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.

Role of Bronchoscopy in Diagnosis of Sarcoidosis.

Sarcoidosis is a multisystem inflammatory disorder with unclear etiology and can often pose a diagnostic challenge. A tissue diagnosis is often necessary to illustrate the non-caseating granulomas on histopathology. This review aims to synthesize current evidence related to tissue diagnosis of sarcoidosis using various bronchoscopic techniques. We start by discussing standard bronchoscopic techniques which have remained the cornerstone of diagnostic workup such as bronchoalveolar lavage (BAL), endobronchial biopsy (EBB), conventional transbronchial needle aspiration (cTBNA) and transbronchial lung biopsy (TBLB) followed by newer modalities that incorporate real-time image guidance using endobronchial and endoscopic ultrasound. Although BAL, EBB, and TBLB have been employed as a diagnostic tool for several decades, their sensitivity and diagnostic yield is inferior to ultrasound-based endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). More recently, convincing evidence has also emerged to support the diagnostic accuracy and tissue yield of transbronchial lung cryobiopsy which will also be discussed in this review. These advances in bronchoscopic equipment and techniques over the last 2 decades have made it possible to obtain tissue samples using minimally invasive techniques thus avoiding invasive open lung biopsy and the risks that inherently follow. Up-to-date knowledge of these modalities is imperative for ensuring evidence-based medicine and improving patient-centric outcomes.

Sarcoidosis cardíaca como causa muy infrecuente de muerte súbita en pacientes jóvenes asintomáticos / Cardiac sarcoidosis as an infrequent cause of sudden death in asymptomatic young patients

La afectación cardíaca en la sarcoidosis ha sido descrita tanto en presencia de síntomas como en su ausencia. Este trabajo ayuda a comprender la sarcoidosis y su presentación clínico-morfológica. Presentamos dos pacientes jóvenes (37 y 27años), con muerte súbita, a quienes se les realizó la autopsia completa con estudio toxicológico. El hombre de 37años presentaba una sarcoidosis pulmonar generalizada, en ganglios mediastínicos y granulomas sarcoideos intramiocárdicos en el ventrículo izquierdo, que producían un espesor de pared de 14mm. Esto derivó en una miocardiopatía dilatada secundaria que debutó como muerte súbita. El segundo caso, un varón de 27años, presentaba sarcoidosis con importante afectación pulmonar y mediastínica. La presencia de granulomas en el tabique cardíaco sobre un fondo fibrótico podría ser el origen de un mecanismo arritmogénico de muerte súbita. La autopsia clásica y el examen del sistema de conducción cardíaco son cruciales en la muerte súbita.(AU)

Cardiac involvement in sarcoidosis has been described in both symptomatic and asymptomatic patients. The aim of this report is to further the understanding of sarcoidosis and its clinical presentation. We report the autopsy and toxicology results of two cases of sudden death in young men. A 37-year-old male had generalized sarcoidosis, in mediastinal glands and intramyocardial sarcoid granulomas in the left ventricle, which had caused a 14mm thickening of the ventricular wall and a secondary dilated myocardiopathy causing sudden death. A 27-year-old male had extensive sarcoidosis of the lungs and mediastinum. Granulomas with a fibrotic background were found in the cardiac wall which could have originated an arrhythmogenic mechanism causing sudden death. Post-mortem study including careful examination of cardiac conduction pathways are vital to ascertain the cause of sudden death.(AU)

Clinical and Histopathologic Characteristics of Recurrent Sarcoidosis in Posttransplant Lungs: 25 Years of Experience.

Lung transplantation is the definitive therapy for end-stage pulmonary sarcoidosis. While recurrent sarcoidosis in allografts has been described in several case reports, the incidence and clinicopathologic characteristics remain unclear. In this study, we characterize the clinical and histopathologic features of recurrent sarcoidosis diagnosed in posttransplant lung surveillance transbronchial biopsies (TBBx). We identified 35 patients who underwent lung transplant for pulmonary sarcoidosis during the study period. Among them, 18 patients (51%) experienced recurrent sarcoidosis posttransplant. These included 7 females and 11 males with mean age at recurrence of 51.6 years. The average time interval from transplant to recurrence was 252 days (22 to 984 d). All TBBx contained >4 pieces of alveolated lung tissue with no evidence of International Society for Heart and Lung Transplantation (ISHLT) grade A2, A3, or A4 acute cellular rejection; chronic rejection; or antibody-mediated rejection. There were 33 surveillance TBBx that contained granulomatous inflammation with a mean of 3.6 well-formed granulomas per TBBx (range: 1 to >20). Multinucleated giant cells were identified in 11 TBBx (33.3%), with 1 case containing asteroid bodies. While most of the granulomas were "naked granulomas," 5 cases (15.2%) showed prominent lymphoid cuffing. Two cases showed evidence of fibrosis. One of the granulomas had focal necrosis; however, no infectious organisms were identified by special stains and clinical correlation suggested this case represented recurrent sarcoidosis. Biopsies of recurrent sarcoidosis usually show multiple well-formed granulomas with giant cells in more than half of the cases, while lymphoid cuffing, fibrosis, asteroid bodies, and necrotizing granulomas are uncommon findings. Pathologists should be aware of these features, as recurrence of sarcoidosis following lung transplant occurs in more than half of patients.

