Idiopathic Interstitial Pneumonias: A Radiology-Pathology Correlation Based on the Revised 2013 American Thoracic Society-European Respiratory Society Classification System

doi:10.1067/j.cpradiol.2014.07.005

Current Problems in Diagnostic Radiology

Volume 44, Issue 1, January–February 2015, Pages 15-25

https://doi.org/10.1067/j.cpradiol.2014.07.005 Get rights and content

The idiopathic interstitial pneumonias (IIPs) are a group of diffuse lung diseases that share many similar radiologic and pathologic features. According to the revised 2013 American Thoracic Society-European Respiratory Society classification system, these entities are now divided into major IIPs (idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, respiratory bronchiolitis–associated interstitial lung disease, desquamative interstitial pneumonia, cryptogenic organizing pneumonia, and acute interstitial pneumonia), rare IIPs (idiopathic lymphoid interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis), and unclassifiable idiopathic interstitial pneumonias. Some of the encountered radiologic and histologic patterns can also be seen in the setting of other disorders, which makes them a diagnostic challenge. As such, the accurate classification of IIPs remains complex and is best approached through a collaboration among clinicians, radiologists, and pathologists, as the treatment and prognosis of these conditions vary greatly.

Introduction

The widespread use of high-resolution computed tomography (CT) has greatly advanced our understanding of diffuse lung diseases. The idiopathic interstitial pneumonias (IIPs) are a group of diseases that share similar radiologic and pathologic features. In 2002, the American Thoracic Society and the European Respiratory Society issued the first international multidisciplinary classification of the IIPs.¹ In 2013, this classification system was revised to reflect the substantial progress that has been made over the interim period to further our understanding of these entities.² The IIPs are now divided into 3 groups: major IIPs, rare IIPs, and unclassifiable IIPs (Table 1). Some of the radiologic and histologic patterns encountered in IIPs can also be seen in the setting of other disorders, such as collagen vascular diseases. As such, accurate classification of IIPs remains complex and is best approached through a collaboration among clinicians, radiologists, and pathologists, as the treatment and prognosis of these conditions vary greatly. This article reviews the unique clinical, imaging, and pathologic features used to differentiate between the IIPs, as this remains a complex and evolving topic.

Section snippets

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a clinical syndrome that is associated with the radiologic and pathologic findings of usual interstitial pneumonia (UIP).³ IPF is more commonly seen in men and usually presents in patients older than 50 years.⁴ The presenting symptoms often include progressive shortness of breath and nonproductive cough with fine crackles appreciated on auscultation and clubbing present in more than 50% of patients. Pulmonary function testing usually demonstrates a

Idiopathic Lymphoid Interstitial Pneumonia

Most cases of lymphoid interstitial pneumonia (LIP) are associated with other conditions, such as Sjögren syndrome and AIDS, but idiopathic cases occur rarely.² For this reason, LIP is now considered a rare IIP. The clinical presentation of LIP usually reflects that of the underlying systemic illness.

On high-resolution CT images, the dominant findings in LIP are ground-glass opacities and peribronchovascular cysts (Fig. 7A and B).24, 25 Reticulations, nodules, and widespread consolidation may

Unclassifiable IIPs

Even after lengthy multidisciplinary discussions, a final diagnosis of the IIP may still not be possible. For this situation, an “unclassifiable” category is reserved in the American Thoracic Society -European Respiratory Society system. The causes for this include inadequate clinical, radiologic, or pathologic data or the presence of a major discordance between them. Many cases that are “unclassifiable” because of an overlap of histologic patterns often prove to be related to collagen vascular

Conclusion

The IIPs are a group of diffuse lung diseases that share many similar radiologic and pathologic features. In this article, we have reviewed the unique clinical, imaging (Table 3), and pathologic features used to differentiate between the IIPs. This remains a complex and evolving topic that is best approached using a multidisciplinary team.

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Cited by (23)

