Bilateral, multifocal renal tumors diagnosed as Birt-Hogg-Dubi syndrome by genetic analysis = Bilateral, multifocal renal tumors diagnosed as Birt-Hogg-Dubi syndrome by genetic analysis

다국어 초록 (Multilingual Abstract)

Birt-Hogg-Dubi syndrome (BHD) is an autosomal dominant cancer susceptibility syndrome characterized by skin fibrofolliculomas, pulmonary cysts and spontaneous pneumothorax, and renal cancers. The syndrome is caused by various mutations of the FLCN gene located in 17p11.2 encoding folliculin. The risk of renal cancer is seven times higher in BHD-affected patients. Bilateral, multifocal and chromophobe renal cell carcinoma is characteristic of renal cancers in BHD. Among about 110 pathogenic mutations reported in BHD, only twenty six of them have been associated with renal cancer. In this study, we described a case of 50-year-old woman with chromophobe renal cell carcinoma who had c.1557delT mutation in the FLCN gene. A 50-year-old-woman presented with flank pain for the past 2 weeks. Computed tomography (CT) of her abdomen and pelvis showed multifocal tumors with heterogeneous enhancement in both kidneys, including a 3.5-cm mass on the upper pole of the right kidney. To differentiate metastatic cancer from primary kidney tumors, we performed positron emission tomography (PET)-CT, which showed no other hypermetabolic lesions. Her chest CT showed a few lentiform cysts of up to 1.5 cm in both lower lungs. A needle biopsy revealed that the 3.5-cm mass was a chromophobe renal cell carcinoma. Given multifocal distribution of the renal cell carcinoma, we suspected an inherited type of kidney cancer, such as Von Hippel-Lindau disease or BHD. In the current case, the cystic change of both lungs and chromophobe renal cell carcinoma pointed towards the possibility of BHD. DNA sequencing of the entire FLCN gene using mononuclear cells found out a heterozygous c.1557delT mutation in exon 14 [p.Phe (TTT) 519Leu (TTA) fs*18]. A son and a daughter of the patient also went through the genetic analysis which illustrated the same mutation, although both of them did not have any clinical signs suggesting BHD. Considering that renal cancer might be the principal determinant of life expectancy, early suspicion and diagnosis of BHD is crucial. In our patient, identification of genetic mutation aided in the diagnosis which is novel DNA sequence variation in BHD-associated renal cancers.