A 44-year-old woman is found to have an incidental anterior mediastinal mass as revealed by a preemployment chest radiograph. The patient has no known medical problems, and she denies respiratory and gastrointestinal symptoms. On examination, she is found to have mild bilateral ptosis and no neck masses. The results of the cardiopulmonary examination are unremarkable, and there is no generalized lymphadenopathy. The neurologic examination reveals normal sensation and diminished muscle strength in all the extremities with repetitive motion against resistance. A CT scan of the chest reveals the presence of a 4.5-cm well-circumscribed solid mass in the anterior mediastinum.
What is the most likely diagnosis?
What is the best therapy?
ANSWERS TO CASE 41: Thymoma and Myasthenia Gravis
Summary: A 44-year-old woman has a 4.5-cm anterior mediastinal mass and symptoms suggestive of myasthenia gravis (MG).
• Most likely diagnosis: An incidentally identified thymoma in a patient with class IIA MG.
• Best therapy: The best treatment for thymoma is complete resection.
1. Know the pathogenesis and the medical management of MG.
2. Learn the role of thymectomy in the treatment of MG, with and without the presence of a thymoma.
3. Learn the strategies for diagnosing anterior mediastinal masses.
MG is a disorder of the neuromuscular junction resulting from autoimmune damage to the nicotinic cholinergic receptor. Symptoms include weakness that worsens after exercise and improves after rest. Other symptoms include ptosis, diplopia, dysarthria, dysphagia, and respiratory complications. MG is evidenced by history and physical examination and can be confirmed by provocative testing (the Edrophonium-Tensilon test). The Osserman classification is a commonly used system for characterizing the severity of MG (Table 41–1). Medical management of MG varies depending on the response of the patient, including the response to anticholinesterase drugs, glucocorticoids (prednisone), and immunosuppressive drugs (azathioprine, cyclophosphamide). Acute exacerbations or myasthenic crises are treated medically and with plasmapheresis. Thymectomy should be avoided during an acute crisis.
Table 41–1 • OSSERMAN CLASSIFICATION FOR SEVERITY OF MYASTHENIA GRAVIS
Thymomas are the most common mediastinal tumors, and thymomas are considered borderline malignant because of the potential for local invasion and systemic spread. MG is one of the immune disorders that can occur with thymomas. MG is identified in 30% to 50% of patients with thymoma, whereas 15% of myasthenic patients have thymoma. Pathologic staging of thymoma relies on both the surgical assessment at the time of resection and the microscopic evaluation (Table 41–2).
Table 41–2 • STAGING AND PROGNOSIS OF THYMOMA
Diagnostic sampling of anterior mediastinal masses suspected to be thymoma is usually unnecessary if the radiographic studies indicate a well-circumscribed mass within the thymus. Biopsy of anterior mediastinal masses may prove useful for patients in whom the diagnosis is not clear, in patients with very extensive anterior mediastinal masses causing invasion of adjacent vital structures, and for those in whom lymphoma or germ cell tumor is suspected. The primary treatment of thymoma remains surgical resection via a median sternotomy. Complete thymectomy includes removal of the entire thymus gland, pericardial fat, and thymoma en bloc. If macroscopic invasion of the thymoma is encountered, adjacent structures may be sacrificed (eg, pericardium, lung, a single phrenic nerve [but never both], great vessels), understanding that the best prognosis relies on a complete resection. Adjuvant therapies can be used accordingly.
APPROACH TO: Thymoma and Myasthenia Gravis
MYASTHENIA GRAVIS (MG): An uncommon autoimmune disorder of peripheral nerves in which antibodies form against acetylcholine (ACh) nicotinic post-synaptic receptors at the myoneural junction. A reduction in the number of ACh receptors results in progressively reduced muscle strength with repeated use of the muscle and recovery of muscle strength following a period of rest. The eye muscles tend to be affected.
THYMOMA: The most common type of tumor of the thymus, located in the anterior mediastinum. Most are benign, although they can be malignant. They can cause autoimmune disorders such as MG, red cell aplasia, or hypogammaglobulinemia. Approximately 40% of thymomas present as stage I disease, 25% present as stage II disease, 25% present as stage III disease, and approximately 10% present as stage IV disease.
At 5 years postresection, 25% to 30% of patients show complete remission of MG; 35% to 60% have an improvement in symptoms with a decrease in their medication requirement; 20% show no change in status; and 10% to 15% have a worsening of their symptoms.
Evaluation and Treatment of an Anterior Mediastinal Mass
The mediastinum is divided into three compartments: anterior (superior), middle, and posterior. Neurogenic tumors (20%), usually located in the posterior mediastinum, are the most common mediastinal tumor, followed by thymomas (15%-20%), which are located in the anterior mediastinum. An estimated 25% to 40% of mediastinal masses are malignant.