Checkpoint Inhibitor Immune-Related Adverse Events: A Multimodality Pictorial Review
2022, Academic Radiology
Citation Excerpt :
Radiographic patterns of pneumonitis on CT include organizing pneumonia (OP) (Fig 2A-B), bronchiolitis (Fig 2C), and hypersensitivity pneumonitis (HP) (Fig 2D) (58). The most common histopathological findings include organizing pneumonia, cellular interstitial pneumonitis, or less commonly diffuse alveolar damage (59). An OP pattern is most commonly seen and manifests as peribronchovascular patchy airspace opacities with mid to lower lung predominance; the reversed halo sign or atoll sign is a relatively specific finding when identified (60).
Cancer immunotherapies are drugs that modulate the body's own immune system as an anticancer strategy. Checkpoint inhibitor immunotherapies interfere with cell surface binding proteins that function to promote self-recognition and tolerance, ultimately leading to upregulation of the immune response. Given the striking success of these agents in early trials in melanoma and lung cancer, they have now been studied in many types of cancer and have become a pillar of anticancer therapy for many tumor types. However, abundant upregulation results in a new class of side effects, known as immune-related adverse events (IRAEs). It is critical for the practicing radiologist to be able to recognize these events to best contribute to care for patients on checkpoint inhibitor immunotherapy. Here, we provide a comprehensive system-based review of immune-related adverse events and associated imaging findings. Further, we detail the best imaging modalities for each as well as describe problem solving modalities. Given that IRAEs can be subclinical before becoming clinically apparent, radiologists may be the first provider to recognize them, providing an opportunity for early treatment. Awareness of IRAEs and how to best image them will prepare radiologists to make a meaningful contribution to patient care as part of the clinical team.
Interstitial lung abnormality in stage IV non-small cell lung cancer: A validation study for the association with poor clinical outcome
2019, European Journal of Radiology Open
Citation Excerpt :
The diagnosis of ILA was based on CT image findings without pathologic confirmation. However, we used established sequential reading method for CT evaluation to increase the accuracy of diagnosis, and the results were correlated with pathological findings in the previous studies [18,19]. Additionally, in most patients presenting with stage IV NSCLC, it is difficult to obtain histological analyses of ILA.
The presence of interstitial lung abnormality (ILA) at diagnosis of stage IV non-small cell lung cancer (NSCLC) patients has previously shown to be associated with shorter overall survival (OS). The present study aimed to validate the association between ILA and shorter OS in a larger cohort of treatment-naïve stage IV NSCLC patients.
This study includes 484 patients (205 men and 279 women) with a pathological diagnosis of stage IV NSCLC with pretreatment baseline CT available for review. ILA was visually scored on the baseline chest CT with a 3-point scale (0=no ILA, 1=indeterminate for ILA, 2 = ILA) as published previously. Clinical characteristics and overall survival (OS) were compared in patients with ILA score 2 vs. those with ILA score 0 or 1.
ILA was present (score 2) on baseline CT in 19 of 484 patients (3.9%, 95%CI2.4–6.1%). Patients with ILA were significantly older (p = 0.0008) and more commonly male (p = 0.03) compared to those with ILA score 0 or 1. Patients with ILA score 2 showed significantly shorter OS compared to those with ILA score 0 or 1 (median OS 9.95 months vs. 16.95 months; p = 0.0002). In multivariate analyses, baseline ILA score 2 remained significant as a marker for shorter OS (HR = 2.09, p = 0.004) after adjustments for age (HR = 1.48; p = 0.001), gender (HR = 1.22, p = 0.06), and smoking (HR = 0.79; p = 0.051).
ILA on baseline CT at diagnosis of stage IV NSCLC patients was associated with shorter OS (HR = 2.09, p = 0.004), validating ILA as an independent marker for poor clinical outcome.
Interstitial lung disease: Elementary lesions and diagnosis
2018, Seminars in Diagnostic Pathology
Citation Excerpt :
ALI also may be observed in diffuse alveolar damage, drug reactions, rheumatologic diseases, exposure to toxins, acute eosinophilic pneumonia, alveolar hemorrhage syndromes, and allograft transplant rejection. Some examples are idiopathic in nature.34 Pulmonary fibrosis is characterized by the presence of dense collagen deposition in the lung parenchyma, with structural remodeling and alveolar loss.
An effective approach to the diagnosis of interstitial lung diseases requires a standardized method of evaluation with a structured analysis, beginning with scanning microscopy and proceeding to a more detailed assessment. This article is structured around the histologic patterns defined by Leslie that facilitate this process. They include acute injury, fibrosis, cellular infiltrates, airspace filling, formation of nodules, and minimal changes. Illustrations of all of these patterns are provided, together with a discussion of the disease entities that manifest them.
Pathology and radiology correlation of idiopathic interstitial pneumonias
2018, Human Pathology
Citation Excerpt :
