the presence of a megaoesophagus and a thymic mass. Serum antibodies against ACHRs confirmed the diagnosis of MG. Treatment with pyridostigmine was started, and the thymic mass was surgically excised, and a diagnosis of thymoma was confirmed by histology. 24 hours after surgery, the dog developed a third-degree atrioventricular block. Severe arrhythmia and increased troponin serum levels suggested myocarditis which rapidly led to cardiopulmonary arrest. Histopathologic examination of the heart, esophagus and diaphragm revealed a lymphocytic and macrophagic infiltration, consistent with myocarditis and polymyositis. Scattered rare giant multinucleated cells were also detected in the myocardium., Conclusion: To the author's knowledge, this is the first report of thymoma-associated MG with concurrent polymyositis and giant cell-like myocarditis in a dog., Competing Interests: The authors declare that they have no conflict of interest.

Neurological signs and serum acetylcholine receptor antibody (AChR-Ab) levels before and after thymectomy were monitored in a 6-year-old male cat with acquired Myasthenia Gravis (MG) as a paraneoplastic syndrome of thymoma. Soon after surgery, the neurological symptoms relapsed, and the cholinesterase inhibitor was administered to control them. The AChR-Ab levels increased postoperatively until 90 days after surgery. This is the first report on long term measurements of serum AChR-Ab levels in a cat with MG. Although thymectomy is valuable for the removal of thymoma, it may not resolve MG symptoms, neurological signs and serum AChR-Ab levels, without medication early after surgery. Also, this case report indicates that the AChR-Ab level might be a guide to detect a deterioration of MG symptoms.

A 10-year-old captive male Siberian tiger (Panthera tigris altaica) presented with acute onset collapse, vomiting and dyspnoea, preceded by a 6-month period of progressive muscle wasting. Following humane destruction, post-mortem examination revealed a large multilobulated mass in the cranial mediastinum, which was diagnosed as a T-lymphocyte-rich thymoma with the aid of immunohistochemistry. Retrospective serology for acetylcholine receptor antibodies (titre 3.90 nmol/l) confirmed a diagnosis of thymoma-associated myasthenia gravis. Thymomas are reported rarely in wild carnivores, but when detected they appear to be similar in morphology to those seen in domestic carnivores and may also be accompanied by paraneoplastic syndromes. The clinical signs of myasthenia gravis in the tiger were consistent with those reported in cats and dogs and the condition is proposed as an important differential diagnosis for generalized weakness in captive Felidae., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Paraneoplastic pemphigus (PNP) is a rare and severe autoimmune blistering skin disease of humans. It is associated mainly with haematopoietic neoplasia and a unique autoantibody profile. At this time and in animals, PNP has only been reported in dogs., Objectives: To report clinical, histological and immunological findings in a cat with suspected thymoma-associated PNP., Animal: An 8-year-old female spayed Himalayan cat., Results: The cat presented with a thoracic mass diagnosed as a lymphocytic thymoma. Two weeks postremoval, the cat developed myasthenia gravis, which was controlled with prednisolone and pyridostigmine. The myasthenia gravis resolved, but the cat developed severe cutaneous erosions and ulcers primarily affecting the caudal ventral abdomen and perineum, but also the ventral chest, axillae and medial pinnae. Histopathological analysis revealed changes consistent with pemphigus vulgaris and erythema multiforme, a combination of lesions highly suggestive of PNP. Direct immunofluorescence revealed intercellular epidermal IgG deposition in the lower epidermis, especially in areas of suprabasal clefts. Indirect immunofluorescence revealed antikeratinocyte IgG to basal keratinocytes and bladder epithelial cells. Immunological results supported a diagnosis of PNP. Skin lesions were treated with prednisolone and chlorambucil and, after clinical remission was obtained, the drugs were tapered and eventually discontinued without further recurrence of skin lesions., Conclusions and Clinical Importance: In this cat, clinical, microscopic and immunological findings were consistent with a diagnosis of PNP, with thymoma being the suspected cause., (© 2013 ESVD and ACVD.)

