**3. Clinical presentation**

Patients with a thymus malignancy can present themselves with complaints due to local compression/invasion or due to a paraneoplastic autoimmune phenomenon, but ~40% of the thymic neoplasms are asymptomatic incidental findings.

Local symptoms are related to the site and size of tumor and compression or invasion on the surrounding tissue. Patients can present themselves with symptoms as chest pain, cough, dysphagia, or stridor. A superior vena cava syndrome can cause swelling of the face and arms and dyspnea. Dyspnea can also be the result of unilateral or bilateral phrenic nerve palsy and pleural or pericardial involvement. The latter can also elicit tachycardia [3]. Systemic symptoms such as fever or weight loss are possible.

## **3.1 Paraneoplastic autoimmune syndromes**

About 40–50% of thymomas are associated with a variety of paraneoplastic autoimmune syndromes, and over 30 associations have been described [1, 15, 16] (**Table 1**). Up to 25% deaths in thymoma are due to the complications of autoimmune syndromes.

The most common paraneoplastic syndrome is myasthenia gravis, followed by pure red cell aplasia and hypogammaglobinemia (Good syndrome).

Ten to twenty percent of patients with myasthenia gravis have a thymoma, and 30–50% of patients with thymoma have myasthenia gravis. It is a neuromuscular disease that leads to varying degrees of muscle weakness. It is caused by autoantibodies that interfere with the acetylcholine receptors in the neuromuscular junction of the voluntary muscles, but the exact mechanism how has yet to be discovered. Systemic symptoms consist of fatigue and general muscle weakness leading to troubles with walking. Myasthenia gravis can antedate the diagnosis of thymoma, be diagnosed concurrently, or occur after thymectomy, with or without recurrence of thymoma [15–17].

Pure red cell aplasia is a profound non-regenerative anemia, characterized by a severe reduction in reticulocytes and absence of erythrocyte precursors in the bone marrow. Five to fifteen percent of patients with thymoma have pure red cell aplasia [16]. It is more common in older women. Remission following surgical excision of the thymoma is uncommon [18].


#### **Table 1.**

*Examples of autoimmune syndromes associated with thymoma.*

Patients suffering from hypogammaglobulinemia (or Good syndrome) suffer from recurrent episodes of diarrhea, pulmonary infections, urinary tract infections, and several other bacterial and viral infections. Five percent of patients with Good syndrome have a thymoma, and 10% of patients with a thymoma have hypergammaglobulinemia. Thymectomy does not normalize immunoglobulin levels. Treatment consists of administration of intravenous immunoglobulin [16, 19].

Thymoma-associated multiorgan autoimmunity (TAMA) is a severe and often fatal graft-versus-host-like disease that requires special mention. Symptoms are T-cell mediated and cause skin disruptions, liver failure, and diarrhea [3]. Immunoglobulin and methylprednisolone have been described as treatment [20].

#### **4. Diagnostics**

#### **4.1 Imaging**

Thymic epithelial tumors arise in the anterior mediastinum and are most commonly located between the sternum, the great vessels, and the pericardium. All anterior mediastinal masses should be assessed with a chest computed tomography (CT) with IV contrast [21]. Chest CT can usually show if a thymic tumor is well circumscribed and if invasion in mediastinal fat, the surrounding vessels, or the adjacent lung is present. It can also show the presence of pericardial and/or pleural seeding [16]. Magnetic resonance imaging (MRI) can be used to assess involvement of surrounding tissues [22] and can also be useful to differentiate between

**79**

*Thymoma and Thymic Carcinoma*

*DOI: http://dx.doi.org/10.5772/intechopen.87132*

cannot tolerate radiocontrast administration.

metastases in thymus carcinoma [24].

diagnostic and treatment purposes [21].

biopsies are preferred [31].

the most commonly used.

patients staged according to the Masaoka-Koga system.

**5. Staging**

**4.2 Biopsy**

in both invasive thymoma and thymic carcinoma [23].

thymoma and thymic cysts that demonstrate increased CT attenuation due to hemorrhage or high mucinous content [16]. It can also be considered in patients that

Thymomas are usually encapsulated, homogenous, and round or oval structures with smooth contours. A cystic component is common. They can range from microscopic size to >30 cm in diameter. Type B thymomas and thymic carcinomas can show calcifications [22]. Thymic carcinomas tend to have irregular borders and necrotic areas and are usually much larger than thymomas. Pleural seeding is seen

Positron-emission tomography (PET) can be useful in the case of thymic carcinoma. Thymic carcinomas have a higher fludeoxyglucose (FDG-18) PET uptake than thymomas. Using a standardized uptake value (SUV) cutoff point of 5.0, thymic carcinoma can be distinguished from thymomas with a sensitivity of 84.6% and a specificity of 92.3%. PET can also be useful for diagnosis of extra thoracic

When a thymic tumor is considered likely and microscopical complete resection is considered possible, pathological evaluation should be done following surgery. Most thymomas can reliably be identified on the clinical presentation and imaging without the need for a biopsy. Histological classification may be difficult when there is a limited amount of tissue, and invasion in the surrounding tissue cannot be identified on biopsy alone. So even when the diagnosis is uncertain based on clinical presentation and imaging alone, complete surgical resection is advised for both

