Diagnosis of Pulmonary Sarcoidosis.

Diagnosis of sarcoidosis depends on a compatible clinical and imaging presentation, histologic finding of non-necrotizing granulomatous inflammation, and exclusion of alternative causes of granulomatous diseases. This study has reviewed the diagnostic algorithms and approaches of sarcoidosis.

An Artificial Intelligence Platform for the Radiologic Diagnosis of Pulmonary Sarcoidosis: An Initial Pilot Study of Chest Computed Tomography Analysis to Distinguish Pulmonary Sarcoidosis from a Negative Lung Cancer Screening Scan.

PURPOSE: To determine the reliability of an artificial intelligence, deep learning (AI/DL)-based method of chest computer tomography (CT) scan analysis to distinguish pulmonary sarcoidosis from negative lung cancer screening chest CT scans (Lung Imaging Reporting and Data System score 1, Lung-RADS score 1). METHODS: Chest CT scans of pulmonary sarcoidosis were evaluated by a clinician experienced with sarcoidosis and a chest radiologist for clinical and radiologic evidence of sarcoidosis and exclusion of alternative or concomitant pulmonary diseases. The AI/DL based method used an ensemble network architecture combining Convolutional Neural Networks (CNNs) and Vision Transformers (ViTs). The method was applied to 126 pulmonary sarcoidosis and 96 Lung-RADS score 1 CT scans. The analytic approach of training and validation of the AI/DL method used a fivefold cross-validation technique, where 4/5th of the available data set was used to train a diagnostic model and tested on the remaining 1/5th of the data set, and repeated 4 more times with non-overlapping validation/test data. The probability values were used to generate Receiver Operating Characteristic (ROC) curves to assess the model's discriminatory power. RESULTS: The sensitivity, specificity, positive and negative predictive value of the AI/DL method for the 5 folds of the training/validation sets and the entire set of CT scans were all over 94% to distinguish pulmonary sarcoidosis from LUNG-RADS score 1 chest CT scans. The area under the curve for the corresponding ROC curves were all over 97%. CONCLUSION: This AL/DL model shows promise to distinguish sarcoidosis from alternative pulmonary conditions using minimal radiologic data.

RISK FACTORS FOR GC-RESISTANT PULMONARY SARCOIDOSIS.

OBJECTIVE: The aim: The study aimed to conduct a retrospective analysis of unfavorable outcome rate and to search for clinical and anamnestic criteria for predicting glucocorticoid-resistant pulmonary sarcoidosis. PATIENTS AND METHODS: Materials and methods: There were examined 37 women and 31 men with stage II to III pulmonary sarcoidosis from 2018-2022. The mean patients' age was (35.7±6.6) years. All patients underwent a chest computed tomography scan on the Toshiba Aquilion Prime CT scanner before the start of treatment and after the three-month glucocorticoid therapy. Anamnestic, age- and gender related factors of unfavorable treatment outcomes were studied. RESULTS: Results: Dyspnea (86%), coughing (67%), general weakness and fatigue (29%) on the background of maintaining the indicators of lung tissue density at the level of -893.5 Hounsfield units and above according to the chest computed tomography imaging represented the three-month treatment failure. Glucocorticoid-resistant sarcoidosis was most diagnosed in patients with stage III disease; the mean patients' age was (44.3±3.2) years; B positive men prevailed; 85% of patients developed extrapulmonary manifestations; in 43% of cases, concomitant cardiovascular pathology was diagnosed. CONCLUSION: Conclusions: Age, gender, comorbid conditions, extrapulmonary lesions, and blood type can be used as predictive criteria for GC-resistant sarcoidosis.

