Necrotizing sarcoid granulomatosis simulating pulmonary malignancy: A case report.

RATIONALE: Necrotizing sarcoid granulomatosis (NSG) has recently been termed "sarcoidosis with NSG pattern" for the disease entity representing nodular sarcoidosis with granulomatous pulmonary angiitis. It is characterized by sarcoid-like granulomas, vasculitis, and a variable degree of necrosis. Its rarity and nonspecific clinical symptoms can easily lead to misdiagnosis or delayed diagnosis. PATIENT CONCERNS: We report a 67-year-old female with a biopsy-confirmed sarcoidosis with NSG pattern mimicking pulmonary malignancy on initial chest computed tomography scan. DIAGNOSES: Sarcoidosis with NSG pattern. INTERVENTIONS: The patient underwent video-assisted thoracoscopic surgery with a lung biopsy. No further treatment was performed after the lung biopsy. OUTCOMES: Follow-up imaging studies revealed spontaneous regression of the disease after 2 months. LESSONS: Awareness of this rare benign disease entity and overlapping radiologic manifestations with pulmonary malignancy or other granulomatous diseases can be helpful for making a precise diagnosis with a better differential diagnosis.

Lung transplantation for sarcoidosis: outcome and prognostic factors.

STUDY QUESTION: In patients with sarcoidosis, past and ongoing immunosuppressive regimens, recurrent disease in the transplant and extrapulmonary involvement may affect outcomes of lung transplantation. We asked whether sarcoidosis lung phenotypes can be differentiated and, if so, how they relate to outcomes in patients with pulmonary sarcoidosis treated by lung transplantation. PATIENTS AND METHODS: We retrospectively reviewed data from 112 patients who met international diagnostic criteria for sarcoidosis and underwent lung or heart-lung transplantation between 2006 and 2019 at 16 European centres. RESULTS: Patient survival was the main outcome measure. At transplantation, median (interaquartile range (IQR)) age was 52 (46-59) years; 71 (64%) were male. Lung phenotypes were individualised as follows: 1) extended fibrosis only; 2) airflow obstruction; 3) severe pulmonary hypertension (sPH) and airflow obstruction; 4) sPH, airflow obstruction and fibrosis; 5) sPH and fibrosis; 6) airflow obstruction and fibrosis; 7) sPH; and 8) none of these criteria, in 17%, 16%, 17%, 14%, 11%, 9%, 5% and 11% of patients, respectively. Post-transplant survival rates after 1, 3, and 5 years were 86%, 76% and 69%, respectively. During follow-up (median (IQR) 46 (16-89) months), 31% of patients developed chronic lung allograft dysfunction. Age and extended lung fibrosis were associated with increased mortality. Pulmonary fibrosis predominating peripherally was associated with short-term complications. ANSWER TO THE STUDY QUESTION: Post-transplant survival in patients with pulmonary sarcoidosis was similar to that in patients with other indications for lung transplantation. The main factors associated with worse survival were older age and extensive pre-operative lung fibrosis.

Distinct Airway Involvement in Subtypes of End-Stage Fibrotic Pulmonary Sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease that in most patients affects the lung. Pulmonary fibrotic sarcoidosis is clinically, radiologically, and pathologically a heterogeneous condition. Although substantial indirect evidence suggests small airways involvement, direct evidence currently is lacking. RESEARCH QUESTION: What is the role of the (small) airways in fibrotic sarcoidosis? STUDY DESIGN AND METHODS: Airway morphologic features were investigated in seven explant lungs with end-stage fibrotic sarcoidosis using a combination of CT scanning (large airways), micro-CT scanning (small airways), and histologic examination and compared with seven unused donor lungs as controls with specific attention focused on different radiologically defined sarcoidosis subtypes. RESULTS: Patients with central bronchial distortion (n = 3), diffuse bronchiectasis (n = 3), and usual interstitial pneumonia pattern (n = 1) were identified based on CT scan, showing a decrease and narrowing of large airways, a similar airway number and increased airway diameter of more distal airways, or an increase in airway number and airway diameter, respectively, compared with control participants. The number of terminal bronchioles per milliliter and the total number of terminal bronchioles were decreased in all forms of fibrotic sarcoidosis. Interestingly, the number of terminal bronchioles was inversely correlated with the degree of fibrosis. Furthermore, we identified granulomatous remodeling as a cause of small airways loss using serial micro-CT scanning and histologic examination. INTERPRETATION: The large airways are involved differentially in subtypes of sarcoidosis, but the terminal bronchioles universally are lost. This suggests that small airways loss forms an important aspect in the pathophysiologic features of fibrotic pulmonary sarcoidosis.

Imaging and the Lung Transplant Patient.

