Silicoproteinosis: High-Resolution CT Findings in 13 Patients

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1 CT of Silicoproteinosis Chest Imaging Clinical Observations Edson Marchiori 1 Carolina lthoff Souza 2 Tatiana Gontijo arbassa 1 Dante L. Escuissato 3 Emerson L. Gasparetto 1 rthur Soares Souza, Jr. 4 Marchiori E, Souza C, arbassa TG, Escuissato DL, Gasparetto EL, Souza S Jr Keywords: CT, lung, silicoproteinosis, silicosis DOI: /JR Received pril 11, 2007; accepted after revision June 25, Department of Radiology, Federal University of Rio de Janeiro, Rio de Janeiro, razil. 2 Department of Diagnostic Imaging, The Ottawa Hospital, 501 Smyth Rd., Ottawa, ON, Canada K1H 8L6. ddress correspondence to C.. Souza (carolina_althoff@yahoo.ca). 3 Department of Radiology, Federal University of Parana, Curitiba, razil. 4 Department of Radiology, Faculty of Medicine of São José do Rio Preto, São José do Rio Preto, razil. JR 2007; 189: X/07/ merican Roentgen Ray Society Silicoproteinosis: High-Resolution CT Findings in 13 Patients OJECTIVE. The purpose of this study was to evaluate the high-resolution CT findings of silicoproteinosis. CONCLUSION. Silicoproteinosis usually manifests as bilateral consolidation in the posterior portions of the lungs and as numerous centrilobular nodules. Calcification within areas of consolidation is a common finding. ilicosis, caused by the inhalation of S crystalline free silica, is the most common occupational disease involving the lungs. Most cases occur after decades of exposure to relatively small amounts of silica, which causes chronic pulmonary damage [1, 2]. n acute form of silicosis, silicoproteinosis, can occur after relatively short exposure to very high levels of fine particulate silica. The disease manifests within a few years of the initial exposure and causes rapid deterioration, which invariably leads to acute respiratory failure. The pathologic features of silicoproteinosis differ substantially from those of chronic silicosis and resemble those of primary alveolar proteinosis [3 6]. High-resolution CT has an important role in the diagnosis of diffuse lung disease, allowing better characterization of the abnormalities than does chest radiography. lthough the high-resolution CT findings of primary alveolar proteinosis have been well described [7], to our knowledge, there has been no study of high-resolution CT findings in a series of patients with silicoproteinosis. The purpose of this study was to describe the high-resolution CT findings in a series of 13 patients with proven silicoproteinosis. Materials and Methods The study included 13 consecutively enrolled patients with the diagnosis of silicoproteinosis who underwent high-resolution CT at one of the four institutions involved in the study. Institutional review board approval was not required at any of the centers. ll patients were men with a median age of 29.5 years (range, years). They were sandblasters with a history of exposure to silica varying from 11 months to 8 years (median, 3.2 years). Two of the patients were previously described in a case report [4]. Dry cough and dyspnea were the most common clinical manifestations, present in seven (54%) of the 13 patients. In five (38%) of the patients, dyspnea was the only symptom; in one case it was associated with low fever. The diagnosis of silicoproteinosis was based on a clinical history of rapidly progressive respiratory symptoms and a history of environmental exposure to silica after other possible causes of lung disease were excluded on the basis of clinical history and laboratory tests. In 10 patients, bronchoalveolar lavage at presentation showed a considerable amount of proteinaceous material with a positive reaction to periodic acid Schiff (PS) stain. Necropsy performed in three cases revealed intraalveolar accumulation of PS-positive proteinaceous material, mild peribronchial granulomatous inflammation, and a few silica particles (Fig. 1). High-resolution CT examinations were performed with different scanners but similar protocols: 1- to 2-mm collimation at 10-mm intervals, supine position, acquisition at end inspiration, and reconstruction with a high-spatial-frequency algorithm. The high-resolution CT images were available in hard copies photographed at lung (width 1,000 or 1,500 H; level, 650 or 750 H) and mediastinal (width, 350 or 400 H; level, 40 or 60 H) window settings. The interval between the highresolution CT examination and bronchoalveolar lavage varied from 1 to 7 days (median, 3.9 days). In three cases, autopsy was performed approximately 1, 2, and 4 months after high-resolution CT. Two chest radiologists retrospectively reviewed the images for the presence and distribution of airspace consolidation, ground-glass opacity, and nodules. ssociated findings such as air bron JR:189, December 2007

