Genomic landscape of TCRαß and TCRγδ T-large granular lymphocyte leukemia.

Large granular lymphocyte (LGL) leukemia comprises a group of rare lymphoproliferative disorders whose molecular landscape is incompletely defined. We leveraged paired whole-exome and transcriptome sequencing in the largest LGL leukemia cohort to date, which included 105 patients (93 T-cell receptor αß [TCRαß] T-LGL and 12 TCRγδ T-LGL). Seventy-six mutations were observed in 3 or more patients in the cohort, and out of those, STAT3, KMT2D, PIK3R1, TTN, EYS, and SULF1 mutations were shared between both subtypes. We identified ARHGAP25, ABCC9, PCDHA11, SULF1, SLC6A15, DDX59, DNMT3A, FAS, KDM6A, KMT2D, PIK3R1, STAT3, STAT5B, TET2, and TNFAIP3 as recurrently mutated putative drivers using an unbiased driver analysis approach leveraging our whole-exome cohort. Hotspot mutations in STAT3, PIK3R1, and FAS were detected, whereas truncating mutations in epigenetic modifying enzymes such as KMT2D and TET2 were observed. Moreover, STAT3 mutations co-occurred with mutations in chromatin and epigenetic modifying genes, especially KMT2D and SETD1B (P < .01 and P < .05, respectively). STAT3 was mutated in 50.5% of the patients. Most common Y640F STAT3 mutation was associated with lower absolute neutrophil count values, and N647I mutation was associated with lower hemoglobin values. Somatic activating mutations (Q160P, D170Y, L287F) in the STAT3 coiled-coil domain were characterized. STAT3-mutant patients exhibited increased mutational burden and enrichment of a mutational signature associated with increased spontaneous deamination of 5-methylcytosine. Finally, gene expression analysis revealed enrichment of interferon-γ signaling and decreased phosphatidylinositol 3-kinase-Akt signaling for STAT3-mutant patients. These findings highlight the clinical and molecular heterogeneity of this rare disorder.

Functional Speech and Voice Disorders: Case Series and Literature Review.

BACKGROUND: Functional disorders of speech and voice, subtypes of functional movement disorders, represent abnormalities in speech and voice that are thought to have an underlying psychological cause. These disorders exhibit several positive and negative features that distinguish them from organic disorders. METHODS AND RESULTS: We describe the clinical manifestations of functional disorders of speech and voice, and illustrate these features using six clinical cases. CONCLUSIONS: Functional disorders of speech and voice may manifest in a variety of ways, including dysphonia, stuttering, or prosodic abnormalities. Given that these disorders have been understudied and may resemble organic disorders, diagnosis may be challenging. Appropriate treatment may be quite effective, highlighting the importance of prompt and accurate diagnosis.

Time-of-day effect and the yield of endoscopic ultrasound fine needle aspiration.

BACKGROUND AND OBJECTIVES: The timing of the endoscopic procedures has been recently proposed to be a factor in the quality of colonoscopic polyp detection. We aimed to investigate whether the time-of-day has an effect on the diagnostic yield and specimen adequacy of endoscopic ultrasound fine needle aspiration (EUS-FNA). MATERIALS AND METHODS: The retrospective study was set in a safety net community hospital. The 212 EUS-FNAs performed at our institution between July 2011 and January 2014 were retrospectively analyzed. Pancreatic masses, pancreatic cysts, and lymphadenopathy were most common indications for EUS-FNAs. Data were collected with regard to the timing of the procedure, presence of on-site cytopathologic evaluation, the number of needle passes, diagnosis, and specimen adequacy for cytopathologic evaluation. Statistical analysis was performed using unpaired two-tailed Student's t-test. RESULTS: There was no difference in the diagnostic yield for malignancy across all indications between the AM and PM groups. In the morning group 31/87 (36%) procedures and in the afternoon group 50/125 (40%) procedures were diagnostic for malignancy (P = 0.522). There was no difference in the specimen adequacy for cytopathologic evaluation across all indications between the AM and PM groups. In the morning group, 58/87 (67%) procedures and in the afternoon group 90/125 (72%) procedures were adequate for cytopathologic evaluation (P = 0.408). On-site cytopathologist was more available for AM than PM procedures; however, the lack of AM vs. PM difference in the yield and specimen adequacy persisted regardless of on-site cytopathologist presence. CONCLUSIONS: Time-of-day of the procedure (morning vs. afternoon) does not affect EUS-FNA diagnostic yield for malignancy or specimen adequacy for cytopathologic evaluation.

Iatrogenic pleuropulmonary charcoal instillation in a teenager.

Activated charcoal given through a nasogastric tube is a standard intervention for many types of toxic ingestions in the emergency department. This case study describes a teenage girl whose multidrug overdose was complicated by accidental charcoal instillation into her left lung and pleural space through a misplaced nasogastric tube. The ensuing empyema did not respond to antibiotic therapy alone, probably due to the inherent properties of charcoal, and required a chest tube placement with continuous irrigation. Unlike previously reported cases, this patient did well clinically, without long-term morbidity.

Fluorescence in situ hybridization and K-ras analyses improve diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses.

OBJECTIVES: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is the main diagnostic modality for pancreatic mass lesions. However, cytology is often indeterminate, leading to repeat FNAs and delay in care. Here, we evaluate whether combining routine cytology with fluorescence in situ hybridization (FISH) and K-ras/p53 analyses improves diagnostic yield of pancreatic EUS-FNA. METHODS: Fifty EUS-FNAs of pancreatic masses in 46 patients were retrospectively analyzed. Mean follow-up was 68 months. Thirteen initial cytologic samples (26%) were benign, 23 malignant (46%), and 14 atypical (28%). We performed FISH for p16, p53, LPL, c-Myc, MALT1, topoisomerase 2/human epidermal growth factor receptor 2, and EGFR, as well as K-ras/p53 mutational analyses. RESULTS: On final diagnosis, 11 (79%) of atypical FNAs were malignant, and 3 benign (21%). Fluorescence in situ hybridization was negative in all benign and all atypical samples with final benign diagnosis. Fluorescence in situ hybridization plus K-ras analysis correctly identified 60% of atypical FNAs with final malignant diagnosis. Combination of routine cytology with positive FISH and K-ras analyses yielded 87.9% sensitivity, 93.8% specificity, 96.7% positive predictive value, 78.9% negative predictive value, and 89.8% accuracy. CONCLUSIONS: Combining routine cytology with FISH and K-ras analyses improves diagnostic yield of EUS-FNA of solid pancreatic masses. We propose to include these ancillary tests in the workup of atypical cytology from pancreatic EUS-FNA.