INTRODUCTION: Usual interstitial pneumonia (UIP) refers to a typical pathologic finding in patients with suspected idiopathic pulmonary fibrosis (IPF). It theoretically occurs due to immunologic activity against specific antigens in genetically predisposed individuals. A specific antigen, however, has never been found although there are reports of an association between UIP and viral infections. 1 To our knowledge, alveolar osseous metaplasia has not been well described in association with UIP. We present a patient who presents with radiographic and histologic evidence of UIP but also peripherally located, alveolar osseous metaplasia.
CASE PRESENTATION: A 68 year old male without past medical history was referred for evaluation of shortness of breath. The shortness of breath had been present for 2-3 months, worsened with heavy activity and associated with diffuse muscle pain and jaw claudication. He denied a prior history of cardiopulmonary disease, smoking, drug use, asbestos exposure or travel. He worked as a horse rancher and lived in California his whole life. On exam, his oxygen saturation was 96% on room air but 84% with ambulation. Pulmonary function tests (PFT) showed a restrictive pattern and severely reduced DLCO. A chest x-ray showed moderate bilateral increased interstitial markings at the bases. Chest CT scan showed peripherally located areas of honeycombing and fibrosis that spared the central zones. Tiny flecks of calcification were seen in the peripheral regions abutting the pleural surface. A diagnostic bronchoscopy was performed showing no evidence of infection. Given his muscle pains, he underwent a muscle biopsy showing perivascular inflammation consistent with vasculitis. He was placed empirically on prednisone and later azathioprine. Unfortunately, repeat PFTs did not show improvement, and his dyspnea eventually worsened despite therapy. After much discussion, the patient chose to pursue open lung biopsy. The results showed microscopic honeycombing, chronic inflammation, temporal heterogeneity, and fibrosis in the subpleural areas consistent with UIP. There was also osseous metaplasia with dendriform calcification involving alveolar spaces. The patient was given a presumptive diagnosis of IPF associated with a non-specific vasculitis and referred for lung transplant.
DISCUSSION: Pulmonary calcifications can be seen in a wide variety of systemic disorders such as hyperparathyroidism, renal failure, intravenous calcium therapy, massive osteolysis, amyloidosis or multiple myeloma. Infections such as tuberculosis or exposures such as silicosis can also lead to nodular calcifications. In each case, calcium deposition occurs in response to chronic inflammation. Although the exact mechanism remains unknown, pulmonary ossification theoretically occurs due to osteoblast metaplasia of pulmonary fibroblasts rather than conversion of metastatic calcium into bone. This metaplasia occurs as a response to chronic insults. In cases of diffuse pulmonary ossification, the response likely represents a protective response to chronic irritation and injury. 2 While the pathogenesis of IPF remains unknown, it also results from chronic inflammation. Risk factors associated with the disease include cigarette smoking, infection, environmental pollutants, chronic aspiration and drugs. However, none of these factors adequately explain the progressive nature of the disease alone, and a genetic predisposition likely plays a role. The disease leads to chronic fibrosis and eventually severe, unremitting respiratory impairment.
CONCLUSIONS: To our knowledge, alveolar osseous metaplasia has rarely been associated with IPF. Its presence illustrates an unusual response to inflammation that occurred in this patient. While its long term clinical significance remains unknown, understanding risk factors that lead to its presence may be helpful in determining some of the similar mechanisms that perpetuated IPF in this case.
Reference #1 Geist LJ, Hunninghake GW. Potential role of viruses in the pathogenesis of pulmonary fibrosis. Chest 1993; 103:119S-120S
Reference #2 Kanne JP, Godwin JD, Takasugi JE, et al. Diffuse pulmonary ossification. J Thorac Imaging 2004; 19:98-102
DISCLOSURE: The following authors have nothing to disclose: Charles Poon
No Product/Research Disclosure Information