+ General Considerations

• Thymoma is classified as invasive or non-invasive
• Thymoma is non-invasive in 50% dogs
• Non-invasive thymomas are well-encapsulated
• Invasive thymoma will invade adjacent structures such as cranial vena cava, thoracic wall, and pericardium
• Thymomas can also be cystic
• Thymoma arises from thymic epithelium and has variable mature lymphocyte involvement which can predominate, but the epithelium is the malignant component
• Lymphoid component exfoliates more readily than epithelial component and hence it can be difficult to differentiate thymoma from cranial mediastinal LSA
• DDx: thymic LSA, thymic carcinoma, thymic branchial cyst, ectopic thyroid and parathyroid neoplasia, aortic body tumor, metastatic carcinoma, and rib and sternal sarcomas extending into mediastinal space

+ Clinical Features

• Thymoma is rare in dogs
• Breed predisposition: medium and large breeds with Labrador Retriever and GSD over-represented
• No sex predilection ± females with a male-to-female ratio of 1:7.5
• median age 11 years
• Thymoma is associated with a high incidence of non-thymic neoplasia
• Paraneoplastic hypercalcemia is uncommon but reported in 5% of canine thymoma
• Histopathologic features: mixture of thymic epithelial cells and small lymphocytes in variable proportions with occasional eosinophils and mast cells
• Mast cells detected in 85% of canine thymoma
• Thymic carcinoma has been reported but are rare and associated with more aggressive histologic appearance and widespread metastases
• Metastatic thymoma is rare

+ Non-Invasive Thymoma

• Asymptomatic or non-specific signs associated with large space-occupying thoracic mass
• Exercise intolerance, coughing, dyspnea, dysphagia, and weight loss
• Coughing and dyspnea due to pleural effusion or compression of trachea or segmental bronchi
• Dysphagia and drooling secondary to esophageal compression or megaesophagus
• Laryngeal paralysis with peripheral nerve entrapment
• Paraneoplastic syndromes associated with thymoma: myasthenia gravis, hypogammaglobulinemia, hypercalcemia, and aplastic anemia

+ Invasive Thymoma

• Clinical signs and paraneoplastic syndromes are the same as non-invasive thymoma
• Cranial vena cava syndrome: edema of submandibular area, neck, thoracic inlet, and thoracic limbs, and association with pleural effusion (particularly chylothorax)
• Pneumothorax and hemothorax have also been reported with invasive thymoma

+ Paraneoplastic Syndromes

• Paraneoplastic syndromes associated with thymoma include:
• Myasthenia gravis
• Hypogammaglobulinemia
• Hypercalcemia
• Aplastic anemia
• Myasthenia gravis is present in the Okas cat and 40% of dogs with thymoma
• Myasthenia gravis may be either focal or generalized with megaesophagus and generalized weakness
• Thymic monocytes may become immunogenic resulting in formation of antibodies directed against acetylcholine receptors and resulting in development of myasthenia gravis
• Thymoma is also associated with other immunogenic diseases with 20%-40% of dogs presenting with autoimmune disease such as immune-mediated anemia, polymyositis, and exfoliative dermatitis (cats)
• Cardiac myositis causes 3rd degree atrioventricular block

+ Non-Thymic Neoplasia

• High incidence of 2nd non-thymic malignancy associated with thymoma due to possible association with deficient immunologic surveillance
• 2nd tumors include both sarcomas and carcinomas

+ Diagnosis

• Clinical signs
• Physical examination: caval syndrome and auscultation changes associated with pleural effusion
• Hematology and serum biochemistry are usually unremarkable
• Lymphocytosis (> 20,000 cells/µL) and pseudohyperparathyroidism are occasionally observed
• Thoracic radiographic findings include:
• Space occupying mass with dorsal elevation of trachea and esophagus
• Caudal displacement of cardiac silhouette
• Megaesophagus and aspiration pneumonia with paraneoplastic myasthenia gravis
• Minimal pleural effusion with non-invasive thymoma
• Pleural effusion which may obscure mass with invasive thymoma
• Pulmonary metastasis

• Ultrasonography: mixed echogenicity with cavitation compared to homogenous hypoechogenicity with LSA
• Advanced imaging (i.e., CT or MRI)
• FNA or needle-core biopsy: predominance of lymphocytes rather than epithelial cells may confuse diagnosis
• Immunohistochemistry may be required for definitive diagnosis (cytokeratin)

+ Clinical Staging

• Sub-staging based on presence of paraneoplastic syndromes:
• P 0: no paraneoplastic syndrome
• P 1: myasthenia gravis
• P 2: non-thymic malignant tumor

+ Surgery

• Exploratory thoracotomy required to differentiate non-invasive and invasive thymoma
• Median sternotomy usually required due to size of tumor, but lateral intercostal thoracotomy can be used for smaller lesions or in cats (although adjacent rib resection sometimes required)
• Non-invasive thymomas do not adhere to intrathoracic structures and removed using blunt-sharp dissection
• Cranial vena cava and phrenic nerves are located along the craniodorsal aspect of cranial mediastinal mass
• Invasive thymomas usually invade vital structures and are difficult surgical candidates
• Venous grafts are used in humans, and has been reported in the dog, for thymomas invading the cranial vena cava

+ Radiation Therapy

• Thymomas are radiation-sensitive tumors in cats, dogs, and humans
• 75% response rate in cats and dogs with thymomas, including 20% CR
• Lymphoid component of thymoma may determine completeness of response
• Adverse effects: pneumonitis and pericarditis

+ Chemotherapy

• Chemotherapy is usually ineffective, but can be attempted in combination with corticosteroids for invasive thymoma
• Partial and complete responses are uncommon
• Corticosteroids may provide either prolonged stable disease or even partial or complete response
• Response to corticosteroids is due to cytotoxic effects on T lymphocytes which can represent a large non-neoplastic component of thymoma
• Cisplatin, ifosfamide, corticosteroids, doxorubicin, maytansine, cyclophosphamide, vincristine, and procarbazine are used in single or multiple agent protocols in humans with invasive and metastatic thymomas

+ Other Treatment

• Immunosuppressive therapy or anticholinesterase treatment for myasthenia gravis
• Motility drugs, H 2 antagonists, and antibiotics for prophylactic management of megaesophagus

+ Prognosis

• Prognosis is excellent for non-invasive thymoma without megaesophagus as majority of dogs die from unrelated causes and 1-year survival rate 83%
• MST for dogs with radiation therapy: 248 days
• Poor prognostic factors include age, megaesophagus, and histology:
• Age < 8 years associated with a significantly decreased survival time (MST 1 day v 18 days)
  • MST for dogs with megaesophagus is 4 days
• MST for lymphocyte-rich thymomas is significantly better than other histologic types of thymoma (MST 237 days v 13 days for differentiated epithelial, 1 day for undifferentiated epithelial, 1 day for oval cells, and 0 days for spindle cells)
• Prognosis is guarded for invasive thymoma or thymoma associated with megaesophagus
• 28% (2/7) local tumor recurrence rate