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BACKGROUND: Sarcoidosis is a heterogeneous granulomatous disease with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential biomarkers. METHODS: Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of sarcoidosis diagnosis and progression phenotype, adjusting for age, sex, smoking, and principal components of the data. We built a supervised multi-omics model using a subset of features from each dataset. RESULTS: We identified 1,459 CpGs, 64 mRNAs, and five miRNAs associated with sarcoidosis versus controls and four mRNAs associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis. CONCLUSIONS: Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing is required for confirmation.
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Líquido da Lavagem Broncoalveolar , Multiômica , Sarcoidose Pulmonar , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Estudos de Casos e Controles , Progressão da Doença , Metilação de DNA , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Sarcoidose Pulmonar/genética , Sarcoidose Pulmonar/metabolismo , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologiaRESUMO
Granulomas are frequently encountered by pathologists in all types of lung specimens and arise from diverse etiologies. They should always be reported as necrotizing or non-necrotizing, with microorganism stains performed to evaluate for infection. With attention to distribution, quality (poorly vs well-formed), associated features, and correlation with clinical, radiologic, and laboratory data, the differential diagnosis for granulomatous lung disease can usually be narrowed to a clinically helpful "short list." This review describes a practical approach to pulmonary granulomas and reviews the clinicopathological aspects of common entities, including infectious (mycobacteria, fungi) and noninfectious (hypersensitivity pneumonitis, sarcoid, and vasculitis) causes.
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Pneumopatias , Humanos , Diagnóstico Diferencial , Pneumopatias/patologia , Pneumopatias/diagnóstico , Granuloma do Sistema Respiratório/patologia , Granuloma do Sistema Respiratório/diagnóstico , Granuloma/patologia , Granuloma/diagnóstico , Pulmão/patologia , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/patologia , Sarcoidose Pulmonar/patologia , Sarcoidose Pulmonar/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/patologiaRESUMO
INTRODUCTION: Observational data suggest that the 19-gauge (G) needle for endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) offers a higher diagnostic yield than the 22-G needle in sarcoidosis. No randomized trial has compared the yield of the two needles. METHODS: We randomized consecutive subjects with suspected sarcoidosis and enlarged thoracic lymph nodes to undergo EBUS-TBNA with either the 19-G or the 22-G needle. We compared the study groups for diagnostic sensitivity (primary outcome) assessed by the yield of granulomas in subjects finally diagnosed with sarcoidosis. We also compared the sample adequacy, difficulty performing the needle puncture assessed on a visual analog scale (VAS), the subject's cough intensity on an operator-rated VAS, and procedure-related complications (secondary outcomes). RESULTS: We randomized 150 (mean age, 43.0 years; 55% women) subjects and diagnosed sarcoidosis in 116 subjects. The diagnostic sensitivity of the 19-G needle (45/60, 75.0%) was not higher (p = 0.52) than the 22-G needle (39/56, 69.6%). We obtained adequate aspirates in 90.0% and 85.7% of subjects in the respective groups (p = 0.48). The operators had greater difficulty puncturing lymph nodes with the 19-G needle (p = 0.03), while the operator-assessed cough intensity was similar in the groups (p = 0.41). Transient hypoxemia was the only complication encountered during EBUS-TBNA (two subjects in either group). CONCLUSION: We did not find the 19-G needle superior to the 22-G in diagnostic sensitivity, specimen adequacy, or safety of EBUS-TBNA in sarcoidosis. Puncturing the lymph nodes was more difficult with the 19-G needle.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfonodos , Sarcoidose Pulmonar , Humanos , Feminino , Masculino , Adulto , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pessoa de Meia-Idade , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Linfonodos/patologia , Agulhas , Broncoscopia/métodos , Sensibilidade e Especificidade , Sarcoidose/diagnóstico , Sarcoidose/patologiaRESUMO
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.
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Sarcoidose Pulmonar , Sarcoidose , Humanos , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Sarcoidose/diagnóstico , Sarcoidose/patologia , Diagnóstico por Imagem , Biópsia/métodosRESUMO
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.
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Sarcoidose Pulmonar , Sarcoidose , Humanos , Broncoscopia/métodos , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Sarcoidose/diagnóstico , Sarcoidose/patologia , Pulmão/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Dimercaprol , Linfonodos/patologiaRESUMO
BACKGROUND: Different patterns of fibrosis on high-resolution CT scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT scan patterns and survival in sarcoidosis. RESEARCH QUESTION: Will a detailed description of the extent and pattern of HRCT scan fibrosis in patients with stage IV pulmonary sarcoidosis impact pulmonary function and survival? STUDY DESIGN AND METHODS: Two hundred forty patients with stage IV sarcoidosis at two large tertiary institutions were studied. The earliest HRCT scan with fibrosis was reviewed for extent of fibrosis (< 10%, 10%-20%, and > 20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground-glass opacities (GGOs), large bullae, and mycetomas. Presence of sarcoidosis-associated pulmonary hypertension (SAPH) and pulmonary function testing performed within 1 year of HRCT were recorded. Patients were followed up until last clinic visit, death, or lung transplantation. RESULTS: The mean age was 58.4 years. Seventy-four percent were Black, 63% were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). Thirty-one percent had > 20% fibrosis, 25% had 10%-20% fibrosis, and 44% had < 10% fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). Twelve percent had basal subpleural honeycombing, and 32% had SAPH. Patients with > 20% fibrosis had more severe pulmonary impairment, were more likely to have SAPH (53%), and had worse survival (44% mortality; P < .001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55% mortality; P < .001). GGOs were associated with worse pulmonary function but not worse survival, and mycetomas were associated with worse survival but not worse pulmonary function. A Cox proportional hazards model indicated that basal subpleural honeycombing (hazard ratio, 7.95), diffusion capacity for carbon monoxide < 40% (HR, 5.67) and White race (hazard ratio, 2.61) were independent predictors of reduced survival. INTERPRETATION: HRCT scan features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20% fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.
