INTRODUCTION
Among a wide spectrum of radiologic manifestations of sarcoidosis, pulmonary cavitary lesions appear to be uncommon and often confusing18,33. Indeed, such an aspect may be solely related to sarcoidosis or associated with concomitant comorbidities, mainly aspergilloma21,23,42,44. These cavitary lesions have been reported to be present in 0.6% to 8.3% of patients with pulmonary sarcoidosis on the basis of chest X-ray15,28. In a 2002 retrospective study using computed tomography (CT)30, cavitary lesions were observed in 2 of 70 patients (2.8%). However, the few sparse case reports provide an incomplete CT description of cavitary lesions in sarcoidosis25,30.
It remains largely obscure whether cavitary lesions solely related to sarcoidosis develop in patients with specific underlying clinical or radiologic features. According to the few data available, the natural history of these lesions is quite variable: they may resolve spontaneously30, they may steady or worsen16, and their course may be punctuated by several complications including hemoptysis11,25, pneumothorax3,13,16,31,37, and aspergilloma25. However, the respective incidence of each of these evolution profiles and events is unknown.
In the current study we present a large series of patients with cavitary sarcoidosis in the absence of concomitant comorbidities. We conducted the study to assess the prevalence of pulmonary cavitary lesions and to describe the clinical characteristics of affected patients and their high-resolution computed tomography (HRCT) features at initial diagnosis and during follow-up.
PATIENTS AND METHODS
We conducted this retrospective, single-center study in the pneumology department of Avicenne Hospital, a tertiary-care center that is highly specialized in sarcoidosis. This study received institutional review board approval, and the requirement for informed consent was waived.
Patient Selection
Patients are usually referred to the pneumology department for clinical evaluation and/or therapeutic advice. At first admittance they all undergo a full workup including chest HRCT. HRCT can be repeated during follow-up if necessary on clinical grounds. Since 1988, all HRCT carried out in the radiology department are reviewed by 1 radiologist (MWB), and the presence of atypical features of pulmonary sarcoidosis is systematically noted in a database. Based on this database of 1060 patients with pulmonary sarcoidosis, 41 patients with cavitary lesions seen on HRCT were identified between 1988 and 2005.
Inclusion Criteria
Patients' medical records were retrospectively reviewed by 2 of us (SH, HN). Patients were included if they met the following criteria:
- Sarcoidosis diagnosis according to the statement of the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders39.
- Pulmonary cavitary lesions at HRCT43 either at initial workup or during follow-up. A cavitary lesion was defined as an air-containing lesion of more than 1-cm diameter with either thin walls (≤4 mm) or thick walls (>4 mm or located within an infiltrate or a mass)36. These lesions differed from the honeycombing feature occasionally observed in fibrotic sarcoidosis based on the heterogeneity of the size of the cysts and based on the presence of normal lung separating rows of clustered cysts1.
- Absence of comorbidities known to induce pulmonary cavitary lesions at the time of initial HRCT diagnosis. Patent bacterial infection, aspergilloma, tuberculosis or nontuberculosis mycobacterial infection, and Wegener granulomatosis were looked for in all patients on the basis of clinical history, analysis of HRCT, repeated sputum, bronchoalveolar lavage or bronchial aspiration, Aspergillus fumigatus precipitins, and antineutrophil cytoplasmic antibody measured by immunoelectrophoresis. Aspergilloma was defined as the evidence of a fungus ball in the cavitary lesion found on HRCT and/or Aspergillus species growth in at least 1 respiratory specimen and/or the presence of Aspergillus fumigatus precipitins.
Study Design
First, we estimated the prevalence of cavitary lesions solely attributable to sarcoidosis, that is, excluding patients with concomitant comorbidities. Second, we evaluated the natural history of these lesions. Inclusion in the study (named initial diagnosis) was the date of first HRCT showing cavitary lesions. The end of follow-up was defined as the date of the last available HRCT, surgical resection, or the occurrence of an infectious complication that could modify the natural history of pulmonary cavitary lesions, including aspergilloma.
Clinical, Laboratory, Radiographic, and Histopathologic Investigations
At initial diagnosis, the patients had a complete clinical assessment, radiographic staging39, HRCT, pulmonary function tests, and serum angiotensin-converting enzyme (SACE) measure. For the follow-up evaluation, we focused on the therapeutic response of cavitary lesions and on specific complications.
