特发性间质性肺炎

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特发性间质性肺炎
青岛大学医学院附院放射科
殷 泽 富
脱屑性间质性肺炎
DIP
病 理
鉴于许多方面与UIP的差别,Leibow (1965)提出为单独病种.
组织学特点:肺泡腔大量巨噬细胞(AM)聚集,肺泡壁轻度增厚(主要由慢性炎性细胞浸润和纤维母细胞增生).原以为肺泡腔内的细胞是脱落的肺泡上皮,故名DIP.
与UIP的显著区别:除肺泡腔大量巨噬细胞聚集外,间质纤维化轻或无,无蜂窝肺,不同肺野病变基本一致.
临 床
M >F,起病隐匿,主要症状为干咳和呼吸困难.
与UIP相比年龄较轻,杵状指等缺氧症状无或轻,类固醇治疗反应好.预后好,存活期长,病死率低.
实验室检查一般无明显异常.
肺功能正常,或限制性通气障碍,弥散障碍.
X 线 表 现
1 片状稍高密度影,边缘模糊,主要分布于两侧中下肺野
2 网状或网合结节阴影,两侧肺弥漫性分布,以中下肺野为主(少见)
3 Kerley 's B 线,主见于肋隔角区
4 部分病例胸片表现正常
CT 表 现

1 磨玻璃样密度灶
边缘模糊,两侧分布,以中下肺野,尤以基底部外围肺区和肋隔角区为著
2 网状或网合结节阴影
两侧肺弥漫性分布,以中下肺野为主,常见于磨玻璃灶吸收后
诊 断
1 两侧中下肺野磨玻璃样密度增高,小叶间隔增厚,可伴有网或网结节阴影.
2 起病隐匿,干咳,轻度呼吸困难,化验无特殊,肺功正常或轻度限制通气障碍可拟诊此病.
3 确诊须开胸或胸腔镜活检,肺泡腔大量巨嗜细胞聚集伴肺泡隔炎性细胞,纤维母细胞增生.
DESQUAMATIVE INTERSTITIAL PNEUMONIA
(DIP)
The term DIP is retained in this document but it presents several problems. The name originated from the belief that the dominant histologic feature was desquamation 脱落of epithelial cells. However, this is now recognized to be intra-alveolar macrophage accumulation rather than desquamation of epithelial cells as originally thought by Liebow and Carrington. Second, the condition is considered by many to represent the end of a spectrum of RB-ILD in view of its similar pathology and almost invariable association with cigarette smoke . However, rare cases occur in nonsmokers, some of whom have had exposure to environmental inhalation exposures including passive exposure to cigarette smoke. The panel seriously considered changing this term to alveolar macrophage pneumonia, which is a more accurately descriptive term. After considerable discussion, particularly in light of the rarity of this entity, it was decided to retain the term DIP.
Clinical Features
DIP affects primarily cigarette smokers in their fourth or fifth decades of life. DIP is more common in men than in women by a ratio of 2:1. Insidious onset of dyspnea and dry cough over weeks or months is usual and patients may progress to respiratory failure. Digital clubbing develops in about half. Lung physiology confirms normal lung volumes or a mild restrictive abnormality, and the DLCO is moderately decreased.
Clinical course The prognosis of DIP is generally good. Most patients improve with smoking cessation and corticosteroids. The overall survival is about 70% after 10_yr.
Bronchoalveolar lavage findings Bronchoalveolar lavage fluid invariably contains increased numbers of alveolar macrophages, a large proportion of which have granules of \"smoker's pigment\" consisting of intracellular yellow, golden, brown, or black smoke particulates 微粒. Increases in neutrophils, eosinophils, and lymphocytes may also be found.
Radiologic Features
Chest radiographic features The chest radiograph is relatively insensitive for detection of DIP, and has been reported to be normal in 3-22% of biopsy-proven cases (Table 3). Reported radiographic signs of DIP include widespread patchy ground glass opacification, with a lower zone predilection and sometimes a peripheral predominance (Table 3). A granular or nodular texture to ground glass opacification has been reported.