2 CT of Silicoproteinosis Fig. 1 Photomicrograph of autopsy specimen from male cadaver (age at death, 28 years; cause of death, silicoproteinosis) shows abundant intraalveolar proteinaceous material and positive reaction to stain. (Periodic acid Schiff, 100) chograms and foci of calcification within areas of consolidation, interlobular septal thickening, fibrosis (defined as the presence of traction bronchiectasis and architectural distortion), pleural effusion or thickening, and mediastinal or hilar adenopathy also were recorded. The definition of these findings followed the glossary of terms proposed by the Fleischner Society [8]. Nodules were classified according to size (< 15 mm or 15 mm in diameter), number (< 10 or > 10), and distribution (centrilobular, peribronchovascular, random). The overall distribution of the parenchymal findings was classified as unilateral or bilateral and as upper or lower zone predominance based on the tracheal carina or random if no zonal predominance was found. The Fig year-old man with silicoproteinosis., High-resolution CT scan shows air-space consolidation (arrowhead) within superior segment of right lower lobe and innumerable ill-defined centrilobular nodules. Confluent nodules (arrows) are present in upper lobes., Unenhanced CT scan obtained at mediastinal window settings shows consolidation involving predominantly dependent portions of lungs. Foci of calcification (arrows) are present within area of consolidation. Small bilateral pleural effusions and calcified mediastinal lymph node (arrowhead) are evident. final decision about the presence and distribution of abnormalities was reached by consensus between the two radiologists. Results High-resolution CT depicted parenchymal abnormalities in all 13 patients. ir-space consolidation was the most common finding, present in 12 (92%) of the 13 patients; it was always bilateral and associated with air bronchograms. In four (33%) of the 12 patients, the areas of consolidation had a predominantly lower-zone distribution; in the other eight patients, no zonal predominance was detected. Interestingly, in all 12 patients consolidation involved mainly the posterior portions of the lungs. Foci of calcification within areas of consolidation were seen in 10 (83%) of the patients (Figs. 2 and 3). In the only patient without consolidation, high-resolution CT showed ground-glass opacities and small centrilobular nodules throughout the lungs (Fig. 4). Nodules were identified in 11 (85%) of 13 patients. In all cases the lesions were numerous (> 10), were predominantly smaller than 15 mm, and were centrilobular in distribution. Most of the nodules had homogeneous soft-tissue attenuation. Nodules with ground-glass attenuation were present in five (45%) of the 11 cases (Figs. 2 5). In nine (82%) of the 11 cases JR:189, December

3 confluent nodules were also seen (Fig. 5). Patchy ground-glass opacities were identified in eight (62%) of the 13 patients, always in association with consolidation or nodules. few septal lines were seen in seven (54%) of the 13 patients, always associated with other abnormalities. In none of the cases was superimposition of reticular and groundglass opacities, the so-called crazy-paving pattern, present. None of the patients had findings of marked pulmonary fibrosis. Minimal architectural distortion and traction bronchiectasis, however, were found in four (31%) of the patients. Calcified lymph nodes were present in 11 (85%) of the 13 patients, predominantly in the Fig year-old man with silicoproteinosis., High-resolution CT scan shows innumerable bilateral centrilobular nodules, some of them confluent. Punctate calcification is present within area of consolidation (arrow) in right upper lobe. Mild dilatation of trachea is evident., High-resolution CT scan obtained at lower level than shows multiple air-space nodules. Some of these nodules are poorly defined and have ground-glass attenuation (thin arrows). Calcified mediastinal and hilar nodes (thick arrows) are evident. hilar regions (Figs. 2 and 3). The pattern of calcification varied. Most of the patients presented with diffuse nodal calcification, although punctate calcification and predominant