CT of Nontuberculous Mycobacterial Pulmonary Infection Tae Sung Kim 1 Won-Jung Koh 2 Joungho Han 3 Myung Jin Chung 1 Ju Hyun Lee 1 Kyung Soo Lee 1 O Jung Kwon 2 Kim TS, Koh W-J, Han J, et al. Received June 4, 2004; accepted after revision August 17, 2004. Supported by grant R11-2002-103 from the Korea Science & Engineering Foundation. 1 Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Gangnam-Ku, Seoul 135-710, South Korea. Address correspondence to T. S. Kim. 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea. 3 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea. AJR 2005;184:1247 1252 0361 803X/05/1844 1247 American Roentgen Ray Society Hypothesis on the Evolution of Cavitary Lesions in Nontuberculous Mycobacterial Pulmonary Infection: Thin-Section CT and Histopathologic Correlation OBJECTIVE. The objectives of our study were to evaluate the thin-section CT findings of the cavitary form of nontuberculous mycobacterial pulmonary infection and correlate these imaging findings with the histopathologic findings concerning the development of bronchiectasis and of centrilobular nodules and cavitary lesions. MATERIALS AND METHODS. We retrospectively reviewed thin-section CT scans (2.5- mm collimation, both axial and coronal reformation images) of 24 cases (male female ratio, 13:11; mean age, 61 years; age range, 43 82 years) of the cavitary form of culture-proven Mycobacterium avium-intracellulare complex pulmonary infection including two cases with lobectomy specimens. Any changes in CT findings detected on the follow-up CT scans that were available for seven patients (follow-up interval, 6 24 months; mean, 12 months) were also assessed. RESULTS. Thin-section CT findings were bronchiectasis (24/24 patients, 100%), a patent bronchus running into a cavitary lesion (the feeding bronchus appearance) (18/24, 75%), nodules less than 10 mm (17/24, 71%), centrilobular nodules (17/24, 71%), nodules of 10 30 mm (13/24, 54%), peribronchial nodules (8/24, 33%), lobular consolidation (6/24, 25%), bronchial wall thickening (4/24, 17%), and consolidation (2/24, 8%). Two lobectomy specimens showed large cavitary consolidations with the feeding bronchus appearance on pathologic specimens. In two patients, small peribronchial nodules had changed into cavitary nodules with the feeding bronchus appearance on follow-up CT, which represented inflamed focal cystic bronchiectasis. CONCLUSION. In the cavitary form of M. avium-intracellulare complex pulmonary infection, the feeding bronchus appearance is another very frequent thin-section CT finding. This appearance may suggest that peribronchial nodules of M. avium-intracellulare complex infection evolve into inflamed focal cystic bronchiectasis manifesting as cavitary lesions. ontuberculous mycobacterial pulmonary infection in immunocompe- N tent hosts, being increasingly recognized as one of the significant causes of chronic pulmonary infection [1, 2], is known to have two distinct radiologic manifestations: an upper lobe cavitary form and a nodular bronchiectatic form [2 4]. The characteristic CT features of the upper lobe cavitary form are heterogeneous nodular and cavitary opacities, and those of the nodular bronchiectatic form are bronchiectasis and branching centrilobular nodules (tree-in-bud pattern). Several previous studies suggested that the bronchiectasis was not a preexisting condition but resulted from nontuberculous mycobacterial infection [5 10]. To our knowledge, nothing has been described in the Englishlanguage literature concerning the possible relation between bronchiectasis and the centrilobular nodules and cavitary lesions in both forms of nontuberculous mycobacterial pulmonary infection or how these lesions develop and evolve. We retrospectively reviewed thin-section CT images of 24 cases of the cavitary form of Mycobacterium avium-intracellulare complex (MAC) pulmonary infection in immunocompetent patients with CT pathologic correlation of two lobectomy specimens to suggest a possible hypothesis about how bronchiectasis and centrilobular nodules and cavitary lesions develop and evolve in MAC pulmonary infection. Materials and Methods Between April 2002 and March 2004, 50 immunocompetent patients (male female ratio, 25:25; mean age, 61 years; age range, 25 87 years) with cultureproven MAC pulmonary infection (Mycobacterium AJR:184, April 2005 1247