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.

An unusual case of pleural effusion.

CASE PRESENTATION: A 63-year-old man presented with fever, thoracalgia, weight loss, diffuse lymphadenopathy, and a massive pleural effusion. Extensive laboratory and radiologic investigations for possible autoimmune, infectious, hematologic, and neoplastic conditions all resulted negative. A lymph node biopsy showed a granulomatous necrotizing lymphadenitis, suspicious for tuberculosis. Although mycobacterium tuberculosis (MT) was never isolated and tuberculin skin test resulted negative, diagnosis of extrapulmonary tuberculosis was made and anti-tubercular therapy was started. Despite the strict adherence to 5 months of treatment, he returned to the emergency ward complaining of fever, chest pain and pleural effusion; total-body CT and PET scans demonstrated a progression of new disseminated nodular consolidations. DIAGNOSTIC WORK-UP: Microscopic and cultural search for MT and other micro-organisms resulted again negative on urine, stool, blood, pleural fluid, and spinal lesion biopsy. We therefore started considering alternative diagnosis for necrotizing granulomatosis, including multidrug-resistant tuberculosis, Wegener granulomatosis, Churg Strauss syndrome, necrobiotic nodules of rheumatoid arthritis, lymphomatoid granulomatosis and Necrotizing Sarcoid Granulomatosis (NSG). Having already rejected other autoimmune, hematological, and neoplastic disorders, NSG resulted the most consistent hypothesis. With an expert we thus re-examined histological specimens that were suggestive for an atypical presentation of sarcoidosis. Steroid therapy was initiated, achieving symptoms improvement. DISCUSSION: Sarcoidosis is a rare condition that can be challenging to diagnose, due to its variability in clinical presentation, often mimicking alternative conditions like disseminated tuberculosis. A high degree of suspicion and an experienced lab in anatomical pathology are essential for final diagnosis.

Metastasis of lung cancer?

BACKGROUND: Sarcoidosis is a multi-system, idiopathic, inflammatory disorder that affects the lungs in over 90% of patients. The incidence of bone lesions in sarcoidosis is only 1-13%. CASE REPORT: This study describes a 60-year-old woman with a previous history of thyroid cancer, and a more recent diagnosis of lung cancer with suspicious metastatic lesions, which were confirmed to be sarcoidosis. CONCLUSION: This case suggests that pulmonary neoplasms and pulmonary sarcoidosis can coexist and be easily confused. When lung cancer is accompanied by symmetric hilar lymph node enlargement and multiple lung nodules, sarcoidosis should be considered in addition to metastasis, and a biopsy should be performed for confirmation.

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.

Immune mapping of human tuberculosis and sarcoidosis lung granulomas.

Tuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB and sarcoidosis patients using in situ sequencing (ISS) transcriptomic analysis and multiplexed immunolabeling of tissue sections. TB lesions consisted of large necrotic and cellular granulomas, whereas "multifocal" granulomas with macrophages or epitheloid cell core and a T-cell rim were observed in sarcoidosis samples. The necrotic core in TB lesions was surrounded by macrophages and encircled by a dense T-cell layer. Within the T-cell layer, compact B-cell aggregates were observed in most TB samples. These B-cell clusters were vascularized and could contain defined B-/T-cell and macrophage-rich areas. The ISS of 40-60 immune transcripts revealed the enriched expression of transcripts involved in homing or migration to lymph nodes, which formed networks at single-cell distances in lymphoid areas of the TB lesions. Instead, myeloid-annotated regions were enriched in CD68, CD14, ITGAM, ITGAX, and CD4 mRNA. CXCL8 and IL1B mRNA were observed in granulocytic areas in which M. tuberculosis was also detected. In line with ISS data indicating tertiary lymphoid structures, immune labeling of TB sections expressed markers of high endothelial venules, follicular dendritic cells, follicular helper T cells, and lymph-node homing receptors on T cells. Neither ISS nor immunolabeling showed evidence of tertiary lymphoid aggregates in sarcoidosis samples. Together, our finding suggests that despite their heterogeneity, the formation of tertiary immune structures is a common feature in granulomas from TB patients.

