Thymoma is an uncommon canine and feline neoplasm of thymic epithelial cells. It is seen in various breeds but may occur more frequently in Labrador Retriever and German Shepherd Dogs. Middle-aged or older dogs (average age of 11 years) can be affected and no sex predilection exists. Affected cats are usually older than 9 years of age. A paraneoplastic syndrome of myasthenia gravis, nonthymic malignant tumors, and/or polymyositis occurs in a significant number of dogs with thymoma. Clinical signs are variable and are related to a space-occupying cranial mediastinal mass and/or manifestations of the paraneoplastic syndrome. Dyspnea is the most common presenting clinical sign. Thoracic radiographs usually show a cranial mediastinal mass. Lymphoma is the main differential diagnosis. A definitive diagnosis may be made by fine needle aspiration of the mass under ultrasound guidance or closed biopsy, but is more likely to be confirmed by thoracotomy. Thymomas may be completely contained within the thymic capsule or may spread by local invasion or metastasis. A staging system allows for an accurate prognosis and a therapeutic plan. Surgical removal of encapsulated thymomas may result in long-term survival or cure. Invasive or metastatic thymomas carry a guarded prognosis. Manifestations of the paraneoplastic syndrome complicate treatment. Adjuvant radiation and chemotherapy may be of value for advanced cases; however, adequate clinical trials have not been done in the dog or cat.
Most dogs and cats with a cranial mediastinal mass will present with signs of dyspnea, coughing, and/or exercise intolerance. Other signs may include regurgitation, vomiting, or gagging secondary to esophageal compression or paraneoplastic myasthenia gravis. Generalized myasthenia gravis may also occur with a primary complaint by the owner of recurrent weakness or collapse. Precaval syndrome (swelling of the head, neck, and/or thoracic limbs) is possible if the mediastinal mass causes compression of or invades the cranial vena cava. On physical examination, if the cranial mediastinal mass is extremely large, muffled lung sounds will be noted. While most cranial mediastinal masses are usually thymoma or lymphosarcoma, other causes may include ectopic thyroid tissue, branchial cyst, chemodectoma, or thoracic wall tumor. Lymphadenopathy due to infectious or inflammatory causes can also be found in the cranial mediastinum. Fluid within the cranial mediastinum (transudate, exudate, hemorrhage) can occasionally mimic a mediastinal mass. Hypercalcemia may occur in both thymoma and lymphoma. Non-specific azotemia secondary to pre-renal and renal causes may be found. Animals with lymphoma and liver involvement may have variable increases in serum ALP, ALT, and total bilirubin. Hyperphosphatemia can be seen with renal failure, and hypophosphatemia is usually associated with hypercalcemia of malignancy. Two or three thoracic view radiographs (ventrodorsal or dorsoventral and one or two lateral views) are the preferred way to diagnose an intrathoracic mass versus pulmonary, airway, or pleural diseases causing respiratory signs. Tracheal elevation is a consistent sign of a mediastinal mass on the lateral image. Differentiating a pulmonary or thoracic wall mass from a mediastinal mass may be done with the ventrodorsal view. The mediastinum should be twice the width of the spine in the dog. Fat in obese dogs can widen the mediastinum in the absence of a true mass. Pulmonary masses will usually be positioned lateral to the mediastinum, and thoracic wall masses will be peripheral and often cause rib lysis or spreading and cats with a cranial mediastinal mass will present with signs of dyspnea, coughing, and/or exercise intolerance. Other signs may include regurgitation, vomiting, or gagging secondary to esophageal compression or paraneoplastic myasthenia gravis.
Dogs and cats with thymoma and paraneoplastic myasthenia gravis may also exhibit signs of megaesophagus. Myasthenia gravis is an immune-mediated disorder where autoantibodies directed against nicotinic acetylcholine receptors (ACHRs) on the postsynaptic membrane of the neuromuscular junction cause abnormal neuromuscular transmission. Antibody binding to the ACHRs leads to the loss of functional receptors by complement lysis, accelerated internalization, and degradation of ACHRs; blockage of acetylcholine from the receptors; and decreased synthesis of new receptors. The lack of functional receptors impedes the transfer of the action potential from the neuron to the muscle. There are many presenting clinical signs and 3 clinical syndromes may be present:
- Focal MG with muscle weakness restricted to specific groups of the pharyngeal, esophageal, laryngeal, or facial muscles
- Generalized MG with exercise induced appendicular muscle weakness and megaesophagus
- Acute fulminating MG that involves a rapid onset of appendicular muscle weakness, megaesophagus, and collapse
Due to the striated musculature in the canine esophagus, megaesophagus is present in 85% of canine cases of MG. Thymoma combined with MG and megaesophagus has a poor prognosis. Aspiration pneumonia is a common complication. Dogs with acquired MG have a 1-year mortality rate of 60%, and 48% of affected dogs may die within 2 wk of being diagnosed, due to severe respiratory compromise. In a review of thymoma in dogs, 30% to 50% of dogs had MG. The link between thymic disease and MG is complex and may involve the following: general immune dysfunction and loss of self-tolerance, antigenic similarity between the proteins of the neurofilaments of the thymic myoid cells and ACHRs, expression of an ACHR by thymic myoid cells when challenged by a virus or bacterium. Myasthenia gravis associated with thymic disease in dogs is usually generalized and acute.
