A Puzzling Pneumothorax in a 36-Year-Old Woman

Medscape

24-07-2025

A 36-year-old woman with no significant medical history presented with recurrent spontaneous pneumothorax accompanied by acute chest pain and shortness of breath, an unusual occurrence, particularly in non-smokers without underlying lung disease.
The case was reported by Farman H. Fatah, MD, and colleagues from the University of Sulaymaniyah, Sulaymaniyah, Iraq.
The Patient and Her History
The patient presented to the emergency department with acute left-sided chest pain and shortness of breath. She had a history of asthma and right-sided spontaneous pneumothorax 7 years earlier, which was treated with video-assisted thoracoscopic surgery (VATS) and pleurodesis. Her family history was notable for asthma on her mother's side and colonic cancer on her father's side. She denied any history of smoking or environmental exposures.
On physical examination, breath sounds were markedly decreased over the left hemithorax. A chest x-ray was performed, revealing a left-sided apical pneumothorax characterised by a region of radiolucency with absent lung markings, indicating air accumulation in the pleural space. A pigtail catheter was inserted to relieve the pneumothorax.
Despite appropriate pigtail placement and conservative management, the pneumothorax persisted. The patient was referred for surgical evaluation and underwent VATS with pleurodesis and wedge resection. Intraoperatively, a ruptured subpleural bleb in the left upper lobe was identified and excised. Histopathology of the resected tissue was non-specific and showed no malignancy.
A chest CT was performed to investigate the underlying cause. Imaging revealed the site of the bleb rupture and multiple thin-walled cysts scattered throughout the lung parenchyma. Given the history of recurrent spontaneous pneumothorax, presence of bilateral pulmonary cysts, and family history of cancer, Birt-Hogg-Dubé syndrome (BHDS) was suspected.
Findings and Diagnosis
Genetic testing for mutations in the FLCN gene confirmed the diagnosis. The test included sequencing and deletion/duplication analyses of FLCN .
A pathogenic mutation in FLCN , confirmed by molecular testing, established a diagnosis of BHDS. BDHS is a rare autosomal dominant disorder caused by mutations in the FLCN gene and is characterised by a clinical triad of pulmonary cysts with spontaneous pneumothorax, cutaneous fibrofolliculomas, and renal tumours.
Although the estimated prevalence of BHDS is approximately two cases per million, its actual incidence is believed to be higher due to frequent underdiagnosis and highly variable clinical presentations, even among members of the same family. BHDS is often suspected in patients presenting with cystic lung lesions, a family history of related manifestations, recurrent pneumothorax, and characteristic dermatologic findings. A definitive diagnosis is established through genetic testing to confirm pathogenic variants in the FLCN gene.
The patient had no known renal or dermatologic manifestations at the time of diagnosis of the disease. She continued to experience mild postoperative dyspnoea and chest discomfort but resumed her daily activities and returned to work. She was scheduled for routine follow-up, including pulmonary function testing and renal surveillance imaging, according to the BHDS management guidelines.
Discussion
Pulmonary manifestations are often the earliest and most prominent clinical features of BHDS, frequently preceding skin and renal findings. The syndrome is characterised by multiple bilateral pulmonary cysts that tend to be irregular, thin-walled, and predominantly located in the basal and subpleural regions of the lungs. These cysts predispose affected individuals to spontaneous pneumothorax, which can be the first and sometimes the only presenting symptom.
One of the key challenges in diagnosing BHDS is its variable presentations. While the classical triad includes skin fibrofolliculomas, renal tumours, and pulmonary cysts, some individuals, like our patient, may present solely with pulmonary involvement. This phenotypic variability can lead to delayed or missed diagnoses, particularly when cutaneous or renal signs are absent or subtle. Approximately 41% of pulmonary cysts present with spontaneous pneumothorax, with a recurrence rate of 41%.
The majority of patients (> 90%) develop multiple fibrofolliculomas, especially on the face and upper trunk, in the second or third decade of life, with dermatologic findings serving as the first clinical clue in 25%-50% of cases. Renal tumours are observed in nearly 30% of patients, at a mean age of 50 years.
Although the estimated prevalence of BHDS is approximately two cases per million, its actual incidence is believed to be higher due to frequent underdiagnosis and highly variable clinical presentations, even among members of the same family.
This highlights the importance of considering BHDS in the differential diagnosis of spontaneous pneumothorax, particularly when it is recurrent or associated with atypical cystic lung disease.
Genetic confirmation through FLCN mutation testing is crucial not only to establish a definitive diagnosis but also to initiate appropriate long-term surveillance for potentially life-threatening renal malignancies. Surgical intervention, such as VATS pleurodesis, may be necessary when conservative approaches fail.
This case underscores the importance of considering BHDS in patients presenting with recurrent spontaneous pneumothorax, particularly when bilateral pulmonary cysts are evident and no other clear aetiology is identified.