- Email: [email protected]
Diffuse pulmonary ossification: an uncommon incidental autopsy finding
Pathology (February 2006) 38(1), pp. 45–48
ANATOMICAL PATHOLOGY
Diffuse pulmonary ossification: an uncommon incidental autopsy finding JASON TSEUNG
AND
JOHAN DUFLOU
Department of Forensic Medicine, Central Sydney Laboratory Service, Glebe, New South Wales, Australia
Summary Aim: To determine the incidence of diffuse pulmonary ossification (DPO) and its subtypes at autopsy and correlation with clinical and histological features. Methods: Autopsy reports from our institution over a 64month period were reviewed for findings of DPO. The pattern of ossification, demographics and clinical data were obtained from both paraffin sections and final autopsy reports. In a selected case, chest radiograph and wet tissue were obtained. Results: Seventeen histologically confirmed cases of DPO were found in 10 426 autopsy cases, representing an incidence of 1.63 cases/1000 autopsies. There was a predilection in males (88%) and underlying pulmonary disease (88%). In contrast to published studies, dendriform DPO was more common than the nodular type in our cohort (11 and 6 cases, respectively). The dendriform type was more commonly associated with marrow elements. Conclusions: Diffuse pulmonary ossification is uncommon and rarely diagnosed during life, but can easily be identified when sectioning the lungs at autopsy. There is recent renewed interest in diagnosing and determining the significance of DPO using high resolution computed tomography and thoracoscopic biopsy. Key words: Lung, heterotopic ossification, autopsy.
review of DPO found in our institution to correlate the clinical and histological features.
MATERIALS AND METHODS Materials Autopsy cases between January 2000 and April 2005, describing either microscopic or macroscopic bone formation in the lung, were electronically retrieved from the Department of Forensic Medicine, Central Sydney Laboratory Service. In all cases, both the completed autopsy report and the H&E-stained slides were available. Actual radiograph and formalin-fixed tissue were obtained for one case. Methods The autopsy reports were examined to eliminate cases of focal ossification, or ossification of bronchial cartilage. The clinical data of the deceased, including age, gender, cause of death and significant pulmonary/systemic comorbidities, were extracted from the case report. Where mentioned, the location and extent of pulmonary ossification were recorded. All histological lung sections were reviewed to confirm and classify the diagnosis of DPO, based on the morphology of the bone fragments and the preservation of alveolar septae. The presence of background pulmonary pathology, parenchymal calcification, marrow fat and/or haematopoietic cells in the bone fragments were also noted. In one of the cases, a piece of lung tissue was digested overnight with commercial 5% sodium hypochlorite to recover the bone fragments.2,4
Received 15 August, accepted 9 October 2005
RESULTS INTRODUCTION Diffuse pulmonary ossification (DPO) represents an unusual metaplastic response of the lung to injury. The definition of DPO is qualitative, with authors describing ‘disseminated, widespread or extensive’ bone formation in the lung.1–5 In essence, it implies an underlying cause affecting diffuse areas of the lung, as opposed to ossification within focal lesions such as an abscess or tumour. Two patterns—dendriform pulmonary ossification and nodular pulmonary ossification—have been described histologically.1–3 The dendriform type arises within the alveolar septae forming a coral-like network of bone, whereas the nodular type forms lobulated bone fragments within the alveolar spaces. Although numerous reports of DPO have been published since its first description by Luschka in 1856,1 it remains a poorly defined entity of uncertain clinical significance. In life, it is masked by pulmonary disease clinically and radiologically, and is mostly identified incidentally during autopsy. We have conducted a case
A total of 10 426 adult and paediatric post-mortem reports were found during the 64-month period. There were 17 cases of DPO, none of which were diagnosed prior to death. This represented 0.16% of all autopsies, or 3.2 cases per year. The incidence had not changed significantly compared with the period of 1991–1999, where 26 cases were identified (2.9 cases per year, unpublished). The clinical and histological features of the cohort are summarised in Table 1. Analysis of the data showed the median age was 72 (range 32–91), with a 7.5:1 male predominance. Most had a history of chronic pulmonary disease, most commonly chronic obstructive pulmonary disease (COPD, 35%), followed closely by established pulmonary fibrosis (29%). Only 18% (3/17) died directly from a respiratory cause. Ossification was mostly of the dendriform type (Fig. 1), with 73% (8/11) containing bone marrow elements. In contrast, bone marrow elements were only present in 17% (1/6) cases of nodular type DPO (Fig. 2). In six cases where the site of ossification was described, there was a predilection to the subpleural area of the lower lobes. Four
