Podoplanin‐positive myofibroblasts: a pathological hallmark of pleuroparenchymal fibroelastosis

Abstract

Pathological differential diagnoses of pleuroparenchymal fibroelastosis (PPFE) include usual interstitial pneumonia (UIP) and pulmonary apical cap (PAC); however, there are no specific immunostaining makers to distinguish between these diseases. We performed immunohistochemistry using several pleural mesothelial cell-related markers, including cytokeratin-5/6, CAM5.2, WT-1, calretinin, desmin and podoplanin, for PPFE (n = 4), UIP (n = 10) and PAC (n = 3) lung sections. Among the examined markers, in PPFE and PAC lungs podoplanin commonly showed positivity for spindle cells both in thickened pleura and subpleural fibroelastosis lesions; these cells were also stained with α-smooth muscle actin, a marker of myofibroblasts. However, even in elastic fibre-rich cases, UIP lungs did not show such podoplanin-positive myofibroblasts in pleura/subpleura and fibroblastic foci. These findings were also verified using immunofluorescence. By contrast, immunohistochemically as well as morphologically, the difference between PPFE and PAC was not apparent. The presence of podoplanin-positive myofibroblasts could be a pathological hallmark of PPFE, suggesting a pathogenic process distinct from UIP but common to PAC.

Acute Exacerbation of Pleuroparenchymal Fibroelastosis Secondary to Allogenic Hematopoietic Stem Cell Transplantation

“…Last, we found an accumulation of podoplanin-positive spindle cells in the fibrotic region of autopsied lungs. Enomoto et al reported that podoplanin-positive myofibroblasts might reflect mesothelial-to-mesenchymal transition, and this could be a pathological hallmark of iPPFE (38). Our findings suggest that a fibrotic process similar to iPPFE was also involved in the current case with post-HSCT PPFE.…”

Paradoxical Formation of a Pleuroparenchymal Fibroelastosis-like Lesion in the Chronic Course of Pulmonary Sarcoidosis

“…One of the pathological characteristics of PPFE is lymphatic proliferation, which may be a compensatory event secondary to impaired lymphatic drainage (13). It is necessary to investigate whether or not subpleural consolidations on chest CT in the present case were associated with particular pathological findings, such as fibrosis and the confluence of granulomas; increases in elastic fibers, proliferation of podoplaninpositive myofibroblasts (14), and lymphatic proliferation (13) as seen in PPFE cases; and increases in smooth muscle and collagenous fibers as seen in idiopathic pulmonary fibrosis/usual interstitial pneumonia cases.…”

Perinatal mesenchymal stromal cells of the human decidua restore continence in rats with stress urinary incontinence induced by simulated birth trauma and regulate senescence of fibroblasts from women with stress urinary incontinence

“…Here we have shown co-localization of α-SMA and smoothelin in SUI myofibroblast. Myofibroblasts that co-express α-SMA and smoothelin ( Lepreux et al, 2013 ), podoplanin ( Braun et al, 2011 ; Nazari et al, 2016 ; Enomoto et al, 2018 ; Hirayama et al, 2018 ), cadherin ( Hinz et al, 2004 ; Bowler et al, 2018 ), tenascin ( Katoh et al, 2020 ) or collagen I ( Zhang et al, 1994 ) have been found during the fibroblast-to-myofibroblast transition and are associated with advanced stages of fibrosis in several diseases. All these myofibroblast markers have also been found in the control group of women, as described by others for women operated on for other gynecological indications ( Ruiz-Zapata et al, 2020 ).…”