Neurofibromatosis type-1 (NF1) is a genetic disorder characterized by café-au-lait spots, neurofibroma and other associated features. The risk of malignancy is approximately 2.5 to 4-fold higher as compared to general population. However, primary pulmonary sarcoma is rarely reported in patients with NF1. Here, we describe a case of NF1 complicated with primary pulmonary sarcoma.
Neurofibromatosis type-1 (NF1) or Von Recklinghausen disease is an autosomal dominant disorder with an incidence of approximately 1 in 2600 to 1 in 3000 individuals . It is a neurocutaneous disorder that manifests as café-au-lait spots, skinfold freckling, cutaneous neurofibromas and iris hamartomas. Systemic manifestation involving the eyes, skeleton, blood vessels and central nervous system (CNS) may be found in patients with NF1 . The diagnostic criteria are based on specific clinical features and developed by the National Institute of Health (NIH) Concensus Conference in 1987 and updated in 1997 . Patients with NF1 are at risk of developing both benign and malignant tumors with increased frequency throughout life [4, 5]. Here, we described a case of NF1 complicated with primary pulmonary sarcoma.
A 62-year-old man presented with cough associated with loss of appetite and loss of weight for the past two months. He denied any infective symptoms and no history of tuberculosis contact. Examination revealed multiple skin lesions consistent with cutaneous neurofibromas, café-au-lait spots and axillary frecklings (both his mother and sister had similar skin lesions). He was diagnosed with NF1 based on the diagnostic criteria from NIH. Examination of the respiratory system revealed right pleural effusion. His neurological examination was unremarkable.
His chest radiograph showed right pleural effusion with solitary rounded lesion in the right middle zone. Pleural tapping was carried out and pleural fluid examination showed exudative effusion with raised protein and lactate dehydrogenase level compared to serum level. Computed tomography (CT) of thorax was carried out revealed well defined enhancing broad base lesion at the right upper lobe (3.9 cm x 2.6 cm) with right pleural effusion. Other hematological and biochemical parameters were normal.
He was subsequently planned for CT-guided biopsy during the clinic follow-up. Unfortunately, he was readmitted to hospital two months later presented with worsening breathlessness and cough. Examination of the respiratory system revealed reduced breath sound right lung field. Repeated chest radiography showed homogenous opacity right lung. Pleural tapping was carried out with minimal fluid drained. CT scan showed enlarging mass filling the entire right hemithorax and CT guided biopsy was performed. Histopathological examination of the biopsy specimen showed myxoid tumor in favor of low grade sarcoma. He was referred for chemoradiation therapy. Unfortunately, he succumbed to death while receiving treatment.
NF1 is commonly associated with increased risk of benign and malignant tumors [4, 5]. It can be divided into both central nervous system (CNS) tumors and non-CNS tumors. With overall risk of malignancy in NF1 is estimated at between 5 and 15 percent of affected individuals, primary pulmonary sarcoma is uncommon compared to other tumors such as peripheral neurofibromas, gliomas or other central nervous system tumors [6-8]. Mutations in NF1 gene located in chromosome 17q11.2 lead to tumor development and results in malignancies . Pulmonary sarcomas overall comprise only 0.5% of all lung malignancies . They are rare with frequencies of 1:100 as compared to pulmonary carcinoma . In patients with NF1, primary pulmonary sarcoma is rarely reported . Relatively more common are lung secondaries from malignant peripheral nerve sheath tumors (MPNST).
Patients with NF1 present with cough and breathlessness will warrant further investigations. They may have neurofibroma, diffuse lung disease or malignant transformation of benign tumors . Chest radiography and CT scan are modalities of choice for evaluation. In this case, serial CT scan done between 3 months apart showed rapid growing of the mass over right hemithorax. Subsequent CT-guided biopsy confirms the diagnosis of myxoid tumor favoring low grade sarcoma. Due to limited biopsy sample, we were not able to identify the exact tumor type. The possibility of an alternate primary source should be excluded as lung is the most common metastatic sites for soft tissue sarcoma . In this case, there was no evidence of metastasis from other primary lesions. Thus, the diagnosis of primary pulmonary sarcoma was made. To date, there are only a few case reports on pulmonary sarcoma in association with NF1 [12, 15].
Primary pulmonary sarcoma complicating NF1 was reported by Abe et al in 2002 and was successful removed surgically . To date, the modalities of treatment are not well described due to the rarity of the case. However, surgical treatment remains the preferred modality. In this case, due to the extensive disease, he was referred for chemoradiotherapy. Unfortunately, he succumbed to death while receiving treatment.
Malignancy still represents the most important cause of morbidity and mortality in NF1 patient. A minority of patients with NF1 develops malignancy as a complication of their disorder. This includes malignant peripheral nerve sheath tumors (MPNST), gliomas and leukemia. Although the coexistence of NF1 and primary pulmonary sarcoma is distinctly uncommon; the awareness of clinicians in this condition is extremely crucial to prevent morbidity and mortality in patients with NF 1.
The abstract of this case report was presented in the poster format at Asia Pacific Lung Cancer Conference (APLCC), Kuala Lumpur, Malaysia on 6th to 8th November 2014.
The authors would like to thank the Director General of Health Malaysia for permission to publish this article.
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