Bubbles in the lung. Page 1 of 29

Bubbles in the lung. Poster No.: C-1048 Congress: ECR 2015 Type: Educational Exhibit Authors: A. Arango, A. Martínez de Alegría, R. García Figueiras, S. Baleato González, M. C. Ageitos Casais, M. V. Trujillo Ariza, I. Sánchez Paniagua, A. L. Carballeira; Santiago de Compostela/ES Keywords: Thorax, Lung, CT-High Resolution, Conventional radiography, Diagnostic procedure, Cysts DOI: 10.1594/ecr2015/C-1048 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 29

Learning objectives To describe the spectrum of pulmonary lesions that look like bubbles. To highlight the distinguishing features of pulmonary cysts. To review the gamut of cystic lung diseases illustrating their thoracic and extrathoracic manifestations. To emphasize the differences in the distribution of cysts within the lung. Page 2 of 29

Background Lungs can be affected by many air-containing lesions that look like bubbles: bullae, cavities, bronquiectasis, cysts... The most important imaging modality used in its evaluation is CT, being essential for the radiologist to know their typical features. Pulmonary cysts are uncommon lesions found in rare diseases such as Pulmonary Langerhans Cell Histyocitosis, Lymphangioleiomyomatosis and Birt-Hogg-Dubé Syndrome (multisystem disorders that usually lack of respiratory symptoms). As a result, recognizing pulmonary cysts can lead to the diagnosis of unusual pathologies. Page 3 of 29

Findings and procedure details PULMONARY BUBBLE-LIKE LESIONS Lungs can be affected by different gas-attenuation lesions that look like bubbles including bronquiectasis, cavities, cysts, areas of honeycombing, areas of emphysema, bullae and pneumatoceles. They are defined in The Fleischner s Society "Glossary of Terms for Thoracic Imaging" (1) according to their histological and radiological features. We have focused on its appearance on CT. Bronquiectasis are permanent dilatations of the bronquial tree that look like bubbles in cross-section images. This appearance is called the "signet ring sign" (2), which consists in annular images created by the dilated bronchus and its corresponding pulmonary artery. A cavity is a lucent area within a lung consolidation, mass or nodule with or without air-fluid levels. It is produced after the expulsion of a necrotic part of the lesion into the airway. Cavities are usually thick-walled (more than 4 mm). Pulmonary cysts are well-defined areas of hypodense parenchyma, usually thin-walled (less than 2 mm) and air-filled, but occasionally with fluid or solid contents. They are not associated with emphysema but they are the predominant finding of rare diseases such as Pulmonary Langerhan s cell Histiocytosis and Lymphangioleiomyomatosis. Moreover, they can be found in other situations like honeycombing. Honeycombing represents destruction and fibrosis of pulmonary parenchyma. It is defined as an area with reticular opacities and multiple cysts arranged in layers, usually affecting the subpleural lung. Emphysema consists in permanent enlargement of air-spaces with destruction of alveolar wall. It can affect the central lung (centrilobular emphysema), its periphery (paraseptal emphysema) or both (panlobular emphysema). Focal areas of centrilobular emphysema can look like cysts, but it is important to note that centrilobular emphysema lacks of perceptible wall and has central vascular structures (3) (4). Bullae are lucent thin-walled lesions larger than 1 cm of diameter, often associated with areas of emphysema. They are called "blebs" when subpleural and less than 1 cm of diameter, but the use of this term is discouraged. Page 4 of 29

Pneumatoceles are thin-walled cystic lesions located in areas previously affected by infections or traumas. They are probably sencondary to necrosis of lung parenchyma and check-valve mechanisms. Fig. 1: Spectrum of air-filled lung lesions that can look like bubbles: Bronchiectasis with the "signet ring sign" (a), thin-walled cysts in a patient with Pulmonary Langerhan s cell Histiocytosis (b), lesion with thick wall and central gas-attenuation area corresponding to cavitating nodule / cavity (c), honeycombing representing fibrosis of lung parenchima (d), centrilobular emphysema (e), paraseptal emphysema (f), large bulla (g) and panlobular emphysema (h). References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES PULMONARY CYSTIC DISEASES Many diseases show pulmonary cysts, including: Pulmonary Langerhan s cell Histiocytosis, Lymphangioleiomyomatosis (sporadic or associated with Tuberous Page 5 of 29

