Journal of the New Zealand Medical Association, 16-February-2007, Vol 120 No 1249
Multi modality treatment of an extensive pleural thymoma
Elizabeth Clayton, Yasotha Kathiravel, Harsh Singh
A 47-year-old male presented with numbness of his tongue, and altered taste sensation. He subsequently complained of malaise and right-sided pleuritic chest pain, with an associated cough, slight mucoid sputum, and fever. He was a lifelong non-smoker with no significant past medical history. A provisional diagnosis of lower respiratory tract infection was made, and he was initially managed with oral antibiotics. A chest radiograph subsequently revealed pleurally based lesions.
After the patient developed further symptoms of weight loss, anorexia, dysphonia, increasing fatigue, and nasal regurgitation of water, a clinical diagnosis of myasthenia gravis (MG) was made.
An initial computed tomography (CT) scan of the thorax showed extensive multifocal pleural thickening and nodularity of the right lung, with involvement of the fissure and intra parenchymal pulmonary nodules were noted. The right paratracheal and sub carinal lymph nodes were enlarged. The core biopsy (under CT guidance) revealed features of a type B1 thymoma.1 Based on the Masaoka clinical staging system2 this was considered as stage IVA disease, defined as pleural or pericardial metastatic spread.
Figure 1. Inoperable extensive right pleural thymoma
However the initial size and extent of the tumour, made it unsuitable for surgical resection (Figure 1). Following a multimodality discussion, it was thought that surgical debulking, and possible complete resection, could be considered, following review of response to neoadjuvant chemotherapy. He underwent a chemotherapy regime of cisplatin, doxorubicin, and cyclophosphamide for four cycles over an 8-week course.
Post chemotherapy CT demonstrated marked interval reduction in the size of the mediastinal and right pleural disease (Figure 2). He underwent an extended right pleuro pneumonectomy with excision of the diaphragm and pericardium. The thymus gland and a large area of pericardium with tumour involvement were excised. The pleural cavity showed no further evidence of tumour seedlings.
Figure 2. Post chemotherapy marked interval reduction of pleural thymoma
Postoperatively he spent less than 24 hours in the intensive care unit prior to transfer to the cardiothoracic ward. On the fifth postoperative day he developed an episode of acute shortness of breath, and tachycardia. He underwent a VQ scan, which showed no evidence of a pulmonary embolus. He returned home 9 days postoperatively.
Histology revealed an extensive thymoma mixed type B2/B31 with extensive focal capsular invasion and tumour identified abutting lung parenchyma, involving pleura, and pericardium, with no evidence of lymph node metastases.
Two months postoperatively the patient presented to clinic with a week’s history of productive cough associated with pyrexia. Chest radiography was unchanged from previous films. He was commenced on intravenous antibiotics and admitted to hospital for observation. He was found unresponsive the next morning.
Post mortem revealed that the cause of death was respiratory failure in the context of acute bronchitis in his remaining left lung. It was noted that his co-existing myasthenia gravis might have been the cause for his respiratory depression. There was no evidence of tumour reoccurrence at post mortem.
Thymomas are derived from epithelial cells of the thymus and are the commonest anterior mediastinal neoplasm; in the adult population, however, the overall incidence is rare.3 The propensity of the tumour to be malignant is determined by the invasiveness of the thymoma, locally, via pleural dissemination, or systemic metastases.4
Peak incidence of onset is between 40 and 60 years of age, with no sexual predilection.5 Presentation of thymomas varies, from local symptomatic symptoms such as cough, to incidental detection on chest radiographs, or from screening due to its associations with autoimmune and immunodeficiency disorders.5,6
Up to 30 to 65% of patients with thymoma have been reported to suffer from myasthenia gravis. Furthermore, 28% will present with other immune disorders such as lupus erythematous, pure red cell aplasia, Cushing's syndrome, and hypogammaglobulinaemia.6
Traditionally, thymomas are classified into three histological types based on the predominant cell type of lymphatic, epithelial and lymphoepithelial.4 Recently the World Health Organization reached a histological classification based on both morphology and lymphocyte to epithelial cell ratio.1 In 1981, Masaoka developed an anatomic classification based on the presence or absence of gross or microscopic invasion of the capsule and the presence or absence of metastases.7 This has since been upgrade in 1994 to the modified Masaoka staging system and is now the most widely accepted staging system on which current management options are based.2
We present a case of an extensive pleural malignant thymoma (IVa) with myasthenia gravis. Management involved a multimodality team of cardiothoracic surgeons, oncologists, radiologists, histopathologists, and neurologists. The extensive tumour, thought to be initially unresectable, was subsequently completely resected, following neoadjuvant chemotherapy. His death was thought to be related to infection, possibly complicated by myasthenia gravis.
Surgical intervention is the treatment of choice by wide consensus, as complete resection remains an important factor in the survival of patients with locally advanced malignant thymoma.8.9 However, radical resection is not always feasible for invasive and metastatic lesions (stages III and IVa).2
Thymomas are seen to be both chemo- and radio-sensitive, and recent reports using preoperative (neoadjuvant or induction) chemotherapy to transform a patient with inoperable disease into a patient with operable disease have shown good results.8,9
Venuta et al analysed multimodality treatment of thymomas compared to historical controls (those who received surgery alone). They showed that the complete resection rates were improved in the multi modality group relative to the surgery alone group (77% vs 33.3% for stage IV tumours).9
Shin et al have shown good response to neoadjuvant chemotherapy of 92% in 12 patients (stage III and IVA), and subsequent complete resection in 82%. Following adjuvant chemotherapy and radiotherapy they have shown disease-free survival at 7 years to be 73%.8 Ongoing problems with research relate to low incidence, and therefore small numbers of patients with thymoma to produce randomised control trials.
This case demonstrates that thymomas are often associated with paraneoplastic syndromes such as myasthenia gravis and therefore their treatment may affect prognosis.10 Furthermore, as this case highlights, multimodality treatment with neoadjuvant chemotherapy, followed by radical surgical resection, is highly effective and may cure locally advanced, unresectable thymomas.
Author information: Elizabeth S J Clayton; Yasotha Kathiravel; Harsh P Singh; Department of Cardiothoracic Surgery, Christchurch Hospital, Christchurch
Acknowledgement: We acknowledge the assistance of Dr Sharyn MacDonald for radiographic images and interpretation.
Correspondence: Harsh P Singh, Department of Cardiothoracic Surgery, Christchurch Hospital, Private Bag 4710, Christchurch. Fax: 03 364 1361; email: HarshS@cdhb.govt.nz
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