Amyotrophic lateral sclerosis associated with pleuroparenchymal fibroelastosis

An autopsy case of sporadic amyotrophic lateral sclerosis (ALS) associated with pleuroparenchymal fibroelastosis (PPFE), a rare form of idiopathic interstitial pneumonia, is reported. The patient, a 76-year-old man, presented with shortness of breath and dyspnea and died of progressive respiratory failure after a clinical course of 9 months. Muscle weakness and motor disturbance were mild, and the diagnosis of ALS was not established until one month prior to death. He had serum IgM-kappa monoclonal gammopathy (IgM: 1,232 mg/dL). Autopsy demonstrated ALS of the lower neuron-predominant type. The density of motor neurons in the spinal anterior horn showed a moderate decline, and many remaining neurons contained round inclusions that were immunoreactive for pTDP-43 (phosphorylated transactivation responsive DNA-binding protein of 43 kD) and ubiquitin. Betz cells and the pyramidal tracts were well preserved. The lung showed typical features of PPFE predominantly affecting the upper lobe: fibro-hyalinous thickening of the visceral pleura, a marked increase and aggregation of elastic fibers in the subpleural zone, and intra-alveolar collagenous fibrosis with an increase of elastic fibers in the alveolar septa. Although the complications from interstitial lung diseases including PPFE in ALS patients are usually regarded as incidental, PPFE is clinically important because of its markedly adverse influence on the clinical course. IgM-monoclonal gammopathy is another notable finding in the present case, which is occasionally seen in ALS patients, and the pathogenesis of PPFE is also considered to be associated with immunological derangements.