Sclerosis Complex), Follicular bronchiolitis, Lymphocytic Interstitial Pneumonia (LIP), Amyloidosis, Light-chain deposition disease (LCDD), Birt-Hogg-Dubé syndrome, metastases (3) and Pneumocystis jiroveci pneumonia (4) (5). The most important pulmonary cystic diseases are described below. Pulmonary Langerhan s cell Histiocytosis. Langerhan s cell Histiocytosis are a rare group of diseases consisting in Langerhan s cell accumulation in different organs (6). They are more common in childhood and range from unique lesions (Eosinophilic Granuloma) to fulminant disseminated disease (LetterSiwe disease). Pulmonary Langerhan s cell Histiocytosis is a smoking-realted disease typically affecting young adults (between 20-40 years). It is often limited to the lung, but eventually courses with bone lesions, diabetes insipidus, and skin lesions (6)(7). CT findings of Pulmonary Langerhan s cell Hystiocitosis change with the evolution of the disease. Initially, the principal finding are nodules (that correspond to Langerhan s cell granulomas). These nodules tend to cavitate and, finally, to form cysts. Both cysts and nodules predominate in upper lobes. Moreover, cysts are usually confluent and with bizarre shapes and irregular sizes (8). Smokers with lung nodules, cavitating nodules and cysts in upper lobes are likely affected by Langerhan s cell Histiocytosis (8). Page 6 of 29

Fig. 2: 31-year-old man with a lucent lesion in the left angle of the jaw found incidentally (a). The biopsy showed findings suggestive of Langerhan s cell Histiocytosis. CT confirmed the lytic lesion in the jaw (b) and demonstrated multiple thin-walled cysts in both lungs (c) predominantly in upper lobes, more evident on MiniMIP reconstructions (d). References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Page 7 of 29

Fig. 3: 51-year-old man. Smoker. CT demonstrated multiple pulmonary cysts (arrows) and a number of micronodules (asterisks), some of them peribroncovascular resembling the "tree in bud" pattern (a, b). Note the absence of findings in the lower lobe of the lung (c). Findings suggestive of Pulmonary Langerhan s cell Histiocytosis. References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Lymphangioleiomyomatosis. Lymphangioleiomyomatosis is an uncommon interstitial disease characterised by the proliferation of inmature smooth muscle cells in lungs and thoracic and retroperitoneal lymphatics (9). It typically affects women during their childbearing age. Lymphangioleiomyomatosis is indistinguishable from pulmonary involvement of Tuberous Sclerosis, which can also occur in men (5). Clinical manifestations include dyspnea, cough, hemoptysis and spontaneous pneumothorax, although it can be asymptomatic. Page 8 of 29

CT shows multiple cysts in both lungs, often with diffuse involvement of pulmonary parenchyma. Cysts tend to be rounded, thin-walled and affect juxtaphrenic recesses. These features, and the absence of nodules, are useful to differentiate Lymphangioleiomyomatosis from Pulmonary Langerhan s cell Histiocytosis (8). However, cysts coalesce and become irregular-shaped in end-stage diseases. Other findings are pleural effusions (chylothorax) and pneumothorax. Extra-pulmonary manifestations include lymphadenopathies, renal angiomyolipomas, chylous ascites and uterine leiomyomas (9). Fig. 4: 40-year-old woman with shortness of breath with exertion and normal plain chest film (a, b). CT revealed multiple cysts with irregular size and shape affecting both lungs suggestive of Lymphangioleiomyomatosis (c, d). References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Page 9 of 29

Fig. 5: 45-year-old woman with recurrent pneumothorax. CT showed a small right pneumothorax and multiple cysts with irregular size and shape in both lungs. (a, b). Age, sex and CT findings suggestive of Lymphangioleiomyomatosis. References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Tuberous Sclerosis Complex. Tuberous sclerosis is an inheritable autosomal dominant disease characterised by development of multiple hamartomas in central nervous system, eye, skin, heart, kidneys and other organs. It was initially described with the Vogt triad (epileptic seizures, mental retardation and facial angiofibromas), although it is only present in less than 30% of patients (9). Pulmonary involvement of Sclerosis Tuberosa has radiologic and histological features identical to Lymphangioleiomyomatosis. Page 10 of 29

