Thymic carcinoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Thymic carcinoma, also known as type C thymoma, is a rare condition (less than 0.13/100,000/year) but should be included in the differential diagnosis of anterior mediastinic masses. It is a tumor of the thymic epithelium, like thymoma, but it is associated with lack of immature lymphocytes and often presents with more invasive or metastatic disease. Thymic carcinomas can metastasize, generally to pleura, kidney, bone, liver, or brain. The thymic carcinoma is a tumor of the thymic epithelium, but it is associated with lack of immature lymphocytes and often presents with more invasive or metastatic disease.^[1] The pathophysiology of thymic carcinoma depends on the histological subtype. On microscopic histopathological analysis, thymic carcinoma is divided into squamous cell carcinoma, basaloid carcinoma, mucoepidermoid carcinoma, lymphoepithelioma-like carcinoma, sarcomatoid carcinoma (carcinosarcoma), clear cell carcinoma, papillary adenocarcinoma, carcinoma with t(15;19) translocation, neuroendrocrine carcinomas, undifferentiated carcinoma, and combined thymic epithelial tumors.^[2] Thymic carcinoma has not been reported in association with myasthenia gravis, in contrast with thymoma.^[3] The cause of thymic carcinoma has not been identified. The most common differential diagnosis of thymic carcinoma is thymoma, which is the most common pathology of the thymus. Thymic carcinoma must be differentiated from other mediastinal masses such as germ cell tumors, lymphoma, thyroid tumors, and metastatic carcinoma to the mediastinal lymph nodes.^[4] The prevalence of thymic carcinoma is approximately 0.00006 per 100,000 individuals worldwide. Males are more commonly affected with thymic carcinoma than females. The male to female ratio is approximately 3 to 1. It is more common in Asians and African Americans than in Caucasians. There are no established risk factors for thymic carcinoma.^[5] Thymic carcinomas are generally considered indolent tumors due to the long recurrence intervals (median of 68 months). The most common sites of distant recurrence are lung, liver, bone, kidney, brain and bone marrow.^[6] The most important factor for prognosis is the stage and grade of the thymic carcinoma. The 5-year and 10-year overall survival rates in patients with thymic carcinoma are 38% and 28% respectively.^[7] The subtypes squamous cell carcinoma, mucoepidermoid carcinoma, and basaloid carcinoma have a better prognosis than other histological subtypes. The staging of thymic carcinoma is based on the Masoka and GETT staging system.^[8] Symptoms of thymic carcinoma include dull chest pain, cough, dyspnea, and constitutional symptoms. Chest CT scan may be helpful in the diagnosis of thymic carcinoma. On CT scan of the chest, thymic carcinoma is characterized by lobulated mass with irregular borders, heterogeneous attenuation, and mediastinal fat invasion with areas of necrosis, hemorrhage, calcification, or cyst formation. Chest MRI scan may be diagnostic of thymic carcinoma. Findings on chest MRI suggestive of thymic carcinoma include isointense to slightly hyperintense signal compared to muscle on T1 weighted image and heterogeneous signal on T2 weighted image. On T1 weighted image with gadolinium contrast, linear regions of enhancement may be observed coursing through the mass, which are thought to represent fibrous septae.^[9] Other imaging studies for the diagnosis of thymic carcinoma include FDG PET scan. The standarized uptake value (SUV) in the FDG PET is much higher for the thymic carcinoma than thymoma, with a high sensitivity (84.6%) and specificity (92.3%).^[10][11] Other diagnostic studies for thymic carcinoma include immunohistochemistry. The predominant therapy for thymic carcinoma is surgical resection. Adjunctive cisplatin-basedchemotherapy may be required.^[12] Surgery is the mainstay of treatment for thymic carcinoma.^[12] There is no established method for primary prevention of thymic carcinoma. There are no secondary preventive measures available for thymic carcinoma.

The thymic epithelial tumor staging system was initially proposed by Bergh and his colleagues in 1978, modified by Wilkins and Castleman in 1979, and further developed by Masaoka et al. in 1981. Staging of thymic epithelial tumors was initially proposed by Bergh and his colleagues in 1978. Staging of thymic epithelial tumors was modified by Wilkins and Castleman in 1979.It went through further development by Masaoka et al. in 1981.

