Universal Germline Panel Testing for Individuals with Pheochromocytoma and Paraganglioma Produces High Diagnostic Yield

Background Practice guidelines to identify individuals with hereditary pheochromocytomas and paragangliomas (PPGLs) advocate for sequential gene testing strategy guided by specific clinical features and predate the routine use of multigene panel testing (MGPT). Objective To describe results of MGPT for hereditary PPGL in a clinically and ancestrally diverse cohort. Setting Commercial laboratory based in the United States. Methods Clinical data and test results were retrospectively reviewed in 1727 individuals who had targeted MGPT due to suspicion of hereditary PPGL from August 2013 through December 2019. Results Overall, 27.5% of individuals had a pathogenic or likely pathogenic variant (PV), 9.0% had a variant of uncertain significance, and 63.1% had a negative result. Most PVs were identified in SDHB (40.4%), followed by SDHD (21.1%), SDHA (10.1%), VHL (7.8%), SDHC (6.7%), RET (3.7%), and MAX (3.6%). PVs in FH, MEN1, NF1, SDHAF2, and TMEM127 collectively accounted for 6.5% of PVs. Clinical predictors of a PV included extra-adrenal location, early age of onset, multiple tumors, and positive family history of PPGL. Individuals with extra-adrenal PGL and a positive family history were the most likely to have a PV (85.9%). Restricting genetic testing to SDHB/C/D misses a third (32.8%) of individuals with PVs. Conclusion Our data demonstrate a high diagnostic yield in individuals with and without established risk factors, a low inconclusive result rate, and a substantial contribution to diagnostic yield from rare genes. These findings support universal testing of all individuals with PPGL and the use of concurrent MGPT as the ideal platform.

Optimization of the Lung Biopsy Procedure: A Primer

Image-guided lung biopsy plays a very important role in the diagnosis and management of lung lesions. As a diagnostic tool, it demands a high diagnostic yield and a low complication rate. It is imperative to balance the diagnostic yield and patient safety during lung biopsies. The aim of this article is to review the standard practice guidelines of lung biopsy, to describe the techniques used to minimize the complications associated with lung biopsy, and to describe the management of complications.

Diagnostic Peritoneal Aspirate Revisited: Its Diagnostic Accuracy for the Detection of Intraabdominal Hemorrhage

Background The use of Focused Assessment with Sonography for Trauma (FAST) in combination with computed tomography (CT) has become the mainstay of diagnostic workup in patients with suspected intraabdominal hemorrhage (IAH). However, diagnostic peritoneal aspirate (DPA) can be an important adjunct in hemodynamically unstable patients. The aim of this study was to evaluate the utility and diagnostic accuracy of DPA in detecting IAH. Methods Retrospective analysis of all patients who presented to the LAC+USC Medical Center and underwent evaluation with DPA between January 2010 and December 2016. Intraoperative, CT, and autopsy findings were used as gold standards in determining the diagnostic accuracy of DPA for the detection of IAH. Results A total of 73 consecutive patients were included in the study. The median age was 42 years (interquartile range [IQR]: 25-56), median injury severity score was 29 (IQR: 21-41), and 82.2% sustained blunt trauma. The most common indications for DPA were hemodynamically unstable patients with suspected IAH and patients with return of spontaneous circulation following resuscitative thoracotomy. Overall, the positive and negative predictive values of DPA were 89.4% and 88.9%, respectively. In 14 cases (19.2%), DPA correctly identified false positive/negative FAST results. Conclusion Our data suggest that DPA has high diagnostic yield for IAH. The use of DPA should be considered in unstable patients with inconclusive FAST results who cannot safely be evaluated with CT.

Conventional Transbronchial Needle Aspiration (cTBNA) and EBUS-Guided Transbronchial Needle Aspiration (EBUS-TBNA): A Retrospective Study on the Comparison of the Two Methods for Diagnostic Adequacy in Molecular Analysis

