A rare cause of spontaneous pneumothorax: radiological findings and surgical approach

INTRODUCTION

Birt-Hogg-Dubé Syndrome (BHDS) is a genetic disease equally affecting men and women with a germline autosomal dominant mutation of the folliculin (FLCN) gene, a tumor suppressor gene coding for a protein called FLCN^[1-3]. This modifies the normal signal of the mTOR growing pathway. BHDS commonly causes cutaneous alterations, renal tumors, and cystic lung lesions^[1,3]. In fact, more than 80% of patients with BHDS develop bilateral pulmonary cysts during their lifetime, putting them at risk for recurrent spontaneous pneumothorax (estimated recurrence rate of 75%-82%)^[4].

From a radiological point of view, BHDS is characterized by a predominant basal, subpleural distribution of the cysts, which are usually thin-walled and variable in size ranging from a few millimeters to several centimeters^[1-4].

CASE REPORT

A 63-year-old male was transferred to the Emergency Department (E.D.) of our tertiary center because of dyspnea. A pneumothorax affecting the left apex and base was diagnosed at a chest X-ray [Figure 1A].

Figure 1. (A) The chest X-ray of the 63-year-old patient admitted to the E.D. well-showing the left pneumothorax extending from the apex to the base (yellow arrows); in (B), the chest X-ray performed two days later showed the increase of the pneumothorax.

In his clinical history, two previous homolateral episodes of pneumothorax were reported and treated with drainage. Moreover, he referred to being affected by several comorbidities, such as previous colon cancer surgically treated, obstructive sleep apnea syndrome, obesity, hypertension, and hypothyroidism. He denied any drug abuse or tobacco smoke.

Two days after hospitalization, due to the worsening of the clinical conditions, a second chest X-ray was performed, and it demonstrated an increase of the pneumothorax with partial collapse of the left lower lobe [Figure 1B]. Generally, an X-ray showing a recidivant apico-basal episode of pneumothorax is sufficient to consider surgery to be strictly indicated, especially if the patient is symptomatic, as in the case we reported.

Therefore, to better characterize such findings, we preferred to execute a chest Computed Tomography (CT). The CT scan confirmed the severe pneumothorax, but it also revealed the presence of multiple bilateral cysts ranging from a few millimeters to 4 cm, mainly distributed in the lower lobes in the subpleural regions and along the fissures [Figure 2A-C]; the partial collapse of the left lower lobe was also clear [Figure 2A and C].

Figure 2. Axial (A), coronal (B), and sagittal (C) chest CT images of the 63-year-old patient confirm the great extension of the spontaneous left pneumothorax (yellow arrows in A, B, and C). Moreover, it is highlighted the partial collapse of the left lower lobe (blue arrowhead in A and C). It is shown multiple bilateral cysts with a predominant subpleural distribution in the lower lobes and along the fissures (white asterisks in A).

Given this evidence, a more thorough anamnesis was done, and it was revealed that the patient was previously diagnosed with BHDS through a specific genetic test. He came from another peripherical hospital and brought just a few clinical documents, so electronic files were unavailable.

Subsequently, the patient underwent surgical exploration through a biportal Video-Assisted Thoracic Surgery (VATS) approach. In this case of recidivant pneumothorax, we explored the chance to perform a bullectomy. Multiple strong pleuro-parietal and mediastinal adhesions involving the upper lobe and the presence of numerous diffuse cysts in both lobes, mainly affecting the lower segments, were identified [Figure 3].

Figure 3. Intraoperative images of a cyst due to Birt-Hogg-Dubé syndrome: the frailty of lung parenchyma affected by folliculin (FLCN) mutation is related to the thin wall of the cysts.

Due to these findings, we did not remove the cysts because we could not have been resolutive. Moreover, no intraoperative air leak was registered. Consequently, electrical cauterization of the parietal pleura followed by the instillation of 2 gr of sterile talc was carried out. We carefully spread the sterile talc through an aerosolizing device, which helped the ubiquitarian distribution in the pleural cavity and a homogenous inflammatory reaction. We especially avoided any talc accumulation during distribution in the pleural cavity because of the risk of granuloma formation.

After completing the hemostasis and pulmonary re-expansion, two apical drains were placed to gain better lung inflation in both chest sides (anterior wall and in the back) to ameliorate the mechanical adhesion of pleural layers. We removed the drains on the third postoperative day; after two days of suction, there was no evidence of postoperative air leakage. The procedure has been well tolerated by the patient: no fever or any other inflammatory reaction was registered during the hospital length.

