Pulmonary Sarcoidosis: Imaging and Diagnostic Limitations

Abstract

Background

Pulmonary sarcoidosis is a multisystemic granulomatous disease with a broad spectrum of pulmonary manifestations, ranging from reversible hilar lymphadenopathy and perilymphatic nodules to irreversible pulmonary fibrosis. The heterogeneity complicates clinical and radiological differentiation.

Objective

This review presents the typical radiological patterns of pulmonary sarcoidosis, evaluates diagnostic modalities, and highlights the importance for prognosis and therapy of distinguishing between reversible and irreversible lesions.

Materials & Methods

A comprehensive literature search focused on recent publications and guidelines, emphasizing imaging techniques and clinically relevant correlations.

Results

Conventional chest radiography using Scadding criteria provides a simple and cost-effective method of stage classification, but it also has limitations in terms of accuracy and in correlation with lung function. Computed tomography (CT) is the most precise imaging modality, showing characteristic features such as symmetrical hilar and mediastinal lymphadenopathy, multiple micro- and macronodules with confluent consolidations, and upper lobe predominance. Advanced stages reveal fibrotic remodeling with linear opacities, traction bronchiectasis, and prognostically relevant honeycombing. Complications include pulmonary hypertension, venous compressions, and secondary fungal infections. Magnetic resonance imaging (MRI) is used primarily for cardiac sarcoidosis detection, while positron emission tomography (PET) can better assess inflammatory activity and therapy monitoring. Differential diagnosis with regard to other granulomatous, infectious, and neoplastic diseases is essential, and it requires an interdisciplinary approach.

Conclusion

Pulmonary sarcoidosis requires a multimodal diagnostic approach, with CT playing a central role in staging and prognosis. Differentiation between reversible and fibrotic lesions is critical for therapeutic decisions. Future research should optimize imaging and integrate clinical, radiological, and functional parameters to improve patient care.

Key Points

• Pulmonary sarcoidosis presents a wide spectrum of pulmonary manifestations ranging from reversible nodules and lymphadenopathy to irreversible fibrotic patterns, with diagnosis being clinically and radiologically challenging.

• Computed tomography is the most precise imaging modality for stage classification and prognosis.

• Differentiating reversible inflammatory from irreversible fibrotic lesions is crucial for therapy planning.

• Differential diagnosis from other granulomatous, infectious, and neoplastic diseases requires an interdisciplinary approach.

Citation Format

• Kostova J, Andreisek G, Müller MA. Pulmonary Sarcoidosis: Imaging and Diagnostic Limitations. Rofo 2025; DOI 10.1055/a-2722-6934

Keywords

sarcoidosis - CT-high resolution - thorax - diagnostic radiology - treatment effects - fibrosis, cystic

Introduction

Sarcoidosis is a chronic, multisystemic granulomatous disease that was first described in the 19th century as a skin disease [1] [2]. Contrary to earlier assumptions that it primarily affects the skin, sarcoidosis is actually a multisystem disease that can affect any organ in the body, including the nervous system, heart, GI tract, and lungs [3]. Pulmonary involvement is the most common form, with a prevalence of more than 90%, and is thus the focus of this review.

The histological hallmark of sarcoidosis is non-caseating granulomas in the affected organs. These are composed of macrophages, epithelioid cells, and mononuclear cells, surrounded by CD4 T cells in the center and CD8 T cells in the periphery [4] [5].

Sarcoidosis typically manifests between the ages of 40 and 50. Epidemiologically, there is an increased prevalence among women, African Americans, and Northern Europeans [6] [7]. A familial clustering is evident, and molecular genetic studies have demonstrated associations with specific HLA alleles, suggesting a genetic predisposition [8] [9]. Despite the disease’s common features, functional impairment, treatment response, and prognosis can vary considerably among sarcoidosis patients. The heterogeneous course has even led to the hypothesis that sarcoidosis could possibly be a collective term for various granulomatous diseases [10] [11]. Diagnosis is based on clinical presentation, imaging, laboratory parameters, and histological evidence of non-caseating granulomas. The treatment spectrum includes corticosteroids, immunosuppressants, and newer therapeutic approaches such as TNF-alpha inhibitors [12]. Antifibrotic therapies are currently under evaluation [13].

The overall mortality rate in sarcoidosis is about 5% and is therefore low, generally. Sarcoidosis-related deaths predominantly result from respiratory failure due to advanced pulmonary involvement, usually in the context of pulmonary fibrosis, which can occur in 10–40% of patients during the course of the disease. This corresponds to radiological stage IV, in which over 40% of patients die within five years [14]. The mortality rate correlates closely with lung function: in one study, all deceased patients had a vital capacity of less than 2.5 l (normal: approx. 3–5 l) [15]. In addition, pulmonary hypertension is an independent mortality factor with an up to 10-fold increased risk [16].

