The Clinical Respiratory Journal LETTER TO THE EDITOR
Dystrophic ossification on trachea and bronchus
Introduction Diffuse pulmonary ossification (DPO) is an uncommon condition defined by widespread heterotopic bone formation within the pulmonary tissue and divided into two types: dendriform and nodular form. Dendriform pulmonary ossification is a rare condition of unknown origin wherein mature bone, usually containing marrow, is found within the pulmonary parenchyma. The nodular form is characterized by intra-alveolar bone deposits usually without marrow elements. DPO is usually found in the elderly. Patients can be asymptomatic or have symptoms due to underlying diseases. Laboratory findings have no diagnostic value because serum alkaline phophatase activity, calcium and phosphorus levels are usually normal. DPO is usually invisible on chest X-ray, but highresolution computed tomography (HRCT) scan using 1-mm slices of appropriate mediastinal window settings shows branching lesions of bone density in the subpleural parts. Histopathologic analysis via transbronchial lung biopsy or open lung biopsy usually gives the definitive diagnosis (1). Here we report an idiopathic case of DPO detected during evaluation of chronic cough.
Case reports An 84-year-old woman was presented with cough for 4 months. There was no history of specific occupation or smoking. Chest posterior-anterior projection (PA) showed a mass on right lower lung. CT of the chest showed 8.5 cm-sized heterogeneous enhancing mass and multiple lymph nodes enlargements in the mediastinum, and multiple tiny high densities of indentations on the mucosa from trachea to main bronchus in addition to lung mass (Fig. 1A). Bronchoscopy showed that multiple whitish, small and hard humps were
Figure 1. A. HRCT finding, B. Bronchoscopic biopsy showed dystrophic ossification.
tightly attached to the wall from trachea to main bronchus, looking like an appearance that stalagmites and stalactites studded (Fig. 2), and there was no lesion that suspected to be an endobronchial metastasis. Bronchoscopic biopsy revealed a dystrophic ossification (Fig. 1B). She was diagnosed as a squamous-cell carcinoma of the lung, stage IV. The cough was well controlled under codein. She has been under observation without a management including chemotherapy because of her old age and poor performance status.
Discussion Received: 30 April 2013 Revision requested: 28 August 2013 Accepted: 22 September 2013
130
Dystrophic calcification and ossification is relatively more commonly seen in bronchi of cystic fibrosis patients, and it is thought to be the result of sustained
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Kim and Lee
Letter to the editor
Figure 2. Bronchoscopy finding.
bronchial infection and chronic inflammation, and is an additional contributory factor to bronchiectasis and airway instability (2). The ossification appears to stem from the stroma of fibrotic lung. At certain points, the bone pierces the interstitium and projects into the alveolar spaces (3). DPO has been reported in individual cases of busulfan therapy, cystic fibrosis, amyloidosis, histoplasomosis and chronic abscess (4). Pathogenesis is not precisely understood. Presumably, ectopic ossification is a result of various factors including cell and tissue injury, alkaline environment, cessation of pulmonary blood flow, presence of collagen and profibrogenic cytokines, extravasation and metallic deposition (1). In DPO, HRCT scans of the thorax reveal lines of 1–4 mm in the form of either branching calcifications of bronchovascular districution in the dendriform type or multiple areas of tiny calcified subpleural nodules in the nodular type (5). In our case, the CT showed multiple tiny high densities of indentations on the mucosa from trachea to main bronchus. This case was diagnosed as a dystrophic ossification pathologically. The lesions in trachea and bronchus
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
were only found incidentally and are thought to apart from lung cancer. The lesions were tightly fixed on bronchus. The cough might have been induced by these lesions, even though it could have also resulted from lung cancer. There has not been appropriate management for the dystrophic calcification and ossification. But because dystrophic calcification and ossification has been thought to be resulted from chronic inflammation and infection on bronchus, the control of inflammation and infection is important. According to a few reports of DPO diagnosed during life, the clinical course of the disease seems to be indolent or slowly progressive (1). Prognosis probably depends upon the age and underlying conditions of the patient. Bisphophonates inhibit osteoclasts and indirectly, by coupling between bone resorption and formation, also inhibit the bone formation of osteoblasts, and it has been suggested that delaying the mineralization of heterotropic ossification (6). Warfarin is a vitamin K antagonist that is able to inhibit γ-carboxlyation of osteocalcin, which has a role in bone formation, so Warfarin had been introduced to diminishing of heterotopic ossifications (7). 131
Letter to the editor
There had been trials to evaluate the role of bisphosphonate and warfarin in delaying or preventing ectopic ossification in pulmonary tissue, but the results remain to be determined. In conclusion, we herein presented a case of idopathic DPO that was detected during evaluation of chronic cough. We did observation without any management because of her old age and poor performance status. However, recently there had been a report of a 26-year-old man diagnosed with DPO (8), so more studies on early diagnosis and proper treatment of DPO are needed in the future. Min Suk Kim and June-Hyuk Lee Department of Internal Medicine, Respiratory-Allergy, and Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University, Bucheon City, Republic of Korea
References 1. Peros-Golubicic T, Tekavec-Trkanjec J. Diffuse pulmonary ossification: an unusual interstitial lung disease. Curr Opin Pulm Med. 2008;14(5): 488–92.