peripheral calcification also were present. Noncalcified mildly enlarged mediastinal nodes, defined as lymph nodes larger than 1 cm in short-axis diameter, were identified in two (15%) of the patients. Minimal pleural thickening or pleural effusion was common, present in 11 (85%) of 13 patients (Fig. 2). Tracheal dilatation, defined as transverse tracheal diameter greater than 2.5 cm on axial images, was an unexpectedly common finding, seen in nine (69%) of the 13 patients (Figs. 3 and 5). Fig year-old man with silicoproteinosis. High-resolution CT scan shows patchy bilateral ground-glass opacities and multiple ill-defined centrilobular nodules (arrows). Discussion Silicosis is the most common and oldest recognized occupational lung disease. Silicainduced lung disease is classified as chronic, accelerated, or acute depending on the intensity and duration of the exposure to silica dust [1, 2]. The chronic or classic form of silicosis typically manifests after years of exposure to low concentrations of silica dust. n accelerated form of silicosis occurs within 4 10 years of heavier exposure. part from the early onset and rapid progression, the radiologic and pathologic manifestations of accelerated silicosis are identical to those of classic silicosis, consisting of pulmonary fibrosis and multiple small nodules containing 1404 JR:189, December 2007

4 CT of Silicoproteinosis mature collagen and birefringent silicate crystals [2]. cute silicosis is a fulminating respiratory illness resulting from relatively short exposure to high concentrations of fine silica dust [2 6, 9]. The term silicoproteinosis was introduced by uechner and nsari [3] in 1969, when the histologic similarity between acute silicosis and primary alveolar proteinosis was first described. Silicoproteinosis usually manifests within 3 years of the initial exposure as rapidly progressive shortness of breath often associated with constitutional symptoms. The course of the disease is relentlessly progressive. Most of the reported cases have been fatal within months [3 5, 9]. cute silicosis most commonly affects sandblasters, although it has been described in quartzite millers, tunnel workers, silica flour workers, and workers in the scouring powder industry [4 6, 10]. Isolated cases associated with domestic exposure also have been reported [11]. The diagnosis of acute silicosis, as of the occupational diseases in general, is based on clinical and radiologic manifestations and appropriate history of environmental exposure. There is no need for pathologic confirmation [2]. The 13 patients included in this study were sandblasters with a history of occupational exposure varying from approximately 1 to 8 years with a median of 3.2 years. The most common initial manifestation was dyspnea and dry cough, accompanied by low fever in one case. Nine patients presented with rapidly progressive respiratory impairment, and eight of them died within 2 years of the initial Fig year-old man with silicoproteinosis., High-resolution CT scan shows air-space consolidation with air bronchograms in right upper lobe and multiple bilateral centrilobular nodules (arrows). Mild dilatation of trachea is evident., High-resolution CT scan obtained at lower level than shows multiple centrilobular nodules (arrows), some of them confluent. diagnosis. The other four patients did not return for clinical follow-up. The histologic findings of silicoproteinosis resemble those of primary alveolar proteinosis, that is, PS-positive lipoproteinaceous material filling the air spaces [2, 3, 7]. Unlike classic silicosis, silicoproteinosis manifests as minimal collagen deposition and fibrosis. Silicotic nodules, the hallmark of classic silicosis, when present, are smaller than in classic silicosis and may or may not contain weakly birefringent silicate crystals [2, 3]. The radiographic manifestation of silicoproteinosis, like that of primary alveolar proteinosis, is bilateral parenchymal consolidation [3, 5, 6, 9, 10]. The high-resolution CT findings of primary alveolar proteinosis have been described in several studies and consist of bilateral ground-glass opacities and smooth septal thickening. The crazy-paving pattern has been considered characteristic of primary alveolar proteinosis and is highly suggestive of the diagnosis in the appropriate clinical setting [7]. The predominant (92%, 12/13) high-resolution CT finding in the 13 cases of silicoproteinosis described in this study consisted of bilateral air-space consolidation mainly involving the