The following were considered severe extrarespiratory localizations of sarcoidosis: ophthalmic localization unresponsive to local treatment; central nervous system, heart, sinonasal, or renal involvement; chronic intrahepatic cholestasis; hypercalcemia >3 mmol/L, and lupus pernio39. Recovery from sarcoidosis was defined as the disappearance of all sarcoidosis symptoms and no disease recurrence for at least 6 months in the absence of treatment. When a surgical biopsy or resection of the cavitary lesion was performed, samples were reviewed by a pathologist (MK).
HRCT Analysis
HRCT examinations were performed in supine position at the end of a suspended full inspiration without administration of intravenous contrast medium. Scans consisted of 1 or 1.5 mm thick slices with 10 mm intersection spacing from the apex of the lung to the diaphragm. All HRCT scans were interpreted in consensus by 2 senior radiologists who specialized in interstitial lung diseases (MWB, PYB).
HRCT Analysis of Cavitary and Pericavitary Lesions
We noted the following characteristics of cavitary lesions: a) number, b) side (uni- or bilateral), and c) craniocaudal, antero-posterior, and axial distribution. According to craniocaudal distribution, lungs were divided into 3 regions: upper zone above the level of the carina, middle zone between the level of the carina and the level of the inferior pulmonary veins, lower zone under the level of the inferior pulmonary veins. According to antero-posterior distribution, lungs were divided into 3 regions: anterior, hilar, and posterior zones. According to axial distribution, lungs were divided into 2 regions: central and peripheral zones, the limit between both zones being fixed at 3 cm from the pleura. For each patient the largest cavitary lesion was specifically analyzed: a) wall thickness: thin or thick; b) diameter: largest diameter; c) shape: unilocular with a circular shape or multilocular with a polycyclic or irregular shape; d) content: empty or septate. For cavitary lesions with thick walls, we measured the mean wall thickness and determined whether the walls were circumferentially thickened or not.
The pericavitary area was also examined. Active lesions included micronodules, nodules, alveolar consolidations, and ground-glass attenuation41. Fibrotic lesions were classified into 3 patterns: bronchial distortion, honeycombing, or linear patterns26.
Evolution of Cavitary and Pericavitary Lesions During Follow-Up
The evolution of cavitary and pericavitary lesions was assessed between the first and the last available HRCTs and graded as improvement, stability, and worsening. The evolution of overall cavitary lesions was adapted from Response Evaluation Criteria in Solid Tumors (RECIST) guidelines22, by targeting up to 5 cavitary lesions per patient. Global improvement was defined as a decrease >30% of the sum of the largest diameter of the targeted lesions; worsening as an increase >20%, and stability as a change in between both thresholds. The changes of pericavitary lesions were noted subjectively.
Statistical Analysis
Statistics were generated using Statview for Windows (version 5.0.1; SAS Institute, Cary, NC). Results are expressed as frequencies for categorical variables and as mean ± standard deviation or as median (range), according to cases. The Fisher test, Mann-Whitney test, or Kruskal-Wallis test were used for comparisons. A p value < 0.05 was considered statistically significant.
RESULTS
Among the 41 patients with pulmonary cavitary lesions listed in our database, 23 patients (56%) fulfilled the inclusion criteria and 18 (44%) had aspergilloma on initial HRCT. These latter patients were excluded from analysis. Therefore, the estimated prevalence of cavitary lesions with no concomitant comorbidities was 2.2%.
Features at Initial Diagnosis
Clinical, Laboratory, and Radiographic Results
The population characteristics are summarized in Table 1. There were 12 men and 11 women with a mean age of 42 ± 12 years. Nine patients (39.1%) were black and 8 (34.8%) were current smokers. The median time between the diagnosis of sarcoidosis and the discovery of cavitary lesions was 6 months (range, 0-14 yr). Cavitary lesions were associated with an extrarespiratory localization of sarcoidosis in almost all patients (n = 20, 96.9%) and occurred in patients with severe disease (n = 16, 69.6%), as defined by radiographic stage IV (n = 12, 52.2%) and/or severe extrarespiratory involvement (n = 11, 47.8%). Five patients (21.7%) had normal flows and lung volumes on pulmonary function tests, 18 (78.3%) had a restrictive syndrome (total lung capacity <80% of predicted value), in addition to airway obstruction (forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC] <70%) in 6 patients (26.3%). Based on SACE levels, sarcoidosis was considered highly active in most cases (SACE ≥2 times the upper limit of normal range: 63.6%). Among the 12 patients with radiographic stage IV disease, 9 (75%) had abnormal SACE.
