Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals.

Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. Herein, through a fine-needle aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant recipients (KTXs). We found that, unlike healthy subjects, KTXs presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cell, SARS-CoV-2 receptor binding domain-specific memory B cell, and neutralizing antibody responses. KTXs also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals and suggest a GC origin for certain humoral and memory B cell responses following mRNA vaccination.

Fine needle aspiration of human lymph nodes reveals cell populations and soluble interactors pivotal to immunological priming.

Lymph node (LN) fine needle aspiration (LN FNA) represents a powerful technique for minimally invasive sampling of human LNs in vivo and has been used effectively to directly study aspects of the human germinal center response. However, systematic deep phenotyping of the cellular populations and cell-free proteins recovered by LN FNA has not been performed. Thus, we studied human cervical LN FNAs as a proof-of-concept and used single-cell RNA-sequencing and proteomic analysis to benchmark this compartment, define the purity of LN FNA material, and facilitate future studies in this immunologically pivotal environment. Our data provide evidence that LN FNAs contain bone-fide LN-resident innate immune populations, with minimal contamination of blood material. Examination of these populations reveals unique biology not predictable from equivalent blood-derived populations. LN FNA supernatants represent a specific source of lymph- and lymph node-derived proteins, and can, aided by transcriptomics, identify likely receptor-ligand interactions. This represents the first description of the types and abundance of immune cell populations and cell-free proteins that can be efficiently studied by LN FNA. These findings are of broad utility for understanding LN physiology in health and disease, including infectious or autoimmune perturbations, and in the case of cervical nodes, neuroscience.

New window into hepatitis B in Africa: Liver sampling combined with single cell omics enables deep and longitudinal assessment of intrahepatic immunity in Zambia.

In Lusaka, Zambia, we introduced liver fine needle aspiration (FNA) into a research cohort of adults with treatment-naïve chronic hepatitis B virus (HBV) infection, with and without HIV coinfection, as well as with acute HBV infection. Over 117 enrollment and 47 longitudinal FNAs (at 1 year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.

Elevated Cancer-Associated Hyaluronan Correlates With Diagnosis and Lymph Node Metastasis of Papillary Thyroid Cancer.

The glycosaminoglycan hyaluronan (HA) plays an important role in tumor progression. However, its biological and clinical significance in papillary thyroid cancer (PTC) remains unknown. Immunohistochemistry was performed to examine HA expression in tissues from PTC patients. Two PTC cell lines were treated with HA synthesized inhibitor against HA production to assess its function. Serum HA levels from 107 PTC patients, 30 Hashimoto thyroiditis patients, and 45 normal controls (NC) were measured by chemiluminescence immunoassay. HA levels in fine needle aspiration (FNA) washouts obtained from thyroid nodules and lymph nodes (LNs) were measured by chemiluminescence immunoassay. Area under the curve (AUC) was computed to evaluate HA's clinical value. HA was highly expressed in PTC. Reducing HA production significantly inhibited PTC cell proliferation and invasion. Importantly, serum HA levels in PTC were significantly higher than those in NCs and Hashimoto thyroiditis and allowed distinguishing of thyroid cancers from NCs with high accuracy (AUC = 0.782). Moreover, elevated serum HA levels in PTC correlate with LN metastasis. HA levels in FNA washouts from PTC patients were significantly higher than those in benign controls, with a high AUC value (0.8644) for distinguishing PTC from benign controls. Furthermore, HA levels in FNA washouts from metastatic LN were significantly higher than those in nonmetastatic LN, with a high AUC value (0.8007) for distinguishing metastatic LNs from nonmetastatic LNs. HA levels in serum and FNA washout exhibited a potential significance for PTC diagnosis and an indicator for LN metastasis in patients with PTC.

Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitis.

