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THYMIC CANCER

Hamza Hashmi, MD

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.

ETIOLOGY/RISK FACTORS

PRESENTATION

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.

a.   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.

b.   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.

c.   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.

d.   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 morbilliform skin eruption, chronic diarrhea, and liver enzyme abnormalities.

DIAGNOSTIC WORKUP

Biochemical Test

Although no biochemical study exists that can be used as a screening test to determine the presence of a thymoma or thymic cancer, laboratory studies can be helpful to identify a syndrome associated with thymoma.

Molecular Biology

•   KIT overexpression is seen in 86% of thymic cancer. Mutation is rarely seen, only in about 10% of cases.

•   Human epidermal growth receptor 2 (HER2) and B cell leukemia/lymphoma 2 promoting tumorigenesis (BCL2) overexpression is more commonly seen in thymic cancer than thymoma.

•   Epidermal growth factor receptor (EGFR) overexpression is commonly seen in thymic cancer, but mutation is seen in only 10% of patients.

•   Cytogenetics: There are alterations in chromosome 6p21.3 (major histocompatibility complex locus).

•   Karyotype abnormalities involve gain of chromosome 1q, 17q, 18, and loss of 3p, 6, 16q, 17p.

CHEST RADIOGRAPHY

Most thymic neoplasms are visualized on standard chest radiography. The lateral chest radiograph is very helpful in the determination of the involved compartment of the mediastinum.

COMPUTED TOMOGRAPHY

Computed tomography is the preferred imaging modality to visualize a thymoma. However, thymomas have no absolute diagnostic features; they are usually homogeneous and enhance with contrast. CT scans can reveal evidence of local invasion of adjacent structures by a mass or the presence of intrathoracic metastases (Figure 24-1). CT has been found to be able to differentiate stage I/II from stage III/IV and may be useful for predicting the need for neoadjuvant therapy.

Figure 24-1. Thymic cancer (arrowhead) with pleural metastases (pointer).

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is useful in both the initial diagnosis of a mediastinal mass and the follow-up evaluation after treatment. Nevertheless, MRI adds little that CT does not provide and should not be performed except under special circumstances.

Positron Emission Tomography

A high 18-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) reflects the invasiveness of the malignant nature of thymic tumors and can be used to differentiate these from benign thymomas.

TISSUE BIOPSY

The definitive diagnosis of a thymoma or thymic carcinoma requires a tissue diagnosis.²

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