Thymic carcinoma, a rare malignant anterior mediastinal tumour in adults, typically presents as an invasive mass with areas of necrosis and haemorrhage on imaging.
Description
Thymic carcinoma is a malignant neoplasm arising from the epithelial cells of the thymus. It is characterised by its aggressive nature and poor prognosis. Unlike thymomas, which are typically encapsulated, thymic carcinomas tend to invade adjacent structures and metastasise.
Pathogenesis
The pathogenesis of thymic carcinoma is not well understood due to its rarity. However, genetic alterations and Epstein-Barr virus infection have been implicated in some cases. It is postulated that tumourigenesis involves a multi-step process, possibly starting from thymic epithelial cells, leading to thymoma and eventually thymic carcinoma.
Subtypes
Thymic carcinomas are histologically diverse and can mimic any form of carcinoma seen elsewhere in the body. They are classified by the World Health Organisation (WHO) into several subtypes based on histological characteristics, including:
- Squamous cell carcinoma: This is the most common subtype, representing about 70% of thymic carcinomas. These tumours demonstrate keratinisation and intercellular bridges. Squamous cell carcinomas are often locally invasive.
- Basaloid carcinoma: A rare subtype, these tumours consist of small basaloid cells often exhibiting a palisading arrangement.
- Mucoepidermoid carcinoma: These are characterised by a mixture of squamous cells, mucus-secreting cells, and intermediate cells. High-grade tumours have greater cytologic atypia and fewer mucus-secreting cells.
- Lymphoepithelioma-like carcinoma: This subtype resembles undifferentiated nasopharyngeal carcinoma and has a dense lymphocyte-rich stroma.
- Neuroendocrine carcinomas: These can be further divided into small cell and large cell types, similar to neuroendocrine tumours seen in the lung. Small cell type neuroendocrine carcinomas are more likely to present with distant metastases
- Others: Rare variants include clear cell carcinoma, sarcomatoid carcinoma, and undifferentiated carcinoma.
Epidemiology, Risk Factors & Associations
- Thymic carcinoma is rare, representing only 1-4% of anterior mediastinal tumours.
- Most patients are adults, with a peak incidence in the fifth decade of life.
- It has a slight male predominance.
- Unlike thymoma, it is not associated with myasthenia gravis.
Clinical Features
Patients typically present with symptoms due to local invasion or metastasis. Symptoms may include chest pain, dyspnoea, cough, superior vena cava syndrome and hoarseness.
Complications
- Local invasion of surrounding structures such as the heart, great vessels, and lungs.
- Distant metastasis most commonly to the lungs, bones, and liver.
- Paraneoplastic syndromes such as pure red cell aplasia, hypogammaglobulinaemia, and others.
Pathological Features
Histopathology
- Macroscopic: Typically presents as a large, invasive, and poorly defined mass. Areas of necrosis and haemorrhage are often seen.
- Microscopic: Characterised by atypical epithelial cells with overtly malignant cytological features, including high mitotic activity and necrosis.
Radiological Features
General Features
- Typically demonstrates a lobulated anterior mediastinal mass with heterogeneous enhancement due to areas of necrosis and haemorrhage.
- Invades adjacent structures.
CT
- Non-contrast: Heterogeneous mass with areas of necrosis and calcification (seen in 20% of cases).
- C+ Arterial: Shows heterogeneous enhancement.
- C+ Venous: Persistent enhancement.
MRI
- T1: The tumour is typically isointense to muscle.
- T2: Heterogeneous, often hyperintense to muscle.
- T1 Gad+: Heterogeneous enhancement.
PET FDG
- Shows increased uptake due to high metabolic activity of the tumour.
Grading and Staging
The Masaoka-Koga staging system is the most widely used staging system for thymic malignancies, including thymic carcinoma, and is based on the extent of the tumour at the time of surgery. It comprises four stages with two substages:
- Stage I: The tumour is completely encapsulated.
- Stage II: The tumour invades through the capsule into surrounding fatty tissue or mediastinal pleura.
- IIa: Invasion into the mediastinal pleura
- IIb: Invasion into the pericardium
- Stage III: The tumour directly invades neighbouring organs (e.g., pericardium, great vessels, lung).
- Stage IV: The tumour has disseminated intrathoracically or intraperitoneally.
- IVa: Pleural or pericardial dissemination
- IVb: Lymphatic or haematogenous metastasis
It’s worth noting that thymic carcinoma is generally diagnosed at later stages compared to thymomas due to its aggressive nature.
Diagnosis
Diagnosis is made based on histological examination of a biopsy or surgical specimen, often with immunohistochemical staining.
Differential Diagnosis
- Thymoma: Typically presents as a well-defined, encapsulated mass and is associated with myasthenia gravis.
- Lymphoma: May also present as an anterior mediastinal mass but usually has a different clinical and imaging presentation.
Management
Management typically involves a multidisciplinary approach with surgery, radiation, and chemotherapy. The mainstay of treatment is complete surgical resection, but due to the invasive nature of thymic carcinoma, this is often not achievable.