CT Screening for pulmonary cysts to identify potential BHD patients

As discussed in our blog post from the beginning of this year a greater level of BHD awareness among pulmonologists and associated professionals could help increase early diagnoses. It has been reported that up to 10% of spontaneous pneumothorax patients are carrying FLCN mutations (Ren et al., 2008, Johannesma et al., 2015, Ding et al., 2015). The identification of BHD in these patients results in screening for the development of renal cell carcinoma in patients and their families leading to earlier detection and treatment.

As part of a larger, international awareness campaign to increase early diagnoses the BHD Foundation have been at the BTS Winter Meeting this week to interact with pulmonary clinicians and researchers. The conference features hundreds of presentations and posters, including a session focused on rare lung diseases featuring a talk from Dr Frank McCormack from the University of Cincinnati. Dr McCormack discussed the expanding spectrum of cystic lung diseases and their characteristics.

BHD is one of several diffuse cystic lung diseases (DCLD) with characteristic cyst development and distribution. CT imaging of the DCLD patient lungs can be used in the differential diagnosis of BHD, LAM, PLCH and other underlying conditions that can cause a spontaneous pneumothorax. Recently there have been several excellent reviews of these DCLD and their characteristic CT findings – Richards et al., 2015, Gupta et al., 2015 part I and part II, Ferreira Francisco et al., 2015 – which will also contribute to raising awareness.

In addition a recent report from Johannesma et al., (2015b) discussed the potential for CT screening to identify BHD in renal cell carcinoma (RCC) patients. Over half of RCC patients are detected incidentally, with a high mortality in those presenting with malignant disease. Increasing early and pre-symptomatic diagnosis by the identification of genetic predisposition conditions such as BHD would therefore increase patient survival. BHD cohort studies report characteristic pulmonary cysts in all RCC patients who have a thoracic CT scan available; the presence of such cysts in a presumed-sporadic RCC patient could therefore be useful as an indicator for further BHD testing.

Johannesma et al. analysed the thoracic CT scans from 112 non-metastatic RCC. Of these, 11 patients had at least one pulmonary cyst below the carina, and eight patients agreed to genetic testing for FLCN mutations. Although no FLCN mutation were identified in these patients, comparison of their cysts to those in confirmed BHD patients with RCC suggest that CT screening for pulmonary cysts could still be valuable. BHD patients generally have a larger number of pulmonary cysts and are also more likely to have either a personal or family history of pneumothorax with a high recurrence rate or RCC. Therefore further investigations for BHD, such as a dermatological examination or genetic testing, could be useful in patients with one or more of these attributes.

Raising awareness of BHD across the medical community will enable the earlier identification of more patients and families, resulting in earlier screening and treatment. The characteristic nature of BHD cysts makes them a diagnostic attribute that should be further utilised when pneumothorax and RCC patients first present.

  • Ding Y, Zhu C, Zou W, Ma D, Min H, Chen B, Ye M, Pan Y, Cao L, Wan Y, Zhang W, Meng L, Mei Y, Yang C, Chen S, Gao Q, Yi L (2015). FLCN intragenic deletions in Chinese familial primary spontaneous pneumothorax. Am J Med Genet A. 167A(5):1125-33. PMID: 25807935.
  • Ferreira Francisco FA, Soares Souza A Jr, Zanetti G, & Marchiori E (2015). Multiple cystic lung disease. European respiratory review : an official journal of the European Respiratory Society, 24 (138), 552-64 PMID: 26621970.
  • Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX (2015). Diffuse Cystic Lung Disease. Part I. Am J Respir Crit Care Med. 191(12):1354-66. PMID: 25906089.
  • Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX (2015). Diffuse Cystic Lung Disease. Part II. Am J Respir Crit Care Med. 192(1):17-29. PMID: 25906201.
  • Johannesma PC, Reinhard R, Kon Y, Sriram JD, Smit HJ, van Moorselaar RJ, Menko FH, Postmus PE; Amsterdam BHD working group (2015). Prevalence of Birt-Hogg-Dubé syndrome in patients with apparently primary spontaneous pneumothorax. Eur Respir J. 45(4):1191-4. PMID: 25537564.
  • Johannesma PC, Houweling AC, Menko FH, van de Beek I, Reinhard R, Gille JJ, van Waesberghe JT, Thunnissen E, Starink TM, Postmus PE, & van Moorselaar RJ (2015). Are lung cysts in renal cell cancer (RCC) patients an indication for FLCN mutation analysis? Familial cancer PMID: 26603437.
  • Ren HZ, Zhu CC, Yang C, Chen SL, Xie J, Hou YY, Xu ZF, Wang DJ, Mu DK, Ma DH, Wang Y, Ye MH, Ye ZR, Chen BF, Wang CG, Lin J, Qiao D, Yi L (2008). Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax. Clin Genet. 74(2):178-83. PMID: 18505456.
  • Richards JC, Lynch DA, Chung JH (2015). Cystic and nodular lung disease. Clin Chest Med. 36(2):299-312, ix. PMID: 26024606.


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