avium Mycobacterium intracellulare ratio, 20:30) were identified in our institute. All these patients fulfilled the 1997 American Thoracic Society criteria for the diagnosis of nontuberculous mycobacterial disease [3]. Helical thin-section CT scans were available in all patients. On review of the thin-section chest CT scans, 24 of the 50 patients showed cavitary nodules or cavitary consolidations in the lung (male female ratio, 13:11; mean age, 61 years; age range, 43 82 years). We retrospectively reviewed the thin-section CT scans (2.5-mm collimation, both axial and coronal reformation images) of these 24 cases of the cavitary form of MAC pulmonary infection including two cases with lobectomy specimens. Follow-up CT scans were available in seven patients (follow-up interval, 6 24 months; mean, 12 months). Any changes in the CT findings detected on follow-up CT scans were also assessed. Chest CT scans were obtained with a LightSpeed QX/i scanner (GE Healthcare) without IV injection of contrast medium. All CT data were reconstructed using a high-spatial-frequency algorithm. Helical volumetric scanning data using MDCT (120 kvp, 70 ma, 2.5-mm collimation, pitch of 6, and 2-mm reconstruction interval) were obtained through the thorax. The data obtained were reconstructed with a 2.5-mm thickness for transaxial images and a 1.2- to 2.0-mm thickness for coronal images. The scanning data were displayed directly on monitors (four monitors, 1,536 2,048 image matrices; 8-bit viewable gray-scale; and 60-foot-lamberts luminescence) of a PACS workstation (Path- Speed, GE Healthcare Integrated Imaging Solutions). Thin-section CT scans were retrospectively reviewed by two independent chest radiologists with 7 and 4 years of experience, respectively. Both axial and coronal reformation images of thin-section CT scans were reviewed on the PACS workstation using the cine mode with scrolling a mouse up and down, which facilitated more accurate evaluation of the relation between an airway and a cavitary lesion. Final conclusions were reached by consensus. Thin-section CT scans were evaluated with regard to the presence or absence of bronchiectasis, a patent bronchus toward a cavitary lesion, well-defined small nodules (< 10 mm in diameter), branching centrilobular nodules (tree-in-bud pattern), nodules of 10 30 mm in diameter, peribronchial nodules, lobular consolidation (polygonal, 10 25 mm in diameter), bronchial wall thickening, and subsegmental or segmental consolidation. Two lobectomy specimens were reviewed by a pathologist with 10 years of experience and correlated with the findings of the corresponding thinsection CT scans. Results The thin-section CT findings of the 24 cases of the cavitary form of MAC pulmonary infection are summarized in Table 1. Of 24 cases of the cavitary MAC infection, 18 (75%) had the feeding bronchus appearance, D Fig. 1. 64-year-old man with Mycobacterium avium-intracellulare complex pulmonary infection. A, Coronal reformation CT image (2-mm collimation) shows cavitary mass with feeding bronchus appearance (arrowheads) in left upper lobe. B, Axial thin-section CT scan (2.5-mm collimation) obtained at thoracic inlet level shows cavitary mass. Note bronchiolar wall thickening with ectatic change (arrows). C, Photograph of gross specimens from left upper lobectomy shows large necrotic cavitary masses (stars). Note centrally located ectatic bronchi running into cavitary masses (feeding bronchus appearance) (arrows). These gross findings suggest segmental destruction of bronchi forming necrotic cavities or focal cystic bronchiectasis. Scale = centimeters. D, Photomicrograph of histopathologic specimen shows thickened membranous bronchiole (arrowheads) owing to inflammatory cell infiltration. Also note granuloma with central caseating necrosis (arrow) at end of thickened bronchiole. (H and E, 12) E, Photomicrograph of histopathologic specimen shows bronchiolar lumen is diffusely narrowed by bronchiolar wall thickening (arrows) owing to transmural lymphoplasma cell infiltration. (H and E, 40) E 1248 AJR:184, April 2005
CT of Nontuberculous Mycobacterial Pulmonary Infection TABLE 1 Thin-Section CT Findings of 24 Cases of the Cavitary Form of Mycobacterium avium-intracellulare Complex No. of Pulmonary infection Cases (%) Bronchiectasis 24 (100) Patent bronchus toward a cavitary 18 (75) lesion (the feeding bronchus appearance) Well-defined small nodules (< 10 mm 17 (71) in diameter) Branching centrilobular nodules 17 (71) (tree-in-bud pattern) Nodules of 10 30 mm in diameter 13 (54) Peribronchial nodules 8 (33) Lobular consolidation (polygonal 6 (25) shape of 10 25 mm in diameter) Bronchial wall thickening 4 (17) Subsegmental or segmental 2 (8) consolidation which denotes a centrally located, patent, thickened bronchus running into a cavitary lesion (Figs. 1 4). In the remaining six patients (25%), the communication between the accompanying bronchus and a cavitary lesion was also suggested but we could not find an open bronchus. Two patients who underwent lobectomy showed large cavitary consolidations with a centrally located, thickened, patent bronchus (the feeding bronchus appearance) on both thin-section CT and pathologic specimens (Fig. 1). On histopathologic examination, bronchial