STATdx 精选（002）：Birt-Hogg-Dubé综合征（文末有福利）

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

• Terminology

• Rare inherited disorder characterized by triad of lung cysts (pneumothorax) and renal and cutaneous lesions

• Imaging

• 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

• Top Differential Diagnoses

• Lymphangioleiomyomatosis

• Pulmonary Langerhans cell histiocytosis

• Lymphoid interstitial pneumonia

• Pneumocystis jirovecii pneumonia

• Clinical Issues

• 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

• Diagnostic Checklist

• Consider Birt-Hogg-Dubé syndrome in young patients with spontaneous pneumothorax (or family history of pneumothorax) and skin and renal lesions

TERMINOLOGY

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• Definitions

• Rare inherited disorder characterized by triad of lung cysts (often complicated with pneumothorax) and renal and cutaneous lesions

IMAGING

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• General Features

• Round, 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

• Best diagnostic clue

• Location

• Size

• Morphology

• Radiographic Findings

• May be normal; lung cysts usually not visible

• May demonstrate pneumothorax (recurrent)

• Radiography

• CT Findings

• 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

• Imaging Recommendations

• HRCT for assessment and characterization of lung cysts

• Abdominal imaging for detection and characterization of renal lesions

• Best imaging tool

DIFFERENTIAL DIAGNOSIS

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• Lymphangioleiomyomatosis

• 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

• Pneumocystis jirovecii Pneumonia

• Immunosuppression, acute or subacute symptoms

• Ground-glass opacities ± upper lung zone cysts

• Light-Chain Deposition Disease

• Lymphoproliferative or autoimmune disorder

• Systemic immunoglobulin light chain deposition

• Diffuse lung cysts with vessels in cyst walls and pulmonary nodules

PATHOLOGY

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• General Features

• Major: ≥ 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)

• Gross Pathologic & Surgical Features

• 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

• Microscopic Features

• Lung cysts lined by pneumocytes, abut septa, vessels, &/or pleura; small pulmonary veins may protrude into cyst

CLINICAL ISSUES

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• Presentation

• Typically normal pulmonary function

• Typically asymptomatic; diagnosed incidentally

• Chest pain and dyspnea related to spontaneous pneumothorax

• Chronic cough and dyspnea with severe lung involvement

• Most common signs/symptoms

• Other signs/symptoms

• Demographics

• Rare disorder; autosomal dominant inheritance

• ~ 200 affected families described

DIAGNOSTIC CHECKLIST

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• Consider

• Birt-Hogg-Dubé syndrome in young patients with spontaneous pneumothorax (or family history of pneumothorax) and skin and renal lesions

SELECTED REFERENCES

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1. Dal 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

2. Jawad H et al: Cystic interstitial lung diseases: recognizing the common and uncommon entities. Curr Probl Diagn Radiol. 43(3):115-27, 2014

3. Furuya M et al: Birt-Hogg-Dube syndrome: clinicopathological features of the lung. J Clin Pathol. 66(3):178-86, 2013

4. 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

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