Sarcoidosis in the older person: diagnostic challenges and treatment consideration.

BACKGROUND: Sarcoidosis is a multi-system disorder with an increasing propensity to present in older patients. Diagnostic uncertainty is common and understandable given the higher prevalence of co-morbidities in older patients and broad differential for multi-system clinical presentations. Excluding malignancy and infection with a high degree of certainty is challenging and may require repeated confirmatory investigation where the diagnosis remains in doubt. SUMMARY OF MAIN FINDINGS: There are a paucity of studies examining late-onset sarcoidosis. Female predominance, pulmonary, ocular, skin and systemic symptoms are common, while more classical presentations such as Lofgren's syndrome are uncommon. Positivity rates of biopsies vary between studies; however, targeted biopsies of accessible sites with organ involvement are the most successful. Therapeutic management is directed at reducing inflammation, and thereby reducing symptom burden, improving quality of life and avoiding progression of organ damage. While most older patients will require corticosteroid therapy, they are also more prone to developing adverse effects. Most older patients will experience a clinical remission; however, the risk of developing chronic sarcoidosis and organ damage is higher compared with younger counterparts. Patients with evidence of pulmonary fibrosis and pulmonary hypertension are at particular risk. IMPACT ON CLINICAL PRACTICE: Health care providers who care for older adults should be aware of the increasing prevalence of late-onset sarcoidosis and consider the diagnosis in those who present with otherwise unexplained systemic symptoms, thoracic abnormalities on imaging and/or evidence of other organ involvement. Earlier diagnosis and therapeutic intervention to halt the development of pulmonary fibrosis and pulmonary hypertension and monitoring for treatment-related adverse effects will confer a mortality benefit.

Does miliary sarcoidosis really exist? A case report and review of the literature.

BACKGROUND: Miliary sarcoidosis is a rare form of sarcoidosis characterized by numerous miliary-like micronodules dispersed throughout the lungs. It has been documented in less than 1% of all sarcoidosis cases. We first described a rare case of miliary sarcoidosis and then conducted a literature review on the subject. CASE PRESENTATION: A 51-year-old male complained about a progressive loss of appetite, significant weight loss, occasional night sweats, and fatigue. After a thorough clinical exploration, a differential diagnosis of miliary lung disease was suspected - miliary tuberculosis, fungal infection, metastatic pulmonary carcinoma, or sarcoidosis. High-resolution chest computed tomography revealed bilateral diffuse micronodules with mediastinal lymphadenopathy. Histopathological analysis of transbronchial bioptic tissue identified non-caseating epithelioid granulomas, while no malignant cells were found. Lung tuberculosis and fungal infections were excluded. The levels of angiotensin-converting enzyme in the blood, as well as serum's and 24-hour urine calcium levels, were elevated. After a multidisciplinary discussion, the diagnosis of miliary pulmonary sarcoidosis was established. The patient was treated with prednisone for a total of 9 months, with full clinical and radiological recovery. Using PubMed, we also conducted a review of the literature on this topic and discovered only a few case reports of patients with miliary sarcoidosis, with just one systematic review accessible. The key findings of studies investigating patients diagnosed with miliary sarcoidosis are tabularly displayed. CONCLUSIONS: Miliary sarcoidosis is an uncommon type of pulmonary sarcoidosis that can mimic several entities that manifest as miliary nodules. Most patients require treatment since it can have a significant impact on lung function.

Mimicking the mimicker: Necrotizing sarcoid granulomatosis.

Necrotizing sarcoid granulomatosis (NSG) is a rare disease that shares similarities with pulmonary vasculitides and sarcoidosis. This is a report of two cases of NSG with a review of literature. The first case is a 33-year-old black female with a one-year history of malaise and cough. Lung imaging revealed scattered pulmonary nodules. Histopathology showed multiple necrotizing granulomas without prominent neutrophilic infiltrates. The second case is a 58-year-old white female with a one-year history of fatigue, dyspnea, and ophthalmoplegia on the left eye. Imaging showed multiple pulmonary nodules. Lung biopsy was consistent with NSG. The challenge of the NSG diagnosis is to distinguish it from other mimickers. Pathology often shows necrotizing granulomatous vasculitis, distinguishing it from classical sarcoid. Laboratory markers for vasculitis like neutrophil cytoplasmic antibodies and antibodies against myeloperoxidase and proteinase 3 are negative or only low titers. NSG responds well to immune-suppression, most commonly with glucocorticoids.

