Abstract With the latest classification of idiopathic interstitial pneumonia jointly developed by the American Thoracic Society and the European Respiratory Society, the understanding of this type of lesion has been gradually advanced. Since the imaging manifestations of various diseases in this group of lesions are similar, which often makes the diagnosis and mutual differentiation difficult, this paper reviews the HRCT features and related pathological characteristics to provide a basis for clinical imaging diagnosis. Lei Zhidan, Department of Radiology, Henan Provincial People’s Hospital
Keywords: Idiopathic interstitial pneumonia; Pathology; HRCT
Idiopathic interstitial pneumonia (IIP) is a group of non-neoplastic, non-bacterial diffuse interstitial lung diseases with predominantly inflammatory lesions in the interstitial lung. Although the etiology of IIP is unknown, there are many factors associated with it, including viruses, mycoplasma, immune-mediated diseases (e.g., SLE, scleroderma, polymyositis, etc.), smoking, congenital immunodeficiency diseases, acquired immunodeficiency syndrome, tumor radiation therapy, chemotherapy, immunosuppressive drugs or high-dose adrenocorticosteroid therapy [1].
1 New classification of IIP
In the 1960s, the American pathologist Liebow first classified chronic interstitial pneumonia into five types, namely, common interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), bronchiectatic interstitial pneumonia (BIP), lymphocytic interstitial pneumonia (LIP), and giant cell interstitial pneumonia (GIP) [2]. (GIP) [2]. In 1998, the American pathologist Katzenstein added acute interstitial pneumonia (AIP) and non-specific interstitial pneumonia (NSIP), proposed in 1994, as two subtypes of idiopathic interstitial pneumonia [3].
Although the above subtypes have played a positive role in clinical application, their former lack of uniform terminology among clinicians, radiologists and pathologists has often caused confusion in clinical practice. With the advances in the treatment of fibrotic lung disease and the recognition of the important role of HRCT in diagnosis, there is an urgent need to develop an internationally uniform classification.The definition and diagnostic criteria of idiopathic interstitial pneumonia (IIP) were clearly proposed in the latest consensus opinion reached between the American Thoracic Society (ATS) and the European Respiratory Society (ERS) in 2001, which identified the clinical manifestations, pathological features and imaging The clinical manifestations, pathological features and imaging characteristics are defined [4]. In order of incidence of each type of interstitial pneumonia are (1) idiopathic pulmonary fibrosis (IPF)/cryptogenic fibrosing alveolitis (CFA)/universal interstitial pneumonia (UIP); (2) nonspecific interstitial pneumonia (NSIP); (3) cryptogenic mechanized pneumonia (COP); (4) acute interstitial pneumonia (AIP); (5) respiratory fine bronchiectasis- interstitial lung disease (RB-ILD); (6) desquamative interstitial pneumonia (DIP); and (7) lymphocytic interstitial pneumonia (LIP).
2 Application of HRCT examination technique for IIP
HRCT of the lung consists of two main components: namely, thin layer thickness scanning (1 mm to 2 mm) and reconstruction with high-spatial-frequency (bone) algorithms. Its main role is to optimally display the microstructure of the lung (including airways, blood vessels, lobular septa and intralobular septa at the level of lung lobules). Since the introduction of HRCT in 1985, it has provided a new method for the diagnosis and differential diagnosis of diffuse lung diseases, especially for the diagnosis of interstitial lung diseases, which is significantly better than chest radiography and conventional CT. diseases [5-8].
The basic conditions of HRCT scanning of the lungs include: the intrinsic spatial resolution of the CT scanner should be less than 0.5 mm; thin layer scanning (1-2 mm); high-resolution reconstruction (bone reconstruction) algorithm; the use of 512х512 matrix. The kV, mA and time (S) of the scan are generally 120-140 kVp, 100-200 mA, 1-2S. The scan range is generally from above the aortic arch to the diaphragm surface, with a layer spacing of 10-20 mm, and the scan level includes at least the level of the aortic arch, the level of the pulmonary hilum and the level of the diaphragm surface. The lung window is usually used for observation [5-8]. It is worth noting that the parameters and scanning methods of HRCT should be adjusted appropriately for different patients and different CT models.
