Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules.

CONTEXT: - Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant. OBJECTIVE: - To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material. DESIGN: - A total of 24 residual needle rinse specimens with malignant (n = 6), indeterminate (n = 9), or benign (n = 9) thyroid FNA diagnoses were analyzed in our clinical molecular diagnostics laboratory using next-generation sequencing assays designed to detect gene mutations and translocations that commonly occur in thyroid cancer. Results were correlated with surgical diagnoses and clinical outcomes. RESULTS: - Interpretable data were generated from 23 of 24 residual needle rinse specimens. Consistent with its well-known role in thyroid malignancy, BRAF V600E mutations were detected in 4 malignant cases. An NRAS mutation was detected in 1 benign case. No mutations were detected from specimens with indeterminate diagnoses. CONCLUSIONS: - Our data demonstrate that residual thyroid FNA needle rinses are an adequate source of material for molecular diagnostic testing. Importantly, detection of a mutation implicated in thyroid malignancy was predictive of the final surgical diagnosis and clinical outcome. Our strategy to triage thyroid nodules with indeterminate cytology with molecular testing eliminates the need to perform additional FNA passes into dedicated media or to schedule additional invasive procedures. Further investigation with a larger sample size to confirm the clinical utility of our proposed strategy is underway.

Comparison between cytologic examination of fungi in bronchial washings and bronchoalveolar lavage specimens and culture: a review of 100 cases with emphasis on diagnostic pitfalls.

INTRODUCTION: Microbiology culture is the "gold standard" for diagnosis of fungal infections; however, culture has a lengthy turnaround time. A more timely assessment is possible with cytology and Gomori-methamine silver (GMS) staining. MATERIALS AND METHODS: A total of 100 respiratory tract specimens with a positive fungal Gomori-methamine silver stain and corresponding culture were selected. The cytology slides were reviewed for factors contributing to discrepant results. Specimens were classified as 2 types of variances: interpretative and sampling. Concordant diagnoses were also evaluated. RESULTS: Eighty-two cases had fungal organisms that grew in culture. The remaining 18 cases were composed solely of fungal organisms that did not grow in culture (17 cases with Pneumocystis jirovecii; 1 case with Pityrosporum ovale). These 18 cases were excluded from the variance analysis. Thirty-three of 82 cases (40%) had concordant cytology and microbiology results, whereas 49 cases were discrepant. Variances were both sampling (41 cases) and interpretive (8 cases). Interpretive variances were predominantly Aspergillus species misinterpreted as Candida. Difficulty identifying true septate hyphae was the major contributing factor for misinterpretation. CONCLUSIONS: Cytologic evaluation of respiratory specimens remains a useful preemptive diagnostic tool in the rapid diagnosis of fungal infection. Cytology samples significantly contribute to the diagnosis of respiratory fungi. However, interpretive variances between Aspergillus and Candida organisms are common. Awareness of the characteristic features that distinguish fungal organisms can further improve the diagnostic utility of cytology.