Pulmonary Sarcoidosis: Typical and Atypical Manifestations at High- Resolution CT with Pathologic Correlation Recent Advances in Sarcoidosis Chest 2011;139;结节病CT典型和不典型表现结节病进展OrganLungPleuraLymph NodesSkinEyeNasal Mucosa（鼻粘膜）Larynx（喉）Bone MarrowSpleenLiver%901-575-90252520515-4050-6060-90OrganKidneyCalcium MetabolismNervous SystemBoneJointsHeartEndocrine GlandsParotid GlandGastrointestinal System%Rare1-25525-505Rare10RareSarcoidosis is a multisystem disorder that is characterized by noncaseous epithelioid cell granulomas, which may affect almost any organ. 结节病是一种以非干酪样坏死的上皮细胞肉芽肿为特点的多系统疾病，几乎可以累及所有器官。Sarcoidosis may be asymptomatic or chronic. It commonly improves or clears up spontaneously（自愈或好转）. More than 2/3 of people with lung sarcoidosis have no symptoms after 9 years. About 50% have relapses. About 10% develop serious disability. Sarcoidosis of the lung is primarily an interstitial lung disease in which the inflammatory process involves the alveoli, small bronchi, and small blood vessels. Typical and Atypical Features of Pulmonary Sarcoidosis at High-Resolution CT Typical features 1 Lymphadenopathy: hilar, mediastinal (right paratracheal), bilateral, symmetric, and well defined 2 Nodules: micronodules (24 mm in diameter; well defined, bilateral); macronodules (5 mm in diameter, coalescing) 3 Lymphangitic spread: peribronchovascular, subpleural, interlobular septal 4 Fibrotic changes: reticular opacities, architectural distortion, traction bronchiectasis, bronchiolectasis, volume loss Bilateral perihilar opacities 5 Predominant upper- and middle-zone locations of parenchymal abnormalities 结节病原本是肺间质性病变，累及肺泡，支气管和小血管淋巴结增大，两侧对称，境界清楚大小结节淋巴管播散，支气管血管鞘，胸膜下，小叶间隔纤维化改变，网状阴影，肺结构扭曲，牵拉性支扩，肺容积缩小，两肺门旁致密影中上肺为主典型特征 Atypical features 1 Lymphadenopathy: unilateral, isolated, anterior and posterior mediastinal 2 Airspace consolidation: masslike opacities, conglomerate masses, solitary pulmonary nodules, confluent alveolar opacities (alveolar sarcoid pattern) 3 Ground-glass opacities 4 Linear opacities: interlobular septal thickening, intralobular linear opacities 5 Fibrocystic changes: cysts, bullae, blebs, emphysema, honeycomb-like opacities with upper- and middle-zone predominance 单侧孤立前后纵隔淋巴结增大肺泡实变：肿块，实质性结节，实变融合毛玻璃阴影线状阴影小叶间隔增厚小叶年线状阴影不典型表现囊性纤维化改变：囊，大泡，小泡，肺气肿，蜂窝样改变 6 Miliary opacities 粟粒样改变 7 Airway involvement: mosaic attenuation pattern, tracheobronchial abnormalities, atelectasis 气道累及：马赛克改变，气管支气管异常，肺不张 8 Pleural disease: effusion, chylothorax, hemothorax, pneumothorax, pleural thickening, calcification Pleural plaquelike opacities 9 Mycetoma, aspergilloma 霉菌球During the past decade, advances have been made in the study of sarcoidosis The Mycobacterium tuberculosis catalase-peroxidase (mKatG) protein, a potential antigen, has been identified,结核分枝杆菌过氧化氢酶过氧化物酶（mkatg）蛋白，作为一个潜在的抗原已被确定。 PET scanning has proven valuable in locating occult sites for diagnostic biopsy. PET扫描已被证明在定位活检诊断隐匿性病灶的价值 Endobronchial ultrasound- guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal lymph nodes has facilitated diagnosis, often eliminating the need for more-invasive procedures, such as mediastinoscopy. 支气管内超声引导下经支气管针吸活检（EBUS-TBNA）的纵隔淋巴结有利于诊断，往往避免更具侵袭性的操作，如纵隔镜。Gene expression analyses have more clearly defined cytokine dysregulation in sarcoidosis Currently, no reliable prognostic biomarkers have been identified. 目前，还没有可靠的预后标志物已被确定。The tumor necrosis factor (TNF) inhibitors, a relatively new class of steroid-sparing agents, have been used in patients with refractory disease. It is unclear whether medications used to treat pulmonary arterial hypertension are safe and effective for the treatment of sarcoidosis-associated pulmonary hypertension. 