Lung transplantation can prolong and improve quality of life for patients affected by end-stage lung disease. Potential lung transplant patients undergo a rigorous preoperative assessment that includes multiple medical imaging studies. These studies provide information that help physicians determine whether the patient is a surgical candidate, as well as the surgical technique that should be used during transplantation. Imaging studies also are used in long-term care to detect complications in patients after lung transplantation.

Lung transplantation for pulmonary sarcoidosis.

Although relatively few patients with pulmonary sarcoidosis develop advanced disease that progresses to respiratory insufficiency despite receiving best practice pharmacologic interventions, lung transplantation may be the only therapeutic option for such patients to both prolong survival and provide improved quality of life. Lung transplant can be successfully performed for patients with end-stage pulmonary sarcoidosis, and post-transplant survival is similar to that for other transplant indications such as idiopathic pulmonary fibrosis. However, appropriate timing of referral, comprehensive assessment of potential candidates for lung transplant, placement of patients on the lung transplant waiting list when within the transplant window as appropriate, choosing the best procedure (bilateral versus single lung transplant), and optimal peri-operative and post-transplant management are key to successful lung transplant outcomes for patients with sarcoidosis.

[Mediastinitis following endobronchial ultrasound-guided transbronchial needle aspiration]. / Médiastinite au décours d'une échoendoscopie bronchique (EEB) avec cyto-aspiration ganglionnaire.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure designed to explore mediastinal lymphadenopathy. Its use and indications have increased recently and severe, though rare, complications have been reported. CASE REPORT: EBUS-TBNA was performed in a 64-year-old patient presenting with mediastinal lymphadenopathy, probably due to sarcoidosis, but without histological proof. Within hours of the aspiration of subcarinal lymph nodes (station 7), the patient developed fever and dry cough associated with progressive dysphagia and dysphonia that persisted for four weeks. Mediastinitis was diagnosed after a CT-scan revealed a collection in the subcarinal space previously tapped using CT guidance. Intravenous antibiotics were started and both symptoms and the mediastinal collection resolved without need of a surgical procedure. The patient recovered fully. CONCLUSION: EBUS-TBNA is associated with a risk of mediastinitis that may manifest as an isolated fever arising within hours of the procedure. The pathogens responsible are usually contaminants from the oropharynx such as Streptococcus sp, probably inoculated directly into the mediastinum during transbronchial needle aspiration. Rapid diagnosis and treatment are necessary in order to reduce morbidity and mortality associated with mediastinitis.

Necrotizing Sarcoid Granulomatosis with Natural Resolution after a Surgical Lung Biopsy.

Necrotizing sarcoid granulomatosis (NSG) is a rare disease that is diagnosed based on pathological findings. We herein report the case of a 27-year-old man who had multiple nodular shadows in bilateral lung fields on chest radiography and elevated levels of C-reactive protein (CRP). The pathological evaluation of a lung biopsy specimen showed the infiltration of lymphocytes, granulomas with necrosis and granulomatous angiitis. He was therefore diagnosed with NSG. He has been followed without treatment, as his fever and CRP levels decreased immediately after the surgical lung biopsy. Thereafter, the pulmonary nodular shadows gradually recovered without any treatment within a few months. Our experience suggests the possibility that surgical invasion might trigger an improvement in disease activity.

[Multiple Pulmonary Sclerosing Pneumocytoma with Abnormal Accumulation of Fluorodeoxyglucose-positron Emission Tomography Diagnosed by Surgical Treatment;Report of a Case].

A 36-year-old Chinese woman was referred to our hospital for further examination of an abnormal shadow on chest X-ray. Chest computed tomography(CT) revealed a 5 mm circular nodule in diameter in right lung S3 and a 32 mm mass in diameter in right lung S7. The S7 mass showed an abnormal accumulation of SUVmax=4.0 on positron emission tomography( PET)-CT. Transbronchial biopsy was performed, but failed to rule out possible malignancy. Differential diagnoses were multiple lung benign tumor, multiple lung metastases from unknown primary cancer, malignant lymphoma or primary lung cancer, and so on. We performed surgical resection for diagnosis. She underwent lung partial resection of S3 at 1st, and the intraoperative diagnosis of carcinosarcoma was made. Therefore, we performed additional lobectomy of the right lower lobe and mediastinum lymph node dissection. The postoperative course was uneventful. Pathological diagnosis was both pulmonary sclerosing pneumocytoma. No findings of recurrence have been detected at 1-year postoperatively.

Lung transplantation for pulmonary sarcoidosis. Twenty-five years of experience in the USA.