Introduction: In recent years, there has been a growing development of molecularly targeted therapies for various types of solid tumors—in particular, in non-small-cell lung cancer (NSCLC). This has required the need for greater quantities of tissue that is able to support ancillary studies, alongside cyto-histological diagnoses for the assessment of molecular targets. Conventional TBNA (cTBNA) and EBUS-guided TBNA (EBUS-TBNA) have shown a high diagnostic yield for malignant mediastinal and/or hilar lymph node enlargement and peribronchial masses; however, few studies have compared these two procedures. We retrospectively compared TBNA patients (EBUS-TBNA and cTBNA) in order to determine the diagnostic yield and material adequacy for subsequent ancillary analyses. Materials and Methods: We retrospectively evaluated 318 patients with clinical suspicion of lung cancer or with disease recurrence. All of the patients underwent TBNA (either EBUS-TBNA or cTBNA) on enlarged mediastinal and/or hilar lymph nodes and peribronchial masses between January 2017 and June 2021 at the University Hospital of Pisa, Italy. After a definitive diagnosis, molecular analyses and an evaluation of PD-L1 expression were performed in the cases of adenocarcinoma, squamous cell carcinoma, and NSCLC, not otherwise specified (NOS). Results: EBUS-TBNA was performed in 199 patients and cTBNA was performed in 119 patients with 374 and 142 lymph nodes, respectively. The overall diagnostic yield for positive diagnoses was 59% (diagnostic rate of 61% in EBUS-TBNA, and 55% in cTBNA). Adenocarcinoma (ADC) was the most frequent diagnosis in both methods. EBUS-TBNA diagnostic adequacy was 72% for molecular analysis, while it was 55.5% for cTBNA, showing a statistical trend (p = 0.08) towards the significance of EBUS. The average percentage of neoplastic cells was also statistically different between the two methods (p = 0.05), reaching 51.19 ± 22.14 in EBUS-TBNA and 45.25 ± 22.84 in cTBNA. With regard to the PD-L1 protein expression, the percentage of positivity was similar in both procedures (86% in EBUS-TBNA, 85% in cTBNA). Conclusions: Conventional TBNA (cTBNA) and EBUS-guided TBNA (EBUS-TBNA) are minimally invasive diagnostic methods that are associated with a high diagnostic yield. However, EBUS-TBNA has an improved diagnostic adequacy for molecular analysis compared to cTBNA, and is associated with a higher average percentage of neoplastic cells.

Genome sequencing demonstrates high diagnostic yield in children with undiagnosed global developmental delay/intellectual disability: a prospective study

Genome sequencing(GS) has been applied in the diagnosis of global developmental delay(GDD)/intellectual disability(ID). However, the performance in those with inconclusive results from chromosomal microarray analysis(CMA) and exome sequencing(ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test prior to enrollment. Reanalysis of CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 23%. Seven families could have been solved with reanalysis of ES data. 13 families were missed by previous CMA/ES due to improper method. Three remained unsolved after ES reanalysis due to allele dropout, complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this cohort of undiagnosed GDD/ID patients, detecting a wide range of variant types of different sizes in a single workflow.

High diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of adolescent pulmonary tuberculosis

Background The microbiological diagnosis of pulmonary tuberculosis (Tb) in a pediatric population is hampered by both low pathogen burden and noncompliance with sputum sampling. Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been found useful for the evaluation of mediastinal pathologies in adults, for children, sparse data are available. Here, we have evaluated EBUS-TBNA as a diagnostic procedure in children and adolescents with suspected pulmonary Tb. Methods In this retrospective analysis, we reviewed the charts of unaccompanied refugee minors (URM) who were admitted between January 2016 and July 2018 and who, during their initial medical screening upon arrival in Germany, were found to have abnormal radiological pulmonary and mediastinal findings and/or immunological results indicative of Tb. For each patient, basic sociodemographic data, clinical features and data on diagnostic procedures performed were assessed. These included imaging, immunodiagnostic tests and microbiological data derived from sputum, bronchoalveolar lavage, EBUS-TBNA, bronchoscopy and pleural fluid sampling. All patients who underwent invasive sampling procedures were included in the study. Results Out of 42 URM with suspected Tb, 34 fulfilled the study’s inclusion criteria. Ages ranged from 14 to 17 years. All were of African origin, with 70.0% coming from Somalia, Eritrea and Ethiopia. Among the 21 patients for whom EBUS-TBNA was performed, the diagnostic yield was high: 66.7% positive results (MTb detected either by acid-fast stain, culture or PCR in 4.8, 42.9 and 61.9% of samples, respectively). Multidrug-resistant MTb was found in two patients from Somalia. No complications were associated with the procedure. Overall, pulmonary Tb was diagnosed in 29 patients (85.3%), miliary Tb in two patients (5.9%) and latent Tb in three patients (8.8%). Conclusions EBUS-TBNA is a sensitive and safe method with high diagnostic yield in the evaluation of pediatric patients with mediastinal pathology and suspected Tb.