The thymic gland is the site of many neoplasms — thymomas, lymphomas, Hodgkin’s granulomas, and other less common tumors. Thymoma, the most common neoplasm of the thymic gland, may be difficult to differentiate from lymphoma even with an adequate biopsy.
Thymoma classified according to predominant cell type into lymphocytic, epithelial and lymphoepithelial (50%) varieties. Spindle cell tumor, which is sometimes associated with red cell aplasia, is considered among the epithelial tumors. Histologic subtypes, however, classically have not had prognostic significance. Recent reports demonstrate that aneuploidy and the presence of epithelial cells resembling thymic carcinoma have adverse prognostic implications. The histologic classification of thymomas is currently being revised.
Malignant thymoma cannot be determined by the histologic appearance of the tumor alone. Evidence of local invasion grossly or microscopically defines thymoma as malignant. Thymoma is staged according to the Masoaka staging system as set forth in the accompanying box.
Clinical Findings and Signs of thymoma
Fifty percent of thymomas are first identified in an asymptomatic patients on a chest x-ray obtained for another purpose. Symptomatic patient may present with chest pain, dysphagia, myasthenia gravis, dyspnea, superior vena caval syndrome.
CT scans are useful in making the diagnosis in equivocal cases and in assessing the extent of the lesion. MRI is occasionally helpful to assess vascular invasion.
Definitive diagnosis of thymoma is based on histologic study of a tissue sample usually after excisional biopsy or complete resection has been performed. Small, well-encapsulated anterior mediastinal masses should not be biopsied, as the procedure penetrates the tumor’s capsule and can lead to tumor seeding and recurrence and may jeopardize the chance of cure of an early-stage thymoma.
Treatment of malignant thymomas
The treatment of choice is total thymectomy. The operation is usually performed through a median sternotomy. Posterior lateral thoracotomy as well as “clamshell” (bilateral anterior thoracotomy) or “trapdoor” incisions offers excellent exposure for resection of locally advanced thymomas. Cervical incisions, while useful for thymectomy for benign conditions (myasthenia, etc), have a limited role in the surgical treatment of thymoma. A careful but aggressive resection should be performed for stage III lesions when they can be removed completely without sacrificing vital structures. Postoperative radiotherapy is indicated for invasive thymoma (stage II and III).
En bloc resection and associated pericardium, pleura, lung (including lobectomy or extrapleural pneumonectomy) or great vessel (aorta, superior vena cava) reconstruction is warranted when resection is possible. Incomplete resections or debulking procedures do not benefit patients. Administration of neoadjuvant therapy with platinum-based chemotherapy will frequently shrink the tumor and allow subsequent complete resection. Recently, larger thymomas (> 5–6 cm) with evidence of probable invasion are being treated with combined-agent induction chemotherapy. Response rates exceed 70%, and complete resection rates are facilitated.
Large bulky lesions with clinically apparent gross invasion of local structures, pleura, lung should be biopsied to confirm histologically the diagnosis of thymoma. Neoadjuvant chemotherapy with platinum-based regimens has been effective in shrinking bulky high-grade thymomas, thus allowing for complete resection and greater chances of cure.
Anticholinesterase drugs (eg, neostigmine bromide) are given as initial treatment to patient with myasthenia gravis. Corticosteroids may be given in selected cases, but a high incidence of side effects makes them unsuitable for more liberal use. Early thymectomy is now recommended for patient with symptomatic myasthenia gravis whether or not a thymoma is suspected. The course of the disease is usually improved, and subsequent development of a malignant thymoma is eliminated. Thymectomy may be postponed in the occasional patient with mild disease well controlled by anticholinesterase therapy.
Following thymectomy, about 75% of patient with myasthenia are improved and 30% achieve complete remission. Younger patients benefit more from thymectomy than do those over age 40 years, but a positive effect also accrues to the latter group. Recently video-assisted thymectomy for myasthenia patients has resulted in reduced length of stay, decreased blood loss and decreased pain in comparison with more traditional partial sternal splitting procedures.
The rates of complication and death with thymectomy are low except when there are extensive tumors. Respiratory care of patient with myasthenia in the immediate postoperative period now presents little difficulty because of the availability of anticholinesterase drugs.
The stage and histologic type of the tumor are the main determinants of survival after thymectomy, though the presence of myasthenia no longer has an adverse effect.
This tumor is a rare variant (< 15%) of thymic lesions and is histologically and biologically quite different from invasive or malignant thymoma. Thymic carcinomas tend to be very invasive and difficult to resect completely. Unfortunately, even in the setting of complete resection, recurrence is common both locally and at distant sites. Still, when at all possible, an aggressive combined-modality approach (induction chemotherapy, resection, and postoperative chemoradiotherapy) should be employed. Typically, these are young men (< age 50 years) with an otherwise excellent performance status. While a response to induction therapy and complete resection will provide a significant disease-free interval, long-term survival is still unlikely. Better systemic agents and a molecular understanding of this cancer holds hope for significant improvements in cure rates.