OBJECTIVE: Lung transplantation is the ultimate treatment for end-stage pulmonary sarcoidosis. Post-transplant survival outcomes remain unclear. METHODS: Survival models were used to assess survival and graft outcomes in patients with sarcoid among 20,896 lung transplants performed in the USA. RESULTS: 695 lung recipients were transplanted for pulmonary sarcoidosis. Sarcoid lung recipients had similar median survival rate (69.7 months (IQR 60.2-79.3)) compared with the non-sarcoid lung recipients (63.1 months (IQR 61.4-64.8), p=0.88). In multivariate Cox regression, sarcoidosis was not independently associated with worse mortality (HR 0.96 (95% CI 0.85 to 1.08), p=0.51). Among the sarcoid lung recipients, double lung transplantation (HR 0.76 (0.58 to 0.99), p=0.04) and lung allocation score era (HR 0.74 (0.56 to 0.97), p=0.03) were associated with improved survival. CONCLUSIONS: Recipients of lung transplants for pulmonary sarcoidosis had similar outcomes compared with non-sarcoid lung recipients.

Hypoxic Gene Expression of Donor Bronchi Linked to Airway Complications after Lung Transplantation.

RATIONALE: Central airway stenosis (CAS) after lung transplantation has been attributed in part to chronic airway ischemia; however, little is known about the time course or significance of large airway hypoxia early after transplantation. OBJECTIVES: To evaluate large airway oxygenation and hypoxic gene expression during the first month after lung transplantation and their relation to airway complications. METHODS: Subjects who underwent lung transplantation underwent endobronchial tissue oximetry of native and donor bronchi at 0, 3, and 30 days after transplantation (n = 11) and/or endobronchial biopsies (n = 14) at 30 days for real-time polymerase chain reaction of hypoxia-inducible genes. Patients were monitored for 6 months for the development of transplant-related complications. MEASUREMENTS AND MAIN RESULTS: Compared with native endobronchial tissues, donor tissue oxygen saturations (Sto2) were reduced in the upper lobes (74.1 ± 1.8% vs. 68.8 ± 1.7%; P < 0.05) and lower lobes (75.6 ± 1.6% vs. 71.5 ± 1.8%; P = 0.065) at 30 days post-transplantation. Donor upper lobe and subcarina Sto2 levels were also lower than the main carina (difference of -3.9 ± 1.5 and -4.8 ± 2.1, respectively; P < 0.05) at 30 days. Up-regulation of hypoxia-inducible genes VEGFA, FLT1, VEGFC, HMOX1, and TIE2 was significant in donor airways relative to native airways (all P < 0.05). VEGFA, KDR, and HMOX1 were associated with prolonged respiratory failure, prolonged hospitalization, extensive airway necrosis, and CAS (P < 0.05). CONCLUSIONS: These findings implicate donor bronchial hypoxia as a driving factor for post-transplantation airway complications. Strategies to improve airway oxygenation, such as bronchial artery re-anastomosis and hyperbaric oxygen therapy merit clinical investigation.

Histopathology of Explanted Lungs From Patients With a Diagnosis of Pulmonary Sarcoidosis.

BACKGROUND: Pathologic features of end-stage pulmonary sarcoidosis (ESPS) are not well defined; anecdotal reports have suggested that ESPS may mimic usual interstitial pneumonia (UIP). We hypothesized that ESPS has distinct histologic features. METHODS: Twelve patients who received a diagnosis of pulmonary sarcoidosis and underwent lung transplantation were included. Control subjects were 10 age- and sex-matched lung transplant patients with UIP. Hematoxylin and eosin-stained tissue sections were examined for the following features: extent/pattern of fibrosis; presence and quantity (per 10 high-power fields) of fibroblast foci and granulomas; distribution and morphology of granulomas; and presence and extent of honeycomb change. Extent of fibrosis and honeycomb change in lung parenchyma was scored as follows: 1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%; 4 = 76% to 100% of lung parenchyma. RESULTS: Eight of 12 cases demonstrated histologic findings typical of ESPS. All showed well-formed granulomas with associated fibrosis distributed in a distinct lymphangitic fashion. Granulomas were present in hilar or mediastinal lymph nodes from six of six patients with ESPS and none of eight control subjects. The extent of fibrosis, honeycomb change, and fibroblast foci was significantly lower in ESPS cases compared with control cases. Two patients with remote histories of sarcoidosis showed histologic features of diseases other than ESPS (UIP and emphysema) without granulomas. Two patients with atypical clinical findings demonstrated nonnecrotizing granulomas combined with either severe chronic venous hypertension or UIP. CONCLUSIONS: ESPS and UIP have distinct histopathologic features in the lungs. Patients with a pretransplant diagnosis of sarcoidosis may develop other lung diseases that account for their end-stage fibrosis.

Significance of granulomatous inflammation in usual interstitial pneumonia.

