Revised: February 11, 2013
Accepted: February 20, 2013
Published online: February 27, 2013
Processing time: 171 Days and 2.1 Hours
AIM: To investigate pathogenic mutations related to malignant pheochromocytoma in neurofibromatosis (NF).
METHODS: We present a patient with NF and metastatic pheochromocytoma in whom genetic screening for presence of pathogenic mutations in RET proto-oncogene, von Hippel-Lindau (VHL) and succinate dehydrogenase complex subunits B (SDHB) genes were investigated. RET proto-oncogene mutation screening for exons 10, 11, 13, 14, 15, 16 were examined by polymerase chain reaction (PCR) and direct DNA sequencing in patient. Mutation screening for exons 1, 2, 3 of VHL gene was carried out. Both forward and reverse strands were subjected to direct sequencing after PCR amplification. The entire coding sequence of SDHB gene was screened for the presence of pathogenic mutations by PCR-sequencing.
RESULTS: A 45-year-old man presented with abdominal pain and hypertension over the previous year. The patient was a known case of neurofibromatosis type 1 (NF1) who presented at the age of 15 years with hyperpigmented and hypopigmented lesions. After complete evaluation for hypertension, biochemical tests and imagings indicated a malignant pheochromocytoma of 120 mm × 70 mm in size. The patient underwent left adrenalectomy, nephrectomy and splenectomy. After surgery the symptoms improved and blood pressure was controlled. After 5 years he was admitted again for evaluation of hypertensive crisis. Biochemical tests were again consistent with pheochromocytoma and disease relapse. Imaging studies and liver biopsy confirmed metastatic pheochromocytoma to the liver and para-aortic area. 131 Iodine-metaiodobenzylguanidine therapy was carried out. Genetic screening of VHL (exons 1, 2, 3), RET proto-oncogene (exons 10, 11, 13, 14, 15, 16) and SDH complex subunits revealed no pathogenic mutation.
CONCLUSION: We conclude that mutations in the NF1 gene are responsible for the patient’s clinical findings. However, would be helpful to further examine somatic mutations for a more precise study of genotype-phenotype correlation.
Core tip: Malignant pheochromocytoma associated with neurofibromatosis (NF) is very rare. We screened for all possible mutations related to pheochromocytoma in a patient with NF and malignant pheochromocytoma but found no mutations. This negative result shows that the NF1 gene is responsible for this rare presentation.