Other manifestations of Tuberous Sclerosis Complex include multiple bilateral and poorfat renal angiomyolipomas, cardiac rhabdomyomas and multiple bone sclerotic lesion resembling osteopoikilosis. Fig. 6: 37-year-old woman with recurrent pneumothorax (a, b). CT revealed multiple sclerotic lesions in axial skeleton (c), pulmonary disease similar to Lymphangioleiomyomatosis (d) and numerous fat-attenuation lesions in both kidneys compatible with angiomyolipomas (e). Findings suggestive of Tuberous Sclerosis. In addition, cranial CT showed small periventricular calcifications pointing to calcified subependymal hamartomas (f). References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Page 11 of 29

Fig. 7: 79-year-old woman with Tuberous Sclerosis. CT revealed many sclerotic lesions in spine (a), multiple cysts in both lungs (b), several renal cysts (c) and a solid lesion in the inferior pole of the right kidney (arrow in c). MRI showed that this lesion was hypointense in T2 and T1-weighted sequences (d, e), lacking of micro and macroscopic fat but with an enhancing area after gadolinium administration (f). Findings suggestive of fat poor renal angiomyolipoma. References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Lymphocytic Interstitial Pneumonia. Lymphocytic Interstitial Pneumonia (LIP) is an uncommon disease often associated with Sjögren syndrome, AIDS and other collagen-vascular disorders. It especially affects women in the 5 cough ) (8). th decade, generally with respiratory symptoms (shortness of breath, Lymphocytic Interstitial pneumonia is included in the spectrum of lung lymphoproliferative disease, together with Follicular Bronchiolitis and Primary Pulmonary Lymphoma. Page 12 of 29

CT shows ground-glass opacities, centrilobular nodules and thin-walled cysts that usually affect lung basis. Cysts are typically less numerous than in Lymphangioleiomyomatosis or Pulmonary Langerhan s cell Histiocytosis. Other CT findings include peribronchovascular thickening, interlobular septal thickening, subpleural nodules and consolidations (3). Pulmonary cysts are also associated with Sjögren syndrome and Pulmonary Amyloidosis. Fig. 8: 43-year-old woman with temperature and right pleuritic pain. She was affected by Sjögren Syndrome. CT revealed small right pleural effusion, air trapping areas and several gas-density lesions in both lungs. Some of them were thick-walled pointing to infectious cavitating disease (arrows in a, c) but others were thin-walled compatible with cysts (c, d). Pulmonary cysts can represent Lymphocytic Interstitial Pneumonia in patients with Sjögren Syndrome. References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Page 13 of 29

Fig. 9: 65-year-old woman with persistent cough. She had Rheumatoid Arthritis and Sjögren Syndrome. CT showed multiple cysts in both lungs representing Lymphocytic Interstitial Pneumonia (a) and some solid nodules (b) whose biopsy revealed signs of amyloidosis. References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Pneumocystis jiroveci pneumonia. Pneumocystis spp. are ubiquitous fungi that may cause severe pneumonias in 3 immunosuppressed patients, specially in AIDS with CD4 counts below 200 cells/mm. Pneumocystis jiroveci pneumonia usually shows bilateral and multifocal ground-glass opacities on CT. Moreover it may be associated to cysts, often in patients who have suffered several infections (5). Birt-Hogg-Dubé Syndrome. Page 14 of 29

Birt-Hogg-Dubé Syndrome is a rare hereditary autosomal-dominant disorder characterized by renal tumors, skin lesions and pulmonary cysts that may cause spontaneous pneumothorax. The classic cutaneous involvement consists in appearance of multiple fibrofolliculomas on face, neck and upper trunck between third to fourth decade of life. They are 2- to 4mm, whitish, smooth, dome-shaped papules (10). Renal tumours are usually multiple, bilateral and range from benign lesions, such as oncocitomas, to renal cell carcinomas. Pulmonary cysts usually have different sizes and tend to locate in lower lobes. It is important to highlight this feature as it can help to distinguish Birt-Hogg-Dubé Syndrome from Lymphangioleiomyomatosis (11). Fig. 10: 55-year-old man with a sibling diagnosed of Birt-Hogg-Dubé Syndrome. He was right-nephrectomized due to a renal cell carcinoma ten years before. CT revealed Page 15 of 29

