Thymoma

Thymoma is classically seen in a middle-aged adult with Myasthenia Gravis presenting with an anterior mediastinal mass on imaging, which histologically demonstrates spindle cells with admixed lymphocytes.

Description

Thymomas are the most common primary tumour of the anterior mediastinum, arising from the epithelial cells of the thymus. They are typically slow-growing, encapsulated tumours and can be associated with a range of paraneoplastic syndromes, most notably myasthenia gravis. It is considered malignant and may metastasise at any stage.

Pathogenesis

The pathogenesis of thymoma is poorly understood. It is believed to occur due to neoplastic transformation of thymic epithelial cells, resulting in a proliferation of thymic cells and lymphocytes. The disease has been associated with genetic abnormalities, including mutations in GTF2I and alterations in chromosome 6.

Subtypes

The World Health Organisation (WHO) classifies thymomas into the following types based on the morphology of the epithelial cells and the relative proportion of lymphocytes:

• Type A (spindle cell or medullary thymoma): Characterised by a predominance of epithelial cells that are spindle-shaped or oval, with a sheet-like architecture. These are relatively uncommon.
• Type AB (mixed thymoma): These demonstrate both type A and type B characteristics, with areas rich in lymphocytes (B component) and areas where spindle cells predominate (A component). This subtype is the most common.
• Type B1 (lymphocyte-rich thymoma): Resembles normal functional thymus, with scattered epithelial cells within a dense background of immature T lymphocytes. These are less common.
• Type B2 (cortical thymoma): Characterised by a denser population of epithelial cells, with less resemblance to normal thymus. Lymphocytes are still present but are less prominent.
• Type B3 (epithelial-rich thymoma): This subtype is composed predominantly of epithelial cells, with only sparse lymphocytes. These resemble squamous cell carcinomas and are the least common type.

Epidemiology, Risk Factors & Associations

• Middle age (peak incidence in the 5th decade)

Associations include:

• Strong association with Myasthenia Gravis (10-15% of MG patients have a thymoma, and up to 50% of thymoma patients have MG)
• 50% of patients with pure red cell aplasia have a thymoma, and 5% of patients with a thymoma have pure red cell aplasia.
• 5% of patients with hypogammaglobulinaemia have a thymoma, and 10% of patients with a thymoma have hypogammaglobulinaemia.
• Systemic lupus erythematosus (SLE) and rheumatoid arthritis
• Thymoma patients have an increased risk of developing non-thymic cancers.
• Graves disease, an autoimmune disorder that causes hyperthyroidism.
• Pernicious anaemia
• Dermatomyositis-polymyositis, a group of diseases involving inflammation of the muscles
• Cushing syndrome due to ectopic ACTH production by the tumour.

Clinical Features

• Many patients are asymptomatic and tumours are found incidentally on imaging
• Chest pain, cough, dyspnea
• Systemic symptoms of fatigue and weight loss
• Autoimmune phenomena: Myasthenia Gravis, pure red cell aplasia, hypogammaglobulinemia

Complications

• Locally invasive disease: involvement of adjacent structures such as the lung, pericardium, and great vessels
• Distant metastases are rare, but can occur to pleura, bone, liver, and lymph nodes

Pathological Features

Histopathology

• Macroscopic: Encapsulated mass with a smooth or lobulated surface, ranging in size from a few cm to over 10 cm
• Microscopic: Mixture of neoplastic epithelial cells and non-neoplastic lymphocytes, with variation in cellularity, cytologic atypia, and architecture among subtypes

Radiological Features

General Features

• Anterior mediastinal mass.
• Benign thymomas are typically well-defined, smooth or lobulated borders; typically unilateral (involving one lobe of the thymus)¹; cystic changes and mild homogenous enhancement.
• Coarse intratumoural calcifications may be present (15-20%)
• Invasive thymoma demonstrates irregular infiltrative borders, elevated ipsilateral hemidiaphragm, pericardial or pleural nodular metastases. Egg-shell calcification may be seen.
• Absent fat planes between thymoma and mediastinum does not necessarily reflect invasion
• Contrast-enhanced CT is the modality of choice for evaluation.²
• MR usually reserved for further mass characterisation (solid vs cystic differentiation, evaluation of cystic or necrotic components, evaluation for enhancing intracystic septae within cystic lesions, and evaluation of subtle local invasion), iodine contrast contraindication (renal impairment or allergy) or for dose conservation (younger patients).

