Diagnosis Of Fibrosing Mediastinitis Research Articles

Characteristics of SPECT/CT-derived pulmonary perfusion imaging in chronic pulmonary vascular stenosis with different etiologies

Objective: To explore the characteristics of pulmonary blood flow perfusion imaging of single photo emission computer tomography/computer tomography (SPECT/CT) in chronic pulmonary vascular Stenosis (CPVS) caused by different etiological factors. Methods: This is a retropective study. Present study screened 50 consecutive cases diagnosed with chronic pulmonary vascular stenosis from January 2019 to January 2020 in the department of cardiology of Gansu Provincial Hospital and underwent SPECT/CT pulmonary blood flow perfusion examination. Thirteen patients were excluded because of pulmonary vascular lesions with a disease course of less than 3 months and poor image quality. According to the etiology, patients were divided into fibrosing mediastinitis (FM) group, Takyasu's arteritis (PTA) group, and chronic thromboembolic pulmonary hypertension/chronic thromboembolic pulmonary disease (CTEPH/CTED) group. The severity of pulmonary blood flow perfusion was evaluated in accordance with the Begic scoring principle in the three groups. The overall Begic score, lung lobe scores among three groups were compared. CT signs of lung SPECT/CT, such as enlargement of hilar lymph node, atelectasis, bronchial stenosis, were also analyzed in three groups. Results: A total of 37 patients with chronic pulmonary vascular stenosis were finally enrolled (18 in the FM group, 5 in the PTA group, and 14 in the CTEPH/CTED group). The total Begic score of pulmonary perfusions was similar among the three groups (F=0.657,P>0.05). There was a statistically significant difference in the left upper lobe Begic score among the three groups (H=4.081, P<0.05). The left upper lobe Begic score was higher in the FM group than in the PTA group (3.44±2.50 vs. 1.60±0.55, P<0.05). As compared to other two groups, patients in FM group were featured with CT signs of higher percent of hilar enlargement (FM group vs. PTA group: 16/18 vs. 1/5, P=0.008; FM group vs. CTEPH/CTED group: 16/18 vs. 3/14, P=0.000 2), enlargement of the pulmonary hilum lymph nodes (FM group vs. PTA group: 14/18 vs. 1/5, P=0.033; FM group vs. CTEPH/CTED group: 14/18 vs. 2/14, P=0.001), and calcification of mediastinal soft tissue (FM group vs. PTA group: 11/18 to 0/5, P=0.037; FM group vs. CTEPH/CTED group: 11/18 vs. 1/14, P=0.003). The proportion of CT signs of bronchial stenosis (9/18 vs. 0/14, P=0.002) and atelectasis (9/18 vs. 1/14, P=0.002) was also higher in the FM group than in the CTEPH/CTED group. In case of abnormal pulmonary blood flow perfusion, the diagnostic accuracy of CT signs hilar enlargement, hilar lymph node enlargement, mediastinal soft tissue calcification, bronchial stenosis, and atelectasis for the diagnosis of FM were 81.1%, 83.8%, 78.4%, 75.7%, and 73.0%, respectively. Conclusion: There is no significant difference in the Begic score of SPECT/CT pulmonary blood flow perfusion imagines among the three groups of patients. Impaired pulmonary blood flow perfusion combined with typical CT signs is useful for identifying patients with FM.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