Imaging of pulmonary sarcoidosis

Imaging plays a key role in the diagnosis and follow-up of pulmonary sarcoidosis (PS). The classification of radiological stages developed by Scadding and based on conventional radiographs (CXR) remains the most commonly used method. According to these guidelines, a single-plane chest X-ray (PA) is usually sufficient for diagnosis, and a lateral X-ray can be added, if needed. However, the relationship between the individual stages and clinical progression and presentation is controversial [17] [18]. In addition, inter-rater reliability is moderate, depending on the experience level of the assessor [19]. Nevertheless, CXR images have many advantages that significantly impact everyday practice, including ease of execution, high spatial resolution, low radiation exposure, and, last but not least, low costs.

Isotropic, high-resolution reconstructed multi-slice spiral CT (volume CT with ≤1.5 mm slice thickness) is today's gold standard and has replaced older HRCT techniques. Iterative reconstruction algorithms can also achieve significant dose savings with improved image quality. Today’s state-of-the-art CT features higher sensitivity, better inter-rater agreement, and greater reliability in detection of interstitial lung changes and sarcoidosis-specific findings [20].

PET/CT (mostly F18-FDG) is becoming increasingly important. It is particularly suitable for assessing inflammatory activity, detecting extrathoracic manifestations, and evaluating therapeutic effects. It can also help identify suitable biopsy sites. One limitation of PET/CT, in addition to radiation exposure, is its limited specificity, as other inflammatory or malignant lesions can have similar enhancement patterns.

In the past, gallium scintigraphy was frequently used to assess the activity of sarcoidosis. However, it has largely been replaced by PET/CT.

Cardiac and pulmonary MRI diagnostics

Magnetic resonance imaging (MRI) is used, among its many applications, in cases of suspected cardiac sarcoidosis, and it provides detailed, radiation-free, and highly-sensitive imaging of functional and fine structural changes, such as transmural late gadolinium enhancement (LGE), myocardial wall thickening, wall motion abnormalities, and T2 signal alterations in cases of edema formation. LGE reflects fibrosis, granulomatous inflammation, or scar tissue in the myocardium ([Fig. 1]). Especially in young patients, MRI allows users to detect cardiac manifestations at an early stage and in a non-invasive manner, and the technology supports targeted clinical decisions, for example, if an implantable cardioverter defibrillator is indicated [21].

Fig. 1 Cardiac MRI showing myocardial manifestation of stage II sarcoidosis in two male patients (38 and 52 years old) with exertional dyspnea, weakness, and recurrent palpitations. A: T2-weighted sequence: diffuse edema midventricular inferior, extending inferoseptally and inferolaterally. B: T1 mapping and late gadolinium enhancement: transmural, basal inferolateral, and basal septal late enhancement extending to the left and right ventricles. C: T2-weighted fast spin-echo sequence: hilomediastinal lymphadenopathy.

MRI also has great potential for monitoring the progress of pulmonary sarcoidosis. When compared to CT, MRI achieved an equally strong correlation with lung function parameters, especially FVC and DLCO, and was able to reliably predict disease progression in multivariate analyses [22]. As a non-radiation imaging method, MRI is particularly suitable for serial follow-up in patients with an increased radiation risk, especially in young adults and immunosuppressed individuals.

X-ray diagnostics: Scadding classification

Stage I: Bilateral hilar lymphadenopathy without pulmonary involvement

The CXR image shows symmetric enlargement of the hilar and mediastinal lymph nodes without visible lung parenchymal changes (Garland triad) ([Fig. 2]). Approximately 50–60% of all pulmonary sarcoidosis diagnoses are classified under this stage. The spontaneous remission rate here is between 60% and 80% [23] [24], where ethnic differences play a role: for example, in one study, 76% of Japanese patients remitted within a few years, while in Finnish patients it was only 47% [25].

Fig. 2 Scadding stages I and II, upper (A & B); III and IV, lower (C & D).

Stage II: Bilateral lymphadenopathy with pulmonary infiltration

In this stage, hilar and mediastinal lymph node enlargement is accompanied by interstitial infiltration, typically as reticulonodular patterning with upper lobe emphasis ([Fig. 2]). This stage is detected at initial diagnosis in 25–35% of patients. Spontaneous remission is reported to be between 35% and 73%, depending on the study population [23] [25].

Stage III: Diffuse pulmonary infiltration without lymphadenopathy

There is no lymphadenopathy, while diffuse interstitial infiltrates, nodules, and consolidations predominate. The CXR image shows ground-glass opacities or coarse reticular patterns, predominantly in the middle and apical lung segments ([Fig. 2]). Only about 10% of PS cases are diagnosed at this stage. The spontaneous remission rate is below 30%, with individual studies reporting even lower remission rates of 0–10% [23] [25].

Stage IV: Irreversible pulmonary fibrosis

This stage displays fibrotic remodeling processes with honeycombing (cystic air spaces with fibrotic thickened walls), traction bronchiectasis, and scar conglomerates, with emphasis on the upper lobes ([Fig. 2]). Approximately 5% of patients receive this stage classification at initial diagnosis. Spontaneous remission does not occur because fibrosis is an irreversible process.