Unlabelled: HISTORY AND PRESENTATION: A 12 year old, 4.2 kg, domestic long hair, castrated male cat was presented with regurgitation, inability to retract the claws, general weakness, cervical ventroflexion and weight loss. A thymic mass was evident on radiographs. Acetylcholine receptor antibody titer was positive for acquired myasthenia gravis (MG). Thymectomy via midline sternotomy was scheduled. ANESTHETIC MANAGEMENT:  Oxymorphone and atropine were administered subcutaneously as premedication, and anesthesia was induced with etomidate and diazepam given intravenously to effect. The cat's trachea was intubated and anesthesia was maintained with isoflurane in oxygen, and continuous infusions of remifentanil and ketamine. Epidural analgesia with preservative-free morphine was administered prior to surgery. Postoperative analgesia was provided by oxymorphone subcutaneously, interpleural bupivacaine, and fentanyl infusion. Postoperative complications included airway obstruction, hypoxemia and hypercapnia., Follow-Up: The cat was discharged 3 days after surgery. Discharge medications included pyridostigmine and prednisone. Nine days after surgery, the cat had a significant increase in its activity level, and medications were discontinued. Histopathologically, the mass was consistent with a thymoma. Approximately 6 weeks later the cat became weak again and pyridostigmine and prednisone administration was resumed., Conclusion: The perioperative management of patients with MG for transsternal thymectomy is a complex task. The increased potential for respiratory compromise requires the anesthesiologist to be familiar with the underlying disease state, and the interaction of anesthetic and non-anesthetic drugs with MG. Careful monitoring of ventilation and oxygenation is indicated postoperatively., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Thymoma-associated exfoliative dermatitis was suspected in a cat with a cranial mediastinal mass. The dermatopathy resolved with surgical removal of a thymoma. The cat manifested neurologic signs consistent with myasthenia gravis 7 wk after surgery. Exfoliative dermatitis and post-thymectomy myasthenia gravis in the same cat has not been reported previously.

A 16-year-old, spayed female beagle was diagnosed with metastatic thymoma causing a probable paraneoplastic syndrome of generalized acquired myasthenia gravis. Anticholinesterase treatment was initiated; however, 5 days later the dog died.

A 14.6-yr-old, female, multiparous polar bear (Ursus maritimus) acutely developed an apparent hind limb weakness. Physical examination and diagnostic tests including a hemogram, serum biochemistry, electrolytes, radiographs, and myelogram did not provide a definitive diagnosis. No improvement in condition was noted during 4 days of supportive care, and the bear was euthanized. An ovoid mass was present in the anterior mediastinum, and a thymoma was confirmed histologically. Compared with control polar bears, elevated serum acetylcholine receptor (AChR) antibodies (0.13 +/- 0.06 nmol/L vs. 0.86 nmol/L) were detected by immunoprecipitation radioimmunoassay, which is consistent with myasthenia gravis (MG) in other species. Although the AChR antibody test has not been validated in the polar bear, we are confident in the postmortem diagnosis of MG, which is commonly associated with thymoma in other species.

An 8 1/2-year-old neutered male Beagle was diagnosed with acquired myasthenia gravis associated with a non-invasive thymic carcinoma. The thymic mass was surgically excised and the dog was treated with pyridostigmine, prednisolone and azathioprine. Serial acetylcholine receptor antibody titres were increased initially but slowly declined to normal values over a period of 24 weeks. Improved exercise tolerance was seen following therapy, however, oesophageal dysfunction persisted. The dog was euthanased 26 weeks after initial presentation due to a complicating illness. A necropsy showed no regrowth or metastasis of the thymic carcinoma.

An anterior mediastinal cystic lesion in an 11-year-old mongrel dog was examined. The dog showed dysbasia and vomiting due to megaoesophagus, and anterior mediastinal round mass lesion, approximately 35 mm in diameter, was found by X ray. Based on clinical examinations, the dog was diagnosed as acquired myasthenia gravis and was successfully controlled by anticholinesterase treatment for approximately 4 months. The dog died of thermic stroke and was necropsied. Grossly, fatty tissues with cysts containing yellowish fluid and white nodules were found in the anterior mediastinal area. Histopathologically, multiple cysts, neoplastic tissues, and atrophic thymus were found within the examined tissues. The cysts were lined by thin wall consisting of ciliated long cuboidal and non-ciliated round cells and were filled with eosinophilic colloidal fluid. Some extended cysts contained neoplastic foci within their lumen and walls. The neoplastic tissues consisted of mixed population of large epithelial cells with abundant clear cytoplasm and large oval nuclei, and lymphocytes. Immunohistochemically, proliferating epithelial cells were intensely positive for keratin and cytokeratin, and more than half number of infiltrating lymphocytes were intensely positive for CD3 suggesting T cells. All these findings indicate the neoplastic lesion is thymoma and multiple cysts are considered as thymic or brachial cleft cysts.

