Transcriptional Profiling of Endobronchial Ultrasound-Guided Lymph Node Samples Aids Diagnosis of Mediastinal Lymphadenopathy.

BACKGROUND: Endobronchial ultrasound (EBUS)-guided biopsy is the mainstay for investigation of mediastinal lymphadenopathy for laboratory diagnosis of malignancy, sarcoidosis, or TB. However, improved methods for discriminating between TB and sarcoidosis and excluding malignancy are still needed. We sought to evaluate the role of genomewide transcriptional profiling to aid diagnostic processes in this setting. METHODS: Mediastinal lymph node samples from 88 individuals were obtained by EBUS-guided aspiration for investigation of mediastinal lymphadenopathy and subjected to transcriptional profiling in addition to conventional laboratory assessments. Computational strategies were used to evaluate the potential for using the transcriptome to distinguish between diagnostic categories. RESULTS: Molecular signatures associated with granulomas or neoplastic and metastatic processes were clearly discernible in granulomatous and malignant lymph node samples, respectively. Support vector machine (SVM) learning using differentially expressed genes showed excellent sensitivity and specificity profiles in receiver operating characteristic curve analysis with area under curve values > 0.9 for discriminating between granulomatous and nongranulomatous disease, TB and sarcoidosis, and between cancer and reactive lymphadenopathy. A two-step decision tree using SVM to distinguish granulomatous and nongranulomatous disease, then between TB and sarcoidosis in granulomatous cases, and between cancer and reactive lymphadenopathy in nongranulomatous cases, achieved > 90% specificity for each diagnosis and afforded greater sensitivity than existing tests to detect TB and cancer. In some diagnostically ambiguous cases, computational classification predicted granulomatous disease or cancer before pathologic abnormalities were evident. CONCLUSIONS: Machine learning analysis of transcriptional profiling in mediastinal lymphadenopathy may significantly improve the clinical utility of EBUS-guided biopsies.

Rapid diagnosis of mediastinal tuberculosis with polymerase chain reaction evaluation of aspirated material taken by endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic method for tuberculosis (TB). This study was conducted to determine the efficiency of polymerase chain reaction (PCR) testing for detecting TB lymphadenitis in samples obtained by EBUS-TBNA. MATERIALS AND METHODS: A total of 93 consecutive patients with hilar/mediastinal lymphadenopathies and diagnosed with granulomatous diseases through histopathological evaluation were included in the study. The specimens provided by EBUS-TBNA were evaluated through pathological, microbiological, and molecular tests. RESULTS: Eighty-nine (95.7%) of the 93 patients had histopathologically granulomatous diseases by EBUS-TBNA. Tuberculosis was diagnosed in 27 (30.3%) patients and sarcoidosis was diagnosed in 62 (69.7%) patients. Four (4.3%) patients were diagnosed through mediastinoscopy. Endobronchial ultrasound-guided transbronchial needle aspiration had an overall diagnostic efficiency in TB of 96.9%, a sensitivity of 90.9%, and a specificity of 100%. Mycobacterium tuberculosis PCR was positive in 17 of the 30 patients. The sensitivity of PCR was 56.7%, the specificity was 100%, and the general efficiency of the test was 96.4%. CONCLUSIONS: As a result, the use of M. tuberculosis PCR in the EBUS-TBNA specimens provides a rapid and an accurate diagnosis of TB. Therefore, we recommend the use of M. tuberculosis PCR in the EBUS-TBNA specimens as a rapid diagnostic method for mediastinal lymphadenopathies in patients with suspected TB.

Localized mediastinal lymph node amyloidosis showing an unusual unsynchronized pattern of enlargement and calcification on serial CT.

Amyloidosis is an unusual cause of mediastinal lymphadenopathy. A localized form of amyloidosis manifesting solely in the intrathoracic lymphnode is extremely rare. We describe a case of intrathoracic lymphadenopathy caused by a localized form of amyloidosis. Calcification has been reported in amyloidosis; however, it has been considered as non-specific. In our case, serial CT carried out over a period of 3 years and 3 months showed an unusual and unsynchronized pattern of enlargement and calcification.

Familial primary mediastinal nonseminomatous germ-cell tumors.

In this article, we describe the case of 4 brothers, 2 of which had primary mediastinal nonseminomatous germ cell tumors (PMNSGCT), while the other 2 had benign mediastinal disease. We discuss the relationship between these diseases of the mediastinum and the thymic microenvironment. Additionally, we suggest that a genetic predisposition for germ-cell tumors (GCT) may be involved since the parents were relatives.

Mediastinal fibrosis is associated with human leukocyte antigen-A2.

OBJECTIVE: To determine the association between mediastinal fibrosis and human leukocyte antigen (HLA) genes. DESIGN: Case-control study. SETTING: Vanderbilt University Medical Center. SUBJECTS: Nineteen consecutive patients with mediastinal fibrosis who presented to the pulmonary clinic at Vanderbilt University Medical Center from 1987 to 1996. The control subjects were 21,086 whites who were cadaveric kidney donors from October 1987 through December 1993. MEASUREMENTS: HLA testing was performed on blood samples from all 19 cases. Information on HLA typing for the control subjects was obtained from the United Network for Organ Sharing. Frequency of HLA class I and II antigens found in the cases was compared with the frequency in the control subjects. RESULTS: The relative risk of mediastinal fibrosis among subjects with the HLA-A2 antigen was 3.32 times that of those who lacked this antigen (95% confidence interval, 1.19 to 9. 2). CONCLUSION: HLA-A2 was strongly associated with mediastinal fibrosis, suggesting that an abnormal immune response is important in the pathogenesis of this disease. Key words: Histoplasma capsulatum; human leukocyte antigen-A2; mediastinal fibrosis

[Frequency and characters of familial pulmonary sarcoidosis (author's transl)]. / Fréquence et caractères de la sarcoïdose pulmonaire familiale.

A report is given on familial sarcoidosis in four cases. These 4 cases comprise one brother-sister and one mother-son relationship. Brother and sister were young persons in the acute stage (Löfgren-syndrome). In the other two cases diffuse fibroses accompanied by severe functional disturbances were to be observed. In both relationships clinical and radiological picture, course of the illness and response to the treatment were similar: favourable in the first, unfavourable in the second relationship. The frequency of familial occurrence is said to be 3.7% of all sarcoidosis cases.