or peribronchial wall thickening with lymphocytic infiltration and peribronchial caseating granulomas surrounding an ectatic or narrowed bronchus were found (Figs. 1 and 2). Destruction and displacement of bronchial cartilages with inflammatory wall thickening were also noted in the bronchial wall with some intraluminal necrotic debris (Fig. 2). In two of seven patients whose follow-up CT scans were available, small peribronchial nodules had changed into cavitary nodules with the feeding bronchus appearance, which represented inflamed focal cystic bronchiectasis (Figs. 4 and 5). The remaining five patients showed slight improvement (n = 2) or no significant interval change (n = 3) of the overall pulmonary lesions. Discussion Whether bronchiectasis is truly caused by MAC infection or is the predisposing condition for MAC colonization has been debated [11 14]. Several articles have been published about the development of bronchiectasis and centrilobular nodules in nontuberculous mycobacterial pulmonary infection [5 10]. According to these articles, the bronchiectasis was not a preexisting condition but resulted from nontuberculous mycobacterial infection. According to Moore [5], small nodules on CT scans were shown to be peribronchial granuloma formation on pathologic correlation and new areas of bronchiectasis and progression of existing bronchiectasis were shown on serial CT scans. Tanaka et al. [6] suggested that pulmonary lesions slowly progressed from small nodules in the subpleural spaces to those with thickening of the draining bronchi or with both pleural and bronchial thickening and to cystic bronchiectatic changes. According to Tanaka et al. [8] in a study of CT findings of 46 MAC patients with follow-up scans, the common thin-section CT findings of MAC were centrilobular and peribronchovascular nodules, bronchiectasis, consolidation, and pleural thickening. Many nodules located in lobular bronchioles had dilated bronchioles inside them. Bronchiectasis became more severe in five of 38 follow-up patients. The study suggested that the disease might begin in the terminal bronchiole and spread transbronchially along the draining bronchus to produce lesions such as new nodules, cavities, and bronchiectasis. According to Fujita et al. [9, 10] in pathologic studies of nine cases of MAC infection with a surgical specimen, pathologic findings included bronchiectasis, bronchiolitis, centrilobular nodules, consolidation, cavity wall and nodules, and Fig. 2. 52-year-old woman with Mycobacterium avium-intracellulare complex pulmonary infection. A, Transaxial thin-section CT scan (2.5-mm collimation) shows large cavitary consolidation in right lower lobe superior segment. Note proximal and distal thickened bronchus (arrowheads) around cavitary consolidation. B, Transaxial thin-section CT scan shows another large cavitary consolidation with feeding bronchus (arrow) in right lower lobe. C, Photomicrograph shows cross-sectional view of segmental bronchi of right lower lobectomy specimen. Note irregular bronchial wall thickening owing to inflammation and fibrosis resulting in luminal narrowing. Also note destruction and displacement of bronchial cartilages (arrows) and intraluminal necrotic debris (arrowhead). (H and E, 1) AJR:184, April 2005 1249
Fig. 3. 66-year-old woman with Mycobacterium aviumintracellulare complex pulmonary infection with multiple feeding bronchi. Transaxial thin-section CT scan (2.5-mm collimation) obtained at left main bronchus level shows multiple cavitary nodules in left upper lobe. Note multiple feeding bronchi (arrowheads) that are thickened and ectatic and running into cavitary nodules. extensive granuloma formation throughout the airways. Peribronchial granuloma formation was observed from the large airway to the bronchiole. Destruction of bronchial cartilage and the smooth-muscle layer and airway narrowing were caused by extensive submucosal granulomas, and bronchial ulceration involving their whole walls was frequently observed. In some areas, necrotic materials were detached into the lumen of the bronchiole. Because cartilage and smooth muscle play a major role in maintaining airway lumen, destruction of these fundamental bronchial structures could result in bronchiectasis, and this process was likely the main cause of bronchiectasis in MAC infection. Well-known thin-section CT findings of nontuberculous mycobacterial infection include bronchiectasis, small and large nodules, branching centrilobular nodules, consolidation, and cavitary lesions [2 16]. However, to the best of our knowledge, the thin-section CT finding of a patent bronchus toward a cavitary lesion (the feeding bronchus appearance) has not been described before in nontuberculous mycobacterial pulmonary infection. The feeding bronchus appearance, which