Lung malignancies reported in association with neurofibromatosis are sparse. We present the case of a patient with neurofibromatosis, a lung mass and a misleading transbronchial biopsy.
A 55 year-old smoker male with history of neurofibromatosis involving the skin, colon and presumably the lungs was evaluated for a new lung mass. Chest radiograph (CXR) and High Resolution Chest Tomogram (HRCT) done in 2000 for evaluation of dyspnea revealed extensive upper lobe bullous disease and diffuse interstitial lung disease (ILD). Pulmonary function tests were consistent with moderated restrictive pattern and decreased diffusion capacity. CXR in 2002 was unchanged; in early 2003 another CXR revealed a 1.3 cm density in the right upper lobe that increased to 3.4 cm in a following film at the end of 2003. The patient had no new respiratory symptoms. Chest CT showed a 4 x 5 cm mass with no lymphadenopathy. Fiberoptic bronchoscopic biopsy suggested neurofibroma (Fig 1A). In view of the atypical presentation, the risk factors for malignancy and the rapidly enlarging mass, the patient underwent lung resection. The pathologic report revealed adenocarcinoma of the lung (Fig 1B). Staging of lung cancer was T2N0M0.
The most common pulmonary manifestations of neurofibromatosis consist of diffuse interstitial fibrosis and bullae. The prevalence of interstitial fibrosis and bullae is about 10 and 20 percent respectively. Neurofibromas are benign, slow-growing neoplasm that frequently arise from a spinal nerve root but may involve any thoracic nerve; radiologically they are usually sharply marginated, spherical, and lobulated paraspinous masses. Neurofibromin, the protein product encoded by the neurofibromatosis1 gene, is expressed in many tissues; gene mutations result in loss of functional protein, causing the wide spectrum of clinical findings, including neurofibromatosis-associated tumors. Neurofibromin belongs to a family of GTPase-activating proteins that downregulate a cellular proto-oncogene, p21-ras, an important determinant of cell growth and regulation. In most studies, Ras mutations are predominantly associated with adenocarcinoma; a causal relationship between smoking, K-ras mutation and the development of lung cancer have being suggested, but remains speculative . The estimated overall risk of malignancy in neurofibromatosis is 2 to 10 percent of affected individuals; rate higher than that of the general population. Mediastinal atypical carcinoid as well as non-small and small cell cancer has been reported in patients with neurofibromatosis. We found 11 reports of neurofibromatosis associated with lung cancer in the Japanese literature. Adenocarcinoma was observed in 72.9% of cases, and poorly-differentiated tumor was observed in 7 out of 8 patients .
In our opinion this case illustrates the intricacy of management in patients with neurofibromatosis and pulmonary involvement. The etiology of the bullae in our patient is most probable multifactorial due to NF1 and tobacco use; the ILD due to NF1. Development of carcinoma has been associated with emphysematous bullae, with ILD, tobacco use and NF1. As routine screening for gliomas is part of the care of patients with NF1, we suggest screening for lung cancer in this population. If a thoracic mass is identified, aggressive diagnostic intervention should be entertained keeping in mind that transbronchial specimens can be misleading.
L. Varadarajalu, None.