Sarcoidosis is a systemic granulomatous disease of unclear etiology with characteristic pulmonary lesions. We describe 2 unique cases of sarcoidosis where after approximately 20 years of clinical quiescence, patients developed interstitial opacities on chest CT scan and an increase in shortness of breath. With lack of therapeutic response to a course of prednisone, both patients underwent a surgical lung biopsy that revealed a pattern consistent with Usual Interstitial Pneumonia (UIP) with honeycombing and fibroblastic foci. Postoperatively, the course of the disease was consistent with what would be expected in Idiopathic Pulmonary Fibrosis. Ultimately the disease progressed with one patient needed lung transplantation and the other requiring high-flow oxygen supplementation. In conclusion, we present two patients in whom a diagnosis of sarcoidosis preceded the diagnosis of UIP by 20 years or more. The subsequent course of disease in both patients was consistent with Idiopathic Pulmonary Fibrosis.

Disease Recurrence and Acute Cellular Rejection Episodes During the First Year After Lung Transplantation Among Patients With Sarcoidosis.

INTRODUCTION: Sarcoidosis is reported to recur after lung transplantation (LT). We sought to determine the frequency of recurrent disease after LT and predictors of recurrence. We also evaluated the incidence and severity of acute cellular rejection (ACR) episodes among these patients. METHODS: The database of LT patients at Cleveland Clinic was interrogated for sarcoidosis patients who underwent LT between May 1993 and 2011. Charts were reviewed for demographics, type of transplant, posttransplant biopsy findings, and outcomes. RESULTS: Data were available for 30 patients (mean age, 50 ± 9.3 years; range, 30-65 years; M-to-F ratio, 17:13; single-to-double-to-heart lung ratio, 5:24:1). Recurrence of sarcoidosis was noted among 7 patients (pathological recurrence in all and radiological findings suggesting recurrence in 1 patient) with no impact on overall outcomes. Presence of granulomas on explanted lungs was the only predictor of recurrence (85.7% vs 30.4%, odds ratio, 13.7; 1.4-136.2; P = 0.02).Overall burden of ACR episodes on all bronchoscopies was significantly lower in patients with disease recurrence (7.6 % vs 21.3% of biopsies, P = 0.038). Among patients with recurrent disease, ACR did not develop once disease recurrence had been seen on transbronchial biopsy. CONCLUSIONS: A significant proportion of sarcoidosis patients have disease recurrence after LT and presence of active granulomas on explant is associated with subsequent recurrence. There may be an association of recurrence with lower frequency of ACR episodes. There does not appear to be any impact of sarcoidosis recurrence on 1-, 3-, or 5-year survivals.

Videomediastinoscopy: a ten year experience on lung cancer stadiation and non-diagnosed mediastinal lymphoadenopathy.

Cervical Mediastinoscopy (CM) is a surgical procedure in it's own right requiring an operating room and general anesthesia and, in the recent past, the absence of minimally invasive techniques had created the myth of mediastinoscopy as the "gold standard" for the pathological staging of the mediastinum. Nowadays, investigating the mediastinum is different and this calls for a review of the role of the "gold standard" CM. Between January 1999 and December 2012 a total of 303 CM were performed; 167 for pre-operative lung cancer stadiation and 136 for non-diagnosed enlargement of mediastinal nodes. The nodal stations investigated where those usually obtainable with CM. Out of 167 CM for lung cancer stadiation, 102 were positive for metastatic nodal disease, 65 were negative. Out of 136 VAMs performed for other reason (indications other than lung cancer) 15 were diagnostic for lymphoma (NLH LH 2 4), 8 revealed non metastatic lung disease, 55 were suggestive for sarcoidosis, 10 for tubercular adenitis and 48 for non-specific adenitis. The data presented in this paper refer to the activity of a single institution in the period between 1999 and 2012 and the results we have extrapolated correspond with our idea that, despite the progress of new methods, we cannot as yet, do without mediastinoscopy.

Recurrence of sarcoid granulomas in lung transplant recipients is common and does not affect overall survival.

BACKGROUND: Sarcoidosis represents 2,5% of all indications for lung transplantation and criteria are generally assumed to be the same as for pulmonary fibrosis. Recurrence of granulomas in transplanted lungs has earlier been proved to derive from recipient immune cells, but its role in relation to lung function and overall survival after lung transplantation remains uncertain. OBJECTIVE: To identify recurrent granuloma in transbronchial biopsies in patients receiving lung transplant because of sarcoidosis, and relate the findings to overall survival and lung function. DESIGN: A total of 620 patients were transplanted at this centre from 1992 until august 2012. This study comprised all patients (n=25) transplanted due to pulmonary sarcoidosis. Lung functions, trans-bronchial biopsies, and survival were compared in patients with and without recurrence of granulomas. Granulomas were defined as non-necrotizing epitheloid granulomas with multinucleated giant cells according to standard criteria (formation of epitheloid giant cells) without presence of infection. CONCLUSIONS: Approximately 30% of lung transplant recipients due to sarcoidosis have recurrence of sarcoid granulomas. Recurrence of granulomas does not affect overall survival or lung function.