;)
TABLE 1: Clinical, Laboratory, and Radiographic Findings at Initial Diagnosis
HRCT Analysis of Cavitary Lesions
Features of cavitary lesions are described in Table 2. Cavitary lesions were multiple in 21 patients (91.3%). The median number of lesions was 4 (range, 1-20), including 5 patients (21.7%) with 10 or more cavities. The diameter of the largest cavitary lesion was variable, ranging from 11 to 100 mm (median diameter, 20 mm). Its wall was thin in 16 (69.6%) and thick in 7 cases (30.4%). In case of thick wall, the thickening ranged from 10 to 20 mm (median, 10 mm); however, this thickening was not circumferential (Figure 1). The lesions were multiloculated in 16 patients (69.6%; Figures 1-2). Among the 7 patients (30.4%) with uniloculated shape, the presence of septates inside was observed in 3 patients (Figures 1-3). Patients with radiographic stage IV did not differ from those with other radiographic stages according to the type of the largest cavitary lesion and the number of cavities (p = 0.19).
TABLE 2: HRCT Features of Cavitary Lesions at Initial Diagnosis
FIGURE 1: HRCT scans in a 49-year-old woman (Patient 1) with cavitary sarcoidosis at initial diagnosis and during follow-up. A. Initial non-enhanced HRCT shows 2 adjoined cavitary lesions with noncircumferential thickening of the walls (straight arrow) and inner septates (curved arrow). B. Four months later, HRCT shows thinning of the lesion walls (arrow). C. Nine years later, HRCT shows resolution of the posterior lesion and linear scar (arrows).
FIGURE 2: HRCT scans in a 56-year-old woman (Patient 3) with cavitary sarcoidosis showing conflicting evolution of lesions. A. Non-enhanced HRCT preceding the development of cavitary lesions shows distorted hilar-peripheral lines (arrow). B. Initial non-enhanced HRCT shows 2 large cavitary lesions that were polycyclic in shape. C. Fourteen months later, HRCT shows resolution of the right lesion, which was replaced by a linear scar (arrow), and an increase in the size of the left lesion (star). D. Twenty-nine months later, HRCT shows a relapse of the right lesion (star) and a resolution of the left one (arrow).
FIGURE 3: HRCT scans in a 33-year-old woman (Patient 18) who underwent pulmonary surgical resection of a large growing and compressive cyst. A. Initial non-enhanced HRCT shows a small septated cavitary lesion (arrow) surrounded by ground-glass attenuation. B. Three years later, HRCT shows an increase of the size of the lesion, which had a thin wall and was polycyclic in shape. C. Seven years later, HRCT shows a compressive cyst with slight shift of the mediastinum (curved arrow). D. Photomicrograph of the cyst wall after surgical resection shows dense collagenous fibrosis (star) with few granulomas (arrows) (low magnification; hematoxylin-eosin stain, periodic acid-Schiff stain).
HRCT Analysis of Pericavitary Lesions
Features of pericavitary lesions are shown in Table 3. The pericavitary area was absolutely normal in 2 patients. Active lesions were present in most patients (n = 19, 82.6%), particularly alveolar consolidations (Figure 4) and ground-glass attenuation (Figures 3-4). Fibrotic lesions were present in 43.4% of patients, much more frequently in combination with active lesions (n = 7) than as the sole feature (n = 3).
TABLE 3: HRCT Features of Pericavitary Lesions at Initial Diagnosis
FIGURE 4: HRCT scans in a 35-year-old man (Patient 21) who underwent surgical biopsy during follow-up to confirm the diagnosis of sarcoidosis. A. Initial non-enhanced HRCT shows a small septated cavitary lesion (arrow) inside a postero-basilar consolidation (star) surrounded by ground-glass attenuation. B. Six months later, a lesion with a thin wall (arrow) that was polycyclic in shape appears in place of the left consolidation. C, D. Photomicrograph (high magnification; hematoxylin-eosin stain, periodic acid-Schiff stain) of a specimen from open-lung biopsy performed after B. shows multiple granulomas and lymphocyte inflammation with lesions of ischemic eosinophilic necrosis (C, star) and few multinucleated giant cells (arrow). Vascular involvement is noted on this specimen with non-necrotizing granulomas replacing the wall (arrow) of this pulmonary vein (D, star). E. At the end of follow-up, HRCT shows evidence of resolution of the cavitary lesion which was replaced by a stellate scar (arrow).