Computed tomography

Lymphadenopathy

CT typically shows symmetric hilomediastinal lymphadenopathy predominantly without compression effect on the surrounding structures, with the hilar lymph nodes affected in more than 75% of cases. Isolated mediastinal lymph node enlargement and hilar enlargement without mediastinal involvement are rare. Calcifications develop in up to 20% of lymph nodes [26]. The calcification patterns include punctiform, structureless, eggshell-like, or powdered sugar-like shapes ([Fig. 3]). However, the specificity of these forms of calcification is moderate to low. The “cluster of black pearls” sign is considerably more specific. In this case, multiple tiny, homogeneously distributed hypodense nodules (1–2 mm) are detected in the lymph nodes in the venous contrast phase ([Fig. 4]). Venkata et al. demonstrated a specificity of 98% and a sensitivity of 83% for the presence of sarcoidosis [27].

Fig. 3 CT of the thorax in the soft tissue window of a 56-year-old patient with bilateral hilar lymphadenopathy in the context of long-standing sarcoidosis type II. A: eggshell-like, B: powdered sugar-like, C: punctiform.

Fig. 4 CT of the thorax in the mediastinal window showing a “cluster of black pearls” sign (green arrows) within a mediastinal lymph node conglomerate in a 49-year-old female patient with long-standing sarcoidosis.

Nodules and consolidations

With a prevalence of sometimes >90%, nodules are among the most common features of PS [28]. They occur preferentially in the middle and apical lung segments, where micronodules (1–3 mm) with perilymphatic distribution are typical ([Fig. 5]). This distribution pattern is explained by the interaction of antigen-presenting cells with the HLA system along the lymphatic pathways, which mediate continuous activation and local proliferation of lymphocytes. This ultimately leads to the formation of perilymphatic granulomas [29]. This distribution pattern makes it possible to differentiate between hematogenous spreading diseases (e.g. metastases, infections).

Fig. 5 CT of the thorax in the lung window showing perilymphatic micronodules of both upper lobes in the setting of sarcoidosis in a 36-year-old patient; phenotype: non-fibrotic, micronodular pattern. Markings: in yellow schematic perilymphatic distribution, green arrows show exemplary micronodules.

Macronodules occur as a result of the confluence of many smaller nodules, causing their outer contour to appear irregular. These larger nodules may exhibit consolidation-like patterns and air bronchograms. Nodules along the pleural surfaces create a pearl-like appearance. The well-known “galaxy sign” is ultimately a combination in which large nodules are surrounded by many small satellite nodules, which resembles the appearance of a small galaxy [30] ([Fig. 6]).

Fig. 6 CT of the thorax in the lung window with Galaxy sign in the right upper lobe and bipulmonary ground-glass areas in a 44-year-old female patient; phenotype: non-fibrotic, nodular pattern.

Ground-glass opacities

Ground-glass opacities occur neither typically nor frequently in the context of PS. However, they may occur in rare cases and therefore should not be a source of confusion ([Fig. 7]). It is assumed that these are microgranulomas that are below the CT system's resolution limit, and they present in turn as ground-glass opacities. Overall, the ground-glass opacities are a reversible form of manifestation [31].

Fig. 7 CT of the thorax in the lung window showing ground-glass nodules of both upper lobes in the context of sarcoidosis in a 38-year-old male patient with cough; phenotype: non-fibrotic, micronodular pattern. Green arrows show examples of ground-glass nodules.

Bronchial pathologies

In rare cases, peribronchial, heavily calcified lymph nodes can cause mechanical compression or obstruction of the airways or even break through into the bronchial system. In addition, the mechanical stress and tensile forces cause pulmonary fibrosis and traction bronchiectasis over time. In pathologically dilated bronchi, mucinous clearance is impaired, and mucoid impaction, also known as mucus plugging, may be detected by the CT system. In addition to the bronchi, the bronchioles are also affected. Small airway disease plays a crucial role in the pathophysiological development of the disease [32]. Computed tomography reveals it as air trapping in the expiratory images (especially when compared directly with inspiration images) by a mosaic pattern due to uneven ventilation of individual lung sections.

Fibrosis

A fibrosing form of the disease can be observed in up to 25% of cases [33]. Different dominant patterns can be identified, which often occur in combination [34]:

Diffuse linear-fibrotic muster

This phenomenon is characterized by uniform, linear compactions that often spread axially from the hilar region ([Fig. 8]).

Fig. 8 CT of the thorax in the lung window showing linear fibrosis with bronchocentric distribution pattern originating from the hilar region in the context of sarcoidosis in a 47-year-old patient; phenotype: fibrotic pattern with bronchocentric reticulations. The affected areas are highlighted in yellow.

Honeycomb pattern

The honeycomb pattern occurs in a minority of patients, but it is associated with significant impact on respiratory function and survival, particularly when fibrosis affects more than 20% of the lung parenchyma [35]. The reason for this is that the destruction of the lung architecture prevents adequate ventilation in the affected areas. CT detects round-oval cystic cavities with thick fibrotic walls that are localized preferentially on a subpleural and clustered basis ([Fig. 9]). In contrast to idiopathic pulmonary fibrosis, which is a separate clinical picture, the distribution in the case of PS is localized predominantly in the middle to apical lung segments with a typically posterior direction of traction. In rare cases, both diseases occur simultaneously [36].