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Kim and Lee
2. Ogrinc G, Kampalath B, Tomashefski JF, Jr. Destruction and loss of bronchial cartilage in cystic fibrosis. Hum Pathol. 1998;29(1): 65–73. 3. Muller KM, Friemann J, Stichnoth E. Dendriform pulmonary ossification. Pathol Res Pract. 1980;168(1–3): 163–72. 4. Joines RW, Roggli VL. Dendriform pulmonary ossification. Report of two cases with unique findings. Am J Clin Pathol. 1989;91(4): 398–402. 5. Gevenois PA, Abehsera M, Knoop C, Jacobovitz D, Estenne M. Disseminated pulmonary ossification in end-stage pulmonary fibrosis: CT demonstration. AJR Am J Roentgenol. 1994;162(6): 1303–4. 6. Haran M, Bhuta T, Lee B. Pharmacological interventions for treating acute heterotopic ossification. Cochrane Database Syst Rev. 2004;(4): CD003321. 7. Valleala HV, Bohling TO, Konttinen YT. Regression of heterotopic ossification after starting warfarin – an effect mediated by inhibition of gamma-carboxylation of osteocalcin? – a case report. Acta Orthop. 2007;78(5): 693–5. 8. Mizushina Y, Bando M, Hosono T, Mato N, Nakaya T, Yamasawa H, Hironaka M, Tanaka A, Sugiyama Y. A rare case of asymptomatic diffuse pulmonary ossification detected during a routine health examination. Intern Med. 2012;51(20): 2923–7.
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Dystrophic ossification on trachea and bronchus
Introduction Diffuse pulmonary ossification (DPO) is an uncommon condition defined by widespread heterotopic bone formation within the pulmonary tissue and divided into two types: dendriform and nodular form. Dendriform pulmonary ossification is a rare condition of unknown origin wherein mature bone, usually containing marrow, is found within the pulmonary parenchyma. The nodular form is characterized by intra-alveolar bone deposits usually without marrow elements. DPO is usually found in the elderly. Patients can be asymptomatic or have symptoms due to underlying diseases. Laboratory findings have no diagnostic value because serum alkaline phophatase activity, calcium and phosphorus levels are usually normal. DPO is usually invisible on chest X-ray, but highresolution computed tomography (HRCT) scan using 1-mm slices of appropriate mediastinal window settings shows branching lesions of bone density in the subpleural parts. Histopathologic analysis via transbronchial lung biopsy or open lung biopsy usually gives the definitive diagnosis (1). Here we report an idiopathic case of DPO detected during evaluation of chronic cough.
Case reports An 84-year-old woman was presented with cough for 4 months. There was no history of specific occupation or smoking. Chest posterior-anterior projection (PA) showed a mass on right lower lung. CT of the chest showed 8.5 cm-sized heterogeneous enhancing mass and multiple lymph nodes enlargements in the mediastinum, and multiple tiny high densities of indentations on the mucosa from trachea to main bronchus in addition to lung mass (Fig. 1A). Bronchoscopy showed that multiple whitish, small and hard humps were
Figure 1. A. HRCT finding, B. Bronchoscopic biopsy showed dystrophic ossification.
tightly attached to the wall from trachea to main bronchus, looking like an appearance that stalagmites and stalactites studded (Fig. 2), and there was no lesion that suspected to be an endobronchial metastasis. Bronchoscopic biopsy revealed a dystrophic ossification (Fig. 1B). She was diagnosed as a squamous-cell carcinoma of the lung, stage IV. The cough was well controlled under codein. She has been under observation without a management including chemotherapy because of her old age and poor performance status.