ISSN 0031-3025 printed/ISSN 1465-3931 # 2006 Royal College of Pathologists of Australasia DOI: 10.1080/00313020500464912
46
Pathology (2006), 38(1), February
TSEUNG AND DUFLOU
TABLE 1
Summary of identified cases of diffuse pulmonary ossification
Age
Sex
Cause of death
32
M
Acute pneumonia
43 48
M M
Suicide, drug toxicity Seizure
54
M
Suicide, drug toxicity
64 65
M M
65 67
M M
72
M
73
F
74
M
75
M
82
M
Aortic dissection Ischaemic heart disease Suicide, hanging Ischaemic heart disease Ischaemic heart disease Ischaemic heart disease Ruptured aortic aneurysm Ischaemic heart disease Acute pneumonia
85 88 90
M M F
Cholangitis Undetermined Perforated gastric ulcer
91*
M
Acute pneumonia
Significant comorbidity
Pulmonary disease
Extensive third degree burns Renal transplant
Diffuse alveolar damage
Papillary renal cell carcinoma
Gallbladder adenocarcinoma Chronic lymphoid leukaemia Clear cell renal cell carcinoma
Type
Site, if stated
Marrow elements
Lung calcification
Noted in summary
D
COPD
N N
COPD
N
Coalminer’s lung COPD
N N
COPD
D D
Bilateral lower lobes
Yes
Yes Yes
Yes
Yes
Yes
IPF
D
Bilateral
COPD
D
Left lower lobe
Past tuberculosis
D
Yes
IPF
D
Yes
COPD
N
IPF IPF Pulmonary hypertension IPF
D D D D
Bilateral subpleural Left lower lobe Bilateral lower lobes, subpleural
Yes
Yes Yes Yes Yes Yes
Yes
*Radiograph and wet tissue obtained. COPD, chronic obstructive pulmonary disease; IPF, idiopathic pulmonary fibrosis; D, dendriform; N, nodular.
cases had a history of malignancy, only one of which (chronic lymphoid leukaemia) was likely to cause metastatic calcification and subsequent ossification. However, pulmonary calcium deposits were not present in that particular case. Only two other cases showed incidental pulmonary calcification. In one case, a chest radiograph performed a week prior to autopsy showed left lower lobe atelectasis and increased interstitial markings at both bases (Fig. 3). The appearances
were indistinguishable from those of interstitial fibrosis. A conventional chest computed tomography (CT) scan 3 years earlier was reported as showing pleural plaques and subpleural interstitial thickening (films not available). Formalin-fixed lung tissue obtained from the same case showed a subpleural branching network of bone 0.5– 3.0 mm in diameter, recovered after overnight treatment with bleach solution (Fig. 4).
Fig. 1 Dendriform type DPO showing a branching network of bone replacing the alveolar wall, and presence of marrow fat (H&E, 640).
Fig. 2 Nodular type DPO showing ossification within the alveolar spaces (H&E, 640).
DIFFUSE PULMONARY OSSIFICATION
47
Fig.3 Chest radiograph of a case of dendriform type DPO showing prominent interstitial markings at bilateral lower zones.
DISCUSSION Like previously published reports, our data show that diffuse pulmonary ossification is an asymptomatic condition most often found in elderly males with pre-existing respiratory disease.2,4,5 While it is thought to be a slow, progressive process following repeated pulmonary injury, our cohort included a previously healthy 32-year-old who died 1 month following severe burns complicated by pneumonia. Histologically, foci of ossification are present in regions of diffuse alveolar damage, indicating that osseous metaplasia can occur rapidly with relatively acute conditions. A similar case report of dendriform pulmonary ossification in a 40-year-old female who died after artificial ventilation for 36 days is also found.6 The nodular and dendriform types of ossification are thought to reflect different physiological processes and aetiological factors. The nodular type represents ossification of alveolar exudates secondary to chronic congestion (e.g., congestive heart failure or mitral stenosis). The dendriform type is a consequence of chronic inflammation, and ossification occurs in and replaces the alveolar septae. It is reported in up to 9% of patients with pulmonary interstitial fibrosis,7 but our findings show it also complicates COPD. Furthermore, in our study, nodular pulmonary ossification was also present in cases with no clinical or histological evidence of chronic pulmonary congestion. This indicates a degree of overlap between the two patterns. The exact mechanism of pulmonary ossification is uncertain and is generally regarded as a metaplastic response by pulmonary fibroblasts and macrophages into osteoblasts and osteoclasts. Ectopic ossification mediated by growth factors, including transforming growth factor-b, interleukin-1 and interleukin-4, has been shown in a variety of tissues in vitro.5 This in turn is facilitated by environmental conditions such as low pH, low oxygen tension, and decreased mechanical compliance, all of which are present in injured lung tissue. Furthermore, the normal ventilation perfusion ratio of the base of the lung is lower than the apex, the normal pH is also lower (7.39 at the base compared to 7.51 at the apex), explaining the predilection of DPO in the lower lobes.5 Although metastatic or dystrophic calcium deposits can ossify, calcification is usually not present in areas of DPO.