Thymic carcinomas may be classified according to a histological grading system into either low grade subtypes or high grade subtypes.[1]. Primary thymic carcinomas are rare malignant neoplasms of the mediastinum, and combined thymic carcinomas are even less common. Although tumor stage is the single most important prognostic factor in thymoma, a combination of stage and histologic subtype should be considered in predicting survival.

The thymic carcinoma is a tumor of the thymic epithelium, but it is associated with a lack of immature lymphocytes and often presents with a more invasive or metastatic disease.The pathophysiology of thymic carcinoma depends on the histological subtype. On microscopic histopathological analysis, thymic carcinoma is divided into squamous cell carcinoma, basaloid carcinoma, mucoepidermoid carcinoma, lymphoepithelioma-like carcinoma, sarcomatoid carcinoma (carcinosarcoma), clear cell carcinoma, papillary adenocarcinoma, carcinoma with t(15;19) translocation, neuroendrocrine carcinomas, undifferentiated carcinoma, and combined thymic epithelial tumors. Thymic carcinoma has not been reported in association with myasthenia gravis, in contrast with thymoma. Paraneoplasic syndromes has been reported among patients with thymic cancer (neuroendocrine subtype), however the syndrome is not as common as with thymoma patients.

The cause of thymic carcinoma has not been identified.

The most common differential diagnosis of thymic carcinoma is thymoma, which is the most common pathology of the thymus. Thymic carcinoma must be differentiated from other mediastinal masses such as germ cell tumors, lymphoma, thyroid tumors, and metastatic carcinoma to mediastinal lymph nodes.^[4]

The prevalence of thymic carcinoma is approximately 0.00006 per 100,000 individuals worldwide. Males are more commonly affected with thymic carcinoma than females. The male to female ratio is approximately 3 to 1. It is more common in Asians and African Americans than in Caucasians. Thymic malignancies are relatively rare in the range of 0.2% to 1.5% of all malignancies or 0.13 per 100,000 person-years in the United States. Thymic malignancies are among the most common mediastinal primary tumors with up to 50% of anterior mediastinal masses proving to be of thymic descent. Invasive thymomas and thymic carcinomas are relatively rare tumors, which together represent about 0.2% to 1.5% of all malignancies. Thymic carcinoma are rare and have been reported to account for only 0.06% of all thymic neoplasms. The risk of thymic carcinoma increases with age. Thymic carcinoma is uncommon in children, it is seen more often in middle-aged adults. Thymic carcinoma commonly affects individuals between 40-60 years of age.

There are no established risk factors for thymic carcinoma.^[5]

Thymic carcinomas are generally considered indolent tumors due to long recurrence intervals (median of 68 months). The most common sites of distant recurrence are lung, liver, bone, kidney, brain, and bone marrow.The most important factor for prognosis is the stage and grade of the thymic carcinoma. The 5-year and 10-year overall survival rates in patients with thymic carcinoma are 38% and 28%, respectively.[2] The subtypes squamous cell carcinoma, mucoepidermoid carcinoma, and basaloid carcinoma have a better prognosis than other histological subtypes. There are no reported cases of complications regarding the carcinoma by itself. Most complications occur during surgery and biopsy. The most important factor for prognosis is the stage and grade of the thymic carcinoma. The 5-year and 10-year overall survival rates in patients with thymic carcinoma are 38% and 28% respectively. The most common differential diagnosis of thymic carcinoma is thymoma, which is the most common pathology of the thymus. Thymic carcinoma must be differentiated from other mediastinal masses such as germ cell tumors, lymphoma, thyroid tumors, and metastatic carcinoma to mediastinal lymph nodes. Thymic malignancies are among the most common mediastinal primary tumors with up to 50% of anterior mediastinal masses proving to be of thymic descent. Invasive thymomas and thymic carcinomas are relatively rare tumors, which together represent about 0.2% to 1.5% of all malignancies. Thymic carcinoma are rare and have been reported to account for only 0.06% of all thymic neoplasms. The risk of thymic carcinoma increases with age. Thymic carcinomas are generally considered indolent tumors due to long recurrence intervals (median of 68 months). Overall, for patients diagnosed with a resectable thymic tumor, 16% of them will recur after radical resection, either through local pleural or ganglionar recurrence or through distant metastatic spread.The most common sites of distant recurrence are lung, liver, bone, kidney, brain, and bone marrow.

