Characterization of pulmonary cysts in Birt–Hogg–Dubé syndrome: histopathological and morphometric analysis of 229 pulmonary cysts from 50 unrelated patients

Kumasaka, Takashi; Hayashi, Takuo; Mitani, Keiko; Kataoka, Hideyuki; Kikkawa, Mika; Tobino, Kazunori; Kobayashi, Etsuko; Gunji, Yoshio; Kunogi, Makiko; Kurihara, Masatoshi; Seyama, Kuniaki

doi:10.1111/his.12368

Cited by 63 publications

(53 citation statements)

References 33 publications

(36 reference statements)

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“…In the few available pathological descriptions of BHD cysts, the histological features have generally been found to be indistinguishable from those of emphysema. Recently, however, in a study of 229 cysts from 50 patients with BHD, the majority of the cysts (88%) abutted the interlobular septa, and 14% contained intracystic structures composed of interlobular septa (12). The cysts were surrounded by normal lung parenchyma in all patients and lacked evidence of neoplastic cell proliferations or significant inflammation ( Figure 1B) (12).…”

Section: Cystic Lung Diseases Associated With Genetic Mutationsmentioning

confidence: 92%

“…Recently, however, in a study of 229 cysts from 50 patients with BHD, the majority of the cysts (88%) abutted the interlobular septa, and 14% contained intracystic structures composed of interlobular septa (12). The cysts were surrounded by normal lung parenchyma in all patients and lacked evidence of neoplastic cell proliferations or significant inflammation ( Figure 1B) (12). In many cases the cysts did not appear to communicate with the airway or were subtended by a very small airway (12).…”

Section: Cystic Lung Diseases Associated With Genetic Mutationsmentioning

confidence: 99%

“…Other pathways have also been implicated in the tumor-suppressive actions of FLCN, including transforming growth factor-b signaling (9) and the "differentially expressed in normal cells and neoplasia" (DENN) proteins that control intracellular trafficking (9,10). The role of FLCN in the maintenance of pulmonary structural integrity is not well established, but possible mechanisms of cyst formation include activation of the mTOR pathway (11), leading to cell dropout or adhesion protein defects or deficiencies that increase the vulnerability of the alveolar-septal junction to tearing by mechanical forces during the respiratory cycle (12).…”

Section: Cystic Lung Diseases Associated With Genetic Mutationsmentioning

confidence: 99%

“…The cysts were surrounded by normal lung parenchyma in all patients and lacked evidence of neoplastic cell proliferations or significant inflammation ( Figure 1B) (12). In many cases the cysts did not appear to communicate with the airway or were subtended by a very small airway (12). With deeper understanding of the molecular pathways involved, it is possible that distinctive morphological and immunohistochemical characteristics of BHD will emerge and enable the expert pathologist to distinguish BHD pathology from emphysema.…”

Section: Cystic Lung Diseases Associated With Genetic Mutationsmentioning

confidence: 99%

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Diffuse Cystic Lung Disease. Part II

Gupta

Vassallo

Wikenheiser-Brokamp

et al. 2015

Am J Respir Crit Care Med

127

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The diffuse cystic lung diseases have a broad differential diagnosis. A wide variety of pathophysiological processes spanning the spectrum from airway obstruction to lung remodeling can lead to multifocal cyst development in the lung. Although lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis are perhaps more frequently seen in the clinic, disorders such as Birt-Hogg-Dubé syndrome, lymphocytic interstitial pneumonia, follicular bronchiolitis, and light-chain deposition disease are increasingly being recognized. Obtaining an accurate diagnosis can be challenging, and management approaches are highly disease dependent. Unique imaging features, genetic tests, serum studies, and clinical features provide invaluable clues that help clinicians distinguish among the various etiologies, but biopsy is often required for definitive diagnosis. In part II of this review, we present an overview of the diffuse cystic lung diseases caused by lymphoproliferative disorders, genetic mutations, or aberrant lung development and provide an approach to aid in their diagnosis and management.