CT features Ground glass opacification is present on CT in all cases of DIP (Figure 15). This has a lower zone distribution in the majority (73%) of cases, a peripheral distribution in 59% of cases, and is patchy in 23%. The distribution is diffuse and uniform in 18%. Irregular linear opacities and reticular pattern are frequent (59%) but limited in extent and usually confined to the lung bases. Honeycombing is seen in less than one-third of cases, and is usually peripheral and limited in extent.
Figure 15. _ Desquamative interstitial pneumonia. (A and B) HRCT shows peripheral-predominant ground glass abnormality, with some associated cystic changes.
On follow-up HRCT, patients receiving treatment can be expected to show partial or near complete resolution of areas of ground glass opacification . Progression of ground glass opacification to a reticular pattern occurs infrequently (less than 20%).
CT-pathologic correlation There have been no formal studies of CT-pathologic correlation in DIP. The ground glass attenuation, which is the hallmark of this disease, is presumed to be due to a combination of diffuse intra-alveolar cells and diffuse mild septal fibrosis. Irregular linear opacities and honeycombing are presumed to correlate with evidence of lung fibrosis.
Radiologic differential diagnosis Conditions that may be indistinguishable from DIP include RB-ILD, acute or subacute hypersensitivity pneumonitis, sarcoidosis, and infections such as Pneumocystis carinii pneumonia.
Histologic Features
The DIP pattern is characterized by diffuse involvement of the lung by numerous macrophage accumulations within most of the distal airspaces (Figure 16) . The alveolar septa are thickened by a sparse inflammatory infiltrate that often includes plasma cells and occasional eosinophils, and they are lined by plump cuboidal pneumocytes (Table 14 and Figure 16). Lymphoid aggregates聚集物may be present. The main feature that distinguishes DIP from RB is that DIP affects the lung in a uniform diffuse manner and lacks the bronchiolocentric distribution seen in RB. The intralumenal macrophages in DIP frequently contain dusty brown pigment identical to that seen in RB. Finely granular iron may be seen in the macrophage cytoplasm. Emphysema is often present.
Figure 16. _ Desquamative interstitial pneumonia pattern. (A) The alveolar spaces are diffusely involved by marked alveolar macrophage accumulation and there is mild interstitial thickening. (B) The alveolar walls are mildly thickened by fibrous connective tissue and a few chronic inflammatory cells. The alveolar spaces are filled with macrophages.
TABLE 14
_HISTOLOGIC_FEATURES_OF_DESQUAMATIVE INTERSTITIAL_PNEUMONIA
Key Histologic Features
Uniform involvement of lung parenchyma
Prominent accumulation of alveolar macrophages (may show fine granular __positivity with iron stains)
Mild to moderate fibrotic thickening of alveolar septa
Mild interstitial chronic inflammation (lymphoid aggregates)
Pertinent Negative Findings
Dense and extensive fibrosis: inconspicuous or absent
Smooth muscle proliferation: inconspicuous or absent
Honeycomb fibrosis absent
Fibroblastic foci and organizing pneumonia: inconspicuous or absent
Eosinophils: inconspicuous, absent, or only focal
Histologic differential diagnosis The histologic differential diagnosis of the DIP pattern includes a number of interstitial lung diseases because intra-alveolar macrophage accumulation or a focal nonspecific \"DIP-like\" reaction is an expected consequence of cigarette smoking. Because many patients with other IIPs are frequently current or former smokers, this pattern often overlies the histologic patterns of UIP, RB, NSIP, eosinophilic pneumonia, chronic hemorrhage or hemosiderosis, and veno-occlusive disease . Peribronchiolar fibrosis coupled with hyperplasia of peribronchiolar epithelium may mimic the appearance of the UIP pattern. The DIP pattern differs from that of UIP in that the interstitial changes are more diffusely distributed, and the fibrotic reaction has a more uniform temporal appearance without dense widespread fibrosis, fibroblastic foci architectural remodeling, or honeycomb change.
淋巴细胞性间质性肺炎
LYMPHOID INTERSTITIAL PNEUMONIA (LIP)
淋巴细胞性间质性肺炎(LIP) 由Liebow and Carrington 于1969年首先提出,病理特征特征为
肺间质弥漫性淋巴细胞浸润,但又不同于其它类型的特发性间质性肺炎(UIP,DIP,BIP,GIP).然而随着对淋巴样浸润的理解的不断加深,LIP在分类系统中的位置发生了变化,将其分为淋巴增生性病变.由于许多病例最终发展为淋巴瘤,故认为是瘤前病变.