Incidental Lung Cavity in the Heartland.

Necrotizing sarcoid granulomatosis (NSG) is a rare inflammatory disease. Although considered by some to be a subtype of sarcoidosis, this opinion is not universal. NSG is histologically characterized by the presence of necrotizing sarcoid like granuloma and granulomatous vasculitis. The exclusion of potential etiologies for necrotizing granulomatous inflammation is necessary to establish a diagnosis of NSG. A 70-year old female presented to our office after she was incidentally found to have a right lung cavitary lesion on a shoulder X-ray. She had an extensive serologic workup for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, mycobacterial and fungal etiologies, but they were all negative. She subsequently underwent bronchoscopic evaluation and biopsies. The histopathologic analysis revealed sarcoid-like granulomatous inflammation with large necrosis and mild granulomatous vasculitis. The pulmonary function test revealed a restrictive ventilatory defect. The patient was treated with steroid therapy with rapid radiologic and spirometric improvement.

Lymphocytic panhypophysitis and anti-rabphilin-3A antibody with pulmonary sarcoidosis.

PURPOSE: To explore the clinical significance of anti-rabphillin-3A antibody for the differential diagnosis of lymphocytic panhypophysitis. METHODS AND RESULTS: A 58-year-old Japanese man developed uveitis of unknown cause in 2017. In 2019, he became aware of polyuria. In August 2020, he noticed transient diplopia and was diagnosed with right abducens nerve palsy. At the same time, he complained of fatigue and loss of appetite. Head magnetic resonance imaging demonstrated enlargement of the pituitary stalk and pituitary gland, corresponding to hypophysitis. Hormone stimulation tests showed blunted responses with respect to all anterior pituitary hormones. Central diabetes insipidus was diagnosed on the basis of a hypertonic saline loading test. Taking these findings together, a diagnosis of panhypopituitarism was made. Computed tomography showed enlargement of hilar lymph nodes. Biopsies of the hilar lymph nodes revealed non-caseating epithelioid cell granulomas that were consistent with sarcoidosis. Biopsy of the anterior pituitary revealed mild lymphocyte infiltration in the absence of IgG4-positive cells, non-caseating granulomas, or neoplasia. Western blotting revealed the presence of anti-rabphilin-3A antibody, supporting a diagnosis of lymphocytic panhypophysitis. Because the patient had no visual impairment or severe uveitis, we continued physiological hormone replacement therapy and topical steroid therapy for the uveitis. CONCLUSION: To the best of our knowledge, this is the first case of anti-rabphilin 3A antibody positive lymphocytic panhypophysitis comorbid with sarcoidosis, diagnosed by both pituitary and hilar lymph node biopsy. The utility of anti-rabphilin-3A antibody for the differential diagnosis of hypophysitis like this case should be clarified with further case studies.

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.

Potential therapeutic targets to prevent organ damage in chronic pulmonary sarcoidosis.

INTRODUCTION: Sarcoidosis is a granulomatous inflammatory disease with high chances of reduced quality of life, irreversible organ damage, and reduced life expectancy when vital organs are involved. Any organ system can be affected, and the lungs are most often affected. There is no preventive strategy as the exact etiology is unknown, and complex immunogenetic and environmental factors determine disease susceptibility and phenotype. Present-day treatment options originated from clinical practice and are effective in many patients. However, a substantial percentage of patients suffer from unacceptable side effects or still develop refractory, threatening pulmonary or extrapulmonary disease. AREAS COVERED: As non-caseating granulomas, the pathological hallmark of disease, are assigned to divergent activation and regulation of the immune system, targets in relation to the possible triggers of granuloma formation and their sequelae were reviewed. EXPERT OPINION: The immunopathogenesis underlying sarcoidosis has been a dynamic field of study. Several recent new insights give way to promising new therapeutic targets, such as certain antigenic triggers (e.g. from Aspergillus nidulans), mTOR, JAK-STAT and PPARγ pathways, the NRP2 receptor and MMP-12, which await further exploration. Clinical and trigger related phenotyping, and molecular endotyping will likely hold the key for precision medicine in the future.

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.