Nationwide retrospective observational study of idiopathic dendriform pulmonary ossification: clinical features with a progressive phenotype

Abstract

BackgroundDiffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO.MethodsWe conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO.ResultsTwenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22–56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.ConclusionsIDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

Diffuse pulmonary ossification: A case report unveiling clinical and histopathological challenges

“…Diffuse pulmonary ossification (DPO) is a rare pulmonary condition characterized by diffuse formation of mature bone in the lungs [ 5 ]. Based on two retrospective autopsy-based studies, the incidence of DPO ranges from 0.16% to 0.4% [ 6 , 11 ] with 80%–88% of cases occurring in men [ 5 , 6 , 11 ]. It is believed that DPO is a clinically under-recognized entity [ 7 , 13 , 14 ].…”

“…Pulmonary ossification can be subdivided into DPO (i.e., dendriform pulmonary ossification) and nodular pulmonary ossification (NPO) [ [4] , [5] , [6] ]. DPO is characterized by ramifying spicules of mature woven bone arranged in a serpentine fashion along the alveolar septa and is associated with fat or bone marrow elements in most cases [ 7 ]; conversely, NPO has round, and well-circumscribed outlines and is generally devoid of fat and marrow elements [ 6 ].…”

“…DPO, on the other hand, occurs most commonly in the background of chronic lung diseases, including pulmonary fibrosis, especially usual interstitial pneumonia (UIP) and chronic obstructive pulmonary disease (COPD) [ 11 ]. However, a nationwide 2-year survey in Japan [ 5 ] reported twenty-two cases of idiopathic diffuse pulmonary ossification (IDPO) and identified no underlying chronic pulmonary conditions. 80% of patients were asymptomatic with DPO found incidentally during medical check-ups.…”

Idiopathic diffuse pulmonary ossification: a case with 13-year follow-up

“…While most of the described cases were asymptomatic, evaluation of clinical course of the disease revealed signs of slow progression [5].…”

“…An accurate prognosis of DPO is difficult to determine, because of very limited number of cases with long-term follow-up data, but most of the previously published cases were asymptomatic and remained stable for many years [4]. In 2022, Nishioka et al [5] conducted a nationwide survey of patients with idiopathic DPO from 2017 to 2019 in Japan. Authors identified 22 cases of idiopathic DPO and estimated its' prevalence as 0,16 case per million.…”