曾推测LIP可能是起源于淋巴结外的低度恶性的non-Hodgkin's B cell MALT (mucosa-associated lymphoid tissue)淋巴瘤.
常规组织切片很难区分LIP和淋巴瘤.免疫组化和分子生物学分析才能区分淋巴瘤浸润和反应性淋巴样增生和.实际上只有少数LIP发生恶变.
LIP的组织学 弥漫性淋巴样增生所导致的肺间质改变.与此相关的虑泡性细支气管炎主要是细支气管或呼吸性细支气管周围的具有生发中心的淋巴细胞浸润.
LIP的发病率较低,曾一度怀疑其是否为独立病种,也曾一度被排除在间质性肺炎分类系统,而划归为肺部淋巴增生性疾病.
由于临床和影像表现与IIPs的相似性,组织学上为明确的间质性肺炎,因此将其划归为IIPs更合乎逻辑.
然而,应当注意的是以前称为LIP的疾病中按现在的分类标准很可能划为细胞型的NSIP.
Histologic Features
LIP is defined as a dense interstitial lymphoid infiltrate, including lymphocytes, plasma cells, and histiocytes with associated Type II cell hyperplasia and a mild increase in alveolar macrophages .The alveolar septa should be extensively infiltrated.
组织学特征
肺间质密集的淋巴样浸润,淋巴细胞,浆细胞及与肺泡Ⅱ型上皮相关的组织细胞增生.肺泡腔内巨嗜细胞胞轻度增多,肺泡间隔广泛浸润.
淋巴虑泡,包括有生发中心的的淋巴虑泡通常沿淋巴管分布,部分结构改建(包括蜂窝肺),可见非坏死性肉芽肿.有时肺泡内少许机化和巨嗜细胞聚集.
Lymphoid follicles, including follicles with germinal centers, are often present, usually in the distribution of pulmonary lymphatics. Some architectural derangement (including honeycombing) and nonnecrotizing granulomas may be seen. Intra-alveolar organization and macrophage accumulation may also be present, but only as minor components.
_HISTOLOGIC_ FEATURES_OF _LIP
Key Histologic Features
Diffuse interstitial infiltration of involved areas
Predominantly alveolar septal distribution
Infiltrates comprise mostly T lymphocytes, plasma cells, and macrophages
Lymphoid hyperplasia frequent (MALT =_bronchial mucosa-associated lymphoid tissue. )
Pertinent Negative Findings
Lack of tracking along lymphatic routes (bronchovascular bundles, pleura, and __interlobular septa), characteristic of lymphomas
Organizing pneumonia, inconspicuous or absent
Lack of Dutcher bodies
Lack of monoclonal light chain staining pattern of plasma cells (polyclonal __pattern present)
Lack of extensive pleural involvement or lymph node involvement
Lack of necrotizing granulomas
LIP. There is diffuse thickening of alveolar walls by a moderately severe infiltrate of lymphocytes and plasma cells.
临床特征
女性多见,可见于任何年龄,但多见于50～60岁.起病隐匿,进展较慢,咳嗽,憋气渐进性进展,多在3年以上. 偶有发烧,胸痛,体重减轻及关节肿痛.
疾病进展期可闻及Crackles ,有些病例可有淋巴结肿大.
由于特发性的LIP较为罕见,在诊断LIP之前,必须排除已知原因的相似性疾病,如胶原血管病,免疫缺陷性疾病.
可有轻度贫血.在多珠r-球蛋白或单克隆IgG , IgM 增高的病例中75%的病例有低蛋白血症.
单克隆r-球蛋白的存在或低r-球蛋白血症提示恶性淋巴增生的的可能.
