+ General Considerations

  • Thymoma is classified as invasive or non-invasive
  • Thymoma is non-invasive in 50%-100% cats
  • 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 very rare in cats
  • Male predisposition with a male-to-female ratio of 2.5:1
  • Median age: 10.8 years
  • Thymoma occurs in older cats compared to thymic LSA
  • Histopathologic features: mixture of thymic epithelial cells and small lymphocytes in variable proportions
  • Mast cells detected in 50% of feline thymoma
  • SCC has been reported to arise from feline thymoma
  • Invasive thymoma may be more common in cats (55% in one report)
  • Metastasis has not been reported

Clinical Signs

+ 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

  • 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)
  • Other tests include FeLV and FIV in cats and acetylcholine receptor antibody titres
  • Thymoma can be differentiated from cranial mediastinal lymphoma by:

Treatment

+ 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
  • No local recurrence or metastasis in 10 cats surviving perioperative period
  • Myasthenia gravis has been reported in 2 cats postoperatively
  • MST for cats with surgery: 21 months (range, 6-36 months)
  • MST for cats with radiation therapy: 720 days

 

CRANIAL MEDIASTINAL
THYMOMA

 

Factor

Thymoma

Age

Older

FeLV Status

Negative

Cytology

Lymphocytes, epithelial cells, and mast cells

Lymphosarco0ma

Younger

Positive

Lymphoblasts

Chemoresponsiveness

Minimal response

Early and rapid response