This is a retrospective study focusing on the thoracic CT findings of lung cysts characteristics in BHD compared with other DCLD in Chinese. We used quantified methods to confirm that the pulmonary cysts in patients with BHD tend to be fusiform, less numerous, and have a predominance in the lower lobe and near the mediastinum compared with other DCLD.
BHD was always confused with other kinds of DCLD in clinic not only because of its low prevalence but its low awareness as well. Most of our BHD patients were referred to our hospital because of suspected as other kinds of DCLD, such as LAM since our clinic is the largest LAM/TSC centre in China. Among the patients with BHD, almost half of patients were misdiagnosed with primary spontaneous pneumothorax. The longest misdiagnosis duration for patients with BHD was 38 years. The average misdiagnosis delay for patients with BHD was 7.73 years. Extra-pulmonary abnormalities including kidney and skin manifestations are rare in Chinese (7) compared with Caucasians, and respiratory symptom may be the only symptom observed in Chinese BHD patients. So, it is important to recognize the radiologic features of lung in BHD and to differentiate from other diffuse cystic lung diseases. Some researchers believed that pulmonary cysts predominantly localizing the medial and lower zones in BHD compared with other DCLD, nevertheless, the majority of which were based on experiences from specialists (10, 12, 13).
Abundant studies focused on the descriptive characteristics of pulmonary cyst of BHD, whereas, statistical comparison of the lung cysts between BHD and other DCLDs were rare. Tobino and colleagues made a quantitative analysis of pulmonary cysts on CT between BHD and LAM(6). They found that compared with patients with LAM, the cysts in BHD patients had a more irregular shape, more septation, lower and more peripheral distribution, larger maximum size, and more attachment to the pleura. As we all know, it’s not too difficult to differentiate BHD from LAM as the later has more homogeneous cysts compared with BHD. Whether or not the characteristics of pulmonary image of BHD will be different from that of NBNL patients is not determined. In our study, for the first time, we are trying to distinguish BHD from other kinds of NBNL group based on digitalized radiologic pulmonary feature. We verified the speculation suspected by the previous study(6) that the cysts in BHD patients had a more irregular shape, more septation, lower and more peripheral distribution, and larger maximum size compared with LAM. Meanwhile, we also found that NBNL DCLDs have the similar morphology and distribution, and have less fusiform, peripheral, and para-mediastinal cysts. Those findings are consistent with the prior study, which reported that compared with patients with LIP or LAM, patients with BHD syndrome were significantly more likely to have elliptical (floppy) para-mediastinal cysts or a disproportionate number of para-mediastinal cysts(14). Our study also found that compared with patients with NBNL DCLDs or LAM, patients with BHD syndrome have less cysts ,the cysts in most of patients range from 20 to 50, and the largest cyst often located in lower lobe. Therefore, pulmonary cysts in BHD has specific radiologic feature that can different from other kind of DCLDs. However, we found that BHD and NBNL DCLDs have the similar diameters of largest cyst, and both are bigger than the diameters of largest cyst in LAM. As the result, the diameters of largest cyst could not be used to distinguish BHD from NBNL DCLDs.
The pathogenesis of lung cysts distribution is still unknown. There were hypothesises explaining it from the effect of the mutation in FLCN on the epithelial layer at the inside of the pleural cysts. The down-regulation of folliculin was followed by increased cell-cell adhesion(15). It is much more likely to believe that the development and recurrence of pneumothorax in BHD is related to the lack of epithelial layers to stretch, but a therapeutic study is needed(16).
Our study may have several limitations. First, the number of patients with BHD included is relatively small. Second, three-dimensional reconstruction of lung cysts is hard to achieve, the number and distribution of cysts were observed in the horizontal direction, causing some deviation in the data collection. However, two professional respiratory physicians and one radiologist worked independently and in random order to assess the thoracic CT results in patients to decrease the possible counting deviation.