Discussion Received: 30 April 2013 Revision requested: 28 August 2013 Accepted: 22 September 2013
130
Dystrophic calcification and ossification is relatively more commonly seen in bronchi of cystic fibrosis patients, and it is thought to be the result of sustained
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Kim and Lee
Letter to the editor
Figure 2. Bronchoscopy finding.
bronchial infection and chronic inflammation, and is an additional contributory factor to bronchiectasis and airway instability (2). The ossification appears to stem from the stroma of fibrotic lung. At certain points, the bone pierces the interstitium and projects into the alveolar spaces (3). DPO has been reported in individual cases of busulfan therapy, cystic fibrosis, amyloidosis, histoplasomosis and chronic abscess (4). Pathogenesis is not precisely understood. Presumably, ectopic ossification is a result of various factors including cell and tissue injury, alkaline environment, cessation of pulmonary blood flow, presence of collagen and profibrogenic cytokines, extravasation and metallic deposition (1). In DPO, HRCT scans of the thorax reveal lines of 1–4 mm in the form of either branching calcifications of bronchovascular districution in the dendriform type or multiple areas of tiny calcified subpleural nodules in the nodular type (5). In our case, the CT showed multiple tiny high densities of indentations on the mucosa from trachea to main bronchus. This case was diagnosed as a dystrophic ossification pathologically. The lesions in trachea and bronchus
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
were only found incidentally and are thought to apart from lung cancer. The lesions were tightly fixed on bronchus. The cough might have been induced by these lesions, even though it could have also resulted from lung cancer. There has not been appropriate management for the dystrophic calcification and ossification. But because dystrophic calcification and ossification has been thought to be resulted from chronic inflammation and infection on bronchus, the control of inflammation and infection is important. According to a few reports of DPO diagnosed during life, the clinical course of the disease seems to be indolent or slowly progressive (1). Prognosis probably depends upon the age and underlying conditions of the patient. Bisphophonates inhibit osteoclasts and indirectly, by coupling between bone resorption and formation, also inhibit the bone formation of osteoblasts, and it has been suggested that delaying the mineralization of heterotropic ossification (6). Warfarin is a vitamin K antagonist that is able to inhibit γ-carboxlyation of osteocalcin, which has a role in bone formation, so Warfarin had been introduced to diminishing of heterotopic ossifications (7). 131
Letter to the editor
There had been trials to evaluate the role of bisphosphonate and warfarin in delaying or preventing ectopic ossification in pulmonary tissue, but the results remain to be determined. In conclusion, we herein presented a case of idopathic DPO that was detected during evaluation of chronic cough. We did observation without any management because of her old age and poor performance status. However, recently there had been a report of a 26-year-old man diagnosed with DPO (8), so more studies on early diagnosis and proper treatment of DPO are needed in the future. Min Suk Kim and June-Hyuk Lee Department of Internal Medicine, Respiratory-Allergy, and Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University, Bucheon City, Republic of Korea
References 1. Peros-Golubicic T, Tekavec-Trkanjec J. Diffuse pulmonary ossification: an unusual interstitial lung disease. Curr Opin Pulm Med. 2008;14(5): 488–92.
132
Kim and Lee
2. Ogrinc G, Kampalath B, Tomashefski JF, Jr. Destruction and loss of bronchial cartilage in cystic fibrosis. Hum Pathol. 1998;29(1): 65–73. 3. Muller KM, Friemann J, Stichnoth E. Dendriform pulmonary ossification. Pathol Res Pract. 1980;168(1–3): 163–72. 4. Joines RW, Roggli VL. Dendriform pulmonary ossification. Report of two cases with unique findings. Am J Clin Pathol. 1989;91(4): 398–402. 5. Gevenois PA, Abehsera M, Knoop C, Jacobovitz D, Estenne M. Disseminated pulmonary ossification in end-stage pulmonary fibrosis: CT demonstration. AJR Am J Roentgenol. 1994;162(6): 1303–4. 6. Haran M, Bhuta T, Lee B. Pharmacological interventions for treating acute heterotopic ossification. Cochrane Database Syst Rev. 2004;(4): CD003321. 7. Valleala HV, Bohling TO, Konttinen YT. Regression of heterotopic ossification after starting warfarin – an effect mediated by inhibition of gamma-carboxylation of osteocalcin? – a case report. Acta Orthop. 2007;78(5): 693–5. 8. Mizushina Y, Bando M, Hosono T, Mato N, Nakaya T, Yamasawa H, Hironaka M, Tanaka A, Sugiyama Y. A rare case of asymptomatic diffuse pulmonary ossification detected during a routine health examination. Intern Med. 2012;51(20): 2923–7.
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