There is subpleural fibrosis with architectural distortion, traction bronchiectasis, and honeycombing (Fig. 8). Pneumothorax is a common finding [75,76]. PPFE may also present with more fibrosis than previously reported and coexist with different patterns of interstitial lung disease including IPF/UIP or NSIP in the lower zones [74] (Table 3).
By nature, idiopathic interstitial pneumonias have been diagnosed in a multidisciplinary manner. As classifications have been subject to significant refinement over the last decade, the importance of correlating clinical, radiologic, and pathologic information to arrive at a diagnosis, which will predict prognosis in any given patient, has become increasingly recognized. In 2013, the American Thoracic Society and European Respiratory Society updated the idiopathic interstitial pneumonias classification scheme, addressing the most recent updates in the field. The purpose of this review is to highlight the correlations between radiologic and pathologic findings in idiopathic interstitial pneumonias while using updated classification schemes and naming conventions.
Diagnostic Pathology: Thoracic
2017, Diagnostic Pathology: Thoracic
Cryptogenic organizing pneumonia
2016, Revue des Maladies Respiratoires
La pneumopathie organisée est une réaction inflammatoire particulière du parenchyme pulmonaire donnant lieu à un syndrome clinico-pathologique. Elle est dite secondaire lorsqu’une cause a pu être identifiée et cryptogénique dans le cas contraire. La présentation clinique habituelle est caractérisée par l’apparition subaiguë de symptômes généraux et respiratoires, avec classiquement des condensations plurifocales à l’imagerie thoracique.
La pneumopathie organisée cryptogénique est caractérisée histologiquement par la présence de bourgeons de tissu conjonctif intra-alvéolaires. La pathogenèse débute par une lésion de l’épithélium alvéolaire conduisant à un dépôt de fibrine dans les espaces aériens, puis une migration de fibroblastes produisant une matrice myxoïde intra-alvéolaire. Une caractéristique remarquable de la pneumopathie organisée est la résolution complète de ces bourgeons fibroblastiques sous traitement corticoïde, contrairement à ce qui s’observe en cas de fibrose pulmonaire. La réponse clinique aux corticostéroïdes est habituellement rapide et excellente. Les rechutes sont fréquentes mais généralement sans gravité.
Si les caractéristiques clinico-pathologiques de la pneumopathie organisée cryptogénique sont maintenant bien établies, il reste de nombreuses questions à élucider, notamment les mécanismes impliqués dans la réversibilité des lésions pulmonaires, et la place des traitements d’épargne corticoïde, tels que les macrolides à effet immunomodulateur.
Organizing pneumonia is a particular type of inflammatory reaction of the lung which gives rise to a clinico-pathological syndrome. It is called “secondary” when a cause such as an infection, a drug toxicity, or a connective tissue disease can be identified, or “cryptogenic” when no cause is identified. The clinical picture is usually characterized by the subacute onset of fever, fatigue, cough and dyspnea, with multiple subpleural areas of consolidation on thoracic imaging.
Organizing pneumonia is characterised by the presence of buds of endoalveolar connective tissue. These result from an injury to the alveolar epithelium, followed by the deposition of fibrin in the alveolar spaces, and the migration of fibroblasts which produce a myxoid endoalveolar matrix. A remarkable feature of organizing pneumonia is the complete disappearance of these endoalveolar buds with corticosteroid treatment, in sharp contrast with what is seen in pulmonary fibrosis. The clinical response to corticosteroids is usually prompt and excellent. Relapses are frequent but usually benign.
As the clinical, imaging and pathological characteristics of organizing pneumonia are now well established, many questions remain unanswered, such as the mechanisms involved in the complete reversibility of the pulmonary lesions, and the role of steroid-sparing treatments such as immunomodulatory macrolides.

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Idiopathic Interstitial Pneumonias: A Radiology-Pathology Correlation Based on the Revised 2013 American Thoracic Society-European Respiratory Society Classification System

Introduction

Section snippets

Idiopathic Pulmonary Fibrosis

Idiopathic Lymphoid Interstitial Pneumonia

Unclassifiable IIPs

Conclusion

Lancet Respir Med

Am J Med

Chest

Am J Respir Crit Care Med

An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias

Am J Respir Crit Care Med

Idiopathic interstitial pneumonias: CT features

Radiology

Idiopathic pulmonary fibrosis: Diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS)

Am J Respir Crit Care Med

Idiopathic interstitial pneumonias: High-resolution CT and histologic findings

Radiographics

An official ATS/ERS/JRS/ALAT statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management

Am J Respir Crit Care Med

Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance

Am J Surg Pathol

Classification and natural history of the idiopathic interstitial pneumonias

Proc Am Thorac Soc

Idiopathic nonspecific interstitial pneumonia: Prognostic significance of cellular and fibrosing patterns: Survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia

Am J Surg Pathol

Smoking-related interstitial lung diseases: Radiologic-pathologic correlation

Eur Radiol