3 Pathological features of various diseases in IIP and HRCT performance
3.1 Idiopathic pulmonary fibrosis (IPF/ CFA) [3, 4, 9]
3.1.1 Histopathologic features: common interstitial pneumonia (UIP) is the histopathologic manifestation of IPF. (1) Gross specimens show reduced volume, increased weight, harder texture of the diseased lung tissue, and focal scar formation in the dirty pleura. The specimen is diffusely solid, with varying severity of lesions, interspersed with emphysema and “honeycomb lung” changes. (2) Microscopically, the alveolar septum in the fibrotic area had variable amounts of collagen fibrous deposits and a small amount of inflammatory cell infiltration, and hyperplastic alveolar epithelium was seen in the interstitium surrounding the pseudoglandular structures; the earlier lesions in the non-fibrotic area had widened alveolar septum with congestion, chronic inflammatory cell infiltration, alveolar type II epithelial hyperplasia, and fibroblast foci, and some terminal airway septal smooth muscle hyperplasia. In conclusion, the pathomorphology of UIP is characterized by variable severity of lesions, the coexistence of old and new lesions and the presence of fibrosis, fibroblastic foci and cellular lung changes.
3.1.2 HRCT manifestations: (1) Acute phase: manifests as ground glass shadows, lobular shadows, thickening of the interstitial system (reticular shadows), alveolar ducts and respiratory fine bronchial dilatation. This phase is difficult to differentiate from other early stages of interstitial pneumonia. (2) Chronic phase: more widely distributed foveal shadow (cavity with dilated alveolar ducts and respiratory bronchioles, wall with atrophied alveoli and fibrotic interstitium), linear shadow (thickening of subpleural interlobular septa), subpleural curved linear shadow (subpleural interstitial fibrotic changes and surrounding alveolar atrophy), ground glass shadow (interstitial inflammatory exudate and structural changes of alveoli), solid shadow (peribronchiolar alveoli (interstitial inflammation and structural changes of alveoli), solid shadow (atrophy and fibrous hyperplasia around bronchioles), small nodular shadow and micronodular shadow (axial image of striated fibrous lesions or crossed each other), and it is more common in the lower lobe of both lungs. Central lobar emphysema, total lobar emphysema, and traction bronchiectasis (due to fibrous traction) are also very common. The coexistence of a more extensive foveal shadow and new (ground glass shadow, solid shadow) and old (interstitial fibrosis) lesions are the more characteristic HRCT findings when differentiating from other types of IIP.
3.2 Non-specific interstitial pneumonia (NSIP) [10-14]
3.2.1 Histopathologic features: The lesions of NSIP are more diffuse and present as chronic interstitial inflammation with uniform morphology and lesions in the lung. It can be divided into (1) cell-rich type: mild to moderate chronic inflammatory response seen in the alveolar septum and interstitium, alveolar type II epithelial hyperplasia, intra-interstitial lymphocyte aggregates as well as focal alveolar macrophage aggregates; mild to moderate chronic pleuritis, fine bronchiectasis and focal mechanized pneumonia. There is no fibrosis or cellulitic changes in the lung tissue. (2) Fibrotic type: collagen deposition and fibrotic lesions within the interstitial lung are both uniformly altered, while the lung structure is normal with alveolar type II epithelial hyperplasia, fine bronchial hyperplasia, and intimal and mesenteric thickening. There were no fibroblastic foci in the interstitial lung. (3) Mixed type: lung tissue lesions between the two are called mixed type.
3.2.2 HRCT features: (1) The lesions mainly occur in the peripheral parts of the lower and middle lungs, often bilaterally, and the lesions are more limited than those of AIP and IPF, rarely forming more extensive diffuse lesions in both lungs. (2) The lesions mainly involve lung tissue at the lobular level and often show ground glass shadow, patchy airspace solid shadow, intralobular interstitial thickening, fibrosis and lobular core abnormalities. (3) The lung interstitium infiltrated by the lesion is often the intralobular interstitium and lobular core interstitium. (4) The extent of dilated bronchioles is often distal to the terminal bronchioles, while the central bronchioles are less commonly involved. (5) The structure of the lung is generally intact, and even if there is destruction or distortion, it is relatively limited in extent. (6) Cellular lung is less common.