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Bronquiectasia , Sarcoidose Pulmonar , Sarcoidose , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Vesícula , Pulmão/diagnóstico por imagem , Pulmão/patologia , Fibrose , Tomografia Computadorizada por Raios X , Sarcoidose/patologia , Bronquiectasia/patologia , Estudos RetrospectivosRESUMO
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.
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Sarcoidose Pulmonar , Sarcoidose , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Pulmão/patologia , Sarcoidose/patologia , Granuloma/patologia , FibroseRESUMO
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.
Assuntos
Sarcoidose Pulmonar , Sarcoidose , Humanos , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Estudos de Coortes , Estudos Prospectivos , Broncoscopia/métodos , Sarcoidose/diagnóstico por imagem , Granuloma/diagnóstico por imagemRESUMO
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.
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Derrame Pleural , Sarcoidose Pulmonar , Sarcoidose , Masculino , Humanos , Pessoa de Meia-Idade , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Biópsia , Dor no PeitoRESUMO
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.
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Neoplasias Pulmonares , Doenças do Mediastino , Sarcoidose Pulmonar , Sarcoidose , Feminino , Humanos , Pessoa de Meia-Idade , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Sarcoidose/complicações , Sarcoidose/diagnóstico , Sarcoidose/patologia , Neoplasias Pulmonares/patologia , PulmãoRESUMO
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.
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Sarcoidose Pulmonar , Sarcoidose , Masculino , Humanos , Adulto , Feminino , Broncoscopia/métodos , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Sarcoidose/diagnóstico por imagem , Biópsia por Agulha Fina/métodosRESUMO
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.
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Sarcoidose Pulmonar , Sarcoidose , Humanos , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologia , Estudos Retrospectivos , Broncoscopia/métodos , Sensibilidade e Especificidade , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Sarcoidose/patologia , Linfonodos/patologia , InflamaçãoRESUMO
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.
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Mycobacterium tuberculosis , Sarcoidose Pulmonar , Sarcoidose , Tuberculose , Humanos , Granuloma , Sarcoidose Pulmonar/genética , Sarcoidose Pulmonar/patologia , Pulmão/patologia , RNA MensageiroRESUMO
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.
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Hipertensão Pulmonar , Fibrose Pulmonar , Sarcoidose Pulmonar , Sarcoidose , Idoso , Feminino , Humanos , Masculino , Qualidade de Vida , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Sarcoidose/terapia , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/patologiaRESUMO
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.
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Sarcoidose Pulmonar , Sarcoidose , Tuberculose Miliar , Tuberculose Pulmonar , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/patologia , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico , Tuberculose Miliar/patologiaRESUMO
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.
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Granulomatose com Poliangiite , Nódulos Pulmonares Múltiplos , Sarcoidose Pulmonar , Sarcoidose , Vasculite do Sistema Nervoso Central , Adulto , Feminino , Glucocorticoides , Granulomatose com Poliangiite/diagnóstico , Humanos , Pessoa de Meia-Idade , Mieloblastina , Necrose/diagnóstico , Peroxidase , Sarcoidose/diagnóstico , Sarcoidose/patologia , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologiaRESUMO
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.
Assuntos
Sarcoidose Pulmonar , Sarcoidose , Tuberculose Pleural , Tuberculose Pulmonar , Vasculite do Sistema Nervoso Central , Idoso , Feminino , Granuloma/diagnóstico , Humanos , Inflamação/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Necrose/patologia , Sarcoidose/diagnóstico , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/patologia , Tuberculose Pulmonar/patologiaRESUMO
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.
Assuntos
COVID-19 , Sarcoidose Pulmonar , Sarcoidose , Humanos , Masculino , Pandemias , SARS-CoV-2 , Sarcoidose/patologia , Sarcoidose Pulmonar/induzido quimicamente , Sarcoidose Pulmonar/diagnóstico por imagem , Sarcoidose Pulmonar/patologiaRESUMO
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.
Assuntos
Hipofisite Autoimune , Diabetes Insípido Neurogênico , Hipopituitarismo , Sarcoidose Pulmonar , Sarcoidose , Hipofisite Autoimune/diagnóstico , Hipofisite Autoimune/tratamento farmacológico , Diabetes Insípido Neurogênico/diagnóstico , Humanos , Hipopituitarismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Hipófise/patologia , Sarcoidose/complicações , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/patologiaRESUMO
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.