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A 50-year-old white male with no other past medical history presents with gradually worsening shortness of breath for the last 3 months. Chest x-ray reveals a moderate size right-sided pleural effusion. Chest computed tomography (CT) confirms a loculated pleural effusion and pleural-based nodules. A thoracentesis removes 500 mL of fluid and analysis reveals exudative effusion without evidence of malignant cells on cytology. What should be the next step in management of this patient?

Learning Objectives

  1. What are the paraneoplastic syndromes associated with thymoma and thymic cancer?

  2. What is the ideal approach for obtaining a tissue biopsy for a thymic mass?

  3. What is the ideal treatment approach for unresectable and non-metastatic thymic cancer?

  4. What are the two most important prognostic factors for thymic cancer?

  5. What are the common malignancies associated with thymic cancer?

Thymic tumors are rare neoplasms that arise in the anterior mediastinum. Thymomas/thymic cancer account for about 20% percent of mediastinal neoplasms. Most patients are between 40 and 60 years of age. There is a slight male predominance. Asian and African individuals are more commonly affected than Caucasians.



There are no known risk factors, although there is a strong association with myasthenia gravis and other paraneoplastic syndromes.


Approximately 50% of individuals presenting with thymoma are clinically asymptomatic.1 When present, symptoms may be local or systemic. Chest pain, cough, and shortness of breath are the most commonly identified local symptoms. More severe symptoms, such as superior vena cava syndrome, phrenic nerve paralysis, or recurrent laryngeal nerve involvement resulting in hoarseness, are less common. Constitutional symptoms are associated with thymoma in almost 20% of patients and include weight loss, fever, fatigue, and night sweats.

  1. Myasthenia gravis: Up to one half of patients with thymoma have symptoms consistent with myasthenia gravis. Myasthenia gravis is common with all types of thymoma, but it is rare in thymic carcinoma. Common symptoms include diplopia, ptosis, dysphagia, weakness, and fatigue. Patients with thymoma and myasthenia gravis usually present with less advanced disease than those without myasthenia gravis, possibly because neuromuscular symptoms may lead to an earlier diagnosis.

  2. Pure red cell aplasia: Pure red cell aplasia results from an autoimmune-mediated hypoproliferation of erythrocyte precursors in the bone marrow. This paraneoplastic disorder occurs in 5%-15% of patients with thymoma and is more common in older women.

  3. Immunodeficiency: Hypogammaglobulinemia and pure white blood cell aplasia are present in less than 5% of patients with thymoma, most commonly in older women. Conversely, up to 10% of patients with acquired hypogammaglobulinemia have an associated thymoma (Good syndrome), typically of spindle cell histology. Patients usually have recurrent infections, diarrhea, and lymphadenopathy.

  4. Thymoma-associated multiorgan autoimmunity: Several case reports have described a syndrome of thymoma-associated multiorgan autoimmunity (TAMA) that is similar to graft-versus-host disease. Patients present with variable combinations of a ...

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