A ROLLER COASTER RIDE OF IDIOPATHIC FIBROSING MEDIASTINITIS

SESSION TITLE: Medical Student/Resident Disorders of the Mediastinum Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Fibrosing mediastinitis (FM) is a rare benign pulmonary condition characterized by excessive fibrosis in the mediastinum due to an abnormal immune response to infections or inflammatory conditions [1, 2]. CASE PRESENTATION: A 39-year-old man presented to the clinic with a few weeks of left-arm edema with negative ultrasound findings of deep venous thrombosis but found to have axillary lymphadenopathies which warranted further investigation. A chest CT scan revealed a 2.5x2.4 cm round soft tissue mass in the left upper mediastinum that occluded the left brachiocephalic and subclavian vein. Thoracoscopic excisional biopsy of the mass showed hypocellular fibrosis, collagen bands with intervening mesenchymal cells without the presence of Reed-Sternberg cells, granulomas, or morphology suggestive of malignancy. The diagnosis of FM was confirmed by three different Pathologists. Serum antinuclear antibody, histoplasmosis titer, Quantiferon gold tuberculosis assay, and angiotensin-converting enzyme levels were unremarkable. He denied living in or had a travel history to endemic fungal or mycobacterial disease regions. Interval CT scans throughout the next three years showed a stable lung mass without progression. He remained to be clinically stable until he developed right-sided hearing loss due to a transverse sinus thrombosis seen on the cerebral angiogram. A repeat chest CT discovered a new 1.9x1.5 cm spiculated mass in the left upper lung lobe with small satellite nodules adjacent to the previous FM mass. An extensive hypercoagulable workup was unremarkable. The new mass was deemed to be not amenable to navigational bronchoscopy or interventional radiology guided biopsy. He was discharged with anticoagulation and will have repeated imaging studies in the outpatient setting as there were low clinical indications of an urgent biopsy. DISCUSSION: It is extremely rare to have FM with a negative histoplasmosis test result in addition to an extensive unremarkable workup for other potentially related pathologies. Furthermore, there was a low clinical suspicion of a new onset of malignancy in this low-risk patient despite that this new thrombosis could be a prothrombotic effect of malignancy from the new mass or simply just an incidental finding that led to the discovery of the new mass. A few case reports detailed a new lymphoma diagnosed in the setting of an original biopsy-proven FM [3]. However, the new mass could also just be a progression of the original FM given the proximity in location. CONCLUSIONS: Patients with FM are often at a crossroads when there are new suspicious incidental findings found on repeated imaging studies. Close monitoring with interval imaging studies is important and a repeat of invasive biopsy may be required to rule out a possible new malignancy. Reference #1: Rossi SE, McAdams HP, Rosado-de-Christenson ML, et al. Radiographics. 2001;21(3):737-57. PMID: 11353121 https://doi.org/10.1148/radiographics.21.3.g01ma17737. Reference #2: Harman M, Sayarlioglu M, Arslan H, et al. Fibrosing Mediastinitis and Thrombosis of Superior Vena Cava Associated With Behçet's Disease. Eur J Radiol 2003; 48(2):209-12. PMID: 14680916 https://doi.org/10.1016/S0720-048X(0300006-8). Reference #3: Kakuta N, Sumitani M, Sugitani A, et al. Mediastinal Peripheral T-cell Lymphoma Diagnosed by Repeated Biopsies After an Initial Diagnosis of Fibrosing Mediastinitis. Respirol Case Rep 2017;5(6):e00272. PMID: 28932400 https://doi.org/10.1002/rcr2.272. DISCLOSURES: No relevant relationships by Khine Shan, source=Web Response No relevant relationships by Qian Zhang, source=Web Response

FIBROSING MEDIASTINITIS AND RHEUMATOID ARTHRITIS: AN AUTOIMMUNE INFLAMMATORY CONNECTION

SESSION TITLE: Disorders of the Mediastinum 2 SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/10/2018 10:45 am - 11:45 am INTRODUCTION: Fibrosing mediastinitis (FM) is a rare condition characterized by an aggressive fibrotic reaction in the mediastinum. In the United States, the disorder is most commonly seen in patients with a prior infection with Histoplasma capsulatum, presumably due to an excessive immune response. This immune response has been associated with IgG4 and autoimmune disorders. We present a case of a patient with post-infectious FM who subsequently developed seropositive rheumatoid arthritis. CASE PRESENTATION:A 53-year-old gentleman with asthma and recurrent pneumonia presented to our hospital with worsening dyspnea and wheezing. Computed tomography (CT) scan of the chest demonstrated extensive calcified mediastinal lymph nodes with soft tissue encasement of multiple central and segmental bronchi (Image 1 and 2). Additionally, calcified granulomas were noted in the right middle and lingular lobes as well as the liver and spleen. Findings were consistent with a radiographic diagnosis of post-infectious FM. However, infectious workup was negative, including Histoplasma antigen and antibody. Autoimmune workup was also unrevealing. Transbronchial biopsy demonstrated reactive pneumocytes with chronic inflammation and scattered areas of fibrosis. The patient was started on high dose steroids with initial improvement in symptoms; however, he relapsed once tapered off steroids. Two years after the initial presentation, the patient was hospitalized with joint pain and swelling in his hands and right shoulder along with dyspnea and pleuritic chest pain. Cyclic citrullinated peptide antibodies were strongly positive at this time. Rheumatoid arthritis (RA) was diagnosed and controlled with steroids. Progressive pulmonary symptoms prompted rituximab therapy with some stabilization of his disease. DISCUSSION: There is growing evidence that FM is an immune-mediated disorder, yet the etiology remains unknown. A histopathological similarity between FM and IgG4-related disease has been observed, and other autoimmune conditions are associated with FM (1,2). These findings suggest a common pathogenesis or pathway of chronic inflammation. Autoimmune antibodies in RA can activate IgG4, which may perpetuate inflammation by complement activation (3). Immune-targeted therapies likely have a role in the treatment of FM. Patients with FM should be screened for systemic autoimmune disease at diagnosis although new conditions may develop over the course of time as seen in our patient. CONCLUSIONS: We present the unique case of a patient with FM who subsequently developed a systemic autoimmune disease. An association between RA and FM has not been previously reported in the literature. These diseases may share a common pathway of immune-mediated inflammation. Reference #1: Peikert, T et al. Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease. International Journal of Rheumatology 2012 2012:1-7 Reference #2: Rossi, GM et al. Idiopathic Mediastinal Fibrosis: a Systemic Immune-Mediated Disorder. A Case Series and a Review of the Literature. Clinic Rev Allerg Immunol 2017;52:446-459 Reference #3: van de Stadt, LA et al. Antibodies to IgG4 Hinge Can Be Found in Rheumatoid Arthritis Patients During All Stages of Disease and May Exacerbate Chronic Antibody-Mediated Inflammation. Arthritis & Rheumatology 2014,66:1133–1140 DISCLOSURES: No relevant relationships by Timothy Hotze, source=Web Response No relevant relationships by Anthony McClafferty, source=Web Response no disclosure on file for Purvesh Patel

