**2. WHO histological classification**

Numerous classifications for thymic neoplasms, based on different histological and clinical criteria, have been proposed in the past. For universal agreement purposes, the International Committee of the World Health Organization (WHO) developed a classification system that distinguishes five histological subtypes of thymomas that differ in both morphological and clinical presentation and which correlate with invasion [1]. The WHO classification is increasingly more malignant from A to B3. Thymomas are composed of a mixture of neoplastic epithelial cells and normal T lymphocytes and exhibit a resemblance to the normal thymic architecture, which cannot be found in other organs. In contrast, thymic carcinoma (in the past considered as a thymoma type C) is similar to carcinomas found outside the thymus. Although most thymomas have an excellent prognosis, they can be locally invasive and are (although rarely) able to spread to lymph nodes or extrathoracic sites, so the term "benign" should be avoided.

Type A thymoma is composed of spindle cells and a few to no lymphocytes. About 24% of the type A thymomas are found in patients suffering from myasthenia gravis, and pure red cell aplasia may occur. Eighty percent of type A thymomas are Masaoka-Koga stage I on presentation (for explanation on the Masaoka-Koga staging system, see paragraph on staging). Stage IV is rare in this histological subtype [1, 3]. The prognosis of type A thymoma is excellent with 5- and 10-year survival rates close to 100% [10].

Type AB thymoma is composed of a mixture of lymphocyte-poor type A thymoma and more lymphocyte-rich type B. Approximately 14% of type AB thymomas are associated with the development of myasthenia gravis. Paraneoplastic pure red cell aplasia has also been also reported. Seventy-two percent is Masaoka-Koga stage I at presentation, 22% stage II, and 6% stage III. As in WHO type A disease, stage IV is rare [1]. Overall 5- and 10-year survival is reported 80–100% for stages I and II.

Type B1 thymoma is composed of thymic epithelial cells which are practically indistinguishable from the normal thymus cortex and medulla. A prominent population of immature lymphocytes is present. Like the other types, type B1 thymoma is associated with myasthenia gravis, but additionally hypogammaglobulinemia and pure red cell aplasia have been reported. Invasion in adjacent organs occurs in 12% of patients [11]. Complete surgical resection is possible in 94% of the cases with a recurrence rate of 10%. Ten-year survival rate is >90% [10].

Type B2 thymomas are usually at a more advanced stage. They are predominantly composed of large, polygonal tumor cells in the background of a large population of immature T lymphocytes. The most frequent manifestations (up to 80%) are symptoms arising from myasthenia gravis. Pure red cell aplasia, hypogammaglobulinemia, and other paraneoplastic autoimmune diseases have been described. Up to 53% are stage Masaoka-Koga I or III at presentation, and 8.2% is

**77**

*Thymoma and Thymic Carcinoma*

and 100% [1].

survival [1, 10, 14].

loss are possible.

mune syndromes.

of thymoma [15–17].

the thymoma is uncommon [18].

**3.1 Paraneoplastic autoimmune syndromes**

**3. Clinical presentation**

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

stage IV. In 5–15% of cases, they are non-resectable, and recurrence rates are 9% after complete resection [10, 12]. Reported 10-year survival rates are between 50

Like the other types of thymomas, the most frequent association is myasthenia gravis. Pure red cell aplasia and hypogammaglobinemia are rare. The majority of patients are Masaoka-Koga stage II or III at presentation, and stage IV occurs in

Thymic carcinomas are atypical, invasive epithelial tumors that show resem-

Squamous cell carcinomas and undifferentiated carcinomas are the most common subtypes. They are composed of polygonal or round epithelial cells with mild atypia. Invasion of adjacent structures has been reported to occur in 83% of cases. In contrast to thymomas, paraneoplastic syndromes are very rare. Thymic carcinomas have the worst survival rate of the thymic malignancies with only 35% 5-year

Patients with a thymus malignancy can present themselves with complaints due to local compression/invasion or due to a paraneoplastic autoimmune phenomenon,

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

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 autoim-

The most common paraneoplastic syndrome is myasthenia gravis, followed by

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

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

pure red cell aplasia and hypogammaglobinemia (Good syndrome).

but ~40% of the thymic neoplasms are asymptomatic incidental findings.

20%. Ten-year survival rates range between 50 and 70% [10, 12, 13].

blance to carcinomas outside the thymus and show a lot of differentiation.

Type B3 thymomas are almost always invasive and unresectable at presentation.

