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Birt-Hogg-Dubé (BHD) syndrome is a rare genetic disorder characterized by cutaneous fibrofolliculomas, pulmonary cysts and renal cell carcinomas. Affected individuals inherit germline mutations in the folliculin gene (FLCN). Approximately 150 pathogenic FLCN variants have been identified worldwide. Many Japanese probands of BHD syndrome were first identified by pulmonologists and/or radiologists during treatment of pneumothoraces. Lung specimens obtained through video-assisted thoracoscopic surgery (VATS) have characteristic features unique to BHD syndrome; however, pathologists often miss key findings and diagnose patients with "bullae/blebs". The pleural and subpleural cysts of BHD syndrome-associated lung diseases are often modified by tissue remodeling and can be difficult to distinguish from emphysematous bullae/blebs. Intraparenchymal unruptured cysts tend to retain distinctive features that are different from other cystic lung diseases. Here, we review the clinicopathological findings of BHD syndrome in a Japanese population based on data from 200 probands diagnosed by genetic testing and a total of 520 symptomatic family members identified through BHD-NET Japan (http://www.bhd-net.jp/). Detailed morphology of pulmonary cysts obtained from VATS and autopsied lung specimens are described, and pathological clues for differentiating miscellaneous cystic lung disorders are discussed., (© 2019 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a recently recognized neurological disease, and mutations in the MLC1 gene have been identified as the cause of the disorder. A 54-year-old Japanese woman with macrocephaly presented with progressive mental decline, gait disturbance due to spasticity and ataxia, and choreoathetotic movement in the left upper extremity. Brain magnetic resonance imaging (MRI) revealed characteristic subcortical cysts in addition to diffuse white matter involvement. Genetic analysis of the MLC1 gene identified an S93L mutation in a homozygous state. This case is particularly valuable because of the lack of knowledge on the long-term prognosis of MLC.

Purpose: To determine the MR appearance of cerebellar abnormalities in Fukuyama congenital muscular dystrophy., Methods: We reviewed brain MR images of 25 patients with Fukuyama congenital muscular dystrophy and examined the autopsy specimens of a 23-month-old girl with the disease to determine the pathologic nature of the MR findings., Results: MR studies revealed two characteristic cerebellar abnormalities: (a) disorganized cerebellar folia (16 cases) that were recognized as unusual distortions of the cortex; and (b) clusters of intraparenchymal cysts (23 cases). The two lesions were located close to each other, and milder lesions tended to affect only the superior semilunar lobule. The autopsy specimen revealed small cerebellar cysts, which consisted of dilated subarachnoid spaces buried beneath the malformed cortex., Conclusion: The disorganized folia represent cerebellar polymicrogyria, and the presence of cerebellar cysts is related to the polymicrogyria. These two MR changes are often present in Fukuyama congenital muscular dystrophy and are distinct enough to suggest the radiologic diagnosis.