The definitive diagnostic test for MG is an ACHR antibody titer obtained with an immunoprecipitation radioimmunoassay. The sensitivity of this test is more than 90% and false positives have not been documented. Electromyographic (EMG) findings and the results of a tensilon response test can support a diagnosis of MG. The initial EMG is normal, but it is followed by a decremental muscular response to a sustained electric nerve stimulus. The tensilon test uses edrophonium chloride, which temporarily prevents the hydrolysis of acetylcholine at the neuromuscular junction by competing with acetylcholine. This increases the acetylcholine concentration and the probability of an action potential at the neuromuscular junction and decreased muscle weakness.
In cats, a generalized, erythematous, dermatitis with marked, multifocal crusting, and skin thickening is a not uncommon thymoma associated paraneoplastic cutaneous syndrome. This exfoliative dermatosis is characterized by multifocal plaques of inflammatory alopecia, ulceration, easily epilated coat, target lesions, and painful, contracted skin. Histopathology of these lesions is suggestive of erythema multiforme, an immune mediated disease in which lymphocyte mediated attack is directed at epidermal and follicular keratinocytes. Drug reaction, infection, and occult neoplasia are important triggers for EM. Apparently, the abnormal population of mast cells and lymphocytes associated with thymoma is the responsible mechanism by which these characteristic skin changes occur in cats.
Ultrasound of the cranial mediastinum can be useful in differentiating a cranial mediastinal mass from pleural fluid and may be helpful in determining an aspiration or biopsy site. Ultrasound of the abdomen is indicated in staging of lymphoma, to determine intra-abdominal organ involvement. Because thymomas are rarely metastatic, abdominal ultrasound is not routinely performed in these dogs, except when attempting to differentiate thymoma from lymphoma or in the case of potential intra-abdominal organ dysfunction, based on hematologic or serum chemistry profile abnormalities.
Aspiration cytology can differentiate thymoma from lymphoma in many instances. Thymomas contain mature lymphocytes, neoplastic epithelial cells, and often mast cells. Lymphomas are usually lymphoblastic with large, immature lymphocytes. A lymphocytic lymphoma or a cystic thymoma may cause cytology to be misleading, and tissue samples may be required. Cytology of pleural effusion can also be diagnostic for lymphoma if there are exfoliated lymphoblasts present.
Thymomas are invasive or non-invasive. Staging should include thoracic radiography to rule out obvious metastatic disease and further testing based on clinical signs, physical examination, or hematologic and serologic findings.
Imaging of the thoracic cavity may not indicate the invasiveness of disease, and the presence of effusions should not rule out exploratory surgery. Exploratory surgery is still the best staging procedure to determine resectability.
The treatment options for thymoma in dogs and cats include thymectomy, chemotherapy, and radiation. Thymectomy is the treatment of choice for noninvasive thymoma without megaesophagus. Dogs undergoing a thymectomy with megaesophagus have poor survival because of aspiration pneumonia, mass recurrence, and worsening of signs. A combination of chemotherapy and radiation therapy may be the most effective treatment for invasive thymoma with megaesophagus. Dogs without signs of megaesophagus that have their mass completely resected usually have prolonged survival times. Animals with megaesophagus often have very short survival times, and surgery may be contraindicated due to the morbidity and mortality associated with the procedure, usually related to aspiration pneumonia. Paraneoplastic syndromes associated with thymoma may or may not resolve with therapy and may occur later in life despite successful therapy. There have been reports of prolonged survivals in some animals with no therapy for their thymomas, which may indicate the slow-growing nature of some tumors.
As previously mentioned, surgical excision is the treatment of choice. While thymoma tends to be more invasive and difficult to resect in dogs, it is usually less invasive and easier to remove in cats. An intercostal or rib pivot approach is utilized for small masses while median sternotomy is required for removal of large masses. Non-invasive thymomas do not adhere to intrathoracic structures and are removed using a combination of careful blunt-sharp dissection. The cranial vena cava and phrenic nerves are located along the craniodorsal aspect of most cranial mediastinal masses necessitating careful dissection in this area. Invasive thymomas usually invade vital structures and therefore these animals are difficult surgical candidates, with incomplete removal being much more likely.
In a recent study involving patients where complete excision was possible (and without the utilization of adjunctive chemo or radiation therapy), the median overall survival time for the cats was 1,825 days with a 1-year survival rate of 89% and a 3-year survival rate of 74%. The median overall survival time for the dogs was 790 days with a 1-year survival rate of 64% and a 3-year survival rate of 42%. Recurrence of thymoma was observed in 2 cats and 1 dog, and a second surgery was performed in each with subsequent survival times of 5, 3, and 4 years following the first surgery. The percentage lymphocyte composition of the mass was the only factor that was significantly correlated with survival time; animals with a high percentage of lymphocytes lived significantly longer. The results of this study indicated that most cats and dogs with thymomas did well after complete excision. Even cats and dogs with invasive masses that survived the surgery and the few cats and dogs with recurrent thymomas or paraneoplastic syndromes had a good long-term outcome. For these reasons, excision should be considered an effective treatment option for dogs and cats with thymomas. Once again, as mentioned previously, radiation and/or chemotherapy may play a role in management of thymoma in dogs and cats, especially in those cases in which complete removal cannot be obtained at surgery. The lymphoid component of the thymoma may determine the completeness of the response to chemo and/or radiation therapy.