Birt-Hogg-Dubé Syndrome
Melissa L. Rosado-de-Christenson, MD, FACR
Axial CECT of a 68-year-old man with Birt-Hogg-Dubé syndrome demonstrates multifocal bilateral thin-walled pulmonary cysts. One cyst exhibits lentiform (cyan curved arrow) morphology and another a close relationship to a pulmonary vessel (cyan solid arrow).
Coronal CECT of the same patient shows that the cysts are bilateral and basilar predominant, exhibit lentiform shapes (cyan curved arrow), and have a close relationship to the pleural surfaces (cyan open arrow). The adjacent lung parenchyma is normal, and the cysts are not associated with pulmonary nodules.
Axial NECT of a 46-year-old man with Birt-Hogg-Dubé syndrome who presented with a spontaneous pneumothorax (cyan solid arrow) shows lentiform (cyan open arrow) and septated (cyan curved arrow) pulmonary cysts closely associated with the pleural surfaces.
Axial CECT of a 33-year-old woman with Birt-Hogg-Dubé syndrome shows a left upper lobe ovoid thin-walled pulmonary cyst. Note the small vessel (cyan solid arrow) that protrudes into the cyst lumen, a characteristic feature. The patient presented with chest pain related to a spontaneous pneumomediastinum (cyan curved arrow).
Key Facts
Rare inherited disorder characterized by triad of lung cysts (pneumothorax) and renal and cutaneous lesions
Bilateral basilar predominant lung cysts (up to 89% of cases)
Pneumothorax
Rounded, ovoid, lentiform cysts
Thin-walled cysts; may be lobular &/or multiseptate
Cysts may abut pleura, interlobular septa, and vessels
Findings of prior lung resection or pleurodesis for treatment of pneumothorax
May be normal, lung cysts are usually not visible
May demonstrate pneumothorax (up to 38% of cases)
Radiography
CT/HRCT
Lymphangioleiomyomatosis
Pulmonary Langerhans cell histiocytosis
Lymphoid interstitial pneumonia
Pneumocystis jirovecii pneumonia
Rare disorder; autosomal dominant inheritance
Typically asymptomatic; diagnosed incidentally
Chest pain and dyspnea related to spontaneous pneumothorax
Chronic cough and dyspnea with severe lung involvement
Typically normal pulmonary function
Consider Birt-Hogg-Dubé syndrome in young patients with spontaneous pneumothorax (or family history of pneumothorax) and skin and renal lesions
TERMINOLOGY
PREVIOUSNEXTRare inherited disorder characterized by triad of lung cysts (often complicated with pneumothorax) and renal and cutaneous lesions
IMAGING
PREVIOUSNEXTRound, ovoid, lentiform
Variable, ranging from few mm to > 2 cm
Lower lobe and subpleural predominance
Bilateral basilar predominant lentiform cysts abutting pleura, septa, and pulmonary vessels
May be normal; lung cysts usually not visible
May demonstrate pneumothorax (recurrent)
Evidence of prior lung resection &/or pleurodesis for pneumothorax
Rounded, ovoid, or lentiform cysts
Thin-walled cysts
Variable number and size, may be > 2 cm
Morphology: Lobular &/or multiseptate
Lower lobe and subpleural predominant
Abut or incorporate portions of pulmonary vessels
Abut pleura and interlobular septa
Bilateral basilar predominant lung cysts (up to 89% of cases)
Pneumothorax (up to 38% of cases)
Pneumomediastinum
HRCT for assessment and characterization of lung cysts
Abdominal imaging for detection and characterization of renal lesions
DIFFERENTIAL DIAGNOSIS
PREVIOUSNEXTLymphangioleiomyomatosis
Women of childbearing age, progressive symptoms
Diffuse lung cysts, chylothorax, pneumothorax, lymphadenopathy, renal angiomyolipomas
Pulmonary Langerhans Cell Histiocytosis
Smoking-related disease
Upper lung zone predominant cysts with irregular/bizarre shapes ± small stellate nodules
Lymphoid Interstitial Pneumonia
History of Sjögren syndrome
Lung cysts, ground-glass opacities, centrilobular nodules
Immunosuppression, acute or subacute symptoms
Ground-glass opacities ± upper lung zone cysts
Lymphoproliferative or autoimmune disorder
Systemic immunoglobulin light chain deposition
Diffuse lung cysts with vessels in cyst walls and pulmonary nodules
PATHOLOGY
PREVIOUSNEXTMajor: ≥ 5 adult-onset fibrofolliculomas (at least 1 histologically confirmed), FLCNmutation
Minor: Bilateral basilar lung cysts ± pneumothorax, early onset (≤ 50 years), multifocal/bilateral renal cell cancer, 1st-degree relative with Birt-Hogg-Dubé syndrome
Postulated overexpression of metalloproteinases may result in alveolar wall breakdown and cyst formation
Genetic defect on chromosome 17p11.2 (FLCN); encodes folliculin (tumor suppressor protein)
Diagnostic criteria (1 major, 2 minor)
Benign and malignant lesions of numerous organs, including: Thyroid, parathyroid gland, parotid gland, breast, colon, and peripheral nerves
Fibrofolliculomas (hair follicle hamartomas), trichodiscomas (hair disk tumors), achordons (skin tags)
Other skin lesions, including basal and squamous cancers
Multifocal bilateral renal carcinomas, renal cysts, occasional angiomyolipomas
Lentiform, subpleural, involve < 30% of lung
Lung cysts
Renal lesions
Skin lesions
Other organs
Lung cysts lined by pneumocytes, abut septa, vessels, &/or pleura; small pulmonary veins may protrude into cyst
CLINICAL ISSUES
PREVIOUSNEXTTypically normal pulmonary function
Typically asymptomatic; diagnosed incidentally
Chest pain and dyspnea related to spontaneous pneumothorax
Chronic cough and dyspnea with severe lung involvement
Rare disorder; autosomal dominant inheritance
~ 200 affected families described
DIAGNOSTIC CHECKLIST
PREVIOUSNEXTBirt-Hogg-Dubé syndrome in young patients with spontaneous pneumothorax (or family history of pneumothorax) and skin and renal lesions
SELECTED REFERENCES
PREVIOUSNEXTDal Sasso AA et al: Birt-Hogg-Dubé syndrome. State-of-the-art review with emphasis on pulmonary involvement. Respir Med. 109(3):289-96, 2015
Jawad H et al: Cystic interstitial lung diseases: recognizing the common and uncommon entities. Curr Probl Diagn Radiol. 43(3):115-27, 2014
Furuya M et al: Birt-Hogg-Dube syndrome: clinicopathological features of the lung. J Clin Pathol. 66(3):178-86, 2013
Tobino K et al: Characteristics of pulmonary cysts in Birt-Hogg-Dubé syndrome: thin-section CT findings of the chest in 12 patients. Eur J Radiol. 77(3):403-9, 2011
联系客服