Mediastinal peripheral T‐cell lymphoma diagnosed by repeated biopsies after an initial diagnosis of fibrosing mediastinitis

We report a case of mediastinal peripheral T‐cell lymphoma not otherwise specified (PTCL‐NOS) diagnosed by repeated biopsies. A 44‐year‐old man was admitted to our hospital with a 2‐week history of facial swelling, neck distension, and dyspnoea on exertion. Computed tomography of the chest showed a mediastinal mass. Initial needle biopsy and video‐assisted thoracoscopic biopsy revealed the pathological diagnosis of fibrosing mediastinitis (FM). Glucocorticoid therapy (prednisolone) was temporarily effective in reducing tumour size. However, other laboratory features suggested that the diagnosis of FM might not be correct. After repeated biopsies, we established the diagnosis of mediastinal PTCL‐NOS. With this correct diagnosis, appropriate therapy for PTCL resulted in the improvement of the clinical manifestations. This report suggests that the presence of malignant lymphoma should be considered in cases of mediastinal tumours, and repeated biopsies may be occasionally needed for consistent diagnosis.

Fibrosing Mediastinitis

Fibrosing mediastinitis (FM) is a rare disorder characterized by the invasive proliferation of fibrous tissue within the mediastinum. FM frequently results in the compression of vital mediastinal structures and has been associated with substantial morbidity and mortality. Its pathogenesis remains unknown. However, in North America most cases are thought to represent an immune-mediated hypersensitivity response to Histoplasma capsulatum infection. To characterize the clinical disease spectrum, natural disease progression, responses to therapy, and overall survival, we retrospectively analyzed all 80 consecutive patients with a diagnosis of FM evaluated at Mayo Clinic, Rochester, MN, from 1998 to 2007. Furthermore, we characterized the adaptive immune response in 15 representative patients by immunohistochemistry. The majority of patients presented with nonspecific respiratory symptoms due to the compression of mediastinal broncho-vascular structures. Chest radiographic imaging most frequently revealed localized, invasive, and frequently calcified right-sided mediastinal masses. Most patients had radiographic or serologic evidence of previous histoplasmosis. In contrast to earlier reports summarizing previously reported FM cases, the clinical course of our patients appeared to be more benign and less progressive. The overall survival was similar to that of age-matched controls. There were only 5 deaths, 2 of which were attributed to FM. These differences may reflect publication bias associated with the preferential reporting of more severely affected FM patients in the medical literature, as well as the more inclusive case definition used in our consecutive case series. Surgical and nonsurgical interventions effectively relieved symptoms caused by the compression of mediastinal vascular structures in these carefully selected patients. In contrast, antifungal and antiinflammatory agents appeared ineffective. Histologic examination and immunostaining revealed mixed inflammatory infiltrates consistent with a fibroinflammatory tissue response in these histoplasmosis-associated FM cases. The immune cell infiltrates included large numbers of CD20-positive B lymphocytes. As B lymphocytes may contribute to the pathogenesis of the disease, therapeutic B-cell depletion should be investigated as a therapeutic strategy for FM.