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Cryptogenic Organizing Pneumonia: Evolution of Morphological Patterns Assessed by HRCT

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Cryptogenic Organizing Pneumonia: Evolution of Morphological Patterns Assessed by HRCT diagnostics Article Cryptogenic Organizing Pneumonia: Evolution of Morphological Patterns Assessed by HRCT Francesco Tiralongo 1,* , Monica Palermo 1, Giulio Distefano 1 , Ada Vancheri 2, Gianluca Sambataro 2,3 , Sebastiano Emanuele Torrisi 2, Federica Galioto 1, Agata Ferlito 1, Giulia Fazio 1, Pietro Valerio Foti 1, Letizia Antonella Mauro 1, Carlo Vancheri 2, Stefano Palmucci 1 and Antonio Basile 1 1 Radiology Unit 1, Department of Medical Surgical Sciences and Advanced Technologies “GF Ingrassia”—University Hospital “Policlinico-Vittorio Emanuele”, University of Catania, 95123 Catania, Italy; [email protected] (M.P.); [email protected] (G.D.); [email protected] (F.G.); [email protected] (A.F.); [email protected] (G.F.); [email protected] (P.V.F.); [email protected] (L.A.M.); [email protected] (S.P.); [email protected] (A.B.) 2 Regional Referral Centre for Rare Lung Diseases, A. O. U. “Policlinico-Vittorio Emanuele” Dept. of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; [email protected] (A.V.); [email protected] (G.S.); [email protected] (S.E.T.); [email protected] (C.V.) 3 Artroreuma S.R.L., Outpatient of Rheumatology associated with the National Health System, Corso S. Vito 53, 95030 Mascalucia (Catania), Italy * Correspondence: [email protected] Received: 14 April 2020; Accepted: 28 April 2020; Published: 29 April 2020 Abstract: To evaluate the radiological findings in patients with cryptogenic organizing pneumonia (COP) before steroid treatment and their behavior after therapy, we retrospectively evaluated a total of 22 patients with a diagnosis of COP made by bronchoalveolar lavage (BAL), biopsy or clinical/radiological features, and the patients were followed between 2014 and 2018 at the hospital; the demographic data, symptoms, radiologic findings, diagnostic methods and treatment plans of patients were collected from patients’ hospital records. At least two CT scans of 22 patients (16 female and six men) were evaluated, the first one before starting steroid therapy and the others after therapy. At baseline CT scans, the most common radiological finding was the presence of consolidations (18/22 patients, 81.8%); ground-glass opacities were also very common (15/25, 68.1%). The other findings were as follows: nodules and masses (5/22, 22.7%), atoll sign (4/22, 18.1%), perilobular pattern (3/22, 13.6%) and parenchymal bands (3/22, 13.6%). Two patients had a significant relapse after reducing/interrupting therapy, while three had a complete resolution and are not currently under therapy (maintenance of clinical remission with no oral corticosteroid (OCS)). In High-resolution computed tomography (HRCT) scans after therapy, consolidations were still observable in seven patients (five in new areas of the lung-migratory infiltrates), while most of them disappeared, leaving a residual area of ground glass opacity in two patients. One patient had a residual of the perilobular pattern, with the disappearing of the other findings (consolidations and ground-glass opacities). Two patients developed a fibrosing pattern despite the therapy (9.5%). Cryptogenic organizing pneumonia tends to respond to oral corticosteroid treatment, but some patients may have a null or partial response. We highlight the behavior of this disease after proper therapy. Keywords: lung diseases; interstitial; multidetector computed tomography; cryptogenic organizing pneumonia; organizing pneumonia Diagnostics 2020, 10, 262; doi:10.3390/diagnostics10050262 www.mdpi.com/journal/diagnostics Diagnostics 2020, 10, 262 2 of 19 1. Introduction Organizing Pneumonia (OP) is a clinical, radiological and histological pattern characterized by the presence of granulation tissue within the terminal or respiratory bronchioles, in the alveolar ducts and surrounding alveoli, associated with chronic inflammation of the remaining lung parenchyma [1]. OP may be secondary to many extra pulmonary conditions—such as infections [2], drug toxicity [3–6], radiotherapy [4,7,8], autoimmune diseases [9,10], oncologic conditions [11,12], or pulmonary conditions—pneumonia, vasculitis, and lung cancer; when not associated with certain pulmonary or extra pulmonary disorders, it may be labelled as “cryptogenic” [2]. According to different studies, OP accounts for 1.8% up to 13% of all Interstitial Lung Diseases (ILDs) [13–15]; the mean age at onset varies from 50 to 60 years and males and females are usually equally affected. There is a prevalence in non-smokers [16] and it is not clear if (and why) smoking could be considered as a protective factor [17]. The idiopathic form of OP has been called Cryptogenic