posterior aspects of the lungs and often (75%, 9/12) associated with ground-glass opacities. Multiple small nodules, a feature not described in alveolar proteinosis, were identified in 85% of the patients. The nodules were centrilobular in distribution and usually ill-defined, having either soft-tissue or ground-glass attenuation, features that characterize air-space nodules and reflect the inhalational and a bronchiolocentric cause of silicoproteinosis [2, 12]. Confluent nodules were present in a large percentage (82%) of patients. The predominance of air-space disease on high-resolution CT presumably reflects the deposition of proteinaceous material in the alveolar spaces, the pathologic hallmark of silicoproteinosis. Foci of calcification within areas of consolidation were identified in 83% of the cases. This finding is clearly depicted on highresolution CT and can be considered characteristic of silicoproteinosis. Calcification is usually not seen in other diseases presenting with airspace consolidation, such as bacterial and fungal pneumonia, bronchoalveolar carcinoma, and lymphoma. None of the patients had marked pulmonary fibrosis. This finding is not surprising given the acute nature of silicoproteinosis and the absence of marked fibrosis at pathologic examination [2]. lthough a few septal lines were identified in 54% of the cases, the crazypaving pattern was not seen. Hilar lymphadenopathy is a common finding in patients exposed to silica dust and occurs with or without parenchymal disease [1]. Calcified lymph nodes were identified in 85% of the patients in this study and noncalcified enlarged lymph nodes in 15%. The pattern of calcification varied, most commonly being punctate. Eggshell calcification, a finding commonly seen in chronic silicosis, was present in a few patients. In the cases of acute silicosis reported in the literature [3, 9, 10], JR:189, December

5 mediastinal or hilar adenopathy was a prominent finding on the chest radiographs of a considerable number of patients and was strongly suspected in others. Our study had several limitations. It was retrospective and included a relatively small number of patients. lthough the diagnosis was based on well-defined criteria [2], the lack of pathologic data limited high-resolution CT pathologic correlation. However, we believe the goal of our study, to describe the high-resolution CT findings of silicoproteinosis in a series of patients, was met. The high-resolution CT findings of silicoproteinosis consist of bilateral air-space disease with consolidation, typically involving the posterior portions of the lungs, and numerous centrilobular nodules. Punctate calcification superimposed on areas of consolidation and calcified lymph nodes are commonly seen. Unlike pulmonary alveolar proteinosis, silicoproteinosis does not present with the crazy-paving pattern. References 1. Pendergrass EP. Silicosis and a few of the other pneumoconioses: observations of certain aspects of the problem, with emphasis on the role of the radiologist. JR 1958; 80: Travis WD, Koss MN, Rosado-de-Christenson ML, Müller NL, King TE Jr. Non-neoplastic disorders of the lower respiratory tract: atlas of nontumor pathology, 1st ed. Washington, DC: rmed Forces Institute of Pathology and merican Registry of Pathology, 2002: uechner H, nsari. cute silico-proteinosis: a new pathologic variant of acute silicosis in sandblasters, characterized by histologic features resembling alveolar proteinosis. Dis Chest 1969; 55: Marchiori E, Ferreira, Müller NL. Silicoproteinosis: high-resolution CT and histologic findings. J Thorac Imaging 2001; 16: O Donnell DM, Worrell J, Carroll FE. Chest case of the day: acute silicosis. JR 1992; 158: Michel RD, Morris JF. cute silicosis. rch Intern Med 1964; 113: Shah PL, Hansell D, Lawson PR, Reid K, Morgan C. Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis. Thorax 2000; 55: ustin JH, Müller NL, Friedman PJ, et al. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology 1996; 200: Dee P, Suratt P, Winn W. The radiographic findings in acute silicosis. Radiology 1978; 126: Xipell JM, Ham KN, Price CG, Thomas DP. cute silicoproteinosis. Thorax 1977; 32: Dumontet C, iron F, Vitrey D, et al. cute silicosis due to inhalation of a domestic product. m Rev Respir Dis 1991; 143: Murata K, Itoh H, Todo G, et al. Centrilobular lesions of the lung: demonstration by high-resolution CT and pathologic correlation. Radiology 1986; 161: JR:189, December 2007

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