肿瘤坏死因子（TNF）抑制剂，一个相对较新的类固醇保代理类药品，已被用于治疗难治性疾病。目前还不清楚是否用于治疗肺动脉高压的药物治疗结节病相关性肺动脉高压是安全和有效的。Pathologic Correlation 相关病理相关病理 Granulomas in the lung parenchyma have a characteristic distribution in relation to lymphatics in the peribronchovascular interstitial space, subpleural interstitial space, and, to a lesser extent, the interlobular septa (ie, a lymphangitic distribution) 肺肺实质肉芽肉芽肿分布与支气管血管鞘，胸膜下分布与支气管血管鞘，胸膜下结缔组织，小叶，小叶间隔中淋巴管相关隔中淋巴管相关. Thickened bronchovascular bundles and small perivascular nodules seen at CT corresponded to granulomas within the connective tissue sheath surrounding pulmonary airways and vessels. Pleural or subpleural nodules were correlated with granulomas adjacent to the visceral pleuraCT上支气管血管鞘增厚和小结节是与包绕气道血管结缔组织鞘中肉芽肉芽肿，胸膜和胸膜下，胸膜和胸膜下结节与与脏层胸膜旁肉芽胸膜旁肉芽肿相关。相关。 Ground-glass opacities represented an accumulation of many granulomatous lesions, with or without fibrosis, in the alveolar septa and around the small vessels. No alveolitis was seen 肺泡间隔小血管周围大量肉芽肉芽肿是毛玻璃阴影主要原因，可伴是毛玻璃阴影主要原因，可伴纤维化，但没有肺泡炎。化，但没有肺泡炎。 Large parenchymal nodules (1 cm in diameter) represented coalescent granulomas 大结节是肉芽肉芽肿病病变的融合的融合 Air bronchiolograms within regions of dense consolidation on CT images corresponded to bronchiolar dilatation with surrounding fibrosis 支气管充气症是纤维化旁的支扩 honeycomb-like pattern of microscopic cysts seen at pathologic analysis. 蜂窝样改变在显微镜下就是很多的小囊 pulmonary sarcoidosis shows the typical perilymphatic distribution of micronodules (arrow). （外周淋巴分布的微结节） Photomicrograph of a lung biopsy specimen demonstrates numerous epithelioid granulomas (arrow) surrounding the bronchial walls and immediately beneath the normal bronchial epithelium (arrowheads). CT scan shows multiple micronodules with a peribronchovascular distribution in both lungs, predominantly in the upper and middle lobes. One cluster of nodules in the periphery of the left upper lobe (arrow) has coalesced to form a conglomerate lesion (macronodule). Coronal reformatted image from high-resolution CT clearly shows upper-lobe predominance of the micronodules. Low-magnification photomicrograph slice from the lower part of the right upper lobe shows multiple confluent granulomas infiltrating the peribronchovascular (arrows) and subpleural (arrowheads) interstitium. CT scan shows mediastinal lymph node enlargement and a reticular pattern produced by nodularity and thickening of interlobular septa, pleural surfaces, and fissures, CT扫描显示纵隔淋巴结肿大和形成网状图案的小叶间隔增厚，及胸膜表面，及产生的裂缝。 (b) Photomicrograph of a specimen from fine-needle aspiration biopsy of an enlarged right paratracheal lymph node shows a group of histiocytes against a lymphocytic background, a cytologic structure characteristic of sarcoid granuloma. (c) Photomicrograph of a lung biopsy specimen from another patient shows progressive thickening of the interlobular septum (*) because of the accumulation of numerous sarcoid granulomas (arrowheads), an appearance that correlates well with the CT features seen in a. 从从扩大的右气管旁淋巴大的右气管旁淋巴结细针穿刺活穿刺活检标本本显微微镜下下显示一示一组以淋巴以淋巴细胞的背景的胞的背景的组织细胞，具有胞，具有结节病肉芽病肉芽肿细胞的胞的结构特征。（构特征。（C）从另）从另一个病人的肺活一个病人的肺活检标检标本的本的显显微照片微照片显显示小叶示小叶间间隔隔增厚（增厚（*），大量），大量积累的肉芽累的肉芽肿结节（箭（箭头）。）。 expiratory CT scan obtained in a patient with pulmonary sarcoidosis shows a mosaic pattern consisting of multiple areas of low attenuation (arrows) interspersed with larger areas of normal lung parenchyma.This appearance is produced by air trapping. Photomicrographs of a transbronchial lung biopsy specimen show accumulations of sarcoid granulomas (*) in the mucosal and submucosal layers of bronchiolar epithelium (arrows in b).