3.3 Cryptogenic mechanized pneumonia (COP) [4, 15, 16]
3.3.1 Histopathologic features: COP is a mechanized pneumonia with lesions involving mainly small airways in a patchy distribution. The lesions are formed by loose connective tissue composed of fibroblasts extending along the small airways, alveolar ducts and alveoli. They are characterized by granulomatous overgrowth, mild interstitial lymphocytic infiltration, type II alveolar cell hyperplasia, and increased lipid-laden alveolar macrophages in and around the small airways, alveolar ducts, and alveoli. However, the lung is structurally intact and there are no granulomas, necrosis, hyaline membranes, or abscesses.
3.3.2 HRCT manifestations: widely distributed patchy solid shadows of variable size and irregular/blurred margins in the bilateral middle and lower lungs, ground glass shadows and lobar shadows of variable size, and diffuse or scattered lobar central nodular shadows with blurred margins and distribution along small airways and alveolar ducts (the so-called “tree bud sign (so-called “bud sign”), reticular shadows, and columnar bronchial dilatation. Other signs such as pleural tail, pleural spine, pleural thickening, parenchymal band and honeycomb shadow are less common, and lung volumes are mostly normal. Among them, multiple lobar shadows and central lobar nodules in the bilateral lower and middle lungs are the differences between COP and other IIPs.
3.4 Acute interstitial pneumonia (AIP) [4, 9, 17-20]: an interstitial pneumonia of unknown etiology, with an acute onset and a very poor prognosis.
interstitial pneumonia of unknown etiology, rapid onset, and extremely poor prognosis.
3.4.1 Histopathologic features: it is characterized by diffuse alveolar damage with mechanization in both lungs and is divided into an acute phase and a
The acute phase (exudative phase) is characterized by diffuse alveolar damage. The acute phase (exudative phase) occurs 1-2 weeks after the onset of the disease and is characterized by alveolar epithelial and basement membrane damage, with exudate containing fibroblasts, inflammatory cells, macrophages, fibrin, and detached epithelial cells, resulting in edematous changes in the alveolar space and interstitial lung matrix. The proliferative phase occurs within 2-3 weeks and is characterized by thickening of the interstitial system. Fibroblast proliferation is prominent during this period, and extensive fibrosis of the alveolar septum and alveolar cavity is seen.
3.4.2 HRCT manifestations: HRCT changes of AIP are often progressive in development, and each phase of its manifestation has characteristics: (1) Early phase is usually within 1-2 weeks of onset, mainly exudative changes, and the distribution is characterized by scattered patchy solid shadows and ground glass shadows in the periphery of the bilateral middle and lower lungs. (2) In the middle stage (within 2-3 weeks), the exudative lesions progress rapidly and there is extensive thickening of the interstitial system, which is consistent with the overlapping presence of exudation and mechanization in the pathology. (3) In the late stage (after 3-4 weeks), fibrosis progresses rapidly, manifesting as acute interstitial fibrosis and progressive destruction of lung tissue and lung structures, especially the rapid appearance of distended bronchial dilatation is specific and rare in other forms of acute diffuse lung disease. Combined with the above imaging features of early, middle and late stages of AIP, the rapidly progressive imaging change process is a more characteristic HRCT manifestation of AIP.
3.5 Respiratory fine bronchitis-interstitial lung disease (RB-ILD) [4,9,21,22]:This disease is most often seen in smokers or ex-smokers and is closely related to smoking.
3.5.1 Histopathological features: pigmented giant cells in the lumen of the respiratory fine bronchi and alveolar ducts and in the peribronchiolar alveoli, lympho-histiocytic infiltration in the submucosa and around the fine bronchioles, peribronchiolar fibrosis, type II alveolar cell hyperplasia, and alveolar bronchiolization, i.e., alveoli lined with cuboidal fine bronchial epithelium.
3.5.2 HRCT manifestations: widely distributed central emphysema, bronchial wall thickening and ground glass shadow in the upper lobe lungs bilaterally are the most common signs. A central lobar nodular shadow with increased density is also seen, and interstitial thickening and honeycomb-like changes are seen in a few cases. Individual patients may present with severe interstitial fibrosis. A small number of RB-ILD have normal HRCT presentation. Therefore, ground glass shadow, lobular central nodules and widely distributed central emphysema in both upper lungs are valuable HRCT signs for the diagnosis of RB-ILD.
3.6 Desquamative interstitial pneumonia (DIP) [4,9,11,21-23]: has many similarities to RB-ILD and is more likely to occur in patients who are still current smokers.