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Section: Cystic Lung Diseases Associated With Genetic Mutationsmentioning

confidence: 92%

Section: Cystic Lung Diseases Associated With Genetic Mutationsmentioning

confidence: 99%

Section: Cystic Lung Diseases Associated With Genetic Mutationsmentioning

confidence: 99%

Section: Cystic Lung Diseases Associated With Genetic Mutationsmentioning

confidence: 99%

See 2 more Smart Citations

Diffuse Cystic Lung Disease. Part II

Gupta

Vassallo

Wikenheiser-Brokamp

et al. 2015

Am J Respir Crit Care Med

127

View full text Add to dashboard Cite

show abstract

“…3) These cysts appear predominantly at the lower-medial zone of the lung field and adjacent to the interlobar fissure but sometimes abut peripheral pulmonary vessels. 4,5) Thus, the conventional surgical approach in which all subpleural cysts and bullae are resected is not feasible for the management of pneumothorax in BHDS. Here, we describe a patient with BHDS whose recurrent pneumothorax was successfully resolved by applying a pleural covering technique during thoracoscopic surgery.…”

Section: Introductionmentioning

confidence: 99%

Pleural Covering Application for Recurrent Pneumothorax in a Patient with Birt-Hogg-Dubé Syndrome

Ebana

Otsuji

Mizobuchi

et al. 2016

ATCS

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IntroductionBirt-Hogg-Dubé syndrome (BHDS), a hereditary genodermatosis caused by a germline folliculin (FLCN) mutation, was first described in 1975 and 1977. 1,2) The thoracic manifestations of this syndrome are multiple lung cysts and pneumothorax with frequent recurrences. 3) These cysts appear predominantly at the lower-medial zone of the lung field and adjacent to the interlobar fissure but sometimes abut peripheral pulmonary vessels. 4,5) Thus, the conventional surgical approach in which all subpleural cysts and bullae are resected is not feasible for the management of pneumothorax in BHDS. Here, we describe a patient with BHDS whose recurrent pneumothorax was successfully resolved by applying a pleural covering technique during thoracoscopic surgery. 6) This procedure was effective in preventing further recurrence. Case ReportA 30-year-old male presented at the emergency department of our hospital, complaining of a sudden left-sided chest pain. A chest X-ray and computed tomography showed collapse of the left lung and multiple lung cysts. He was diagnosed with left-sided pneumothorax and treated with the insertion of a portable drainage kit Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and recurrent pneumothorax. These cysts occupy predominantly the lower-medial zone of the lung field adjacent to the interlobar fissure, and some of them abut peripheral pulmonary vessels. For the surgical management of pneumothorax with BHDS, the conventional approach of resecting all subpleural cysts and bullae is not feasible. Thus, after handling several bullae by using a stapler or performing ligation as a standardized treatment, we applied to a pleural covering technique to thicken the affected visceral pleura and then to prevent recurrence of pneumothorax. We herein report the successful application of a pleural covering technique via thoracoscopic surgery to treat the recurrent pneumothorax of a 30-year-old man with BHDS. This technique is promising for the management of intractable pneumothorax secondary to BHDS.Keywords: Birt-Hogg-Dubé syndrome, multiple lung cysts, recurrent pneumothorax, thoracoscopic surgery H, et al. (Thoracic Egg ® , Sumitomo Bakelite CO., Ltd. Tokyo, Japan), that enables to manage him in a setting of outpatient clinic. One-week after insertion of the tube, resolution of the pneumothorax enabled removal of the chest drainage tube. The patient was an ex-smoker (10 packs/ year) but had no medical problems in the past. However, a noteworthy comment was that his father and brother had medical histories of pneumothorax. Since this patient had a family history of pneumothorax and had multiple lung cysts localized predominantly at the lower-medial zone of the lung fields (Fig. 1), a diagnosis of BHDS was strongly suspected. Genetic testing was performed using peripheral blood leucocytes, and then demonstrated that he had an insertion of cytosine (C) in exon 11 of the FLCN gene (c.1285dupC), thereby confirming the diagnosis. Subsequently, afte...

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