Advantages and drawbacks associated with the use of endosonography in sarcoidosis.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a real-time, minimally invasive procedure for sampling intrathoracic lymph nodes. Herein, we discuss EBUS-guided procedures, their benefits, and drawbacks in diagnosing sarcoidosis. AREAS COVERED: We first describe the utility of various endosonographic imaging techniques like B-mode, elastography, and doppler imaging. We then review the diagnostic yield and safety of EBUS-TBNA and compare it with the other available diagnostic modalities. Subsequently, we discuss the technical aspects of EBUS-TBNA influencing the diagnostic yield. Recent advances in EBUS-guided diagnostics like EBUS-guided intranodal forceps biopsy (EBUS-IFB) and EBUS-guided transbronchial mediastinal cryobiopsy (EBMC) are reviewed. Finally, we summarize the advantages and disadvantages associated with EBUS-TBNA in sarcoidosis and provide an expert opinion on the optimal use of this procedure in patients with suspected sarcoidosis. EXPERT OPINION: EBUS-TBNA is a minimally invasive, safe procedure with a good diagnostic yield, and should be the preferred diagnostic modality for sampling intrathoracic lymph nodes in patients with suspected sarcoidosis. For optimal diagnostic yield, EBUS-TBNA should be combined with endobronchial biopsy (EBB) and transbronchial lung biopsy (TBLB). Newer endosonographic techniques like EBUS-IFB and EBMC might obviate the need for EBB and TBLB due to their superior diagnostic yield.

High-Definition Videobronchoscopy for the Diagnosis of Airway Involvement in Sarcoidosis: The Enhance Sarcoidosis Multicenter Study.

BACKGROUND: The ability of high-definition (HD) videobronchoscopy to detect airway involvement in sarcoidosis has not been evaluated previously. RESEARCH QUESTION: What is the role of HD videobronchoscopy in the identification of sarcoidosis-associated airway abnormalities (AAs)? What are the patterns of AAs more commonly observed and more frequently associated with the detection of granulomas in endobronchial biopsy (EBB)? STUDY DESIGN AND METHODS: In this prospective international multicenter cohort study, consecutive patients with suspected sarcoidosis underwent airway inspection with an HD videobronchoscope and EBB using a standardized workflow. AAs were classified according to six patterns defined a priori: nodularity, cobblestoning, thickening, plaque, increased vascularity, and miscellaneous. We assessed diagnostic yield of EBB, prevalence of AAs, and interobserver agreement for different patterns of AAs. RESULTS: AAs were identified in 64 of 134 patients with sarcoidosis (47.8%), with nodularity (n = 23 [17.2%]), plaque (n = 19 [14.2%]), and increased vascularity (n = 19 [14.2%]) being the most prevalent. The diagnostic yield of EBB was 36.6%. AAs were significantly more prevalent in patients with than in those without nonnecrotizing granulomas on EBB (67.4% vs 36.5%; P = .001). Likewise, parenchymal disease on CT scan imaging was significantly more common in patients with than in those without nonnecrotizing granulomas on EBB (79.6% vs 54.1%; P = .003). On a per-lesion analysis, nonnecrotizing granulomas were seen especially in EBB samples obtained from areas of cobblestoning (9/10 [90%]) and nodularity (17/29 [58.6%]). The overall diagnostic yield of random EBB was low (31/134 [23.1%]). The interobserver agreement for the different patterns of AA was fair (Fleiss κ = 0.34). INTERPRETATION: In a population with a large prevalence of White Europeans, HD videobronchoscopy detected AAs in approximately one-half of patients with sarcoidosis. The diagnostic yield of EBB was higher in patients with parenchymal involvement on CT scan imaging and in those with AAs, especially if manifesting as cobblestoning and nodularity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT4743596; URL: www. CLINICALTRIALS: gov.

Utility of Narrow-band Imaging Bronchoscopy in the Diagnosis of Endobronchial Sarcoidosis.