Features During Follow-Up
Clinical Evolution
Table 4 shows the treatment and the clinical evolution for each patient. Three patients were lost to follow-up (Patients 6, 15, 20). For the remaining 20 patients the median follow-up was 6.25 years (range, 6 months to 15 years). Among these 20 patients, 16 (80%) received treatment for sarcoidosis after the diagnosis of cavitary lesions. At the end of the follow-up period, 3 (15%) patients had recovered from sarcoidosis disease (Patients 1, 3, 11).
TABLE 4: Clinical and HRCT Evolution of Cavitary Lesions*
Seven patients (35%) experienced some type of complication attributable to cavitary lesions, and 4 of them had multiple complications (see Table 4). Aspergilloma occurred in 3 patients (15%) 2, 6.5, and 12 years after the initial diagnosis of cavitary lesions. Other infectious complications included Mycobacterium xenopi infection (n = 1) and multibacterial infection (n = 1). Six episodes of hemoptysis were observed in 5 patients (25%, Table 4). Bleeding was always moderate, less than 200 mL, but 1 patient required radiologic embolization for recurrence (Patient 19). In 1 patient, pneumothorax revealed both sarcoidosis and cavitary lesion. Two patients required surgical resection of the cavitary lesion: Patient 18 because of a growing cystic lesion (Figure 3) that became compressive, and Patient 23 for aspergilloma. At the point of overt infection and/or surgical resection, patients were not considered for further analysis.
HRCT Evolution of Cavitary Lesions
Twenty patients had serial HRCTs during follow-up. Table 4 details the individual evolution of cavitary lesions from the first to the last available HRCT. The median number of cavitary lesions tended to decrease from 4 (range, 1-20) to 2 (range, 0-15; p = 0.19). This decrease was due to the merging of adjoining cavitary lesions (Figure 5) in most cases.
FIGURE 5: HRCT scans in a 53-year-old woman (Patient 11) with cavitary sarcoidosis revealed by a pneumothorax during an exacerbation phase of the disease that had been diagnosed 8 years earlier. A. Initial non-enhanced HRCT after pleurodesis shows multiple small adjoined cysts of different sizes. B, C. Follow-up non-enhanced HRCT performed 5 and 15 months later during the weaning of steroid treatment shows an increase in the size of the lesions, which became confluent.
Evolution of the size of the largest cavitary lesion was variable. Of note, 5 patients (25%) had complete resolution under treatment (see Table 4), leaving a stellate or linear scar in all cases (see Figures 1, 4). The 5 patients with a thick cavity underwent control HRCT during early follow-up (within 12 mo), and all evidenced a wall thinning, including 1 who had no treatment. In 1 case (Patient 23), the wall initially thinned under treatment and then again thickened at the occasion of aspergilloma. Wall thickening during follow-up (n = 4) was always associated with the further occurrence of an overt infectious complication, including 3 aspergillomas (Figure 6).
FIGURE 6: HRCT scans in a 48-year-old man (Patient 19) with cavitary sarcoidosis complicated by aspergilloma. A. Follow-up non-enhanced HRCT shows a lesion with a thin wall in addition to volume loss of the upper lobe and extrapleural fat hypertrophy. B. Four years later, HRCT shows thickening of the lesion wall (arrow). At this time, extensive investigations were negative for Aspergillus infection. C. Follow-up non-enhanced HRCT performed 1 year later revealed typical fungus ball (arrow), and precipitins for Aspergillus fumigatus were positive.
Regarding overall cavities, conflicting evolution was observed in 2 cases (10%), where the largest cavitary lesion improved while the others worsened (Figure 2). A global worsening was observed in 8 patients (40%), stability in 3 (15%), and improvement in 9 (45%) patients.
HRCT Evolution of Pericavitary Lesions
Among the 20 patients with serial HRCTs, 16 had active and 9 had fibrotic pericavitary lesions at the initial diagnosis. Compared with the last available HRCT, fibrotic lesions remained stable in 8 cases (88.9%). Regarding active lesions, improvement, worsening, and stability were noted in 8 (50%), 4 (25%), and 4 (25%) patients, respectively.