Organizing Pneumonia (COP), and it has been classified as an acute/subacute Interstitial Lung Disease in the American Thoracic Society/European Respiratory Society (ATS/ERS) statement of 2013 [18]. The term COP was first used by Davidson in 1983 [14], even if previously the same pathological entity was known as “Bronchiolitis Obliterans Organizing Pneumonia” (BOOP), as named by Epler [1]. This name was thereafter put aside, due to the semantic similarity with the morphological pattern of bronchiolitis obliterans, which is a completely different entity [19,20]. COP presentation is similar to many pneumopathies; therefore, an accurate clinical evaluation—in order to exclude these conditions before a COP diagnosis—is mandatory for clinicians and radiologists [13]. Classic symptoms include flu-like illness (fever, cough, weakness) and dyspnea, which can be mild or severe (the latter is associated to a rapidly progressive disease). Diagnosis is often delayed because of these unspecific manifestations [18]. On physical examination, crackles are the most common abnormality found. There is no finger clubbing [16]. At pulmonary function tests (PFTs), the most common abnormality is a restrictive ventilatory defect, and diffusing capacity for carbon monoxide (DLCO) often is reduced [18], with a mild hypoxemia in more than 80% of patients [16]. An obstructive ventilatory defect is shown in a minority of patients (20%), usually smokers. Bronchoalveolar lavage (BAL) is helpful for the differential diagnosis and could be used to exclude other disorders. The imaging findings and BAL could be useful for patients with appropriate clinical presentation and for those whose transbronchial biopsy is negative or for whom a confirmatory biopsy cannot be performed [21]. A “mixed pattern”, with increased lymphocytes (20–40%), neutrophils (about 10%), and eosinophils (about 5%), is the most frequent combination found in COP disease [21]. At imaging, COP may show different patterns at the onset. For this reason, its diagnosis could be a challenge. Knowing the onset presentation of a disease, and how it can change in time and during therapy, is essential for radiologists to be able to recognize it and avoid misdiagnosis. A definitive diagnosis of organizing pneumonia cannot be made on the sole basis of clinical findings, but imaging alone may be sufficient for a diagnostic hypothesis of OP; the combination of a compatible clinical history and adequate HRCT signs may enable diagnosis in 80% of cases [20,22]. As reported by Baha A. et al., patients who were not diagnosed histo-pathologically were diagnosed according to clinical and radiological features with a multidisciplinary approach [23]. Therefore, the aim of this work is to evaluate the temporal evolution of the radiological signs of COP, to determine the prevalent baseline pattern and changes after therapy. 1.1. Radiologic Features The main HRCT findings in OP include: consolidation, ground-glass opacity (GGO), perilobular opacity, reversed halo opacity, nodules or masses, parenchymal bands, bronchial wall thickening, bronchial dilatation, mediastinal lymphadenopathy and pleural effusion [24,25]. The radiological Diagnostics 2020, 10, 262 3 of 19 features of COP can be divided into two main groups: typical and atypical patterns (Table1, Figure1). Typical pattern consists of multiple air spaces-opacities or peripheral consolidations with air bronchogram; as reported by Polverosi et al. [22], these consolidations may be limited by GGOs. According to many papers reported in literature, an atypical pattern includes: solitary or multiple nodules or masses (that constitute the nodular pattern), infiltrative opacities (infiltrative COP), atoll sign, bronchocentric lesions, linear and band-like opacities, a crazy paving pattern and progressive fibrosis [20,22,24,26]. Table 1. Patterns of COP. Typical Pattern Atypical Patterns Multiple alveolar opacities Nodular pattern Diagnostics 2020, 10, x FOR PEER REVIEW Perilobular pattern 3 of 18 bronchogram; as reported by Polverosi et al. [22], theseCrazy consolidations paving pattern may be limited by GGOs. According to many papers reported in literature, anProgressive atypical pattern fibrosis COPincludes: solitary or multiple nodules or masses (that constitute the nodular pattern), infiltrativeAtoll sign opacities (infiltrative COP), atoll sign, bronchocentric lesions, linear and band-like Linearopacities, and band-likea crazy paving opacities pattern and progressive fibrosis [20,22,24,26]. Figure 1. Schematic drawing of main imaging patterns of cryptogenic organizing pneumonia (COP). Figure 1. Schematic drawing of main imaging patterns of cryptogenic organizing pneumonia (COP). 1.2. Typical Pattern Table 1. Patterns of COP. The classical form of COP is characterized by multifocal parenchymal consolidations, often bilateral
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