750O - Early detection of hereditary renal cell cancer by improved evaluation of spontaneous pneumothorax patients

Date 27 September 2014
Event ESMO 2014
Session Genetic predisposition to cancer
Topics Renal Cell Cancer
Familial Cancer
Imaging, Diagnosis and Staging
Presenter Paul Johannesma
Citation Annals of Oncology (2014) 25 (suppl_4): iv254-iv254. 10.1093/annonc/mdu335
Authors P.C. Johannesma1, A.C. Houweling2, R. Reinhard3, E. Thunnissen4, F. Menko5, J.H.T. van Waesberghe3, M.A. Paul6, S. Horenblas7, R.J.A. van Moorselaar8, P. Postmus9
  • 1Pulmonary Diseases, VU University Medical Center, 1007MB - Amsterdam/NL
  • 2Clinical Genetics, VU University Medical Center, Amsterdam/NL
  • 3Radiology, VU University Medical Center, Amsterdam/NL
  • 4Pathology, VU University Medical Center, Amsterdam/NL
  • 5Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam/NL
  • 6Thoracic Surgery, VU University Medical Center, Amsterdam/NL
  • 7Urology, The Netherlands Cancer Institute, Amsterdam/NL
  • 8Urology, VU University Medical Center, Amsterdam/NL
  • 9Pulmonary Diseases, VU University Medical Center, Amsterdam/NL

 

Abstract

Aim

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant condition due to germline mutations in the folliculin (FLCN) gene, clinically characterized by skin fibrofolliculomas, lung cysts, (recurrent) spontaneous pneumothorax (SP) and an increased risk of renal cell cancer (RCC). Families with BHD are most often identified through recognition of fibrofolliculomas A less common way to identify a BHD family is through (recurrent) SP. The characteristic pulmonary cystsare generally not visible on standard chest X-ray, and therefore will be missed in the standard – according to British Thoracic Society guidelines - diagnostic work-up for SP cases. We hypothesize that supplementing the diagnostic work-up of SP patients with CT imaging will result in the identification of BHD patients presenting with SP. This provides the opportunity of the identification of (asymptomatic) RCC at an early stage by screening of identified FLCN mutation carriers.

Methods

We retrospectively collected clinical and radiological data of 55 families, including 200 BHD patients with a proven pathogenic FLCN mutation. Our database started in 2004; the mean follow-up time of mutation carriers is 5 years (1-10 years).

Results

Sixty patients in 33 families had (recurrent) SP. In 14 out of 30 families we detected one or more patients with RCC. In total 19 patients had a history of RCC, 7 of them had a history of (recurrent) SP and 15 patients had a positive familial history for SP. We found in 14 cases RCC at an early stage, 5 patients died due metastases. Histological diagnosis were mainly (a combination of) clear cell carcinoma and chromophobe carcinoma.

Conclusions

Based on these results, we suggest that including (low dose) thoracic CT in the standard SP work up should result in the identification of BHD families. In these families annual screening for RCC should be offered to affected relatives, which was shown to result in early detection of BHD associated RCC. We show that a limited period of observation of these families has resulted in detection of 14 patients with RCC at an early stage.

Disclosure

All authors have declared no conflicts of interest.