Fig. 4 (A) Formalin-fixed section of lung showing foci of ossification. (B) Bone fragments after overnight treatment with sodium hypochlorite. (C) Micrograph of specimen showing dendriform type DPO. Haematopoietic precursors and osteoclastic activity are present. There is established adjacent interstitial fibrosis (H&E, 6200).
Idiopathic DPO, where ossification is present without any other identified histological abnormality, is very rare. Two cases have been identified in the literature;1,8 the patients were younger (43 and 51) and presented with intermittent fevers, dyspnoea and a mild restrictive defect on pulmonary function testing. Chest radiographs showed bilateral increased reticulonodular markings in the lower zones. These features are often masked by the interstitial fibrosis present in more conventional cases. The radiological features can also be misdiagnosed as fibrosis,
48
Pathology (2006), 38(1), February
TSEUNG AND DUFLOU
bronchiectasis, pulmonary oedema or past tuberculosis.3 Pulmonary ossification is more easily identified at autopsy, where the firm, brittle bone provides resistance to sectioning of the lung. Because of the signal averaging effect, the fine (1–5 mm) bony deposits in DPO cannot be demonstrated on the usual 10-mm CT slices. They can be visualised on high resolution computed tomography (HRCT) in the bone windows. Because HRCT is becoming more commonplace in the evaluation of fibrotic lung diseases, there is recent renewed interest in diffuse pulmonary ossification.3,8,9 A recently published study by Kim et al. showed pulmonary ossification is associated with usual interstitial pneumonia, and not in cases of non-specific interstitial pneumonia with a generally more benign course.9 In conclusion, diffuse pulmonary ossification is underrecognised because most clinicians and pathologists are unaware of the entity. However, as more is known about the condition, it may well prove to be much more common and of more clinical significance than initially thought. ACKNOWLEDGEMENT This paper was originally presented at the 30th Annual Scientific Meeting of the Australasian Division of the International Academy of Pathology, Sydney, NSW, Australia, June 2005.
Address for correspondence: Dr J. Tseung, Department of Forensic Medicine, Central Sydney Laboratory Service, PO Box 90, Glebe, NSW 2037, Australia. E-mail: [email protected]
References 1. Jaderberg JM, Dunton RF. Rare clinical diagnosis of dendriform pulmonary ossification. Ann Thorac Surg 2001; 71: 2009–11. 2. Lara JF, Catroppo JF, Kim DU, da Costa D. Dendriform pulmonary ossification, a form of diffuse pulmonary ossification, report of a 26-year autopsy experience. Arch Pathol Lab Med 2005; 129: 348–53. 3. Kanne JP, Godwin JD, Takasugi JE, Schmidt RA, Stern EJ. Diffuse pulmonary ossification. J Thorac Imaging 2004; 19: 98–102. 4. Joines RW, Roggli VL. Dendriform pulmonary ossification, report of two cases with unique findings. Am J Clin Pathol 1989; 91: 398–402. 5. Chan ED, Morales DV, Welsh CH, McDermott MT, Schwarz MI. Calcium deposition with or without bone formation in the lung. Am J Crit Care Med 2002; 165: 1654–69. 6. Fried ED, Godwin TA. Extensive diffuse pulmonary ossification. Chest 1992; 105: 1614–5. 7. Gevenois PA, Abehsera M, Knoop C, Jacobovitz D, Estenne M. Disseminated pulmonary ossification in end-stage pulmonary fibrosis: CT demonstration. Am J Roengtenol 1994; 162: 1303–4. 8. Ryan CF, Flint JD, Muller NL. Idiopathic diffuse pulmonary ossification. Thorax 2004; 59: 1004. 9. Kim TS, Han J, Chung MP, Chung MJ, Choi YS. Disseminated dendriform pulmonary ossification associated with usual interstitial pneumonia: incidence and thin-section CT-pathologic correlation. Eur Radiol 2005; 15: 1581–5.