Histopathologic Results
Histopathologic samples of cavitary lesions were available in 2 cases. The first corresponded to the surgical resection of the compressive cyst observed in Patient 18 (see Figure 3); this showed a dense collagenous fibrosis of the cyst wall with few granulomas. The second was a surgical biopsy performed in Patient 21 to confirm the diagnosis of sarcoidosis (see Figure 4). This showed multiple granulomas and lymphocyte inflammation with lesions of ischemic eosinophilic necrosis and few multinucleated giant cells. Vascular involvement of pulmonary veins was noted on some specimens.
Predictive Factors of the Evolution of Cavititary Lesions
None of the clinical, laboratory, or radiologic parameters expressed in Tables 1-3 predicted the evolution of the number of cavities nor the diameter of the largest ones.
DISCUSSION
In our cohort of 1060 patients with pulmonary sarcoidosis, we identified 41 patients with cavitary lesions found on HRCT, including 18 (44%) with proven aspergilloma at initial diagnosis and 23 (56%) with no other cause but sarcoidosis. Thus, the prevalence of cavitary lesions solely related to sarcoidosis could be estimated at 2.2%, but reached 3.9% when taking into account patients with aspergilloma at presentation. Whether or not patients with aspergilloma at presentation had a preexisting cavity is questionable. For that reason, we compared our patients with and without aspergilloma at presentation. In the current series, patients with aspergilloma at presentation were older at diagnosis of pulmonary cavitary lesion than those without (mean age, 49 ± 9 yr vs. 42 ± 12 yr; p = 0.03), presented more commonly with hemoptysis (38.9% vs. 4.3%; p = 0.01), had a longer duration of sarcoidosis (mean, 8.3 ± 5.9 yr vs. 3.4 ± 4.5 yr; p = 0.006), and had a higher frequency of radiographic stage IV (94.4% vs. 52.2%; p = 0.005). These results are in accordance with published data23,42,44, and support the hypothesis that aspergilloma develops in a previously unrecognized cavity until specific symptoms lead to referral and/or HRCT. However, in order to study a homogeneous population of patients with cavitary lesions with a specific focus on the natural history, we excluded patients with aspergilloma at presentation and ended the follow-up at the point of aspergilloma formation.
Patients in the current series had obviously active disease as demonstrated by the high levels of SACE and the presence of HRCT features suggesting granulomatous lesions around the cavitary lesions in 82.6% of patients. Cavitary lesions could occur in all radiographic stages. Although 52.2% of the patients happened to be stage IV, most of them (75%) still exhibited laboratory signs of activity as defined by abnormal SACE. In almost all cases, patients had patent extrarespiratory involvement, including severe extrarespiratory localizations in 47.8% of patients. During follow-up, the evolution of sarcoidosis appeared to be chronic despite treatment, with only a few cases of recovery (15%). Complications of cavitary lesions affected a high rate of patients. The types of complications were similar to those described in the literature11: hemoptysis (25%), aspergilloma (15%), pneumothorax, and other infections.
As seen on HRCT, cavitary lesions were multiple in 91.3% of patients and had a multiloculated aspect with frequent septates. They had thin walls in 69.6% of cases. When the walls were thick, a further thinning was the rule under treatment. Conversely, a further thickening was always associated with an infectious complication, especially aspergilloma. Accordingly, the cavitary wall was thick in 83% of our 18 patients with aspergilloma at initial presentation. Taken together these findings strongly support that the thickening of a cavitary lesion should prompt the clinician to search for a superimposed infection. The merging of adjoined cavitary lesions frequently led to a larger one, initially with persistent inner septates. The evolution of cavitary lesions was unpredictable. Indeed, improvement or worsening of cavitary lesions was not associated with radiographic stage; HRCT features, including the presence of fibrosis in the pericavitary area; or SACE level.