Fig. 9 CT of the thorax in the lung window with honeycomb pattern and traction bronchiectasis in the context of sarcoidosis in a 61-year-old patient; phenotype: fibrotic pattern with bronchocentric reticulations. Yellow arrow = honeycomb pattern; green arrow = traction bronchiectasis.

Pleura

Pleural involvement in the case of sarcoidosis is extremely rare. In one study, it was only confirmed histologically in 0.5% of the patients examined [37]. This form of disease includes pleural thickening with nodular infiltration, pleural effusions, and pneumothoraces. Much more frequent is apparent pleural thickening (pseudoplaques), which is caused by confluent subpleural nodules. In isolated cases, thin-walled, smaller pulmonary cysts are also described. The exact pathogenesis is not fully understood [38].

Complications

Sarcoidosis-associated pulmonary arterial hypertension (SAPH)

The World Health Organization classifies pulmonary hypertension according to five groups; the form caused by sarcoidosis belongs to group 5 (unclear or multifactorial causes) [39]. The following are discussed from an etiological perspective: granuloma-related compression, vascular invasion up to obliteration, hypoxic vasoconstriction, and fibrotic remodeling. SAPH is rare overall – in a Japanese study it occurred in 5.7% of patients [40] – but it poses an increasing problem in advanced stages. In a study of sarcoidosis patients awaiting lung transplantation, the proportion of patients with SAPH was 73.8%. The need for oxygen therapy correlated with the presence of SAPH [41].

With regard to CT, a maximum diameter of the pulmonary artery greater than 29 mm, measured transversely in the axial CT section at the level of the arterial bifurcation, or a ratio of the pulmonary arterial diameter to the ascending aorta greater than 1, may indicate pathologically elevated pulmonary arterial pressure. The size ratio of segmental artery to bronchus of more than one in three lung lobes can also be used as an indication [42]. Echocardiographic pressure assessment and morphological signs in CT do not reliably correlate. As a result, a right heart catheter is recommended for definitive diagnosis – this is considered the gold standard [43].

Pulmonary venous compression

In exceptional cases, pulmonary venous compression can be caused by granulomas or fibrotic changes. A very rare form is venoatrial compression by large subcarinal lymph node conglomerates that compress the left atrium and various pulmonary veins. Long-term mechanical stress can result in right heart strain with pulmonary congestion, arrhythmias and pulmonary hypertension [44].

Fungal superinfections

An aspergilloma develops through the accumulation of fungal material (usually Aspergillus fumigatus) in a pre-existing cavity, and it appears in imaging as a clump-like “fungus ball”. This may remain asymptomatic or typically manifest as recurrent hemoptysis. The CT scan shows a round mass within a cavity, which is separated from the cavity wall by an air gap (Monod sign) ([Fig. 10]). The prevalence in PS is between 2% and 12% [45].

Fig. 10 CT of the thorax in the lung window with cavity and evidence of a Monod sign in a 54-year-old patient with known pulmonary sarcoidosis and secondary aspergillosis. Yellow arrow = cavern.

Chronic cavernous pulmonary aspergillosis (CCPA), on the other hand, is a progressive disease that occurs on the basis of advanced fibrocystic sarcoidosis. This results in destruction of lung tissue, systemic symptoms, and radiologically detectable multiple cavities with irregular walls, infiltrates, and fibrosis. The main cause of death remains the advanced underlying disease, while CCPA leads to immediate death only in a few cases [46].

Differential diagnoses

Accuracy is essential when clarifying potential differential diagnoses of sarcoidosis. However, due to the chameleon-like nature of the disease, it is particularly challenging both clinically and in terms of imaging. Findings are heterogeneous and often overlap with manifestations of other diseases [Fig. 11]. [Table 1] summarizes important differential diagnoses from various disease groups, their cardinal symptoms, and the radiological features that could potentially distinguish these diseases from sarcoidosis [10] [12] [47].

Fig. 11 PET-CT in a 73-year-old female patient with known lung cancer (NSCLC) and sarcoid-like response under bevacizumab therapy; evidence of lymph node conglomerates with pathological FDG uptake. Yellow arrow = lymph node conglomerate.

Table 1 Differential diagnoses of pulmonary sarcoidosis, its imaging features, and other complementary clinical diagnostics.