呼气相呼气相CT扫描在肺描在肺结节病患者病患者显示示马赛克征，由低密度的多个区域（箭克征，由低密度的多个区域（箭头）穿插着大面）穿插着大面积的正常的正常肺肺实质。这种种现象是由空气滞留象是由空气滞留产生。生。一一经经支气管支气管镜镜肺活肺活检标检标本本显显示的示的积积累累结节结节病肉芽病肉芽肿肿的的显显微照片（微照片（）在粘膜和粘膜下的）在粘膜和粘膜下的细细支气管上支气管上皮皮层层（箭（箭头头B）。）。 . (11a) CT scan shows a diffuse ground-glass pattern produced by multiple confluent micronodules, with associated bronchiectasis. CT扫描显示弥漫性磨玻璃影，由多个融合的结节产生，伴支气管扩张 (11b) Magnified axial high-resolution CT scan of the right lung clearly depicts separate nodules in a subpleural (black arrow) and fissural (white arrow) distribution and along the bronchovascular bundles (arrowheads) 放大的轴位高分辨率CT扫描清楚显示右肺胸膜下区分胸膜下的结节（黑色箭头）和沿支气管血管束分布的“裂”（白色箭头）. (11c) High-power photomicrograph shows an accumulation of interstitial granulomas (white *), which causes a thickened appearance of the interalveolar septa, and acinar granulomas (black *), which form in the interstitium of the alveolar wall and protrude into the alveoli (arrowheads). 高倍镜下涂片显示间质肉芽肿集聚（白*），使肺小泡壁的增厚，和腺泡肉芽肿（黑色），形成在肺泡壁的间质和伸入肺泡（箭头）。Sarcoidosis in a patient with a history of stage III primary cutaneous malignant melanoma. 结节病III期原发性皮肤恶性黑色素瘤病史。 (a) Contrast- enhanced CT scans show pulmonary nodules (arrow) in subpleural (right) and fissural (left) regions. A video-assisted thoracoscopic surgical biopsy was performed. (b) Low-power photomicrograph (original magnification, 10; H-E stain) obtained at histopathologic analysis shows a subpleural nodule that is darker in color because of anthracosis（尘肺）. (c) Photo- micrograph obtained at higher power (original magnification, 100; H-E stain) shows multiple nonnecrotic granulomas（坏死性肉芽肿） (arrows) expanding the interstitium that surrounds the subpleural nodule in b. Typical (a, b) and atypical (c, d) radiologic findings of lymphadenopathy in four patients with sarcoidosis四例结节病淋巴结病变的影像学表现. (a) Axial contrast materialenhanced CT scan (mediastinal window) shows typical bilateral and symmetric hilar (ar- rows) and subcarinal (*) lymphadenopathy.CT增强扫描（纵隔窗）显示了典型的双侧对称性肺门（箭头）及隆突下淋巴结肿大（*） (b) Axial unenhanced CT scan (mediastinal window) obtained at the level of the left pulmonary artery shows enlargement of right paratracheal and left hilar lymph nodes (arrows) 右气管旁和左肺门淋巴结肿大. Although the right hilum is not shown, it too was affected. (c) Axial unenhanced CT scan (mediastinal window) shows punctate cal- cifications of hilar lymph nodes (arrows), a pattern that also occurs in other chronic granulomatous diseases. (d) Axial contrast-enhanced CT scan shows bilateral eggshell-like calcifications of hilar and mediastinal lymph nodes双侧纵隔、肺门淋巴结蛋壳样钙化 (arrows), findings that warrant the inclusion of silicosis 矽肺in the differential diagnosis in this case. Axial high-resolution CT scans obtained at the level of the upper lobes (a) and carina (b) in a patient with pulmonary sarcoidosis show a fibrotic-cicatricial pattern of disease, with multiple lesions in a peribronchovascular distribution. Characteristic features of chronic disease are depicted, including traction bronchiectasis牵拉性支气管扩张, severe architectural distortion, volume loss, and interlobular septal thickening. Coales- cent irregular masslike opacities (white arrows) and a calcified right lower paratra- cheal node (black arrow in b) also are seen. Mosaic attenuation, which is most visible in a, presumably results from airway distor- tion due to fibrosis. Axial