The staging of thymic carcinoma is based on the Masoka and GETT staging system.^[8]

Symptoms of thymic carcinoma include dull chest pain, cough, dyspnea, and constitutional symptoms.

The physical examination plays a limited role in the diagnosis of thymic carcinoma.

There are no diagnostic lab findings associated with thymic carcinoma.

Chest x ray may be helpful in the diagnosis of thymic carcinoma.

Chest CT scan may be helpful in the diagnosis of thymic carcinoma. On CT scan of the chest, thymic carcinoma is characterized by lobulated mass with irregular borders, heterogeneous attenuation and mediastinal fat invasion with areas of necrosis, haemorrhage, calcification, or cyst formation.Large and highly aggressive anterior mediastinal mass. Areas of necrosis, haemorrhage, calcification, or cyst formation Aross invasion of contiguous mediastinal structures and wide spread to involve distant intrathoracic sites. High incidence of extrathoracic metastases Lobulated mass with irregular borders, heterogeneous attenuation, and mediastinal fat invasion. Pleural and pericardial effusion might also be seen on CT. Thymic carcinoma is singnificantly larger than thymoma on chest CT scan.

Chest MRI scan may be diagnostic of thymic carcinoma. Findings on chest MRI suggestive of thymic carcinoma include isointense to slightly hyperintense signal compared to muscle on T1 weighted image and heterogeneous signal on T2 weighted image. On T1 weighted image with godalinum contrast, linear regions of enhancement may be observed coursing through the mass, which are thought to represent fibrous septae.^[9]

Other imaging studies for thymic carcinoma include FDG PET scan. The standarized uptake value (SUV) in the FDG PET is much higher for the thymic carcinoma than thymoma, with a high sensitivity (84.6%) and specificity (92.3%).^[10][11]

Other diagnostic studies for thymic carcinoma include immunohistochemistry.

The predominant therapy for thymic carcinoma is surgical resection. Adjunctive cisplatin-basedchemotherapy may be required.^[12]

Surgery is the mainstay of treatment for thymic carcinoma.^[12]

There is no established method for prevention of thymic carcinoma.

There are no secondary preventive measures available for thymic carcinoma.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

The thymic epithelial tumor staging system was initially proposed by Bergh and his colleagues in 1978,modified by Wilkins and Castleman in 1979, and further developed by Masaoka et al. in 1981.

• Staging of thymic epithelial tumors was initially proposed by Bergh and his colleagues in 1978.^[1]
• Staging of thymic epithelial tumors was modified by Wilkins and Castleman in 1979.^[2]
• It went through further development by Masaoka et al. in 1981.^[3][4]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Thymic carcinomas may be classified according to a histological grading system into either low grade subtypes or high grade subtypes.^[1]. Primary thymic carcinomas are rare malignant neoplasms of the mediastinum, and combined thymic carcinomas are even less common. Although tumor stage is the single most important prognostic factor in thymoma, a combination of stage and histologic subtype should be considered in predicting survival.

• Thymic carcinomas may be classified according to a histological grading system into either low grade subtypes or high grade subtypes, which include:^[1]

• Squamous cell carcinoma:

• • This subtype of thymic carcinoma is the most common and exhibits atypia with a clear-cut aspect of keratinization with keratin pearls as seen in squamous cell carcinomas.
  • Squamous cell carcinoma lack of capsule and presents with necrosis and hemorrhage.

• Basaloid carcinoma:

• • This subtype consists of solid lobules of tumor cells with marginal palisading, without keratinization and a basophilic pattern due to an elevated nuclear:cytoplasmic ratio.

• Mucoepidermoid carcinoma:

• • The characteristic features for this rare subtype is the presence of squamous cells and mucus producing cells, with moderate nuclear atypia.
  • It has a mucinous macroscopic appearance.

• Lymphoepithelioma-like carcinoma:
  • The morphology of this subtype resembles the nasopharingeal lymphoepitelioma, with syncytial growth of undifferentiated malignant cells.

