Veterinary Society of
Surgical Oncology

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

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

  • 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

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 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

CRANIAL MEDIASTINAL THYMOMA

Stage

Description

I

Well-encapsulated with no microscopic capsular invasion

II

Microscopic capsular invasion or gross invasion into adjacent tissue, mediastinal pleura, and fat

III

Gross invasion into adjacent organs, pericardium, great vessels, and lungs

IVa

Pericardial or pleural dissemination

IVb

Distant metastasis through hematogenous or lymphatic routes

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