BACKGROUND: There are few reports on the utility of bronchoscopic narrow-band imaging (NBI) for visualizing endobronchial abnormalities in sarcoidosis. Our primary objective was to compare the sensitivity of finding endobronchial abnormality using NBI versus white light bronchoscopy (WLB) in patients with sarcoidosis. The secondary aim was to evaluate the sensitivity of NBI in diagnosing endobronchial sarcoidosis against a reference standard of positive endobronchial biopsy (EBB). METHODS: We retrospectively included subjects with sarcoidosis, where we sequentially recorded WLB and NBI videos to visualize the endobronchial mucosa. We collected data on the demographic findings, sarcoidosis stage, and the histopathological findings of transbronchial needle aspiration, EBB, and transbronchial lung biopsy. Three experienced bronchoscopists viewed the video recordings and noted the abnormalities of the airway mucosa separately on WLB and NBI. RESULTS: We included 28 subjects (mean age, 42.9 y; 53.6% men; 14 each, stages 1 and 2) with a final diagnosis of sarcoidosis. Granulomas were detected on EBB in 11 (39.3%) subjects. We identified endobronchial nodules in 10 and 15 subjects on WLB and NBI. The sensitivity of finding endobronchial abnormality using WLB and NBI was 35.7% (10/28) and 53.6% (15/28), respectively (χ 2 =1.77, df=1, P =0.18). The sensitivity of NBI in diagnosing endobronchial sarcoidosis against a positive EBB was 63.6% (7/11 subjects). There was excellent agreement (Κ=0.86) for detecting nodules on NBI among the 3 observers. CONCLUSION: NBI might allow the identification of additional abnormalities not detected on WLB in sarcoidosis. Larger studies are required to confirm our observations.

Endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of pulmonary sarcoidosis: A 9-year experience at a single center.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is valuable for diagnosing pulmonary sarcoidosis. We aimed to evaluate the diagnostic yield of EBUS-TBNA and cytology in sarcoidosis during the first 9 years at our institution. METHODS: Patients who underwent EBUS-TBNA for suspected sarcoidosis between January 2011 and November 2019 were identified retrospectively. EBUS-TBNA was performed with rapid on-site cytological evaluation of the samples. The final diagnosis was based on the pathology and/or cytology results, radiologic features, and clinical follow-up findings. The yield rate was analyzed annually. RESULTS: Eighty patients underwent 83 EBUS-TBNA procedures for suspected sarcoidosis. In total, 136 lymph nodes were sampled. The mean number of lymph node stations sampled was 2.0 ± 0.6; the mean number of needle passes per lymph node was 3.5 ± 0.8. Sixty-five patients were diagnosed with sarcoidosis, with a total of 68 procedures. Nonnecrotizing granulomatous inflammation was detected in the EBUS-TBNA samples from 49/68 procedures (yield rate: 72.1%). Of 19 patients with sarcoidosis who did not obtain a pathological diagnosis with EBUS-TBNA, epithelioid cells and/or multinuclear giant cells suggestive of granulomatous inflammation were detected in five. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for pathological diagnosis of sarcoidosis using EBUS-TBNA were 72.1%, 100%, 100%, and 24.0%, respectively. On using cytology, the sensitivity and NPV increased to 79.4% and 26.3%, respectively. The yield rate did not increase until 2016. CONCLUSION: EBUS-TBNA is useful for diagnosing sarcoidosis. Cytology resulted in an additional yield rate of 7.3%, which improved as the number of cases increased.

Comparison of a 22G Crown-Cut Needle with a Conventional 22G Needle with EBUS Guidance in Diagnosis of Sarcoidosis.