Differential diagnosis	Main symptoms	Radiological features (vs. sarcoidosis)	Complementary diagnostics
Tuberculosis (mycobacteriosis)	Productive cough, dyspnea, hemoptysis, B symptoms	Cavern formation Asymmetric, centrally necrotic lymphadenopathy Focal or segmental infiltrates with necrotic areas	Microbiological tests (PCR, culture), IGRA test, biopsy with histological examination
Pneumoconiosis (silicosis, berylliosis)	Dry cough, exertional dyspnea, systemic symptoms	Silicosis: small, sharp nodules, especially in the upper fields, eggshell-like hilar lymph node calcifications Berylliosis: morphologically very similar to sarcoidosis	Exposure history, polarization microscopy, BeLPT test (berylliosis); if necessary, biopsy with histological examination
Exogenous allergic alveolitis	Fever, cough, dyspnea, myalgia	Diffuse ground-glass and butterfly-shaped infiltrates, centrilobular ground-glass nodules, or fibrosis Air trapping Minimal hilar lymphadenopathy	Exposure history, IgG antibodies, bronchoalveolar lavage, biopsy with histological examination
Lymphangiosis carcinomatosa	B symptoms, dyspnea, chest pain	Infiltrative, net-like thickenings along the lymphatic vessels (“septal lines,” smooth borders, or pearl-like) Varying degrees of lymphadenopathy	Biopsy with histological and immunohistochemical examination, tumor markers, PET/CT
Lymphoma	B symptoms, lymphadenopathy, fatigue	Large, confluent hilomediastinal lymph nodes (conglomerates) No perilymphatic micronodules No symmetry	Biopsy with histological, immunohistochemical and molecular genetic diagnostics, bronchoalveolar lavage; if necessary, staging (PET/CT)
Lymphoproliferative diseases	Lymphadenopathy, organomegaly, non-specific general symptoms	Diffuse, usually massive lymphadenopathy Non-specific pulmonary infiltrates, rarely micronodules	Biopsy and bone marrow examination with histological, immunohistochemical, and molecular genetic diagnostics
Necrotizing sarcoid granulomatosis	Non-specific	Confluent granulomas with infarct-like necrosis subpleural/peribronchovascular No typical micronodules	Biopsy with histopathological examination, exclusion of tuberculosis
Granulomatosis with polyangiitis	Cough, epistaxis, renal manifestations, fever, arthralgia, malaise	Multiple nodular infiltrates with cavities and focal consolidations, rapidly changing Vascular involvement Often affects the upper respiratory tract, kidneys, and other organ systems	ANCA serology, biopsy with histopathological examination, further serological diagnostics
Crohnʼs disease (pulmonary manifestation)	Cough, dyspnea, gastrointestinal symptoms, systemic signs of inflammation	Nonspecific nodular infiltrates Partial tracheobronchial wall thickening No hilar lymphadenopathy	Clinical diagnosis, endoscopy, biopsy with histological examination, serological markers
Langerhans cell histiocytosis	Chronic cough, dyspnea, pleuritic chest pain, B symptoms, fatigue, extrathoracic manifestations	Irregular cysts with upper lobe emphasis Nodulocystic lesions No significant hilar lymphadenopathy	Biopsy with histological and immunohistochemical examination (CD1a, Langerin), bronchoalveolar lavage
Sarcoid-like response	Variable, often asymptomatic	Morphologically very similar to sarcoidosis [Fig. 11]	Clinical context, usually in the context of immunotherapy, biopsy with histological examination, tumor markers

Follow-up and its challenges

Monitoring of PS requires reliable diagnostics to effectively check the course of the disease and rapidly adapt the therapy. The challenge lies in the heterogeneity of the disease courses, which can range from irreversible damage to stabilization or remission.

Monitoring is carried out at several levels: clinical, laboratory, functional, and radiological.

Despite the valuable insights provided by each individual diagnostic method, no single method is sufficiently sensitive or specific to definitively detect exacerbations. From a clinical perspective, symptoms such as cough or dyspnea may indicate disease activity, but they may also have other causes such as infections or pulmonary hypertension.

Functionally, monitoring is supported by pulmonary function tests. A deterioration in lung function, such as a decrease in forced vital capacity (FVC) of ≥5% or a CO diffusing capacity (DLCO) below 50% of the prediction, correlates with an aggravation of the disease. An FVC value below 80% of predicted values was associated with an increased relative risk of progression [48].

Radiological monitoring is important, but data from studies are mixed when it comes to correlations with other relevant disease parameters. CT imaging shows more consistent results, with negative correlations between patterns, such as consolidation and ground-glass opacities, and the FVC, FEV1, and DLCO parameters, when compared to CXR imaging [49]. Zhang et al. have demonstrated that stage classifications using CXR and CT differed in 50.2% of their patient cohort. Mediastinal lymph node enlargement and smaller nodules were less well detected due to the limited resolution in CXR. Modified CT stages correlated significantly negatively with DLCO and CXR stages [50]. Nevertheless, advanced CXR stages, especially fibrosis, are reliably associated with reduced vital capacity (FVC), impaired diffusion capacity, and a higher level of dyspnea [51] [52].

Although the role of CT in the course of pulmonary sarcoidosis has not yet been fully clarified, there are various established indications for its use that can be derived from current guidelines and protocol recommendations [20] [53] ([Table 2]).

Table 2 Indications and guidelines for use of CT imaging in pulmonary sarcoidosis.