3.6.1 Histopathological features: there is a homogeneous diffuse accumulation of macrophages in the distal air spaces including the alveoli, and the alveolar macrophages contain dusty-brown pigment, similar to RB-ILD. The difference, however, lies in the distribution of the lesions, with RB-ILD showing a lobar-centric distribution, whereas DIP shows a diffuse distribution. The alveolar wall is rarely thickened and may have a little plasma cell infiltration and occasional eosinophil infiltration, with little to no fibrosis. The alveoli are lined with cuboidal bronchial epithelium and may have scattered lymphocytic aggregates. Upper lobe emphysema is common.
3.6.2 HRCT presentation: diffuse in both lungs, mainly in the peripheral parts of the lower and middle lungs, and may appear as large patches or patches. The ground glass shadow of about 18% DIP is diffuse and uniformly distributed throughout the lungs. Irregular linear and reticular shadows accounted for about 59% of DIP, but were confined to the lower part of the lung. Similar to RB-ILD, lobar central emphysema can be found in both upper lungs in almost all cases. The progression of ground glass and reticular shadows is less frequent, less than 20%. A small amount of foveal pulmonary changes may be seen in about 1/3 of patients.The HRCT presentation of DIP differs from that of RB-ILD in that the former is characterized by more prominent ground glass shadowing, whereas the latter is evident by diffuse distribution of lobular central nodules along and around the bronchi.
3.7 Lymphocytic interstitial pneumonia (LIP) [4, 9, 16]: is an interstitial lung disease characterized by an idiopathic diffuse proliferative lymphocytic infiltrate in the lung.
3.7.1 Histopathological features: an interstitial infiltrate due to lymphocytes, plasma cells and histiocytes is seen, while the alveolar lumen may be filled with lymphocytes and type II alveolar epithelial cells. There are excessive lymphocyte-like aggregates along the lymphatic vessels, which can also be vascularly centered. In a few cases, there is mild distortion of the lung structures.
3.7.2 HRCT manifestations: ground glass shadows, bizarre perivascular cysts or perivascular fovea and small nodular shadows in the center of lobules distributed in the subpleural and poorly defined areas in both lungs. About 50% of them are seen as reticular shadows, and extensive solid changes may occur. Thickening of bronchial vascular bundles and thickening of lobular septa are also commonly seen. Patients with LIP secondary to lymphoproliferative disease often have enlarged hilar and mediastinal lymph nodes. Compared with the HRCT manifestation of other IIP, the HRCT manifestation of LIP has more distinctive features such as small nodules along the lymphatic vessels and lymph node distribution area, thickened septa, thickened bronchovascular bundles, and enlarged lymph nodes.
4 Problems and Prospects
Although HRCT can help in the diagnosis of interstitial pneumonia, the imaging characteristics of various types of interstitial pneumonia still need further study. Are there more specific HRCT manifestations for each type of interstitial pneumonia? Is HRCT able to differentiate the various types of interstitial pneumonia in the early stages of IIP? What is the value of HRCT in the evaluation of the efficacy of various types of interstitial pneumonia? How to choose the appropriate HRCT scan parameters? Therefore, there are still many questions that need to be further explored.
In recent years, many scholars at home and abroad have conducted extensive and in-depth researches on this disease from basic to clinical level. Clinically, although there is no major breakthrough in the research on the diagnosis and treatment of IIP, some promising results have been achieved. It can be confirmed that (1) among IIP, NSIP, COP, RB-ILD, DIP and LIP have good efficacy on glucocorticoids, while UIP has poor efficacy and AIP is the worst; (2) in the early stage of lesions, the efficacy of all types of IIP on glucocorticoids is more reliable; (3) the establishment of a new classification of IIP and the clinical, case and imaging characteristics of all types of IIP have been further (3) the establishment of a new classification of IIP and the further recognition of the clinical, case and imaging characteristics of each type of IIP; (4) open lung biopsy and HRCT have become the main methods used to diagnose IIP. At present, the early diagnosis and differential diagnosis of various types of IIP and the selection of their treatment methods have been taken as hot spots for research by the majority of clinical practitioners. With the further development of basic research, the further expansion of clinical treatment research, and the further study of HRCT with clinical and pathological control, the diagnosis and treatment of IIP will be improved.
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