was a centrally located, thickened, mildly ectatic, patent bronchus supplying the cavitary lesion, was another common thinsection CT finding of the cavitary form of MAC infection in our study. We think this finding might have been missed or overlooked on the conventional discontinuous CT images of the previous literature. A bronchus running in the craniocaudal or caudocranial direction is difficult to trace on axial CT images. With a cine mode review of both axial and coronal thin-section CT images of continuous helical volumetric data on a PACS workstation, the feeding bronchus appearance was likely more readily detectable in our study than the axial-only conventional discontinuous CT images of the previous studies, in which focal cystic bronchiectasis might have been interpreted only as a cavitary lesion. In two cases with follow-up CT scans, central cavitation or focal cystic bronchiectatic change of the peribronchial nodule was seen on serial follow-up examinations. With these thin-section CT findings in our study and literature review, the following hypothesis about the developmental relation of bronchiectasis and centrilobular nodules and cavitary lesions in MAC infection can be proposed. We suggest that MAC infection begins with bronchial wall thickening, develops into peribronchial thickening or a peribronchial nodule, and forms inflamed cystic bronchiectasis that manifests as a cavitary mass or cavitary consolidation on both CT and pathologic specimens (Fig. 6). During the inflammatory process, the central necrotic portion Fig. 4. 57-year-old man with Mycobacterium avium-intracellulare complex pulmonary infection with follow-up CT scans. A and B, Transaxial thin-section CT scans (2.5-mm collimation) show multiple cavitary nodules in both lungs. Note feeding bronchi that are thickened and ectatic and running into cavitary nodules (arrows). C, Transaxial thin-section CT scan shows multiple small centrilobular nodules in right lower lobe superior segment. Note feeding bronchus that is mildly thickened and ectatic and running into one of the centrilobular nodules (arrowheads). (Fig. 4 continues on next page) 1250 AJR:184, April 2005
CT of Nontuberculous Mycobacterial Pulmonary Infection Fig. 4. (continued) 57-year-old man with Mycobacterium avium-intracellulare complex pulmonary infection with follow-up CT scans. D, Transaxial thin-section CT scan obtained 6 months after C shows increased size of centrilobular nodules with tiny cavitation (arrowheads). E, Transaxial thin-section CT scan obtained 11 months after D shows increased size of centrilobular nodules with larger cavitation. Also note feeding bronchus (arrowheads) and other thickened ectatic bronchi around cavitary nodules. with destroyed bronchial wall and cartilage seems to be ulcerated and detached into the airway, forming a central cavity. The peripheral portion of the peribronchial nodule extends into the surrounding lung parenchyma. In this circumstance, the central patent bronchus plays the role of a draining bronchus, which disposes of the detached central necrotic debris resulting in cavity formation and bronchogenic spread of the infection. From correlating our hypothesis with the known CT findings of nontuberculous mycobacterial infection, we suggest that the nodular bronchiectatic form (bronchiolectasis with branching centrilobular nodules) on thin-section CT represents stage III inflammation (peribronchial thickening or nodule) mainly involving small airways. In addition, we believe that the large cavitary form on thin-section CT represents stage IV inflammation D mainly involving relatively large airways and more extensive inflammation. According to the proposed hypothesis, MAC pulmonary infection is a mainly bronchocentric inflammatory process. Therefore, the hallmarks of the disease seem to be bronchial or bronchiolar wall thickening, peribronchial thickening, or peribronchial nodules. The disease can show diverse manifestations for example, a nodular bronchiectatic form, a large cavitary form, or a Fig. 5. 65-year-old woman with Mycobacterium avium-intracellulare complex pulmonary infection with follow-up CT scans. A, Transaxial thin-section CT scan (2.5-mm collimation) shows peribronchial nodule in right lower lobe. Note tiny central radiolucency (arrowheads) within nodule, which represents central bronchiole. B, Transaxial thin-section CT scan obtained 6 months after A shows increased size of peribronchial nodule. Note centrally located bronchiole, which gets out of nodule and runs peripherally (arrow). C, Transaxial thin-section CT scan obtained 12 months after B shows increased size of peribronchial nodule with focal cystic bronchiectasis, manifesting as large cavitary nodule. Note distal thickened ectatic bronchus (arrows). E AJR:184, April 2005 1251