Topic	Notes
Baseline CT	Reference finding No binding international requirement, but often recommended
Indications for follow-up CT	Increased diagnostic certainty compared to CXR Assessment of treatment response Determination of reversibility of changes Detection of complications and progression
CT protocol	Isotropic, high-resolution reconstructed multi-slice spiral CT ≤1.5 mm layer thickness Inspiration; if necessary, additional expiratory images to detect bronchial obstructions
Contrast administration	Native CT is Usually sufficient CM only in case of suspected vascular involvement or to differentiate from other suspected diagnoses CT angiography in cases of hemoptysis due to aspergillosis (e.g. vascular invasion, aneurysms, bleeding source, and intervention planning)
Extension to upper abdomen	In case of initial staging or unclear symptoms -> clarification of extrathoracic manifestations (liver, spleen, abdominal lymph nodes)
Radiation exposure and dose	Low-dose CT protocols recommended for follow-up checks Iterative reconstruction algorithms for radiation dose reduction by 30–50% compared to filter back-projection methods, better signal-to-noise ratio and image quality Consideration of the frequency of CT checks based on clinical course

Definition and clinical relevance of CT phenotypes of pulmonary sarcoidosis

An international expert survey of 146 radiologists from 28 countries, including members of the Fleischner Society and WASOG, defined seven CT phenotypes of pulmonary sarcoidosis, divided into “non-fibrotic” and “probably fibrotic” [54] ([Table 3]). This consensus creates a uniform framework for radiological classification. In a recent validation study using a Dutch patient collective, the inter- and intra-rater reliability of the newly proposed CT phenotypes was confirmed as very satisfactory [55].

Table 3 Subtypes of pulmonary sarcoidosis modified according to the classification of HRCT phenotypes based on Desai et al. (2024).

Non-fibrotic subtypes	Probably fibrotic subtypes
Micronodular pattern	Bronchocentric reticulations
Peribronchovascular, perifissural, or subpleural, with or without Galaxy sign, lung architectural impairment, or volume loss.	With or without cavitation and fibrocystic destruction; possibly other CT abnormalities such as parenchymal densities.
Nodular pattern	Bronchocentric masses
Nodules measuring >3 mm to <3 cm, either peribronchovascular/subpleural, or randomly distributed.	Similar to progressive mass fibrosis, possibly with additional CT patterns.
Consolidations
As dominant or single pattern.

The classification is gaining importance, particularly in light of the new disease category “progressive fibrosing lung diseases”, which includes all fibrosing lung diseases except idiopathic pulmonary fibrosis, and for which antifibrotic therapies are currently being studied.

The classification presented by the authors of the study appears suitable to support research on prevalence and prognosis, while its practical clinical applicability still needs to be evaluated. In particular, differences in prognosis and treatment response between the respective phenotypes should be analyzed. It is also important to examine whether the classification is transferable to different ethnic groups, since prevalence, risk, and clinical course of the disease can show considerable variability. In addition, further investigations into the influence of technical factors are necessary to ensure the reliability and reproducibility of the assignment to the defined groups.

Summary

Pulmonary sarcoidosis exhibits a wide spectrum of pulmonary manifestations, ranging from reversible lymphadenopathy to irreversible pulmonary fibrosis. Due to its heterogeneity, precise differentiation of PS is challenging, both clinically and in terms of imaging. Nevertheless, it is essential, because non-fibrotic lesions are usually reversible while fibrotic stages are associated with a worse prognosis.

Conventional chest radiography with Scadding’s classification system offers an easy method for classifying stages, but it also has limitations in terms of accuracy and correlation with lung function.

Computed tomography is known as the gold standard, and it can provide detailed visualization of characteristic findings, such as hilomediastinal lymphadenopathy, micro- and macronodules, as well as consolidations in the context of reversible processes; it also supports visualization of fibrotic remodeling processes in the event of non-reversible and prognostically unfavorable courses. Important complications, such as pulmonary hypertension and secondary fungal infections, can be detected by imaging. Magnetic resonance imaging is used primarily for cardiac diagnostics, while positron emission tomography (PET) is used to evaluate inflammatory activity and monitor therapy.

The differential diagnosis with regard to infectious, neoplastic, and other autoimmune diseases is complex, and it calls for an interdisciplinary approach.

Future developments should continue to improve integration of clinical, imaging, and functional parameters, in order to optimize treatment outcomes.

Conflict of Interest

The authors declare that they have no conflict of interest.

