A 54-year-old man was found to have asymptomatic, bilateral renal tumors by ultrasonography and computed tomography (CT) (Fig. a, b). CT scan also showed left pneumothorax (Fig. c). No apparent cutaneous lesions were found by careful inspection and palpation of the skin. The patient had a history of spontaneous pneumothorax at the age of 30. His son also had a history of spontaneous pneumothorax at the age of 17. Open bilateral and partial nephrectomies were performed. Histopathologic examination revealed that the tumor in the left kidney was chromophobe RCC, nuclear grade G2 (partial G1), and 1.7 cm × 1.5 cm × 1.5 cm in size (Fig. d); the tumor in the right kidney was clear-cell RCC, nuclear grade G2, and 5.0 cm × 4.7 cm × 4.5 cm in size (Fig. e).\nGenomic DNA was extracted from blood samples collected from the patient and his son. Mutation examination revealed that the proband and his son carried a deletion of two bases (AG) at nucleotides c.946-947 in exon 9 (c.946-947delAG) of the FLCN gene (Fig. f), which caused a frameshift mutation starting at the 316th amino acid (p.316fs388x). No RCC was detected by abdominal CT scan on the son.
The first patient was a 37-year-old female who presented with an asymptomatic left renal tumor that was revealed by ultrasound and computed tomography (CT) examinations (fig. ). The CT examination also revealed the presence of asymptomatic bilateral multiple PCs (fig. ). Since the age of 35, a few firm papules had developed on her face and head (fig. ). The patient had no family history of pulmonary, renal, or cutaneous disease. A laparoscopic left nephrectomy was performed. On gross examination, the resected kidney was a yellowish, solid tumor with partial hemorrhage (fig. ). The tumor was identified as a clear cell renal carcinoma (fig. ) positive for vimentin stain (fig. ) and negative for CK-7. A skin biopsy of the papule on her head revealed it was a fibrofolliculoma (FF; fig. ) positive for factor 13a (fig. ) and c-kit (fig. ), and negative for CD34, α-smooth muscle actin (α-SMA), S100, and CD68. Because the findings for this patient met 1 major criterion and 2 minor criteria [], she was diagnosed with Birt-Hogg-Dubé syndrome (BHD).