Considering the few histologic reports in the literature, the pathogenesis of cavitation in the context of sarcoidosis is unclear. Although cavitary lesions are admittedly related to ischemic necrosis with extrusion of hyaline material from conglomerate sarcoid granulomas4,33,35,37, other mechanisms such as vasculitis34,40 may also be involved in the early stage of the disease. Our results highlight the role of conglomerate areas of sarcoid granulomas4,17 as the major determinant of cavitation. This is in keeping with recent data supporting the hypothesis that active granulomatous lesions may incite cellular necrosis via TNF-α release from alveolar macrophages and CD4 lymphocytes12,45. First, most patients had HRCT features suggesting a granulomatous process surrounding the cavities. Particularly, alveolar consolidations and ground-glass attenuation were observed in 21.7% and 52.2% of patients, respectively. This point is notable since alveolar consolidations and ground-glass attenuation are uncommon in sarcoidosis, seen in only about 7% and 16% of patients, respectively6. Both features are markers of disease activity, ground-glass attenuation more likely to mirror alveolitis and consolidations reflecting coalescence of granulomas26,41.
Second, the thickness of the walls of cavitary lesions and the response to treatment may also be signs of granulomatous involvement. At the early stage of its natural history, the cavitation may have thick walls that will progressively become thinner, partially and then circumferentially, due to detachment of diseased tissue.
Another mechanism of cavitation could be granulomatous angiitis, which seems very common in pulmonary sarcoidosis, found in about 70% of patients35,40. Indeed, perivascular granulomas can compress or invade the vessel walls and provoke the obstruction of the lumen with subsequent ischemic necrosis. Angiitis may participate in ischemic necrosis within conglomerate sarcoid granulomas in the early stages of the disease. Both mechanisms were observed in a patient who underwent surgical lung biopsy (see Figure 4). Moreover, angiitis and hypervascularizated granuloma conglomerates11,25 may also explain why hemoptysis occurred frequently in the absence of any patent infection.
However, based on these hypotheses, one would expect to observe a decrease in the size of cavitary lesions in treated patients. This was not the case in the current series. For example, 1 of our patients (see Figure 3) who underwent surgical removal of a large growing cavity showed evidence of only a few granulomas39 on pathologic examination. Therefore, other mechanisms may be involved in the evolution of the cavitary lesions, including merging of adjoined cavities and air trapping, due to bronchiolar involvement of sarcoidosis by granulomas and fibrosis. Finally, one may challenge the role of cigarette smoking in the physiopathology of cavitary sarcoidosis, through smoke-induced inflammation7 and air trapping24, but in the absence of a control group, this point cannot be addressed accurately.
Despite common clinical, laboratory, and HRCT features, cavitary sarcoidosis should be differentiated from other disorders characterized by pulmonary angiitis and granulomatosis14,38, mainly Wegener granulomatosis2,27 and necrotizing sarcoid granulomatosis8,32. Compared to Wegener disease, patients in our series had no antineutrophil cytoplasmic antibodies, and hemorrhagic complications were not due to diffuse pulmonary hemorrhage. The relationship between cavitary sarcoidosis and necrotizing sarcoid granulomatosis is more controversial. From our point of view, these are 2 separate entities. Indeed, the high levels of SACE and the characteristics of cavitary lesions seen on HRCT in patients in the current series sharply contrast with the normality of SACE and the rarity of cavitary lesions (14% of patients) in patients with necrotizing sarcoid granulomatosis32. Yet, the fact that cavitation is rare in necrotizing sarcoid granulomatosis is unexplained.
We are aware that the current study has several limitations, mainly related to its retrospective design. First, patients were extracted from a database of HRCT, and whether all patients with pulmonary sarcoidosis and cavitary lesions were indexed is questionable. Moreover, our hospital is a reference center for sarcoidosis. Therefore, the prevalence of disease may have been misestimated. Second, the HRCT protocol did not include expiratory examinations; hence the role of air trapping as a determinant of cavitation remains hypothetical. Finally, HRCT examinations were performed in follow-up according to patient symptoms and not according to a predetermined protocol. Therefore, the duration of follow-up differed between patients, which could lead to a bias in the identification of parameters affecting the natural history of the cavitary lesions.
In conclusion, cavitary lesions in pulmonary sarcoidosis usually occur in active and severe forms of the disease. The development and evolution of cavitary lesions are unpredictable, but complications are frequent and severe. Further prospective studies are needed to evaluate the real incidence of cavitary lesions in sarcoidosis and to determine their underlying mechanisms.
REFERENCES
1. Abehsera M, Valeyre D, Grenier P, Jaillet H, Battesti JP, Brauner MW. Sarcoidosis with pulmonary fibrosis: CT patterns and correlation with pulmonary function.