Normal Bronchus Stage I Bronchial wall thickening with luminal narrowing mixed form even in one patient, according to the size of the involved airways, the duration of the inflammatory process at each location after pathogen inoculation, and the severity of inflammation, and, possibly, on host immunocompetency. Most patients with cavitary lesions of MAC infection in our study showed small nodules and bronchiectasis, which are the main features of the nodular bronchiectatic form. The possible significance of this hypothesis on the development of bronchiectasis and centrilobular nodules and cavitary lesions in MAC infection is that it might give a comprehensive understanding of the nontuberculous mycobacterial disease process. This process comprises a possible pathologic spectrum from bronchial wall thickening with peribronchial or centrilobular nodules to cavitary lesions or cystic bronchiectasis. In addition, this hypothesis may enable better interpretation of diverse thin-section CT findings and, hence, more accurate diagnosis of nontuberculous mycobacterial pulmonary infection. In conclusion, in the cavitary form of MAC pulmonary infection, the feeding bronchus Stage II Stage III Stage IV Central necrosis Small nodule with or without cavitation (nodular bronchiectatic form) Feeding bronchus Bronchial wall thickening with large cystic bronchiectasis (large cavitary form) Fig. 6. Schematic illustration shows hypothesis about development and evolution of bronchiectasis and centrilobular nodules with or without cavitation and large cavitary lesions in nontuberculous mycobacterial pulmonary infection. appearance is another very frequent thin-section CT finding in addition to bronchiectasis, small and large nodules, branching centrilobular nodules, bronchial or peribronchial thickening or nodules, and consolidation. This appearance may suggest that early bronchial wall thickenings or peribronchial nodules of MAC infection evolve into inflamed focal cystic bronchiectasis manifesting as cavitary lesions. References 1. O Brien RJ, Geiter LJ, Snider DE. The epidemiology of nontuberculous mycobacterial diseases in the United States. Am Rev Respir Dis 1987;135: 1007 1014 2. Goo JM, Im JG. CT of tuberculosis and nontuberculous mycobacterial infections. Radiol Clin North Am 2002;40:73 87 3. [No authors listed]. Diagnosis and treatment of disease caused by nontuberculous mycobacteria: this official statement of the American Thoracic Society was approved by the Board of Directors, March 1997 Medical Section of the American Lung Association. Am J Respir Crit Care Med 1997;156 (2 Pt 2):S1 S25 4. Erasmus JJ, McAdams HP, Farrell MA, Patz EF. Pulmonary nontuberculous mycobacterial infection: radiologic manifestations. RadioGraphics 1999;19:1487 1505 5. Moore EH. Atypical mycobacterial infection in the lung: CT appearance. Radiology 1993;187:777 782 6. Tanaka E, Amitani R, Kuze F. Clinical features of the patients with secondary infection of Mycobacterium avium complex: radiographic pattern of progressions in the patients with and without underlying pulmonary conditions [in Japanese]. Kekkaku 1993;68:57 61 7. Obayashi Y, Fujita J, Suemitsu I, Kamei T, Nii M, Takahara J. Successive follow-up of computed tomography in patients with Mycobacterium aviumintracellulare complex. Respir Med 1999;93:11 15 8. Tanaka D, Niwatsukino H, Oyama T, Nakajo M. Progressing features of atypical mycobacterial infection in the lung on conventional and high-resolution CT (HRCT) images. Radiat Med 2001; 19:237 245 9. Fujita J, Ohtsuki Y, Suemitsu I, et al. Pathological and radiological changes in resected lung specimens in Mycobacterium avium-intracellulare complex disease. Eur Respir J 1999;13:535 540 10. Fujita J, Ohtsuki Y, Shigeto E, et al. Pathologic findings of bronchiectasis caused by Mycobacterium avium-intracellulare complex. Respir Med 2003;97:933 938 11. Hartman TE, Swensen SJ, Williams DE. Mycobacterium avium-intracellulare complex: evaluation with CT. Radiology 1993;187:23 26 12. Swensen SJ, Hartman TE, Williams DE. Computed tomographic diagnosis of Mycobacterium avium-intracellulare complex in patients with bronchiectasis. Chest 1994;105:49 52 13. Primack SL, Logan PM, Hartman TE, Lee KS, Müller NL. Pulmonary tuberculosis and Mycobacterium avium-intracellulare: comparison of CT findings. Radiology 1995;194:413 417 14. Lynch DA, Simone PM, Fox MA, Bucher BL, Heinig MJ. CT features of pulmonary Mycobacterium avium complex infection. J Comput Assist Tomogr 1995;19:353 360 15. Hollings NP, Wells AU, Wilson R, Hansell DM. Comparative appearances of non-tuberculous mycobacteria species: a CT study. Eur Radiol 2002; 12:2211 2217 16. Ellis SM, Hansell DM. Imaging of non-tuberculous (atypical) mycobacterial pulmonary infection. Clin Radiol 2002;57:661 669 1252 AJR:184, April 2005