Evaluation of an anterior mediastinal mass always begins with a review of the history, a physical examination, and a screening chest radiograph demonstrating a mediastinal mass. Particular attention should be given to identifying symptoms and findings that indicate thyroid pathology and to detecting the presence of diffuse adenopathy suggesting the possibility of lymphoma. A CT scan of the chest is often helpful in identifying the exact location, the invasion of adjacent structures, associated lymphadenopathy, and intra- or extrathoracic metastasis. When germ cell tumors (seminomatous and nonseminomatous) are suspected, serum marker, α-fetoprotein, and human chorionic gonadotropin measurements should be obtained (see Table 41–3 for a summary of treatment recommendations).
Table 41–3 • EVALUATION AND TREATMENT OF ANTERIOR MEDIASTINAL MASSES
Indications for Biopsy
Patients with mediastinal masses are often referred for tissue diagnosis, but fine-needle aspiration (FNA) is seldom helpful. It is debatable whether biopsies of localized thymomas should be performed prior to resection. Open resection can be performed directly for most anterior mediastinal masses. If lymphoma, germ cell tumor, or stage III or IV thymoma is suspected, open biopsy via an anterior mediastinotomy or video-assisted thoracoscopy is indicated to direct appropriate therapy.
For Questions 41.1 to 41.3, match the following locations (A-C) within the mediastinum to the most appropriate disorders.
41.1 Neurogenic tumors
41.4 By which of the following is staging of thymoma primarily determined?
A. Surgical evaluation
C. MRI evaluation
D. CT scan evaluation
E. Positron emission tomography (PET) scan
41.5 A 25-year-old medical student is reading a chapter on myasthenia gravis, and recalls that his grandmother had this disorder. She had a thymectomy for her condition. Which of the following statements is most accurate regarding thymectomy and MG?
A. Thymectomy is indicated for all patients with MG.
B. Anticholinesterase is used in the treatment of MG.
C. Thymectomy is most effective for the treatment of MG when performed during an acute crisis.
D. The indication for thymectomy in the setting of a patient with a 3-cm suspected thymoma is the prevention of MG.
E. MG is always associated with the presence of a thymoma.
41.6 In which of the following patients is CT-guided biopsy of the mediastinal mass indicated?
A. A 35-year-old man with HIV who develops a large, ill-defined anterior mediastinal mass that appears to closely involve the mediastinal vessels.
B. A 47-year-old man with enlarged cervical lymph nodes, axillary lymph nodes, mediastinal lymph nodes.
C. A 28-year-old man with a left testicular mass, markedly elevated serum alpha-fetal protein level, and a large ill-defined mass in the anterior mediastinum.
D. A 55-year-old woman with a thyroid mass that has been growing over the past 15 years complains of compressive symptoms whenever she lies flat. There is also evidence of tracheal deviation in the upper mediastinum as the result of mediastinal extension of the mass.
E. A 23-year-old woman with biopsy-proven papillary thyroid cancer with lymphadenopathy involving the right lateral neck and central neck.
41.1 C. Neurogenic tumors are usually located in the posterior mediastinum.
41.2 A. Thymomas are usually found in the anterior mediastinum.
41.3 A. Germ cell tumors (such as teratomas) are also usually found in the anterior mediastinum.
41.4 A. Thymoma staging is based on the pathologic and histologic characteristics of the tumor, and tumor extension regarding the capsule and surrounding structures is important for disease staging.
41.5 B. MG is an autoimmune disease causing injury to the nicotinic cholinergic receptors, and anticholinesterase is a form of treatment. Thymectomy is indicated for the subset of patients with MG who also have thymomas, and in these patients, the basis for the thymectomy is to remove the thymoma that has the potential for malignant transformation. The likelihood of postoperative complications is dramatically increased when thymectomy is performed in patients with inadequately treated acute myasthenia crisis.
41.6 A. A 35-year-old man with human immunodeficiency virus (HIV), who develops a large, ill-defined, anterior mediastinal mass, could have lymphoma that requires tissue diagnosis prior to the initiation of chemotherapy but would not necessarily benefit from surgical resection; even though percutaneous biopsy may not provide the definitive diagnosis, it is worth trying. The patient described in choice B most likely has lymphoma and has other sites from where tissue biopsies can be performed that would be less invasive. The patient described in choice C most likely has nonseminomatous testicular cancer and could have the diagnosis established by radical orchiectomy. The woman described in choice D most likely has a symptomatic goiter with mediastinal extension, surgery for removal is indicated to relieve symptoms, and a biopsy is not going to alter her treatment plan. The woman described in choice E has papillary thyroid cancer with central neck and right cervical lymph node metastases; she needs to undergo total thyroidectomy and functional neck dissection; therefore biopsy of the cervical lymph node is not necessary.
Anterior mediastinal masses often require surgical resection for diagnosis and treatment.
Staging of thymoma takes place at the time of surgical resection by macroscopic inspection.
Proper staging and complete resection determine the prognosis for thymoma.
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