No postoperative complications occurred, and the patient was discharged after five days. One year later, the patient is in good health. He did not have any further episodes of pneumothorax or any other signs or symptoms of lung function decreasing, so we did not further investigate his lung capacity. Moreover, it was previously reported that BHDS does not deteriorate lung function in terms of lung capacity (FEV1, FVC, Tiffenau’s ratio)^[5]. We decided to postpone a contralateral treatment because no previous episodes of pneumothorax were reported there. Moreover, the patients did not develop any other complications, especially no tumors were discovered in one year of follow-up; we are continuing to follow them with other Specialists. We discharged the patients with a personalized surveillance plan, as guidelines suggest. The plan is shown in Table 1. The thyroid, colon, kidneys, and cutis need to be investigated (to avoid the risk of cancer development). In particular, the cutis could hide a growing melanoma.

DISCUSSION

Thus, we hereby report the clinical, radiological, and surgical findings of a case of successful surgical treatment of pneumothorax due to BHDS. The rupture of lung cysts is the base mechanism causing recurrent pneumothorax (RP) in such cases. The high prevalence of RP must be discussed, considering the role of FLCN germline mutation in the lung parenchyma. FLCN is a classic tumor suppressor gene involved in the AKT-mTOR pathway, and it is also implicated in the dysregulation of cell-to-cell interaction, decreasing the adhesion between epithelial cells^[10]. It has been previously assessed that the aberrant expression of E-cadherin and claudin-1 induced a weaker intercellular interaction. Notably, in FLCN-deficient murine models, the aberrant FLCN induces an impaired lung structure due to monolayer Alveolar Epithelial Cells type II apoptosis and alveolar space enlargement. In addition, cell apoptosis decreases alveolar phospholipids, increasing alveolar surface tension and progressively maintaining this pathogenetic enlargement mechanism^[10,11].

Lung bullous diseases encompass several different diagnoses that must be taken into consideration.

In fact, among the main differential diagnoses, lymphoid interstitial pneumonia, Langerhans cell histiocytosis, and lymphangioleiomyomatosis (LAM) should certainly be considered^[12-14]. The main characteristics allowing the distinction of these diseases are summarized in Table 2.

In BHDS and other cases of spontaneous pneumothorax, while the first episode of pneumothorax is usually conservatively treated, surgery is mostly recommended for patients with a second episode. There are several treatments to manage these cases. According to the literature reported [Table 3], different and valuable experiences have been previously published, and the optimal management for each case must be calculated in a case-by-case discussion between Specialists. The most diffused procedures, with advantages, disadvantages, and recurrence percentages, are reported in Table 3.

The VATS approach is certainly a standard validated treatment. Mini-invasive surgery usually resolves pneumothorax with a lower incidence of postoperative morbidity and a good response compared to thoracotomy.

Despite this, in bullous disease, surgeons must also consider impaired lung parenchyma. Because of the frailty of lung tissue and the high number of cysts, bullectomy is poorly effective, so it is generally not performed or, when adopted, it is not definitive.

Intraoperative chemical pleurodesis could be used to enforce the attachment of pleural layers reducing further episodes of pneumothorax, and this procedure, alone or in combination with surgery, has already been employed in BHDS^[28,29]. Pleurodesis is commonly obtained with the instillation of sterile talc in the cavum after pleural abrasion^[30]. A more recent treatment available is the total pleural coverage, employed especially in LAM. An oxidative regenerated cellulose mesh or a polyglycolic acid felt is placed in the visceral pleura covering the entire lung surface. Then a fibrin glue attaches the layers^[31,32]. This treatment was not suitable in our center, so we decided to use pleurodesis.

There is a large expertise among tertiary centers on pleurodesis. Caustication is usually adopted in RP. Talc pleurodesis is diffused as a technique that prevents malignant pleural effusion. In our case, electrical caustication and talc pleurodesis are diffusely and successfully adopted. In this case, one year after surgery, with no recurred episodes, we can maybe be confident to conclude that the selected procedure was correctly suitable for our patients.

In conclusion, although rare, BHDS should be considered among the differential diagnoses in patients with multiple cysts at imaging, especially in the case of spontaneous pneumothorax. Radiologists should support clinicians and surgeons in the identification of this entity, and the proper therapeutic approach should be decided on a case-by-case basis according to the severity of the pattern. When bullectomy appears to be non-resolutive, and there is no evidence of intraoperative air leak, marginal resection could be superseded. In such cases, a mini-invasive electrical caustication and talc pleurodesis might be taken to be considered as a valuable treatment.