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a Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Antwerp, Belgium
b Department of Pathology, Antwerp University Hospital, Antwerp, Belgium
c Department of Neurology, Antwerp University Hospital, Antwerp, Belgium
d Department of Radiotherapy, St. Augustinus Hospital, Antwerp, Belgium
Accepted for publication January 10, 2008.
* Address correspondence to Dr Heyman, Graaf Van Hoornstraat 23, Antwerp, 2000, Belgium (Email: stijn_heyman{at}hotmail.com).
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Introduction |
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A 40-year-old man presented with ptosis, dysarthria, and difficulties with chewing at the department of neurology in 2004. His medical history revealed urge incontinence, stress-induced hematuria, diabetes mellitus type II, and obesity. Electromyography showed disturbed neuromuscular transmission, and anti-acetylcholine receptor antibodies were elevated at 7.49 nmol/L, confirming the diagnosis of myasthenia gravis. On chest computed tomographic scan a polylobular, soft tissue tumor suggestive of thymoma was found in the anterior mediastinum measuring 60 x 30 mm. Because of the severity of the myasthenic symptoms, preoperative plasmapheresis was applied. By median sternotomy, a radical thymectomy was performed with partial resection of the pericardium and the left phrenic nerve due to local invasion.
The patient recovered well without respiratory problems.
Final pathologic diagnosis was mixed thymoma according to the Muller-Hermelink classification, AB thymoma according to the World Health Organization classification and stage II according to Masaoka. Approximately 90% of the tumor cells stained positively for the proliferation marker Ki-67. All removed lymph nodes were tumor free. Because there was a positive anterior section margin, postoperative radiotherapy was indicated. A total dose of 60 Gy was delivered and was given in 30 sessions over a time period of 6 weeks.
The patient was further treated with a cholinesterase inhibitor and steroids. Clinical symptoms gradually disappeared and complete remission was obtained without any medication.
In April 2007, he was reinvestigated because of recurrent myasthenic symptoms. On computed tomographic (Fig 1) and positron emission tomographic (Fig 2) scans, a pleural nodule was detected originating from the parietal pleura above the left hemidiaphragm. There was a slight uptake of the isotope on the positron emission tomographic scan, but there was no evidence for local recurrence in the mediastinum or distant metastases.
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One week postoperatively, an increase in bulbar symptoms with difficulties in speaking and eating were noted, and the steroid dose was increased, which resulted in gradual improvement. Follow-up at 6 months showed some minor remaining difficulties with chewing and swallowing and a normal postoperative status without residual or recurrent tumor on computed tomography.
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Shinkai and colleagues [1] reported a patient who presented with myasthenia gravis 18 years after resection of an invasive thymoma. Recurrent disease was found in the mediastinum, right pleura, pericardium, and left supraclavicular nodes. Similar cases were reported by Umemoto and colleagues [2] and Lava and colleagues [3].
A large study of 126 patients with recurrent thymoma in 19% of the cases after complete resection of the initial tumor was reported by Haniuda and colleagues [4]. Recurrence rate increased with the stage of the thymoma, being more frequently found in stage III or IV and epithelial-rich histology. The average disease-free interval in this study was 68 months. This author also states that detection in an early stage is necessary and that myasthenia can be used as a marker for possible early recurrent disease.
The results in a study of 527 cases of resected thymomas indicate that a late onset of myasthenia gravis after complete resection of a thymoma is probably due to a relapse of the thymoma [5]. Five cases of late recurrent thymoma were reported out of 133 post-thymectomy patients with diagnosis of myasthenia gravis.
In our case, recurrent disease occurred 3 years after initial resection due to a symptomatic pleural implant with similar histologic characteristics as the primary tumor. Most likely the mechanism is microscopic soiling during the first intervention, as there was no evidence of other metastases on positron emission tomography or during exploration of the hemithorax by video-assisted thoracoscopy. Such an isolated pleural implant has not yet been described. Thirty-nine reported cases of recurrent thymomas on the pleural surface are listed in Table 1. 77% of these cases underwent radiotherapy, 36% chemotherapy, and 82% surgery.
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The specific therapy for recurrent thymoma remains controversial [6–14]. Some authors state that an aggressive surgical approach to recurrent thymomas is justified as this is followed by a longer disease-free interval [6, 14]. Awad and colleagues [15] advise prevention of soiling during the first intervention. Others favor chemotherapy, although the benefit has not clearly been demonstrated [7]. Kondo and colleagues [14] and Kazuhiro and colleagues [16] propose a combination of resection followed by chemoradiotherapy. At last, Regnard and colleagues [8] state that if a local recurrence is diagnosed, surgical re-resection is the preferred therapy when a complete resection can be obtained. Combining these proposals we suggest obtaining free resection margins during the initial procedure and performing a repeat resection in case of an isolated pleural recurrence if possible by video-assisted thoracoscopy. Depending on pathologic findings, adjuvant chemoradiotherapy may be added.
Our patient underwent a video-assisted thoracoscopic surgical resection of the mushroom-like shaped tumor. He had a relapse of the bulbar and ocular symptoms 1 week postoperatively. A myasthenic crisis after thymectomy may be observed after thymectomy and is usually characterized by bulbar symptoms, such as difficulties with breathing and chewing. Existence of preoperative bulbar symptoms, history of preoperative crisis, high serum anti-acetylcholine receptor antibodies, and intraoperative blood loss >1,000 mL are predictors for the development of a myasthenic crisis [9]. An immunomodulating therapy is advised.
We can conclude that a recurrent thymoma is often preceded by an increase in myasthenic symptoms, and further investigation is necessary when clinical symptoms reappear.
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This article has been cited by other articles:
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  M. Lucchi and A. Mussi Reply to Heyman and Van Schil Eur. J. Cardiothorac. Surg., September 1, 2008; 34(3): 708 - 708. [Full Text] [PDF]
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S. Heyman and P. Van Schil Surgery for isolated pleural recurrence from thymoma Eur. J. Cardiothorac. Surg., September 1, 2008; 34(3): 707 - 708. [Full Text] [PDF]
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