multiple irregular cysts in both lungs (a), predominantly in lower lobes as seen in MiniMIP reconstruction (b), and a left renal cell carcinoma (c). Moreover he had many fibrofolliculomas on his face (d). Findings of Birt-Hogg-Dubé Syndrome. References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Fig. 11: 84-year-old man with many fibrofolliculomas on his face and father of the previous patient. CT showed multiple irregular cysts in both lungs (a) predominantly in lower lobes as seen in MiniMIP reconstruction (b). Findings tipically related to BirtHogg-Dubbé Syndrome. There were no evidence of renal tumours. References: Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela Santiago de Compostela/ES Page 16 of 29

Images for this section: Fig. 1: Spectrum of air-filled lung lesions that can look like bubbles: Bronchiectasis with the "signet ring sign" (a), thin-walled cysts in a patient with Pulmonary Langerhan s cell Histiocytosis (b), lesion with thick wall and central gas-attenuation area corresponding to cavitating nodule / cavity (c), honeycombing representing fibrosis of lung parenchima (d), centrilobular emphysema (e), paraseptal emphysema (f), large bulla (g) and panlobular emphysema (h). Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela - Santiago de Compostela/ES Page 17 of 29

Fig. 2: 31-year-old man with a lucent lesion in the left angle of the jaw found incidentally (a). The biopsy showed findings suggestive of Langerhan s cell Histiocytosis. CT confirmed the lytic lesion in the jaw (b) and demonstrated multiple thin-walled cysts in both lungs (c) predominantly in upper lobes, more evident on MiniMIP reconstructions (d). Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela - Santiago de Compostela/ES Page 18 of 29

Fig. 4: 40-year-old woman with shortness of breath with exertion and normal plain chest film (a, b). CT revealed multiple cysts with irregular size and shape affecting both lungs suggestive of Lymphangioleiomyomatosis (c, d). Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela - Santiago de Compostela/ES Page 20 of 29

Fig. 6: 37-year-old woman with recurrent pneumothorax (a, b). CT revealed multiple sclerotic lesions in axial skeleton (c), pulmonary disease similar to Lymphangioleiomyomatosis (d) and numerous fat-attenuation lesions in both kidneys compatible with angiomyolipomas (e). Findings suggestive of Tuberous Sclerosis. In addition, cranial CT showed small periventricular calcifications pointing to calcified subependymal hamartomas (f). Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela - Santiago de Compostela/ES Page 22 of 29

Fig. 8: 43-year-old woman with temperature and right pleuritic pain. She was affected by Sjögren Syndrome. CT revealed small right pleural effusion, air trapping areas and several gas-density lesions in both lungs. Some of them were thick-walled pointing to infectious cavitating disease (arrows in a, c) but others were thin-walled compatible with cysts (c, d). Pulmonary cysts can represent Lymphocytic Interstitial Pneumonia in patients with Sjögren Syndrome. Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela - Santiago de Compostela/ES Page 24 of 29

Fig. 10: 55-year-old man with a sibling diagnosed of Birt-Hogg-Dubé Syndrome. He was right-nephrectomized due to a renal cell carcinoma ten years before. CT revealed multiple irregular cysts in both lungs (a), predominantly in lower lobes as seen in MiniMIP reconstruction (b), and a left renal cell carcinoma (c). Moreover he had many fibrofolliculomas on his face (d). Findings of Birt-Hogg-Dubé Syndrome. Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela - Santiago de Compostela/ES Page 26 of 29

Fig. 11: 84-year-old man with many fibrofolliculomas on his face and father of the previous patient. CT showed multiple irregular cysts in both lungs (a) predominantly in lower lobes as seen in MiniMIP reconstruction (b). Findings tipically related to Birt-HoggDubbé Syndrome. There were no evidence of renal tumours. Radioloxia, SERGAS, Hospital Clínico Santiago de Compostela - Santiago de Compostela/ES Page 27 of 29

Conclusion Pulmonary cysts are uncommon bubble-like lesions that may be difficult to distinguish from others such as cavities, bullae and emphysema. Recognizing pulmonary cysts can lead to the diagnosis of unusual pathologies. Page 28 of 29

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