INTRODUCTION: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a standard procedure in cases of enlarged mediastinal lymph nodes. Recently, new tools were developed aiming to improve the diagnostic yield. A novel crown-cut needle is considered to obtain tissue cores which can be beneficial for the evaluation by the pathologist. This study aimed to compare the novel 22G crown-cut needle with a conventional 22G needle with EBUS guidance in the diagnosis of sarcoidosis. METHODS: We designed a single-center prospective randomized clinical trial between March 2020 and January 2021 with 30 patients with mediastinal lymphadenopathy and suspected sarcoidosis. RESULTS: 24 patients (mean age 49.5 vs 54.1, mean FVC 73.7% vs 86.7%, mean DLCO 72.4% vs 72.5% for crown-cut needle vs conventional needle, respectively) were diagnosed with sarcoidosis. In the remaining six patients, sarcoidosis was reasonably excluded. The diagnostic yield for sarcoidosis was 77% with the crown-cut needle vs. 82% with the conventional needle (p > 0.05). In patients with histopathologic hallmarks typical of sarcoidosis (n = 19), the crown-cut needle was superior in detecting granulomas (8.3 vs 3.8 per cytoblock, p < 0.05) and histiocytes (502 vs 186 per cytoblock, p < 0.05). Four of seven bronchoscopists experienced difficulties passing through the bronchial wall with the crown-cut needle and one episode of bleeding occurred in this group which made interventions necessary. CONCLUSIONS: Despite equivalence in diagnostic accuracy, the crown-cut needle was superior to the conventional needle in detecting granulomas and histiocytes. This indicates greater potential for obtaining higher quality sample material with the crown-cut needle in cases of granulomatous inflammation.

Quantitative computed tomography and machine learning: recent data in fibrotic interstitial lung disease and potential role in pulmonary sarcoidosis.

PURPOSE OF REVIEW: The aim of this study was to summarize quantitative computed tomography (CT) and machine learning data in fibrotic lung disease and to explore the potential application of these technologies in pulmonary sarcoidosis. RECENT FINDINGS: Recent data in the use of quantitative CT in fibrotic interstitial lung disease (ILD) are covered. Machine learning includes deep learning, a branch of machine learning particularly suited to medical imaging analysis. Deep learning imaging biomarker research in ILD is currently undergoing accelerated development, driven by technological advances in image processing and analysis. Fundamental concepts and goals related to deep learning imaging research in ILD are discussed. Recent work highlighted in this review has been performed in patients with idiopathic pulmonary fibrosis (IPF). Quantitative CT and deep learning have not been applied to pulmonary sarcoidosis, although there are recent deep learning data in cardiac sarcoidosis. SUMMARY: Pulmonary sarcoidosis presents unsolved problems for which quantitative CT and deep learning may provide unique solutions: in particular, the exploration of the long-standing question of whether sarcoidosis should be viewed as a single disease or as an umbrella term for disorders that might usefully be considered as separate diseases.

Sarcoidosis with hepatic involvement in a 60-year-old patient.

Hepatic involvement of sarcoidosis is usually hard to detect on radiological imaging. We present a case of a 60-year-old female with symptoms of pulmonary sarcoidosis. Subsequent imaging work-up showed diffuse hepatic granulomas consistent with abdominal involvement of sarcoidosis. A literature review regarding hepatic sarcoidosis is provided and radiological appearances as well as considerations for differential diagnosis are described.

Chest high-resolution computed tomography can make higher accurate stages for thoracic sarcoidosis than X-ray.

BACKGROUND: To explore if chest high-resolution computed tomography (HRCT) can make higher accurate stages for thoracic sarcoidosis stage than X-ray (CRX) only. METHODS: Clinical data from medical records of consecutive patients with a confirmed diagnosis of pulmonary sarcoidosis at Shanghai Pulmonary Hospital from January 1 2012 to December 31 2016 and consecutive patients treated at the Sarcoidosis Center of University of Cincinnati Medical Center, Ohio, USA from January 1 2010 to December 31 2015 were reviewed. The clinical records of 227 patients diagnosed with sarcoidosis (140 Chinese and 87 American) were reviewed. Their sarcoidosis stage was determined by three thoracic radiologists based on CXR and HRCT presentations, respectively. The stage determined from CXR was compared with that determined from HRCT. RESULTS: Overall, 50.2% patients showed discordant sarcoidosis stage between CXR and HRCT (52.9% in Chinese and 44.8% in American, respectively). The primary reason for inconsistent stage between CXR and HRCT was failure to detect mediastinal lymph node enlargement in the shadow of the heart in CXR (22.1%) and small nodules because of the limited resolution of CXR (56.6%). Stage determined from HRCT negatively correlated with carbon monoxide diffusing capacity (DLCO) significantly (P < .01) but stage determined from CXR did not. Pleural involvement was detected by HRCT in 58 (25.6%) patients but only in 17 patients (7.5%) by CXR. Patients with pleural involvement had significantly lower forced vital capacity and DLCO than patients without it (both P < .05). CONCLUSION: Revised staging criteria based on HRCT presentations included 5 stages with subtypes in the presence of pleural involvement were proposed. Thoracic sarcoidosis can be staged more accurately based on chest HRCT presentations than based on CXR presentations. Pleural involvement can be detected more accurately by HRCT.

