Thymic carcinoma

by Jason Wasserman MD PhD FRCPC
September 20, 2024

Thymic carcinoma is a rare type of cancer that starts in the thymus, a small organ located in the chest that produces T cells and plays a role in the immune system. Unlike thymomas, thymic carcinomas are more aggressive and have a higher tendency to spread to other parts of the body.

What is the difference between thymic carcinoma and thymoma?

The main difference between thymic carcinoma and thymoma is that thymomas tend to grow slowly and are less likely to spread to other body parts. Thymic carcinoma, on the other hand, is a high grade malignant (cancerous) tumour that behaves more like other cancers by invading nearby tissues and metastasizing (spreading) to distant parts of the body. Thymic carcinomas are also more likely to show abnormal cells under the microscope than thymomas.

What are the symptoms of thymic carcinoma?

Symptoms of thymic carcinoma may include chest pain, cough, shortness of breath, and difficulty swallowing, often caused by the tumour pressing on nearby structures. Some patients may experience symptoms related to autoimmune diseases, though this is less common than in thymomas.

What causes thymic carcinoma?

The exact cause of thymic carcinoma is unknown. Genetic mutations and other factors may play a role, but no specific cause has been identified.

What medical conditions are associated with thymic carcinoma?

Unlike thymomas, thymic carcinomas are less likely to be associated with autoimmune conditions like myasthenia gravis. However, in some cases, patients may still present with paraneoplastic syndromes, which are symptoms caused by the immune system reacting to the tumour.

How is the diagnosis of thymic carcinoma made?

Thymic carcinoma is diagnosed by examining a tumour sample under a microscope. The tumour cells in thymic carcinoma typically look more abnormal than those in thymoma, with features like increased mitotic activity and necrosis (dead tissue). Imaging studies like CT scans or MRIs are used to evaluate the size and extent of the tumour.

What does invasion mean?

Invasion refers to the tumour spreading beyond the thymus into surrounding tissues, such as the lungs or the pericardium (the tissue lining the surface of the heart). This is important because invasive tumours are more difficult to treat and have a higher risk of recurrence. Invasion also often requires more aggressive treatments, including surgery combined with radiation or chemotherapy.

Histologic subtypes of thymic carcinoma

A histologic subtype is a way to classify cancer based on how the tumour cells look under a microscope. Thymic carcinoma has many subtypes, each with different features and behaviours. Most of these subtypes are rare, but understanding them helps doctors predict how the cancer will act and the most effective treatments. Below, we’ll explain the most common subtypes of thymic carcinoma, highlighting what makes each unique and how they might affect your health.

Squamous cell carcinoma of the thymus

Squamous cell carcinoma of the thymus is the most frequent subtype of thymic carcinoma. This tumour consists of squamous cells, which are flat, skin-like cells that may form keratin. Under the microscope, these cells often appear abnormal and may have large, prominent nucleoli. Immunohistochemical staining reveals that the tumour cells are positive for CD5, CK5, p40 and p63. Clinically, squamous cell carcinoma of the thymus tends to grow more slowly than other subtypes, and patients diagnosed at an early stage generally have a better prognosis, particularly if the tumour can be entirely removed with surgery.

Basaloid carcinoma of the thymus

Basaloid carcinoma of the thymus is a rarer and more aggressive subtype. Microscopically, the tumour comprises small, dark cells arranged in nests or cords, with round nuclei and scant cytoplasm. This gives the tumour its characteristic basaloid appearance. Basaloid carcinomas often express p63 on immunohistochemistry, but they are distinguished by their higher degree of aggressiveness compared to other subtypes. Clinically, these tumours are more likely to invade surrounding structures and metastasize, which results in a poorer prognosis, especially in advanced cases.

Lymphoepithelial carcinoma of the thymus

Lymphoepithelial carcinoma of the thymus is another rare subtype, closely resembling nasopharyngeal carcinoma. This tumour is notable for the dense infiltrate of lymphocytes surrounding sheets of malignant epithelial cells. Sometimes, there may be an association with Epstein-Barr virus (EBV), and testing for EBER can help confirm the diagnosis. Immunohistochemical staining often shows positivity for p63, similar to other thymic carcinomas. Lymphoepithelial carcinoma is an aggressive tumour with a high likelihood of spreading to distant parts of the body, contributing to a generally poor prognosis.

