Pleuroparenchymal fibroelastosis with a novel fibrillin-2 gene variant characterized by the expression of prenatal fibrillin-2 antigen and the aberrant proliferations of elastin and reticular fibers, a case report

Abstract

Abstract Background: Pleuroparenchymal fibroelastosis is a recently recognized clinical entity characterized by interstitial pneumonia and has pathological characteristics with proliferating elastin at upper lung regions. Pleuroparenchymal fibroelastosis is categorized as idiopathic or non-idiopathic depending on coexistent initiating factors, however, congenital contractural arachnodactyly which is caused by abnormal production of elastin based on a mutation in fibrillin-2 gene, hardly reported the lung features resembling pleuroparenchymal fibroelastosis. We had a case of pleuroparenchymal fibroelastosis in a Japanese man with a novel mutation in fibrillin- 2 gene, which encode the prenatal fibrillin- 2 protein as a scaffold for elastin.Case presentation: A 45-year-old man, who had hardly open his mouth due to severe micrognathia, was referred to us with a complaint of cough and fever. Following the diagnosis of pneumonia with paraseptal emphysema at right upper lung regions, upper lung fibrosis were progressed to both side resulting in the platythorax and died of respiratory failure with hypercapnia complicated by chronic necrotizing aspergillosis. His severe micrognathia and paraseptal emphysema made it necessary to be considered the possibility of the hereditary connective tissue disease. The result of genetic tests for hereditary connective tissue disease identified his carrying a novel variant of the fibrillin-2 gene (NM_001999.3:c.3160C > A:p.Arg1054Ser). Mutations in fibrillin-2 are responsible for congenital contractural arachnodactyly to be characterized with skeletal features such as joint contracture, arachnodactyly, which share with Marfan syndrome caused by a mutation in fibrillin-1 gene. We explored his autopsied lung specimen for the relationship between the mutation in fibrillin-2 gene and upper lung fibrosis through the morphometry and the occupied area of elastic or reticular fibers, and through the immunohistochemical analysis in expression of fibrillin-2 antigen. The histopathological finding was consistent to pleuroparenchymal fibroelastosis, in which the aberrant and imbalanced proliferations of elastic and reticular fibers, and the expression of fibrillin-2 antigen were observed.Conclusion: Pleuroparenchymal fibroelastosis occurred in the lung in the patient carrying a novel fibrillin-2 gene variant and had the aberrant proliferations of elastic and reticular fibers with the expression of fibrillin-2 antigen.