• References

• 1 Hutchinson J. Mortimerʼs malady. A form of lupus pernio. Arch Surg (London) 1898; 9: 307-315
• 2 Besnier E. Lupus pernio de la face: Synovites fongeuses (scrofulo-tuberculeuses) symétriques des extremities supérieures. Ann Derm Syph 1889; 10: 333-336
• 3 Ungprasert P, Carmona EM, Utz JP. et al. Epidemiology of Sarcoidosis 1946–2013: A Population-Based Study. Mayo Clin Proc 2016; 91: 183-188
• 4 Semenzato G, Pezzutto A, Chilosi M. et al. Redistribution of T lymphocytes in the lymph nodes of patients with sarcoidosis. N Engl J Med 1982; 306: 48-49
• 5 Ma Y, Gal A, Koss MN. The pathology of pulmonary sarcoidosis: update. Semin Diagn Pathol 2007; 24: 150-161
• 6 Rybicki BA, Major M, Popovich Jr J. et al. Racial differences in sarcoidosis incidence: A 5-year study in a health maintenance organization. Am J Epidemiol 1997; 145: 234-241
• 7 Baughman RP, Teirstein AS, Judson MA. et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164: 1885-1889
• 8 Mangalam AK, Taneja V, David CS. HLA class II molecules influence susceptibility versus protection in inflammatory diseases by determining the cytokine profile. J Immunol 2013; 190: 513-519
• 9 Levin AM, Adrianto I, Datta I. et al. Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans. Am J Respir Cell Mol Biol 2015; 53: 206-216
• 10 Valeyre D, Brauner M, Bernaudin JF. et al. Differential diagnosis of pulmonary sarcoidosis: a review. Front Med (Lausanne) 2023; 10: 1150751
• 11 Bailey GL, Wells AU, Desai SR. Imaging of Pulmonary Sarcoidosis – A Review. J Clin Med 2024; 13: 822
• 12 Polverino F, Balestro E, Spagnolo P. Clinical Presentations, Pathogenesis, and Therapy of Sarcoidosis: State of the Art. J Clin Med 2020; 9: 2363
• 13 Chong WH, Agrawal D, Tan ZY. et al. A systematic review and meta-analysis of the clinical benefits and adverse reactions of anti-fibrotics in non-IPF progressive fibrosing ILD. Heart Lung 2024; 68: 242-253
• 14 Belperio JA, Fishbein MC, Abtin F. et al. Pulmonary sarcoidosis: A comprehensive review: Past to present. J Autoimmun 2023; 149: 103107
• 15 Baughman RP, Winget DB, Bowen EH. et al. Predicting respiratory failure in sarcoidosis patients. Sarcoidosis, vasculitis, and diffuse lung diseases. Official journal of WASOG 1997; 14: 154-158
• 16 Nardi A, Brillet P-Y, Letoumelin P. et al. Stage IV sarcoidosis: Comparison of survival with the general population and causes of death. Eur Respir J 2011; 38: 1368-1373
• 17 Karetzky M, McDonough M. Exercise and resting pulmonary function in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 1996; 13: 43-49
• 18 Barros WG, Neder JA, Pereira CA. et al. Clinical, radiographic and functional predictors of pulmonary gas exchange impairment at moderate exercise in patients with sarcoidosis. Respiration 2004; 71: 367-373
• 19 Baughman RP, Shipley R, Desai S. et al. Changes in Chest Roentgenogram of Sarcoidosis Patients During a Clinical Trial of Infliximab Therapy: Comparison of Different Methods of Evaluation. Chest 2009; 136: 526-535
• 20 Kreuter M, Behr J, Bonella F. et al. S1-Leitlinie Interdisziplinäre Diagnostik interstitieller Lungenerkrankungen im Erwachsenenalter. Pneumologie 2023; 77: 269-302
• 21 Athwal PSS, Chhikara S, Ismail MF. et al. Cardiovascular Magnetic Resonance Imaging Phenotypes and Long-term Outcomes in Patients With Suspected Cardiac Sarcoidosis. JAMA Cardiol 2022; 7: 1057-1066
• 22 Griffin I, Pasini R, Mehrad B. et al. The evolving role of MRI in pulmonary sarcoidosis: Comparative analysis with PFTs and progression markers. Sarcoidosis Vasc Diffuse Lung Dis 2025; 42: 15304
• 23 Bilgin B, Bilgin MK, Erol S. et al. Prognosis of sarcoidosis and factors affecting prognosis. Sarcoidosis Vasc Diffuse Lung Dis 2023; 40
• 24 Ag C, Wy C, Hutchings HA. Sarcoidosis: A long-term follow up study. Sarcoidosis, vasculitis, and diffuse lung diseases. Official journal of WASOG 2000; 17 (02) 167-173
• 25 Pietinalho A, Ohmichi M, Ab L. et al. The prognosis of pulmonary sarcoidosis in Finland and Hokkaido, Japan. A comparative five-year study of biopsy-proven cases. Sarcoidosis, vasculitis, and diffuse lung diseases. Official journal of WASOG 2000; 17 (02) 158-166
• 26 Miller BH, Rosado-de-Christenson ML, McAdams HP. et al. Thoracic sarcoidosis: radiologic-pathologic correlation. Radiographics 1995; 15: 421-437
• 27 Venkata Ramanan R, Pudhiavan A, Venkataramanan A. The “cluster of black pearls” sign of sarcoid lymphadenopathy: A new sign on thin-section contrast-enhanced multidetector CT. Clin Radiol 2017; 72: 729-736