Four-year survival rate in pulmonary sarcoidosis with extensive pulmonary hypertension screening.

BACKGROUND: Sarcoidosis is a systemic disease of unknown aetiology with significant morbidity and mortality. The PULSAR study prospectively performed cardiac analysis including systematic pulmonary hypertension screening in sarcoidosis patients newly referred to a tertiary sarcoidosis center. In this manuscript we studied the four-year mortality of this population. METHODS AND MAIN FINDINGS: Between august 2015 and October 2017, 399 patients (58% male, mean age 49.4 years, 90.5% Caucasian) were included and followed for a mean period of 4.3±0.7 years. In total, 10 patients had died at the time of analysis. 1-, 2-, 3- and 4-year survival rate was 100% (n=399), 99.0% (n=399), 98.2% (n=399) and 94.6% (n=276). Most patients died of respiratory failure, other causes were heterogeneous including cardiac, neurological and non-sarcoidosis origin. A low CPI score or modified Walsh score was associated with higher mortality, similar for high PH probability on echocardiography and elevated right ventricular systolic pressure. CONCLUSION: This study highlights that elevated RVSP and presence of PH on echocardiography and progression of fibrotic disease with subsequent decline in pulmonary function test are important factors for mortality in sarcoidosis patients.

COVID-19-induced pulmonary sarcoid: A case report and review of the literature.

BACKGROUND: The COVID-19 pandemic has resulted in dramatic loss of life worldwide, but as the large number of acutely ill patients subsides, the emerging group of "COVID-19 long-haulers" present a clinical challenge. Studies have shown that many of these patients suffer long-term pulmonary disease related to residual fibrosis. Prior studies have shown that while many patients have non-specific findings of fibrotic-like changes, others develop specific patterns of interstitial lung disease. CASE REPORT: Here, we present the first case of a patient developing pulmonary sarcoidosis one year after critical illness from COVID-19. He developed numerous non-necrotizing and well-formed granulomas in mediastinal lymph nodes and pulmonary nodules, compatible radiographically and pathologically with sarcoid. CONCLUSIONS: While the pathophysiology of sarcoid is incompletely understood, inflammation is mediated through the dysregulation of a number of different cytokines (IFNγ, IL-2, IL-12, IL-17, IL-22). This case provides valuable clues for better understanding of the shared pathophysiology of cytokine dysregulation seen in COVID-19 and other interstitial lung diseases such as sarcoidosis.

Evaluation of the Utility of Liquid-based Cytology, Cell-blocks, and Flow Cytometric Immunophenotyping on Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Samples in the Diagnosis of Sarcoidosis.