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

*Thymus*

mediastinum, they can also be found in other mediastinal compartments, as well as

Approximately 1000 new cases are diagnosed per year in Europe [6]. Patients are usually between 20 and 70 years of age, with a peak in 30–40 years for those with myasthenia gravis and 60–70 years for those without myasthenia gravis. Incidence is similar in men and women [3, 7]. There are no known risk factors [3, 7], although clusters of thymoma are described in patients with multiple endocrine neoplasia type 1 (MEN1) syndrome [8] and an association between the Epstein– Barr virus and myasthenia gravis in thymoma patients has been suggested [9].

Numerous classifications for thymic neoplasms, based on different histological and clinical criteria, have been proposed in the past. For universal agreement purposes, the International Committee of the World Health Organization (WHO) developed a classification system that distinguishes five histological subtypes of thymomas that differ in both morphological and clinical presentation and which correlate with invasion [1]. The WHO classification is increasingly more malignant from A to B3. Thymomas are composed of a mixture of neoplastic epithelial cells and normal T lymphocytes and exhibit a resemblance to the normal thymic architecture, which cannot be found in other organs. In contrast, thymic carcinoma (in the past considered as a thymoma type C) is similar to carcinomas found outside the thymus. Although most thymomas have an excellent prognosis, they can be locally invasive and are (although rarely) able to spread to lymph nodes or extrathoracic

Type A thymoma is composed of spindle cells and a few to no lymphocytes. About 24% of the type A thymomas are found in patients suffering from myasthenia gravis, and pure red cell aplasia may occur. Eighty percent of type A thymomas are Masaoka-Koga stage I on presentation (for explanation on the Masaoka-Koga staging system, see paragraph on staging). Stage IV is rare in this histological subtype [1, 3]. The prognosis of type A thymoma is excellent with 5- and 10-year

Type AB thymoma is composed of a mixture of lymphocyte-poor type A thymoma and more lymphocyte-rich type B. Approximately 14% of type AB thymomas are associated with the development of myasthenia gravis. Paraneoplastic pure red cell aplasia has also been also reported. Seventy-two percent is Masaoka-Koga stage I at presentation, 22% stage II, and 6% stage III. As in WHO type A disease, stage IV is rare [1]. Overall 5- and 10-year survival is reported 80–100%

Type B1 thymoma is composed of thymic epithelial cells which are practically indistinguishable from the normal thymus cortex and medulla. A prominent population of immature lymphocytes is present. Like the other types, type B1 thymoma is associated with myasthenia gravis, but additionally hypogammaglobulinemia and pure red cell aplasia have been reported. Invasion in adjacent organs occurs in 12% of patients [11]. Complete surgical resection is possible in 94% of the cases with a

Type B2 thymomas are usually at a more advanced stage. They are predominantly composed of large, polygonal tumor cells in the background of a large population of immature T lymphocytes. The most frequent manifestations (up to 80%) are symptoms arising from myasthenia gravis. Pure red cell aplasia, hypogammaglobulinemia, and other paraneoplastic autoimmune diseases have been described. Up to 53% are stage Masaoka-Koga I or III at presentation, and 8.2% is

recurrence rate of 10%. Ten-year survival rate is >90% [10].

in the neck, lung, pleura, and thyroid, due to ectopic thymic tissue [1, 4, 5].

**2. WHO histological classification**

sites, so the term "benign" should be avoided.

survival rates close to 100% [10].

for stages I and II.

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stage IV. In 5–15% of cases, they are non-resectable, and recurrence rates are 9% after complete resection [10, 12]. Reported 10-year survival rates are between 50 and 100% [1].

Type B3 thymomas are almost always invasive and unresectable at presentation. Like the other types of thymomas, the most frequent association is myasthenia gravis. Pure red cell aplasia and hypogammaglobinemia are rare. The majority of patients are Masaoka-Koga stage II or III at presentation, and stage IV occurs in 20%. Ten-year survival rates range between 50 and 70% [10, 12, 13].

Thymic carcinomas are atypical, invasive epithelial tumors that show resemblance to carcinomas outside the thymus and show a lot of differentiation. Squamous cell carcinomas and undifferentiated carcinomas are the most common subtypes. They are composed of polygonal or round epithelial cells with mild atypia. Invasion of adjacent structures has been reported to occur in 83% of cases. In contrast to thymomas, paraneoplastic syndromes are very rare. Thymic carcinomas have the worst survival rate of the thymic malignancies with only 35% 5-year survival [1, 10, 14].