ANATOMICAL PATHOLOGY
Diffuse pulmonary ossification: an uncommon incidental autopsy finding JASON TSEUNG
AND
JOHAN DUFLOU
Department of Forensic Medicine, Central Sydney Laboratory Service, Glebe, New South Wales, Australia
Summary Aim: To determine the incidence of diffuse pulmonary ossification (DPO) and its subtypes at autopsy and correlation with clinical and histological features. Methods: Autopsy reports from our institution over a 64month period were reviewed for findings of DPO. The pattern of ossification, demographics and clinical data were obtained from both paraffin sections and final autopsy reports. In a selected case, chest radiograph and wet tissue were obtained. Results: Seventeen histologically confirmed cases of DPO were found in 10 426 autopsy cases, representing an incidence of 1.63 cases/1000 autopsies. There was a predilection in males (88%) and underlying pulmonary disease (88%). In contrast to published studies, dendriform DPO was more common than the nodular type in our cohort (11 and 6 cases, respectively). The dendriform type was more commonly associated with marrow elements. Conclusions: Diffuse pulmonary ossification is uncommon and rarely diagnosed during life, but can easily be identified when sectioning the lungs at autopsy. There is recent renewed interest in diagnosing and determining the significance of DPO using high resolution computed tomography and thoracoscopic biopsy. Key words: Lung, heterotopic ossification, autopsy.
review of DPO found in our institution to correlate the clinical and histological features.
MATERIALS AND METHODS Materials Autopsy cases between January 2000 and April 2005, describing either microscopic or macroscopic bone formation in the lung, were electronically retrieved from the Department of Forensic Medicine, Central Sydney Laboratory Service. In all cases, both the completed autopsy report and the H&E-stained slides were available. Actual radiograph and formalin-fixed tissue were obtained for one case. Methods The autopsy reports were examined to eliminate cases of focal ossification, or ossification of bronchial cartilage. The clinical data of the deceased, including age, gender, cause of death and significant pulmonary/systemic comorbidities, were extracted from the case report. Where mentioned, the location and extent of pulmonary ossification were recorded. All histological lung sections were reviewed to confirm and classify the diagnosis of DPO, based on the morphology of the bone fragments and the preservation of alveolar septae. The presence of background pulmonary pathology, parenchymal calcification, marrow fat and/or haematopoietic cells in the bone fragments were also noted. In one of the cases, a piece of lung tissue was digested overnight with commercial 5% sodium hypochlorite to recover the bone fragments.2,4
Received 15 August, accepted 9 October 2005
RESULTS INTRODUCTION Diffuse pulmonary ossification (DPO) represents an unusual metaplastic response of the lung to injury. The definition of DPO is qualitative, with authors describing ‘disseminated, widespread or extensive’ bone formation in the lung.1–5 In essence, it implies an underlying cause affecting diffuse areas of the lung, as opposed to ossification within focal lesions such as an abscess or tumour. Two patterns—dendriform pulmonary ossification and nodular pulmonary ossification—have been described histologically.1–3 The dendriform type arises within the alveolar septae forming a coral-like network of bone, whereas the nodular type forms lobulated bone fragments within the alveolar spaces. Although numerous reports of DPO have been published since its first description by Luschka in 1856,1 it remains a poorly defined entity of uncertain clinical significance. In life, it is masked by pulmonary disease clinically and radiologically, and is mostly identified incidentally during autopsy. We have conducted a case
A total of 10 426 adult and paediatric post-mortem reports were found during the 64-month period. There were 17 cases of DPO, none of which were diagnosed prior to death. This represented 0.16% of all autopsies, or 3.2 cases per year. The incidence had not changed significantly compared with the period of 1991–1999, where 26 cases were identified (2.9 cases per year, unpublished). The clinical and histological features of the cohort are summarised in Table 1. Analysis of the data showed the median age was 72 (range 32–91), with a 7.5:1 male predominance. Most had a history of chronic pulmonary disease, most commonly chronic obstructive pulmonary disease (COPD, 35%), followed closely by established pulmonary fibrosis (29%). Only 18% (3/17) died directly from a respiratory cause. Ossification was mostly of the dendriform type (Fig. 1), with 73% (8/11) containing bone marrow elements. In contrast, bone marrow elements were only present in 17% (1/6) cases of nodular type DPO (Fig. 2). In six cases where the site of ossification was described, there was a predilection to the subpleural area of the lower lobes. Four