Normal imaging appearance of the thymus

The thymus normally appears as a triangular-shaped structure in the prevascular space, usually on the right. Begins to involute from 2 years of age and should not be present after 8 years of age. Does not exert mass effect on vascular or airway structures.

Its appearance on ultrasound and CT should be homogenous soft tissue with smooth microlobulated borders. On MRI, it usually demonstrates chemical shift artefact.

XR

• Frontal CXR:
  • Contour abnormality with widening of the mediastinum, can be located anywhere between thoracic inlet and cardiophrenic angle.
  • Silhouette sign – obscuration of cardiomediastinal contour suggests mass is located in the anterior mediastinum
  • Nodular thickening of anterior junction line
  • May exhibit calcification
  • Diaphragmatic elevation suggests paralysis secondary to phrenic nerve invasion.
  • Pleural nodules suggests drop metastases
  • Usually well-circumscribed. Spiculated margins suggests invasive thymoma.
• Lateral CXR:
  • Effacement of the retrosternal (prevascular) clear space.

CT

• Non-contrast: Well-defined, round or oval, homogeneously enhancing mass in the prevascular space. Typically unilateral. Low attenuation foci reflects necrosis or cystic change.
• C+ Arterial: Enhanced mass with heterogeneous attenuation due to necrosis, cystic change, or haemorrhage. Invasive thymoma demonstrates local invasion and pleural nodules.

MR

• T1: Low to intermediate signal intensity
• T2: High signal intensity, particularly in cystic change

NM

• PET FDG: Variable uptake, typically low to moderate

Grading and Staging

The Masaoka-Koga staging system is used for thymomas.

• Stage I: Completely encapsulated tumours
• Stage II: Microscopic or macroscopic invasion into the thymic fat or mediastinal pleura
• Stage III: Invasion into nearby organs
• Stage IV: Pleural or pericardial dissemination (IVA) or lymphogenous or hematogenous metastases (IVB).

Diagnosis

Diagnosis requires histological confirmation, typically obtained by surgical resection and biopsy.

Differential Diagnosis

• Thymic carcinoma: More aggressive, with higher stage at presentation and poorer prognosis. Imaging may demonstrate invasion of surrounding structures.
• Thymic hyperplasia: Often seen in association with autoimmune conditions. Usually enlarges symmetrically and does not contain cystic areas or calcification.
• Lymphoma: Usually a homogenously attenuating mediastinal mass, with calcification not usually seen unless there has been prior treatment. May be associated with lymphadenopathy and splenomegaly.
• Germ cell tumours: Often occur in younger patients. May demonstrate high levels of serum markers such as beta-HCG and AFP. Pleural metastases can also be seen.

Management

The primary treatment for thymoma is surgical resection. Adjuvant radiotherapy may be considered in cases of incomplete resection or advanced disease. Chemotherapy is reserved for metastatic disease or as neoadjuvant treatment in locally advanced tumours.

References

1. Strange, C.D., Ahuja, J., Shroff, G.S., Truong, M.T. and Marom, E.M., 2022. Imaging evaluation of thymoma and thymic carcinoma. Frontiers in Oncology, 11, p.810419. ↩︎
2. Li, H.R., Gao, J., Jin, C., Jiang, J.H. and Ding, J.Y., 2019. Comparison between CT and MRI in the diagnostic accuracy of thymic masses. Journal of Cancer, 10(14), p.3208. ↩︎