Historically, it is thought that biopsy can cause pleural seeding. This is the main reason it is recommended to avoid a biopsy when resectable thymoma is suspected [21, 25]. However, there are no known exact data available to describe the proportion of this risk. There are only three case reports published for needle tract implantation of a thymoma reported in the chest wall after biopsy [26–28]. To abstain from a needle biopsy in order to avoid the risk of pleural seeding therefore seems unfounded [29]. In the case of potentially resectable or unresectable disease or when another diagnosis, such as lymphoma, is strongly suspected, tissue diagnosis is necessary. Biopsy should avoid a transpleural approach to prevent tumor seeding in the pleural space [21, 30]. Note that differentiation between lymphoma and thymoma can be difficult when a fine needle aspiration is done, so core needle biopsy or surgical

There are several different staging systems for thymoma and thymic carcinoma, but the Masaoka-Koga staging system [32] and the American Joint Committee on Cancer (AJCC) the eighth edition of the TNM prognostic staging system [33] are

Both staging systems are based on the extent of the primary tumor, invasion of adjacent structures and dissemination. In contrast to other thoracic cancers, both lymph node and distant metastases are considered stage IV disease. The Masaoka-Koga staging system (**Table 2**) is a surgical-pathological system that can only be definitely ascertained after surgery is performed. Historically this has been the most widely used staging system, so most data supporting treatment options is based on

#### *Thymoma and Thymic Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.87132*

thymoma and thymic cysts that demonstrate increased CT attenuation due to hemorrhage or high mucinous content [16]. It can also be considered in patients that cannot tolerate radiocontrast administration.

Thymomas are usually encapsulated, homogenous, and round or oval structures with smooth contours. A cystic component is common. They can range from microscopic size to >30 cm in diameter. Type B thymomas and thymic carcinomas can show calcifications [22]. Thymic carcinomas tend to have irregular borders and necrotic areas and are usually much larger than thymomas. Pleural seeding is seen in both invasive thymoma and thymic carcinoma [23].

Positron-emission tomography (PET) can be useful in the case of thymic carcinoma. Thymic carcinomas have a higher fludeoxyglucose (FDG-18) PET uptake than thymomas. Using a standardized uptake value (SUV) cutoff point of 5.0, thymic carcinoma can be distinguished from thymomas with a sensitivity of 84.6% and a specificity of 92.3%. PET can also be useful for diagnosis of extra thoracic metastases in thymus carcinoma [24].

#### **4.2 Biopsy**

*Thymus*

Neuromuscular diseases **Myasthenia gravis**

Hematologic autoimmune diseases Anemia

Dermatologic diseases Pemphigus

Endocrine disorders Addison's disease

Renal and hepatic disease Glomerulonephritis

Systemic autoimmune diseases SLE

*Examples of autoimmune syndromes associated with thymoma.*

Neuromyotonia Rippling muscle disease Polymyositis/dermatomyositis

Encephalitis

Intestinal pseudo-obstruction

**Hypogammaglobinemia/Good syndrome**

**Thymoma-associated multiorgan autoimmunity** (**TAMA**)

**Pure red cell anemia** Pernicious anemia Hemolytic anemia Aplastic anemia Other isolated cytopenia Immunodeficiencies

T-cell deficiencies

Lichen planus Alopecia areata

Cushing's disease Graves' disease

Sjogren's disease Systemic sclerosis

Autoimmune hepatitis

**78**

**4. Diagnostics**

**4.1 Imaging**

**Table 1.**

Patients suffering from hypogammaglobulinemia (or Good syndrome) suffer from recurrent episodes of diarrhea, pulmonary infections, urinary tract infections, and several other bacterial and viral infections. Five percent of patients with Good syndrome have a thymoma, and 10% of patients with a thymoma have hypergammaglobulinemia. Thymectomy does not normalize immunoglobulin levels. Treatment consists of administration of intravenous immunoglobulin [16, 19]. Thymoma-associated multiorgan autoimmunity (TAMA) is a severe and often

Thymic epithelial tumors arise in the anterior mediastinum and are most commonly located between the sternum, the great vessels, and the pericardium. All anterior mediastinal masses should be assessed with a chest computed tomography (CT) with IV contrast [21]. Chest CT can usually show if a thymic tumor is well circumscribed and if invasion in mediastinal fat, the surrounding vessels, or the adjacent lung is present. It can also show the presence of pericardial and/or pleural seeding [16]. Magnetic resonance imaging (MRI) can be used to assess involvement of surrounding tissues [22] and can also be useful to differentiate between

fatal graft-versus-host-like disease that requires special mention. Symptoms are T-cell mediated and cause skin disruptions, liver failure, and diarrhea [3]. Immunoglobulin and methylprednisolone have been described as treatment [20].

When a thymic tumor is considered likely and microscopical complete resection is considered possible, pathological evaluation should be done following surgery. Most thymomas can reliably be identified on the clinical presentation and imaging without the need for a biopsy. Histological classification may be difficult when there is a limited amount of tissue, and invasion in the surrounding tissue cannot be identified on biopsy alone. So even when the diagnosis is uncertain based on clinical presentation and imaging alone, complete surgical resection is advised for both diagnostic and treatment purposes [21].

Historically, it is thought that biopsy can cause pleural seeding. This is the main reason it is recommended to avoid a biopsy when resectable thymoma is suspected [21, 25]. However, there are no known exact data available to describe the proportion of this risk. There are only three case reports published for needle tract implantation of a thymoma reported in the chest wall after biopsy [26–28]. To abstain from a needle biopsy in order to avoid the risk of pleural seeding therefore seems unfounded [29].

In the case of potentially resectable or unresectable disease or when another diagnosis, such as lymphoma, is strongly suspected, tissue diagnosis is necessary. Biopsy should avoid a transpleural approach to prevent tumor seeding in the pleural space [21, 30]. Note that differentiation between lymphoma and thymoma can be difficult when a fine needle aspiration is done, so core needle biopsy or surgical biopsies are preferred [31].