ISSN 0031-3025 printed/ISSN 1465-3931 # 2006 Royal College of Pathologists of Australasia DOI: 10.1080/00313020500464912
46
Pathology (2006), 38(1), February
TSEUNG AND DUFLOU
TABLE 1
Summary of identified cases of diffuse pulmonary ossification
Age
Sex
Cause of death
32
M
Acute pneumonia
43 48
M M
Suicide, drug toxicity Seizure
54
M
Suicide, drug toxicity
64 65
M M
65 67
M M
72
M
73
F
74
M
75
M
82
M
Aortic dissection Ischaemic heart disease Suicide, hanging Ischaemic heart disease Ischaemic heart disease Ischaemic heart disease Ruptured aortic aneurysm Ischaemic heart disease Acute pneumonia
85 88 90
M M F
Cholangitis Undetermined Perforated gastric ulcer
91*
M
Acute pneumonia
Significant comorbidity
Pulmonary disease
Extensive third degree burns Renal transplant
Diffuse alveolar damage
Papillary renal cell carcinoma
Gallbladder adenocarcinoma Chronic lymphoid leukaemia Clear cell renal cell carcinoma
Type
Site, if stated
Marrow elements
Lung calcification
Noted in summary
D
COPD
N N
COPD
N
Coalminer’s lung COPD
N N
COPD
D D
Bilateral lower lobes
Yes
Yes Yes
Yes
Yes
Yes
IPF
D
Bilateral
COPD
D
Left lower lobe
Past tuberculosis
D
Yes
IPF
D
Yes
COPD
N
IPF IPF Pulmonary hypertension IPF
D D D D
Bilateral subpleural Left lower lobe Bilateral lower lobes, subpleural
Yes
Yes Yes Yes Yes Yes
Yes
*Radiograph and wet tissue obtained. COPD, chronic obstructive pulmonary disease; IPF, idiopathic pulmonary fibrosis; D, dendriform; N, nodular.
cases had a history of malignancy, only one of which (chronic lymphoid leukaemia) was likely to cause metastatic calcification and subsequent ossification. However, pulmonary calcium deposits were not present in that particular case. Only two other cases showed incidental pulmonary calcification. In one case, a chest radiograph performed a week prior to autopsy showed left lower lobe atelectasis and increased interstitial markings at both bases (Fig. 3). The appearances
were indistinguishable from those of interstitial fibrosis. A conventional chest computed tomography (CT) scan 3 years earlier was reported as showing pleural plaques and subpleural interstitial thickening (films not available). Formalin-fixed lung tissue obtained from the same case showed a subpleural branching network of bone 0.5– 3.0 mm in diameter, recovered after overnight treatment with bleach solution (Fig. 4).
Fig. 1 Dendriform type DPO showing a branching network of bone replacing the alveolar wall, and presence of marrow fat (H&E, 640).
Fig. 2 Nodular type DPO showing ossification within the alveolar spaces (H&E, 640).
DIFFUSE PULMONARY OSSIFICATION
47
Fig.3 Chest radiograph of a case of dendriform type DPO showing prominent interstitial markings at bilateral lower zones.
DISCUSSION Like previously published reports, our data show that diffuse pulmonary ossification is an asymptomatic condition most often found in elderly males with pre-existing respiratory disease.2,4,5 While it is thought to be a slow, progressive process following repeated pulmonary injury, our cohort included a previously healthy 32-year-old who died 1 month following severe burns complicated by pneumonia. Histologically, foci of ossification are present in regions of diffuse alveolar damage, indicating that osseous metaplasia can occur rapidly with relatively acute conditions. A similar case report of dendriform pulmonary ossification in a 40-year-old female who died after artificial ventilation for 36 days is also found.6 The nodular and dendriform types of ossification are thought to reflect different physiological processes and aetiological factors. The nodular type represents ossification of alveolar exudates secondary to chronic congestion (e.g., congestive heart failure or mitral stenosis). The dendriform type is a consequence of chronic inflammation, and ossification occurs in and replaces the alveolar septae. It is reported in up to 9% of patients with pulmonary interstitial fibrosis,7 but our findings show it also complicates COPD. Furthermore, in our study, nodular pulmonary ossification was also present in cases with no clinical or histological evidence of chronic pulmonary congestion. This indicates a degree of overlap between the two patterns. The exact mechanism of pulmonary ossification is uncertain and is generally regarded as a metaplastic response by pulmonary fibroblasts and macrophages into osteoblasts and osteoclasts. Ectopic ossification mediated by growth factors, including transforming growth factor-b, interleukin-1 and interleukin-4, has been shown in a variety of tissues in vitro.5 This in turn is facilitated by environmental conditions such as low pH, low oxygen tension, and decreased mechanical compliance, all of which are present in injured lung tissue. Furthermore, the normal ventilation perfusion ratio of the base of the lung is lower than the apex, the normal pH is also lower (7.39 at the base compared to 7.51 at the apex), explaining the predilection of DPO in the lower lobes.5 Although metastatic or dystrophic calcium deposits can ossify, calcification is usually not present in areas of DPO.