Similar to human autoimmune myasthenia gravis (MG), canine MG occurs spontaneously and is associated with autoantibodies against the nicotinic acetylcholine receptor (AChR). In addition to AChR, human MG patients with thymoma or late-onset MG have antibodies against titin and ryanodine receptor (RyR). The objective of this study was to establish if dogs with confirmed MG (AChR antibody titer >0.6 nmol/l) also developed titin and RyR antibodies and identify possible associations with thymoma, late age of onset, or severity of clinical signs. Sera from dogs (n=430) with previously diagnosed autoimmune MG (N=415), other immune-mediated neuromuscular disorders including polymyositis (PM) and masticatory muscle myositis (N=5), and control dogs (N=10) were evaluated for the presence of titin antibodies in ELISA using MGT-30 as antigen, a peptide representing the main immunogenic region (MIR) for human titin antibodies. Titin antibody positive sera were further examined for RyR antibodies in Western blots using a RyR fusion protein (pc2-RyR) as antigen, which covers the MIR for human MG sera. Titin antibodies were found in sera of 80/430 dogs. Thymoma was present in 11/80 and age of onset was after 4 years in 66/80 titin positive dogs. Two of the titin positive dogs had PM. RyR antibodies were found in 13/80 sera (8/13 thymoma, 12/13 age of onset after 4 years, and 1/13 PM). Neither titin nor RyR antibodies were found in sera of healthy control dogs. Acute fulminating MG was described in five dogs with both titin and RyR antibodies. From these studies we conclude that titin and RyR antibodies in canine and human MG have a similar association with thymoma, late-onset MG, and possibly with more severe forms of MG.

Two cases of myasthenia gravis associated with thymoma are reported. Both were female German shepherd dogs and the thymoma was surgically resected. Aspiration pneumonia secondary to persistent megaoesophagus was a complication in both cases. The myasthenia gravis did not resolve, but there was a more satisfactory control of clinical signs with anticholinesterase treatment. Corticosteroid therapy was used in one case, but the resulting polydipsia increased the incidence of regurgitation, resulting in recurrent episodes of aspiration pneumonia.

A 10-year-old, neutered male cocker spaniel-cross experienced regurgitation, dry retching, and weight loss. A large, mediastinal mass and dilatation of the esophagus were seen on thoracic radiographs. Cytological, histopathological, immunohistochemical, and serological findings were consistent with a lymphoepithelial thymoma and focal, esophageal myasthenia gravis. Surgical removal of the mass resulted in rapid resolution of the megaesophagus and a decrease in serum acetylcholine-receptor antibody concentration. The dog was clinically normal until the thymoma recurred six months postoperatively. Clinical signs, diagnostic evaluation, management, and treatment of a dog with thymoma and megaesophagus are described.

Third degree atrioventricular block was diagnosed in 4 dogs with acquired myasthenia gravis (serum acetylcholine receptor antibody titer > 0.6 nmol/L). All 4 dogs had megaesophagus. Two dogs also had mediastinal thymomas, which were resected. One dog with thymoma received a permanent pacemaker at the same time that it underwent thymectomy; the other did not develop third degree atrioventricular block until 3 months after thymectomy. Both dogs with thymoma died of severe aspiration pneumonitis within 3 months after surgery. The third dog received a permanent pacemaker and was treated with pyridostigmine bromide, but also died of aspiration pneumonitis 1 month after the pacemaker was implanted. The fourth dog was treated with prednisolone and pyridostigmine bromide and improved, but did not become clinically normal. Because third degree atrioventricular block as well as myasthenia gravis can cause signs of weakness, acquired myasthenia gravis should be considered in dogs with idiopathic cardiac conduction disturbances. Likewise, an ECG should be evaluated in dogs with acquired myasthenia gravis.

A 4-year-old castrated Abyssinian cat was evaluated for profound neuromuscular weakness. Results of electromyography and repetitive nerve stimulation tests were normal. Thoracic radiography revealed a cranial mediastinal mass, which was excised and identified as a thymoma. Serum acetylcholine receptor antibodies were detected at high concentration, supporting a diagnosis of acquired myasthenia gravis. Clinical signs of disease responded to treatment with pyridostigmine and corticosteroids.

A classical combination of myasthenia gravis and a thymoma is reported for the first time in a cat. The clinical symptoms, pathophysiological and histopathological characteristics are discussed.