Invasive thymoma in ocular myasthenia gravis: diagnostic and prognostic implications.

W e read with great interest the recent article by Bruce and Kupersmith (1) discussing the safety of prednisone in treating patients with ocular myasthenia gravis (OMG). Yet before treatment, there are critically important steps in evaluating these patients. We illustrate this point by presenting 2 cases of OMG that were found to have invasive thymoma. Case 1: A 50-year-old Hispanic man presented with a 4-month history of ptosis and diplopia, which was worse in the evening and better in the morning. He had no other symptoms. Visual acuity was 20/20 bilaterally. External examination showed bilateral variable ptosis, which increased with sustained upgaze, mild orbicularis weakness, and positive Cogan lid twitch sign. The pupils were isocoric, and there was no relative afferent pupillary defect. Ocular motility revealed variable exotropia of 12–16 prism diopters and bilateral pseudointernuclear ophthalmoplegia. Ice test was positive, resulting in an improvement in ocular motility and ptosis. Ophthalmoscopy was normal bilaterally. Serum acetylcholine receptor antibodies were elevated: binding antibody = 33.0 nmol/L (positive, .0.5 nmol/L); blocking antibody = 48% (positive, .25%); modulating antibody = 44% (positive, .26%). Electromyographic and nerve conduction studies were diagnostic of myasthenia gravis. Computed tomography (CT) of the chest revealed a thymic mass (Fig. 1A). At surgery, in addition to thymectomy, pericardial resection was performed because the tumor was found to be invading the pericardium. Pathology confirmed invasive thymoma, with mixed pattern grade B1, B2, and focal B3, and no lymphovascular or perineural invasion (stage III). Following surgery, the patient had near complete resolution of his myasthenic symptoms. Case 2: A 67-year-old Caucasian woman developed leftsided ptosis and diplopia, and edrophonium testing and acetylcholine receptor antibodies were positive. CT of the chest disclosed nodular densities in the anterior mediastinum (Fig. 1B). Thymectomy revealed invasive thymic epithelial neoplasm with conventional and atypical features (stage II, grade B3). The patient received postoperative radiation therapy, and positron emission tomography (PET) and CT performed within the first year and a half the following surgery were negative for tumor recurrence or metastases. Nineteen months after initial presentation, the patient developed an acute exacerbation of myasthenia gravis with ptosis, diplopia, shortness of breath, and upper extremity weakness. She had a complicated hospital course including atrial fibrillation and respiratory failure, and she was discharged 4 months later on weekly plasmapheresis, pyridostigmine, and prednisone. On examination, there was mild bilateral orbicularis weakness, but no Cogan lid twitch sign and variable exotropia of 20–50 prism-diopters and right hypertropia. Follow-up PET and chest CT have remained stable. We emphasize 3 important points from our cases. First, it is essential that we remind our referring clinicians to obtain imaging of the mediastinum in patients with ocular and generalized myasthenia gravis (2,3). Second, delayed diagnosis and treatment of thymoma can lead to disease progression, a higher stage at diagnosis, and a worse systemic outcome as more invasive stages correlate with higher mortality rates (4,5). Third, patients who have undergone thymectomy for malignant or invasive disease and present FIG. 1. A. Case 1. Thymic mass measures 20 · 20 · 23 mm. B. Case 2. Thymoma appears as multiple nodular densities measuring 14 · 10 mm. Circle denotes thymoma.