LIP通常是潜在的全身性自身免疫性疾病的表现形式,如类风湿性关节炎, Sj gren's syndrome, Hashimoto's disease,恶性贫血,慢性活动性肝炎,系统性红斑狼疮,自身免疫性贫血,原发性胆汁性肝硬化,重症肌无力,低r-球蛋白血症及严重的自身免疫缺陷,特别是儿童AIDS.在这些疾病中,肺部受累只是伴发性的,并且很快进展为干咳和呼吸困难, 很少进展为肺纤维化.一般没有杵状指,crackles及IIPs的其它体征,或很轻.
病程
多数病例类固醇激素治疗可稳定病情,改善症状.1/3以上进展为弥漫性肺纤维化.治疗是否能改变病程或对肺的生理功能有显著影响尚不清楚. 少数病例可完全消退或显著改善.
BAL:淋巴细胞增多,免疫显型不清楚.
Radiologic Features
Chest radiographic features Two chest radiographic patterns for lymphocytic interstitial pneumonia have been described: basilar with an alveolar component and diffuse with associated honeycombing.
CT features
The dominant CT finding is usually ground glass opacity. Curious perivascular cysts or perivascular honeycombing can also be seen. Reticular abnormality is seen in about 50% of patients. Lung nodules and widespread consolidation may occur. In LIP related to multicentric Castleman's disease, thin-walled cysts, thickening of the bronchovascular bundles, and interlobular septal thickening are the commonest findings.
影像特征
胸片显示间质病变主要位于肺基底部伴有肺泡病变或弥漫性分布伴有蜂窝征.
CT特征
1.磨玻璃密度灶,最常见,血管周围可见气囊或蜂窝.约50%有异常网状改变.可有肺结节和广泛实变.与Castleman's 病相关的LIP则以薄闭气囊,支气管血管束和小叶间隔增厚最常见.
_ Lymphocytic interstitial pneumonia. HRCT shows diffuse ground glass attenuation with multiple lung cysts.
Histologic differential diagnosis
The differential diagnosis for LIP includes
diffuse lymphoid hyperplasia (hyperplasia of bronchial mucosa-associated lymphoid tissue [MALT]),
nodular lymphoid hyperplasia,
lymphoma (of mucosal-associated lymphoid tissue or small lymphocytic types),
the patterns of OP, NSIP,
hypersensitivity pneumonitis, and UIP .
Diffuse lymphoid hyperplasia without alveolar septal infiltration has been included under the category of LIP in previous studies.
Although there may be some overlap in these patterns, for the purposes of this classification the term LIP is limited to those cases with extensive alveolar septal infiltration .
The hypersensitivity pneumonitis pattern usually has less inflammation than LIP, tends to have a peribronchiolar distribution, and also characteristically shows poorly formed granulomas and organizing intralumenal fibrosis .
The cellular NSIP pattern also shows an interstitial lymphocytic and/or plasma cell infiltrate; however, compared with LIP the extent is generally less severe and some alveolar walls are spared.
Pure follicular bronchiolitis or diffuse lymphoid hyperplasia of the bronchus-associated lymphoid tissue differs from LIP in that it lacks extensive alveolar septal infiltration. Lymphoid follicles, including follicles with germinal centers, are often present, usually in the distribution of pulmonary lymphatics. Some architectural derangement (including honeycombing) and nonnecrotizing granulomas may be seen. Intra-alveolar organization and macrophage accumulation may also be present, but only as minor components.
Malignant lymphomas are more likely to show a monomorphous and dense population of lymphoid cells with destruction of alveolar architecture, Dutcher bodies, pleural infiltration, and tracking along lymphatic routes. Immunohistochemistry and/ or gene rearrangement studies may be necessary to exclude a lymphoproliferative disorder .
_CLINICAL_CONDITIONS_ASSOCIATED_WITH LIP _PATTERN
Idiopathic
Infection (especially Pneumocystis carinii, hepatitis B, Epstein-Barr virus)
Collagen vascular disease, especially Sj gren's syndrome, rheumatoid arthritis, ____or systemic lupus erythematosus
Immunodeficiency (HIV, SCID)
Other immunologic disorders
__Autoimmune hemolytic anemia, myasthenia gravis,
pernicious anemia, ____
Hashimoto's thyroiditis,
chronic active hepatitis,
primary biliary cirrhosis
Drug-induced/toxic exposure
SCID =_severely compromised immune deficiency