Fig. 4 (A) Formalin-fixed section of lung showing foci of ossification. (B) Bone fragments after overnight treatment with sodium hypochlorite. (C) Micrograph of specimen showing dendriform type DPO. Haematopoietic precursors and osteoclastic activity are present. There is established adjacent interstitial fibrosis (H&E, 6200).
Idiopathic DPO, where ossification is present without any other identified histological abnormality, is very rare. Two cases have been identified in the literature;1,8 the patients were younger (43 and 51) and presented with intermittent fevers, dyspnoea and a mild restrictive defect on pulmonary function testing. Chest radiographs showed bilateral increased reticulonodular markings in the lower zones. These features are often masked by the interstitial fibrosis present in more conventional cases. The radiological features can also be misdiagnosed as fibrosis,
48
Pathology (2006), 38(1), February
TSEUNG AND DUFLOU
bronchiectasis, pulmonary oedema or past tuberculosis.3 Pulmonary ossification is more easily identified at autopsy, where the firm, brittle bone provides resistance to sectioning of the lung. Because of the signal averaging effect, the fine (1–5 mm) bony deposits in DPO cannot be demonstrated on the usual 10-mm CT slices. They can be visualised on high resolution computed tomography (HRCT) in the bone windows. Because HRCT is becoming more commonplace in the evaluation of fibrotic lung diseases, there is recent renewed interest in diffuse pulmonary ossification.3,8,9 A recently published study by Kim et al. showed pulmonary ossification is associated with usual interstitial pneumonia, and not in cases of non-specific interstitial pneumonia with a generally more benign course.9 In conclusion, diffuse pulmonary ossification is underrecognised because most clinicians and pathologists are unaware of the entity. However, as more is known about the condition, it may well prove to be much more common and of more clinical significance than initially thought. ACKNOWLEDGEMENT This paper was originally presented at the 30th Annual Scientific Meeting of the Australasian Division of the International Academy of Pathology, Sydney, NSW, Australia, June 2005.
Address for correspondence: Dr J. Tseung, Department of Forensic Medicine, Central Sydney Laboratory Service, PO Box 90, Glebe, NSW 2037, Australia. E-mail: [email protected]
References 1. Jaderberg JM, Dunton RF. Rare clinical diagnosis of dendriform pulmonary ossification. Ann Thorac Surg 2001; 71: 2009–11. 2. Lara JF, Catroppo JF, Kim DU, da Costa D. Dendriform pulmonary ossification, a form of diffuse pulmonary ossification, report of a 26-year autopsy experience. Arch Pathol Lab Med 2005; 129: 348–53. 3. Kanne JP, Godwin JD, Takasugi JE, Schmidt RA, Stern EJ. Diffuse pulmonary ossification. J Thorac Imaging 2004; 19: 98–102. 4. Joines RW, Roggli VL. Dendriform pulmonary ossification, report of two cases with unique findings. Am J Clin Pathol 1989; 91: 398–402. 5. Chan ED, Morales DV, Welsh CH, McDermott MT, Schwarz MI. Calcium deposition with or without bone formation in the lung. Am J Crit Care Med 2002; 165: 1654–69. 6. Fried ED, Godwin TA. Extensive diffuse pulmonary ossification. Chest 1992; 105: 1614–5. 7. Gevenois PA, Abehsera M, Knoop C, Jacobovitz D, Estenne M. Disseminated pulmonary ossification in end-stage pulmonary fibrosis: CT demonstration. Am J Roengtenol 1994; 162: 1303–4. 8. Ryan CF, Flint JD, Muller NL. Idiopathic diffuse pulmonary ossification. Thorax 2004; 59: 1004. 9. Kim TS, Han J, Chung MP, Chung MJ, Choi YS. Disseminated dendriform pulmonary ossification associated with usual interstitial pneumonia: incidence and thin-section CT-pathologic correlation. Eur Radiol 2005; 15: 1581–5.