BACKGROUND: There is little information on the value of different processing methods for samples obtained during endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) in suspected sarcoidosis. We evaluated the role of conventional smears, liquid-based cytology (LBC), cell-blocks and flow cytometric immunophenotyping in the diagnosis of sarcoidosis using EBUS-TBNA samples. METHODS: This was a prospective study of consecutive EBUS-TBNA samples from clinically suspected cases of sarcoidosis. In addition to conventional smears, we prepared LBC smears, cell-blocks, and performed flow cytometric evaluation of the CD4:CD8 ratio. The final diagnosis of sarcoidosis was made based on the relevant clinical details and laboratory investigations including the results of transbronchial and endobronchial biopsies (TBLB and endobronchial biopsy). RESULTS: We included 60 subjects [mean age: 45.2 y; 29 (48.3%) men]. The sensitivity of conventional smears, LBC, and cell-blocks for diagnosing sarcoidosis was found to be 75.5%, 37.8%, 35%, respectively, when used alone. However, on combining conventional and LBC smears, the sensitivity increased to 84.4% and on combining all three techniques, the sensitivity was 86.7%. The CD4:CD8 ratio on flow cytometric immunophenotyping of EBUS-TBNA samples ranged from 0 to 11.5 with a mean of 3.17±2.78 in confirmed cases of sarcoidosis and 70% of these cases had CD4:CD8 ratio of more than 2. CONCLUSION: Cell-blocks and liquid-based preparations add to the yield of conventional preparation of EBUS-TBNA samples in the diagnosis of sarcoidosis. A combination of conventional and LBC works well in detecting almost 85% of the cases of sarcoidosis. Higher CD4:CD8 ratio favors a diagnosis of sarcoidosis.

Paradoxical Formation of a Pleuroparenchymal Fibroelastosis-like Lesion in the Chronic Course of Pulmonary Sarcoidosis.

We herein report the long-term changes in chest computed tomography (CT) findings from early sarcoidosis lesions to pleuroparenchymal fibroelastosis (PPFE)-like lesions in a 30-year-old man with granulomas on a transbronchial lung biopsy. Multiple bilateral micronodular and nodular opacities around the bronchovascular bundle in the upper lobes detected by chest CT in 2004 disappeared, but paradoxically, peripheral consolidations continued to grow at the periphery of the original lesions. Chest CT in 2017 confirmed the progression of bilateral shrinkage of the upper lobe, spread of peripheral consolidations and wedge-shaped opacities below the first rib, and bronchiectatic air bronchograms, confirming PPFE-like lesions.

Value of echocardiography using knowledge-based reconstruction in determining right ventricular volumes in pulmonary sarcoidosis: comparison with cardiac magnetic resonance imaging.

Right ventricular (RV) dysfunction in sarcoidosis is associated with adverse outcomes. Assessment of RV function by conventional transthoracic echocardiography (TTE) is challenging due to the complex RV geometry. Knowledge-based reconstruction (KBR) combines TTE measurements with three-dimensional coordinates to determine RV volumes. The aim of this study was to investigate the accuracy of TTE-KBR compared to the gold standard cardiac magnetic resonance imaging (CMR) in determining RV dimensions in pulmonary sarcoidosis. Pulmonary sarcoidosis patients prospectively received same-day TTE and TTE-KBR. If performed, CMR within 90 days after TTE-KBR was used as reference standard. Outcome parameters included RV end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (RVSV) and ejection fraction (RVEF). 281 patients underwent same day TTE and TTE-KBR. In total, 122 patients received a CMR within 90 days of TTE and were included. TTE-KBR measured RVEDV and RVESV showed strong correlation with CMR measurements (R = 0.73, R = 0.76), while RVSV and RVEF correlated weakly (R = 0.46, R = 0.46). Bland-Altman analyses (mean bias ± 95% limits of agreement), showed good agreement for RVEDV (ΔRVEDVKBR-CMR, 5.67 ± 55.4 mL), while RVESV, RVSV and RVEF showed poor agreement (ΔRVESVKBR-CMR, 21.6 ± 34.1 mL; ΔRVSVKBR-CMR, - 16.1 ± 42.9 mL; ΔRVEFKBR-CMR, - 12.9 ± 16.4%). The image quality and time between CMR and TTE-KBR showed no impact on intermodality differences and there was no sign of a possible learning curve. TTE-KBR is convenient and shows good agreement with CMR for RVEDV. However, there is poor agreement for RVESV, RVSV and RVEF. The use of TTE-KBR does not seem to provide additional value in the determination of RV dimensions in pulmonary sarcoidosis patients.