high-resolution CT scan shows several large, ill-defined nodules and areas of con- solidation resulting from the confluence of multiple parenchymal micronodules composed of numerous tiny granulomas in both lungs. Fine nodular opacities are seen around the large nodules (white arrows), and small low-attenuation spots that correspond to the spaces between partially coalescent small nod- ules are visible peripherally.This appearance has been termed the sarcoid “galaxy sign”小结节环绕大结节银河征. Distortion of the right major fissure is also seen 扭曲的叶间胸膜(black arrow). Alveolar sarcoid多房型肉瘤 pattern of airspace consolidation in pulmonary sarcoidosis. Axial high-resolution CT scan shows alveolar consolidation in the left upper lobe and patchy subpleural alveolar opacities in the right upper lobe. Architectural distortion and traction bronchiectasis, signs of fibrosis, also are visible, mainly in the right upper lobe. Axial unenhanced high-resolution CT scan shows asymmetric subpleural honeycomb-like cysts不对称胸膜下蜂窝样囊肿 (ar- rowheads) and architectural distortion associated with left fissure nodularity (arrow). Although these features also are characteristic of idiopathic pulmonary fibrosis特发性肺纤维化, the upper-lobe predominance of honeycomb-like cysts and the peribronchovascular and fissural distribution of micronodules in this case were more suggestive of sarcoidosis.以上叶为主的蜂窝状囊 ，沿支气管血管束周围分布并且更提示结节病。Miliary opacities in sarcoidosis. 粟粒样结节病 Axial un- enhanced high-resolution CT scan shows countless tiny micronodules representing multiple and diffuse granulomas in a random distribution, with bronchial wall thickening. When this pattern is seen, the differential diagnosis should include miliary tuberculosis, pneumo- coniosis, and metastatic lesions. 无数的小结节表现为随机分布的多发弥漫性肉芽肿，支气管壁增厚。鉴别诊断应包括粟粒性肺结核，尘肺，和转移性病变。A, High-resolution CT scan of lungs reveals ill-defined small nodular opacities in peribronchovascular and issural distribution. Small amount of interlobular septal thickening少量的小叶间隔增厚 (arrow) is seen. B, Photomicrograph of histopathologic specimen shows noncaseating ？tightly formed granulomas and epithelioid histiocytes and lymphocytes. Perilymphatic distribution of granulomas is evident. Normal lung parenchyma and small region of fibrotic interlobular septal thickening (arrow) are seen. 组织病理标本的显微照片显示紧密的肉芽肿和上皮样细胞和淋巴细胞。肉芽肿淋巴分布是显而易见的。正常肺组织纤维化和小叶间隔增厚（箭头）。Tracheobronchial and pulmonary involvement of sarcoidosis 主支气管及肺实质受侵 (a) Axial contrast-enhanced CT scan obtained at the subcarinal level shows a soft-tissue mass with punctate calcifications that fills the lumen of the right intermediate bronchus (arrow), causing partial atelectasis of the right middle and right lower lobes. Mild bilateral hilar lymphadenopathy and marked sub- carinal lymphadenopathy also are seen. 造成右中、右下叶肺不张的部分。双侧肺门淋巴结肿大和标记隆突淋巴结肿大也看到。(b) Axial contrast-enhanced CT scan shows that part of the mass encases and occupies the right lower lobe bronchi, causing partial atelectasis. At diagnostic thoracotomy, sarcoidosis with tracheobronchial and pulmonary involvement was found.开胸活检示，支气管及肺实质受累 High-resolution CT images of middle lung zone in 24-year-old woman (nonsmoker) with pulmonary sarcoidosis. A, Inspiratory CT scan shows bilateral hilar lymphadenopathy (arrows) and peripheral small nodular opacities in middle lobe (arrowheads). B, Expiratory CT scan reveals air trapping in lower lobes. inspiratory CT scan shows numerous bilateral small nodules. B, Expiratory CT scan shows minimal air trapping (arrows) in upper lobes. END