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Journal of Clinical Oncology, Vol 26, No 13 (May 1), 2008: pp. 2216-2218 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.6753
Intrathoracic Malignant Peripheral Nerve Sheath Tumor in Neurofibromatosis 1Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA
Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA
Division of Cardiothoracic Surgery, Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA
Division of Hematology and Oncology, Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA A 37-year-old man with a history of neurofibromatosis 1 presented to the hospital with a 3-day history of cough, pleuritic chest pain, and dyspnea. Physical examination showed tachycardia, tachypnea, normal oxygen saturation on room air, markedly decreased breath sounds with faint crackles in the right lung, multiple cutaneous neurofibromas, café au lait macules, and skinfold freckling. Laboratory studies showed leukocytosis (17.8 x 109/L) with 70% neutrophils. ECG showed sinus tachycardia with no evidence of ischemia. Chest radiograph showed a large mediastinal mass causing right-to-left shift of the trachea, multiple smaller mediastinal masses, and a large right-sided pleural effusion (Fig 1A). Computed tomography (CT) confirmed the large mediastinal mass to be heterogeneous and lobulated with significant mass effect on the right upper, middle, and lower bronchi causing collapse of the right lung (Fig 1B). The patient underwent right thoracotomy, where large masses compressing the right upper and middle lobes were resected; however, multiple small satellite masses throughout the chest were not excisable. Bronchoscopy also revealed 50% obstruction of the right main bronchus by an endobronchial tumor originating from the posterior membrane, which was debulked by argon plasma coagulation. Postoperative CT showed improved aeration of the right lung. Biopsy of the lung mass showed malignant spindle cells (Fig 2A; original magnification x400), with hypercellularity, scattered mitotic activity (arrow), and immunohistochemical stains positive for S-100 in a patchy distribution (Fig 2B; original magnification x400) and diffusely positive for vimentin (Fig 2C; original magnification x400), consistent with malignant peripheral nerve sheath tumor.1,2 He returned to the hospital in 3 weeks with rapidly progressive dyspnea. He was bedbound with a respiratory rate of 30 and no breath sounds on the right. Chest radiograph showed complete opacification of the right hemithorax. Chest CT revealed a large heterogeneous tumor occupying the entire right hemithorax, replacing the right lung and pleural space, invading to the distal right trachea and thoracic esophagus, and extending into the aortic pulmonary window with effacement of the transverse aorta, proximal descending thoracic aorta, and left pulmonary artery (Fig 3). There was a thrombus (asterisk) within the superior vena cava. Inpatient palliative care was provided with nebulized fentanyl,3 opioids, and benzodiazepines giving some respiratory comfort, and he died in 3 days.
Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive sarcoma that arises from the nerve sheath or shows features of nerve sheath differentiation, with an incidence of 0.001% in the general population and 0.16% in patients with neurofibromatosis 1.4,5 It is more commonly seen in the extremities, head, and neck.5,6 Intrathoracic MPNST is uncommon.6,7 Neurofibromatosis 1 (NF1) is an autosomal dominant neurocutaneous disorder, with an estimated birth incidence of 1 in 2,500 and a prevalence of 1 in 5,000.8 NF1 is characterized by café au lait macules, skinfold freckling, osseous dysplasia, iris hamartomas, optic glioma, and neurofibromas, whereas neurofibromatosis 2 is characterized by bilateral vestibular schwannomas. Both have high de novo mutation rates and carry a high risk of tumor formation, although NF1 carries a higher risk of high-grade malignancy.9 The presence of a microdeletion of the NF1 gene may be a risk factor for development of MPNST10; however, a more recent study found a variety of mutations in NF1 individuals with MPNST.11 Successful treatment of MPNST requires complete surgical excision.4,12,13 Radiotherapy may delay recurrence but has little effect on long-term survival.13,14 Standard chemotherapy for advanced soft tissue sarcoma in adults involves single-agent doxorubicin and has a poor response rate of 12%15; furthermore, neurofibromatosis 1 is one of the most significant prognostic factors indicating poor outcome with chemotherapy against MPNST.16,17 In this patient, his poor performance status dictated supportive care only. Research is ongoing to investigate the role of selective tyrosine kinase and other inhibitors as novel therapy for MPNST,18,19 but there have been no reported human trials due to the rarity of the cancer. Such agents have shown remarkable activity in GI stromal cell tumors20 and some rare tumors such as medullary thyroid cancer.21 Cytogenetic analysis and comparative genomic hybridization of MPNST cell lines in vitro have been under investigation to determine their association with survival.22 Highly complex and aberrant karyotypes containing numerical structural changes have been described for MPNST; however, there is not a recurrent pattern in structural changes or chromosomal aberrations consistently across all MPNST cell lines.22,23 Additional investigations remain to be done to determine prognostic indicators in MPNST. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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