AJR Am J Roentgenol. 2000;174:1751-1757.
2. Aberle DR, Gamsu G, Lynch D. Thoracic manifestations of Wegener granulomatosis: diagnosis and course.
Radiology. 1990;174:703-709.
3. Akelsson IG, Eklund A, Skold CM, Tornling G. Bilateral spontaneous pneumothorax and sarcoidosis.
Sarcoidosis. 1990;7:136-138.
4. Bistrong HW, Tenney RD, Sheffer AL. Asymptomatic cavitary sarcoidosis.
JAMA. 1970;213:1030-1032.
5. Brauner MW, Lenoir S, Grenier P, Cluzel P, Battesti JP, Valeyre D. Pulmonary sarcoidosis: CT assessment of lesion reversibility.
Radiology. 1992;182:349-354.
6. Brauner MW, Grenier P, Mompoint D, Lenoir S, de Cremoux H. Pulmonary sarcoidosis: evaluation with high-resolution CT.
Radiology. 1989;172:467-471.
7. Churg A, Dai J, Tai H, Wright JL. Tumor necrosis factor-α is central to acute cigarette smoke-induced inflammation and connective tissue breakdown.
Am J Respir Crit Care Med. 2002;166:849-854.
8. Churg A, Carrington CB, Gupta R. Necrotizing sarcoid granulomatosis.
Chest. 1979;76:406-413.
9. Consensus conference: activity of sarcoidosis. Third WASOG meeting, Los Angeles, USA, September 8-11, 1993.
Eur Respir J. 1994;7:624-627.
10. Dorcier F, Grenier N, Dubroca J, Lacoste D, Beylot J, Grelet P. Thoracic sarcoidosis with pulmonary cavitation. Apropos of a case.
J Radiol. 1987;68:451-454.
11. Edelman RR, Johnson TS, Jhaveri HS, Kim D, Kasdon E, Frank HA, Simon M. Fatal hemoptysis resulting from erosion of a pulmonary artery in cavitary sarcoidosis.
AJR Am J Roentgenol. 1985;145:37-38.
12. Fehrenbach H, Zissel G, Goldmann T, Tschernig T, Vollmer E, Pabst R, et al. Alveolar macrophages are the main source for tumour necrosis factor-alpha in patients with sarcoidosis.
Eur Respir J. 2003;21:421-428.
13. Flora G, Dostanic D, Jakovic R, Sharma OP. Pneumothorax in sarcoidosis.
Sarcoidosis. 1991;8:75-79.
14. Frazier AA, Rosado-de-Christenson ML, Galvin JR, Fleming MV. Pulmonary angiitis and granulomatosis: radiologic-pathologic correlation.
Radiographics. 1998;18:687-710.
15. Freundlich IM, Libshitz HI, Glassman LM, Israel HL. Sarcoidosis. Typical and atypical thoracic manifestations and complications.
Clin Radiol. 1970;21:376-383.
16. Froudarakis ME, Bouros D, Voloudaki A, Papiris S, Kottakis Y, Constantopoulos SH, Siafakas NM. Pneumothorax as a first manifestation of sarcoidosis.
Chest. 1997;112:278-280.
17. Hamilton R, Petty TL, Haiby G. Cavitary sarcoidosis of the lung.
Arch Intern Med. 1965;116:428-430.
18. Hamper UM, Fishman EK, Khouri NF, Johns CJ, Wang KP, Siegelman SS. Typical and atypical CT manifestations of pulmonary sarcoidosis.
J Comput Assist Tomogr. 1986;10:928-936.
19. Harada T, Amano T, Takahashi A, et al. Necrotizing sarcoid granulomatosis presenting with elevated serum soluble interleukin-2 receptor levels.
Respiration. 2002;69:468-470.
20. Ichikawa Y, Fujimoto K, Shiraishi T, Oizumi K. Primary cavitary sarcoidosis: high-resolution CT findings.
AJR Am J Roentgenol. 1994;163:745.
21. Israel HL, Lenchner GS, Atkinson GW. Sarcoidosis and aspergilloma. The role of surgery.
Chest. 1982;82:430-432.
22. Jaffe CC. Measures of response: RECIST, WHO, and new alternatives.
J Clin Oncol. 2006;24:3245-3251.
23. Lachkar S, Dominique S, Thiberville L, Nouvet G, Genevois A. Aspergillosis and sarcoidosis.
Rev Mal Respir. 2007;24:943-953.
