Thymic tumours

Introduction

Tumours derived from the thymus (thymomas) comprise approximately 20% of all mediastinal tumours and are the most common tumour in the anterior mediastinum. Thymomas occur at any age but are rare before the age of 20 and peak between 40-60 years. The incidence varies somewhat in different countries with high values in the Far East. The average in Europe is around 0.5 new cases per year per 100 000. Aetiology of these tumours is unknown; a possible relation to Epstein-Barr virus infection has not been proven.

Pathology

Most thymomas are slow-growing 'low-grade' malignant tumours. It is believed that they derive from epithelial elements, but the tumours retain the capacity for production of T cells. The T cells are generally of normal phenotype. According to the relative abundance of epithelial and lymphocytic cells, histological subgroups have been described:

♦ Epithelial

♦ Lymphocytic

♦ Mixed or lympho-epithelial type

These cellular characteristics have no clear influence on prognosis. In contrast, the gross appearance of the tumour is related to clinical prognosis. The presence or absence of an intact capsule is of prognostic importance and local invasiveness remains the most consistent factor in predicting outcome.

The metastatic potential of thymomas is difficult to assess on the basis of histology and cytological features.

A 'benign' thymoma has been defined as a tumour that is well encapsulated and does not invade adjacent mediastinal structures; 50-65% of thymomas fit this definition. The differentiation between benign and malignant thymoma is, however, difficult and thymomas should in general be regarded as potentially malignant. In all cases where residual tumour is left after surgery, adjuvant therapy should be considered.

Presentation and clinical features

♦ Produce paraneoplastic syndromes

♦ 70% associated with an immunological phenomenon

♦ Antibodies target acetylcholine receptor causing myasthenia gravis

♦ Myasthenia occurs in 10-15% of patients with thymoma

♦ 10-25% of patients with myasthenia have a thymoma

♦ Red-cell aplasia occurs in 5% of thymomas

♦ 30-50% of patients with red-cell aplasia have a thymoma

♦ In 30%, low platelets or low white-cell count occur

♦ Hypogammaglobulinaemia occurs in 5-10% of patients with thymoma

♦ 10% of patients with hypogammaglobulinaemia have a thymoma Many of the patients with autoimmune disorders belong to the older age group and removal of the thymoma results in remission in only approximately one-third of these patients. As these symptoms can arise also in small tumours, the possibility of curative treatment may be better when paraneoplastic syndromes prevail. In the absence of paraneoplastic effects, thymomas are often large before they give rise to local symptoms such as cough, dyspnoea, dysphagia, stridor, and chest pain. Superior vena cava obstruction (SVCO) may result.

Thymomas are most commonly located within the anterior mediastinum but half will extend to the superior mediastinum. CT or MR scanning is necessary to:

♦ Direct surgical intervention

♦ Plan radiotherapy treatment

♦ Evaluate treatment response

♦ Monitor recurrence of disease

Treatment and staging

Surgery is the treatment of choice for localized disease. Median ster-notomy is the preferred incision for thymectomy, since it provides excellent exposure of the thymoma and the adjacent organs. The staging of disease is based on the surgical findings as well as radiology: Stage I: tumour confined within intact capsule Stage II: pericapsular growth into the mediastinal fat tissue Stage III: invasive growth into the surrounding organs Stage IV: disseminated disease The most effective therapy of thymoma is complete removal, and modern techniques have made it possible to resect even invasive thy-momas. The superior vena cava can be removed and reconstructed and parts of the lung or pleura can be resected when required.

In Stage I disease adjuvant treatment is not applied. In all other cases, additional antineoplastic treatment is recommended after surgery. In local disease with or without residual tumour, radiotherapy is recommended in doses of 50-60 Gy given in 20-30 fractions. The treatment is delivered via a linear accelerator often using an anterior and two oblique fields, minimizing the dose to the normal lung and the spinal cord.

The reported series are not big enough to have sufficient statistical power to show significant survival benefits of adjuvant treatment. Radically resected invasive thymomas have 5- and 10-year survival rates of 80% and 73% respectively. This should be compared with the results after subtotal resection followed by radiotherapy—59% and 54%. The rate of recurrence is 3% with Stage 1,13% with Stage II, 27% with Stage III disease, and 54% with Stage IV disease.

Paraneoplastic effects such as myaesthenia gravis improve after thymectomy in 30-50% of cases. Patients with persistent myaesthenia require medical treatment with anticholinesterase agents and/or immunosuppressants.

Recurrent and metastatic thymoma should be treated with systemic treatment. The reported series are small, but a commonly used active regimen is cisplatin, doxorubicin, cyclophosphamide. The response rate with combination chemotherapy is 50-70%. This relatively high efficacy has given rise to Phase II studies of adjuvant chemotherapy and neo-adjuvant chemotherapy followed by surgery and radiation, with promising results.

Summary

The contemporary standard of treatment of thymoma is radical surgery whenever possible. Total resection alone is adequate therapy for Stage I thymoma. Adjuvant therapy should be used for local disease with demonstration or suspicion of invasion. Locally advanced, relapsing, or disseminated disease should be treated with combination chemotherapy including corticosteroids. Cisplatin-based regimens are recommended.

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