• 28 Remy-Jardin M, Giraud F, Remy J. et al. Pulmonary sarcoidosis: Role of CT in the evaluation of disease activity and functional impairment and in prognosis assessment. Radiology 1994; 191: 675-680
• 29 Broos CE, van Nimwegen M, Hoogsteden HC. et al. Granuloma formation in pulmonary sarcoidosis. Front Immunol 2013; 4: 437
• 30 Nakatsu M, Hatabu H, Morikawa K. et al. Large coalescent parenchymal nodules in pulmonary sarcoidosis: “sarcoid galaxy” sign. AJR Am J Roentgenol 2002; 178: 1389-1393
• 31 Hiroshige S, Ando M, Okubo F. et al. [A case of pulmonary sarcoidosis demonstrating panlobular ground-glass opacity with mosaic distribution]. Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society 2009; 47 (03) 212-217
• 32 Verleden SE, Vanstapel A, De Sadeleer L. et al. Distinct Airway Involvement in Subtypes of End-Stage Fibrotic Pulmonary Sarcoidosis. Chest 2021; 160: 562-571
• 33 Ganeshan D, Menias CO, Lubner MG. et al. Sarcoidosis from Head to Toe: What the Radiologist Needs to Know. Radiographics 2018; 38: 1180-1200
• 34 Abehsera M, Valeyre D, Grenier P. et al. Sarcoidosis with pulmonary fibrosis: CT patterns and correlation with pulmonary function. AJR Am J Roentgenol 2000; 174: 1751-1757
• 35 Obi ON, Alqalyoobi S, Maddipati V. et al. High-Resolution CT Scan Fibrotic Patterns in Stage IV Pulmonary Sarcoidosis: Impact on Pulmonary Function and Survival. Chest 2024; 165: 892-907
• 36 Collins BF, McClelland RL, Ho LA. et al. Sarcoidosis and IPF in the same patient-a coincidence, an association or a phenotype?. Respir Med 2018; 144s: S20-s27
• 37 [Anonym]. Sarcoidosis of the Pleura. Ann Intern Med 1974; 81: 190-194
• 38 Hennebicque AS, Nunes H, Brillet PY. et al. CT findings in severe thoracic sarcoidosis. Eur Radiol 2005; 15: 23-30
• 39 Galiè N, McLaughlin VV, Rubin LJ. et al. An overview of the 6th World Symposium on Pulmonary Hypertension. Eur Respir J 2019; 53
• 40 Handa T, Nagai S, Miki S. et al. Incidence of Pulmonary Hypertension and Its Clinical Relevance in Patients With Sarcoidosis. Chest 2006; 129: 1246-1252
• 41 Shorr AF, Helman DL, Davies DB. et al. Pulmonary hypertension in advanced sarcoidosis: Epidemiology and clinical characteristics. Eur Respir J 2005; 25: 783-788
• 42 Ratanawatkul P, Oh A, Richards JC. et al. Performance of pulmonary artery dimensions measured on high-resolution computed tomography scan for identifying pulmonary hypertension. ERJ Open Res 2020; 6
• 43 Tello K, Richter MJ, Kremer N. et al. Diagnostic Algorithm and Screening of Pulmonary Hypertension. Pneumologie 2023; 77: 871-889
• 44 Morawiec E, Hachulla-Lemaire A-L, Chabrol J. et al. Venoatrial compression by lymphadenopathy in sarcoidosis. Eur Respir J 35: 1188-1191
• 45 Wollschlager C, Khan F. Aspergillomas complicating sarcoidosis. A prospective study in 100 patients. Chest 1984; 86: 585-588
• 46 Uzunhan Y, Nunes H, Jeny F. et al. Chronic pulmonary aspergillosis complicating sarcoidosis. Eur Respir J 2017; 49
• 47 Bernardinello N, Petrarulo S, Balestro E. et al. Pulmonary Sarcoidosis: Diagnosis and Differential Diagnosis. Diagnostics 2021; 11: 1558
• 48 Yao Q, Ji Q, Zhou Y. Pulmonary Function in Pulmonary Sarcoidosis. J Clin Med 2023; 12
• 49 Aleksonienė R, Zeleckienė I, Matačiūnas M. et al. Relationship between radiologic patterns, pulmonary function values and bronchoalveolar lavage fluid cells in newly diagnosed sarcoidosis. J Thorac Dis 2017; 9: 88-95
• 50 Zhang Y, Du S-s, Zhao M-m. et al. Chest high-resolution computed tomography can make higher accurate stages for thoracic sarcoidosis than X-ray. BMC Pulm Med 2022; 22: 146
• 51 McLoud TC, Epler GR, Gaensler EA. et al. A radiographic classification for sarcoidosis: physiologic correlation. Invest Radiol 1982; 17 (02) 129-138
• 52 Müller NL, Mawson JB, Mathieson JR. et al. Sarcoidosis: Correlation of extent of disease at CT with clinical, functional, and radiographic findings. Radiology 1989; 171 (03) 613-618
• 53 [Anonym]. Protokollempfehlungen der AG DRauE zur Durchführung von Low-Dose-Volumen-HRCT-Untersuchungen der Lunge. RoFo 2017; 189: 553-567
• 54 Desai SR, Sivarasan N, Johannson KA. et al. High-resolution CT phenotypes in pulmonary sarcoidosis: A multinational Delphi consensus study. Lancet Respir Med 2024; 12: 409-418
• 55 Van Woensel J, Krdzalic J, de Jaegere T. et al. Radiological phenotypes in pulmonary sarcoidosis: A reliability study of newly defined high-resolution computer tomography phenotypes. BJR Open 2025; 7: tzaf017

Publication History

Received: 09 June 2025

Accepted after revision: 08 October 2025

Article published online:
12 November 2025