24. Lee KW, Chung SY, Yang I, Lee Y, Ko EY, Park MJ. Correlation of aging and smoking with air trapping at thin-section CT of the lung in asymptomatic subjects.
Radiology. 2000;214:831-836.
25. Lemay V, Carette MF, Parrot A, et al. Hemoptysis in sarcoidosis. Apropos of 6 cases including 4 with fatal outcome.
Rev Pneumol Clin. 1995;51:61-70.
26. Leung AN, Brauner MW, Caillat-Vigneron N, Valeyre D, Grenier P. Sarcoidosis activity: correlation of HRCT findings with those of 67Ga scanning, bronchoalveolar lavage, and serum angiotensin-converting enzyme assay.
J Comput Assist Tomogr. 1998;22:229-234.
27. Maskell GF, Lockwood CM, Flower CD. Computed tomography of the lung in Wegener's granulomatosis.
Clin Radiol. 1993;48:377-380.
28. Mayock RL, Bertrand P, Morrison CE, Scott JH. Manifestations of sarcoidosis. Analysis of 145 patients, with a review of nine series selected from the literature.
Am J Med. 1963;35:67-89.
29. Mihaescu TT, Veres L. Pneumothorax and pulmonary cavitation in a man with systemic sarcoidosis.
Sarcoidosis. 1990;7:129-132.
30. Ozseker ZF, Yilmaz A, Bayramgurler B, Guneylioglu D. Cavitary sarcoidosis: analysis of two cases.
Respirology. 2002;7:289-291.
31. Piaton E, Rafii H, Aoun C, Saugier B, Brune J. Spontaneous pneumothorax disclosing pulmonary sarcoidosis.
Presse Med. 1995;24:1621.
32. Quaden C, Tillie-Leblond I, Delobbe A, et al. Necrotising sarcoid granulomatosis: clinical, functional, endoscopical and radiographical evaluations.
Eur Respir J. 2005;26:778-785.
33. Rockoff SD, Rohatgi PK. Unusual manifestations of thoracic sarcoidosis.
AJR Am J Roentgenol. 1985;144:513-528.
34. Rohatgi PK, Schwab LE. Primary acute pulmonary cavitation in sarcoidosis.
AJR Am J Roentgenol. 1980;134:1199-1203.
35. Rosen Y, Moon S, Huang CT, Gourin A, Lyons HA. Granulomatous pulmonary angiitis in sarcoidosis.
Arch Pathol Lab Med. 1977;101:170-174.
36. Ryu JH, Swensen SJ. Cystic and cavitary lung diseases: focal and diffuse.
Mayo Clinic Proc. 2003;78:744-752.
37. Schiffner RO, Sharma OP. Acute pulmonary cavitation in sarcoidosis.
West J Med. 1977;127:346-349.
38. Staples CA. Pulmonary angiitis and granulomatosis.
Radiol Clin North Am. 1991;29:973-982.
39. Statement on sarcoidosis. Joint statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999.
Am J Respir Crit Care Med. 1999;160:736-755.
40. Takemura T, Matsui Y, Saiki S, Mikami R. Pulmonary vascular involvement in sarcoidosis: a report of 40 autopsy cases.
Hum Pathol. 1992;23:1216-1223.
41. Tazi A, Desfemmes-Baleyte T, Soler P, Valeyre D, Hance AJ, Battesti JP. Pulmonary sarcoidosis with a diffuse ground glass pattern on the chest radiograph.
Thorax. 1994;49:793-797.
42. Tomlinson JR, Sahn SA. Aspergilloma in sarcoid and tuberculosis.
Chest. 1987;92:505-508.
43. Tuddenham WJ. Glossary of terms for thoracic radiology: recommendations of the Nomenclature Committee of the Fleischner Society.
AJR Am J Roentgenol. 1984;143:509-517.
44. Wollschlager C, Khan F. Aspergillomas complicating sarcoidosis. A prospective study in 100 patients.
Chest. 1984;86:585-588.
45. Ziegenhagen MW, Benner UK, Zissel G, Zabel P, Schlaak M, Muller-Quernheim J. Sarcoidosis: TNF-alpha release from alveolar macrophages and serum level of sil-2r are prognostic markers.
Am J Respir Crit Care Med. 1997;156:1586-1592.