• Sarcomatoid carcinoma (carcinosarcoma):
  • It is also known as spindle cell thymic carcinoma, is an infiltrative neoplasm with large areas of coagulative necrosis and without a capsule.
  • It is an uncommon tumor that affects patients between 40-80 years old.

• Clear cell carcinoma:
  • Consist of cells with minimal nuclear atypia with a characteristic lucent cytoplasm and a lobulated architecture without sinusoidal vasculature (in contrast with the renal clear cell carcinoma)

• Papillary adenocarcinoma:
  • It has a tubulopapillary pattern growth with cuboidal cells and psammoma bodies may be present.
  • Type A thymoma may be the origin of this subtype of carcinoma due an expression of malignant transformation.

• Carcinoma with t(15;19) translocation:
  • It is an aggressive tumor with a translocation t(15;19)(q13:p13.1 ) that has the characteristic presence of undifferentiated cells with high mitotic activity and squamous morphology.

• Neuroendocrine Carcinomas:
  • The neuroendocrine thymic carcinomas are classified in 4 categories: typical, atypical, small cell, and large cell carcinomas.
    • The typical and atypical are categorized as well differentiated neuroendocrine carcinomas, and the small cell and large cell carcinomas are categorized as poorly differentiated.

• The table below lists the histological classification of neuroendocrine carcinomas:^[2]

HPF: High power field, SCNEC: Small cell neuroendocrine carcinoma, NEC: Neuroendocrine carcinoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

The thymic carcinoma is a tumor of the thymic epithelium, but it is associated with a lack of immature lymphocytes and often presents with a more invasive or metastatic disease.^[1] The pathophysiology of thymic carcinoma depends on the histological subtype. On microscopic histopathological analysis, thymic carcinoma is divided into squamous cell carcinoma, basaloid carcinoma, mucoepidermoid carcinoma, lymphoepithelioma-like carcinoma, sarcomatoid carcinoma (carcinosarcoma), clear cell carcinoma, papillary adenocarcinoma, carcinoma with t(15;19) translocation, neuroendrocrine carcinomas, undifferentiated carcinoma, and combined thymic epithelial tumors.^[2] Thymic carcinoma has not been reported in association with myasthenia gravis, in contrast with thymoma^[3]

• The thymic carcinoma is a tumor of the thymic epithelium, but it is associated with a lack of immature lymphocytes and often presents with a more invasive or metastatic disease.^[1]
• In contrast to thymoma, thymic carcinoma has not been reported in association with myasthenia gravis.

• Development of thymic carcinoma is the result of multiple genetic mutations.^[3]
• Genetic mutations involved in the pathogenesis of thymic carcinoma include:

• Gain of chromosome 1q, 17q, and 18
• Deletion of chromosome 3p, 6, 13q, 16q, and 17p

• Paraneoplasic syndromes has been reported among patients with thymic cancer (neuroendocrine subtype), however the syndrome is not as common as with thymoma patients.

On microscopic histopathological analysis, characteristic findings of thymic carcinoma are:

• Cytologically malignant – variable morphology
• +/-Squamous differentiation

• CD5 +ve (90% of cases)
• CD117 +ve (87% of cases)
• CD7 +ve
• TTF-1 -ve

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

The cause of thymic carcinoma has not been identified.

The cause of thymic carcinoma has not been identified.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

The most common differential diagnosis of thymic carcinoma is thymoma, which is the most common pathology of the thymus. Thymic carcinoma must be differentiated from other mediastinal masses such as germ cell tumors, lymphoma, thyroid tumors, and metastatic carcinoma to mediastinal lymph nodes.^[1]

Comparison between thymoma and thymic carcinoma:^[1]

• Besides the thymoma, it is also important to differentiate thymic carcinoma from:

• Primary mediastinal lymphoma
• Mediastinal germ cell tumor
• Metastasis of the mediastinum by a bronchogenic carcinoma
• Neuroendocrine tumors
• Germ cell tumors
• Lymphomas
• Stromal tumors
• Tumor-like lesions (such as true thymic hyperplasia)
• Thymic cysts
• Metastatic tumors
• Lung cancer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: , Marjan Khan M.B.B.S.[2]