Clear cell carcinoma of the thymus

Clear cell carcinoma of the thymus is named for the clear appearance of the tumour cells, which results from the accumulation of glycogen in the cytoplasm. These cells are arranged in nests or sheets, and the clear cytoplasm makes them stand out under the microscope. Immunohistochemically, clear cell carcinomas can express markers like CD5 and CD117, typical of thymic carcinomas. Clear cell carcinoma tends to behave aggressively, and the prognosis is often poor, particularly when the tumour is diagnosed at an advanced stage.

Thymic carcinoma with adenoid cystic carcinoma-like features

Thymic carcinoma with adenoid cystic carcinoma-like features is a rare subtype that shares histologic similarities with adenoid cystic carcinoma, a tumour more commonly seen in the salivary glands. Microscopically, this subtype displays a cribriform (sieve-like) pattern, with uniform, round tumour cells arranged in circular or tubular structures. Immunohistochemical staining often shows positivity for CD117. Clinically, this subtype tends to be aggressive, with a high risk of local recurrence and distant metastasis, leading to a poorer prognosis than more common thymic carcinoma subtypes.

Thymic carcinoma with neuroendocrine differentiation

Thymic carcinoma with neuroendocrine differentiation is an uncommon variant showing features of neuroendocrine tumours, such as positive staining for markers like chromogranin and synaptophysin. These tumours often comprise small or intermediate-sized cells arranged in nests or rosettes. Neuroendocrine differentiation is associated with a more aggressive clinical course, and these tumours are prone to metastasizing, resulting in a generally poor prognosis.

Low grade papillary adenocarcinoma of the thymus

Low grade papillary adenocarcinoma of the thymus is a rare, slow-growing tumour subtype. Under the microscope, it shows papillary structures lined by cuboidal or columnar epithelial cells, with relatively mild atypia. Immunohistochemical staining may reveal positivity for markers such as CD117. This subtype generally has a better prognosis than more aggressive forms of thymic carcinoma due to its slow growth and limited potential for invasion.

Adenocarcinoma NOS (not otherwise specified) of the thymus

Adenocarcinoma NOS (not otherwise specified) of the thymus is a rare subtype characterized by glandular differentiation. The tumour forms irregular glandular structures lined by atypical epithelial cells. Immunohistochemical markers such as CD117 may be positive, but the diagnosis is primarily based on histologic features. The prognosis depends on the tumour’s stage at diagnosis, with early-stage cases having a better outcome.

Adenosquamous carcinoma of the thymus

Adenosquamous carcinoma of the thymus is composed of both glandular and squamous components, each with distinct histologic characteristics. Microscopically, the tumour shows squamous differentiation (similar to squamous cell carcinoma) and areas forming gland-like structures (similar to adenocarcinoma). The prognosis for adenosquamous carcinoma is generally poorer due to its aggressive behaviour and the potential for metastasis.

Sarcomatoid carcinoma of the thymus

Sarcomatoid carcinoma of the thymus is a rare, aggressive subtype that shows features of both carcinoma and sarcoma (a type of cancer that starts in connective tissues). Microscopically, it contains spindle-shaped cells and may have areas resembling a sarcoma. Immunohistochemical staining for epithelial markers like cytokeratin helps confirm the diagnosis of a sarcomatoid carcinoma. Sarcomatoid carcinomas tend to behave very aggressively, and the prognosis is poor.

Undifferentiated carcinoma of the thymus

Undifferentiated carcinoma of the thymus refers to a high grade tumour with no clear differentiation into specific cell types. Microscopically, the tumour cells are pleomorphic, meaning they vary in size and shape and often have high mitotic rates. Immunohistochemical staining may reveal positivity for CD117 or p63, but the lack of differentiation makes it difficult to classify. Undifferentiated carcinomas have a poor prognosis due to their aggressive behaviour and a high potential for metastasis.

What is the Masaoka–Koga system and how is it applied to thymic carcinoma?

The Masaoka–Koga system is used to stage thymic carcinomas based on how far the tumour has spread.

• Stage I: The tumour is confined to the thymus.
• Stage II: The tumour has grown into nearby tissues.
• Stage III: The tumour invades nearby organs.
• Stage IV: The tumour has spread to distant organs.

Thymic carcinomas are often diagnosed at more advanced stages, making treatment more challenging.

What is the prognosis for people with thymic carcinoma?

The prognosis for people with thymic carcinoma depends on the stage at diagnosis. Early-stage thymic carcinomas that are completely removed by surgery have a better prognosis. However, advanced-stage tumours that have invaded nearby tissues or spread to distant organs have a poorer prognosis. Treatment usually involves a combination of surgery, radiation, and chemotherapy.