The prevalence of thymic carcinoma is approximately 0.00006 per 100,000 individuals worldwide. Males are more commonly affected with thymic carcinoma than females. The male to female ratio is approximately 3 to 1. It is more common in Asians and African Americans than in Caucasians. Thymic malignancies are relatively rare in the range of 0.2% to 1.5% of all malignancies or 0.13 per 100,000 person-years in the United States. Thymic malignancies are among the most common mediastinal primary tumors with up to 50% of anterior mediastinal masses proving to be of thymic descent. Invasive thymomas and thymic carcinomas are relatively rare tumors, which together represent about 0.2% to 1.5% of all malignancies. Thymic carcinoma are rare and have been reported to account for only 0.06% of all thymic neoplasms. The risk of thymic carcinoma increases with age. Thymic carcinoma is uncommon in children, it is seen more often in middle-aged adults. Thymic carcinoma commonly affects individuals between 40-60 years of age.

• Thymic malignancies are relatively rare in the range of 0.2% to 1.5% of all malignancies or 0.13 per 100,000 person-years in the United States
• Thymic malignancies are among the most common mediastinal primary tumors with up to 50% of anterior mediastinal masses proving to be of thymic descent.
• Invasive thymomas and thymic carcinomas are relatively rare tumors, which together represent about 0.2% to 1.5% of all malignancies.^[1]
• Thymic carcinoma are rare and have been reported to account for only 0.06% of all thymic neoplasms.

• The risk of thymic carcinoma increases with age.^[1]
• Thymic carcinoma is uncommon in children, it is seen more often in middle-aged adults.
• Thymic carcinoma commonly affects individuals between 40-60 years of age.

• Males have a slightly higher risk of developing thymic malignancies than females, and the risk rises with age, reaching a peak in the seventh decade of life, which is in direct contrast to the progressive involution of the thymus with age.
• Males are more commonly affected with thymic carcinoma than females. The male to female ratio is approximately 3 to 1.

• It is more common in Asians and African Americans than in Caucasians.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

There are no established risk factors for thymic carcinoma.^[1]

There are no established risk factors for thymic carcinoma.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]

Thymic carcinomas are generally considered indolent tumors due to long recurrence intervals (median of 68 months). The most common sites of distant recurrence are lung, liver, bone, kidney, brain, and bone marrow.^[1] The most important factor for prognosis is the stage and grade of the thymic carcinoma. The 5-year and 10-year overall survival rates in patients with thymic carcinoma are 38% and 28%, respectively.^[2] The subtypes squamous cell carcinoma, mucoepidermoid carcinoma, and basaloid carcinoma have a better prognosis than other histological subtypes. There are no reported cases of complications regarding the carcinoma by itself. Most complications occur during surgery and biopsy. The most important factor for prognosis is the stage and grade of the thymic carcinoma. The 5-year and 10-year overall survival rates in patients with thymic carcinoma are 38% and 28% respectively. Thymic malignancies are among the most common mediastinal primary tumors with up to 50% of anterior mediastinal masses proving to be of thymic descent. Invasive thymomas and thymic carcinomas are relatively rare tumors, which together represent about 0.2% to 1.5% of all malignancies.

• Thymic carcinomas are generally considered indolent tumors due to long recurrence intervals (median of 68 months).
• Overall, for patients diagnosed with a resectable thymic tumor, 16% of them will recur after radical resection, either through local pleural or ganglionar recurrence or through distant metastatic spread.
• The most common sites of distant recurrence are lung, liver, bone, kidney, brain, and bone marrow.^[1]

• There are no reported cases of complications regarding the carcinoma by itself.
• Most complications occur during surgery and biopsy.

• The most important factor for prognosis is the stage and grade of the thymic carcinoma.
• The 5-year and 10-year overall survival rates in patients with thymic carcinoma are 38% and 28% respectively.^[2]
• The subtypes squamous cell carcinoma, mucoepidermoid, and basaloid carcinoma have a better prognosis than other histological subtypes.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2]

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• A dose of 60-70 Gy should be given to patients with unresectable disease.

• For adjuvant treatment, the radiation dose consists of 45-50 Gy for clear/close margins and 54 Gy for microscopically positive resection margins. A total dose of 60 Gy and above should be given to patients with gross residual disease (similar to patients with unresectable disease), when conventional fractionation (1.8 to 2.0 Gy per daily fraction) is applied.

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