BACKGROUND & AIMS: Chronic viral infections present serious public health challenges; however, direct-acting antivirals (DAAs) are now able to cure nearly all patients infected with hepatitis C virus (HCV), representing the only cure of a human chronic viral infection to date. DAAs provide a valuable opportunity to study immune pathways in the reversal of chronic immune failures in an in vivo human system. METHODS: To leverage this opportunity, we used plate-based single-cell RNA-seq to deeply profile myeloid cells from liver fine needle aspirates in patients with HCV before and after DAA treatment. We comprehensively characterised liver neutrophils, eosinophils, mast cells, conventional dendritic cells, plasmacytoid dendritic cells, classical monocytes, non-classical monocytes, and macrophages, and defined fine-grained subpopulations of several cell types. RESULTS: We discovered cell type-specific changes post-cure, including an increase in MCM7+STMN1+ proliferating CD1C+ conventional dendritic cells, which may support restoration from chronic exhaustion. We observed an expected downregulation of interferon-stimulated genes (ISGs) post-cure as well as an unexpected inverse relationship between pre-treatment viral load and post-cure ISG expression in each cell type, revealing a link between viral loads and sustained modifications of the host's immune system. We found an upregulation of PD-L1/L2 gene expression in ISG-high neutrophils and IDO1 expression in eosinophils, pinpointing cell subpopulations crucial for immune regulation. We identified three recurring gene programmes shared by multiple cell types, distilling core functions of the myeloid compartment. CONCLUSIONS: This comprehensive single-cell RNA-seq atlas of human liver myeloid cells in response to cure of chronic viral infections reveals principles of liver immunity and provides immunotherapeutic insights. CLINICAL TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT02476617). IMPACT AND IMPLICATIONS: Chronic viral liver infections continue to be a major public health problem. Single-cell characterisation of liver immune cells during hepatitis C and post-cure provides unique insights into the architecture of liver immunity contributing to the resolution of the first curable chronic viral infection of humans. Multiple layers of innate immune regulation during chronic infections and persistent immune modifications after cure are revealed. Researchers and clinicians may leverage these findings to develop methods to optimise the post-cure environment for HCV and develop novel therapeutic approaches for other chronic viral infections.

Long-Term Outcomes of Endoscopic Ultrasound-Guided Ablation Vs Surgery for Pancreatic Cystic Tumors.

BACKGROUND & AIMS: Endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) is performed as an alternative to surgical resection in selected patients with pancreatic cystic tumors (PCTs). We aimed to directly compare the long-term outcomes between EUS-PCA and surgery for PCTs. METHODS: We reviewed a PCT database to identify patients with unilocular or oligolocular PCTs who underwent EUS-PCA or surgery between January 2004 and July 2019. We performed 1:1 propensity score matching based on potential confounding factors. The primary outcome was long-term morbidities. Secondary outcomes included early (≤14 days) and late (>14 days) major adverse events (MAEs), development of diabetes mellitus, readmission, length of hospital stay, and therapeutic efficacy. RESULTS: A total of 620 patients (EUS-PCA, n = 310; surgery, n = 310) were selected after propensity score matching. The EUS-PCA group showed a lower 10-year rate of cumulative long-term morbidities (1.6% vs 33.5%; P = .001) as well as lower rates of early MAE (1.0% vs 8.7%; P = .001), late MAE (0.3% vs 5.5%; P = .001), and readmission (1.0% vs 15.2%; P = .001). The EUS-PCA group had a shorter hospital stay (3.5 vs 10.3 d; P = .001) and a lower incidence of diabetes mellitus (2.2% vs 22.8%; P = .001), whereas the surgery group had a higher complete resolution rate (76.5% vs 100%; P = .001) and a lower relapse rate (4.6% vs 0.3%; P = .001). CONCLUSIONS: For select patients with PCTs, EUS-PCA showed superior results to surgery in terms of long-term safety profile and preservation of pancreatic function.

Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations.

Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole-exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine-needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.

Contrast-enhanced endoscopic ultrasound likely does not improve diagnostic adequacy during endoscopic ultrasound guided tissue acquisition: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Solid pancreatic masses are sampled through tissue acquisition by endoscopic ultrasound (EUS). Inadequate samples may significantly delay diagnosis, increasing costs and carrying risks to the patients. AIM: assess the diagnostic adequacy of tissue acquisition using contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) compared to conventional EUS. METHODS: Five databases (PubMed, Embase, CENTRAL, Scopus and Web of Science) were searched in November 2023. Studies comparing diagnostic adequacy, accuracy and safety using CEH-EUS versus conventional EUS for tissue acquisition of solid pancreatic masses were included. Risk of bias was assessed using the Risk of Bias tool for randomized controlled trials (RoB2) and the Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool for non-randomized studies, level of evidence using the GRADE approach, Odds Ratios (RR) with 95 % Confidence Intervals (CI) calculated and pooled using a random-effects model. I2 quantified heterogeneity. RESULTS: The search identified 3858 records; nine studies (1160 patients) were included. OR for achieving an adequate sample was 1.467 (CI: 0.850-2.533), for randomized trials 0.902 (CI: 0.541-1.505), for non-randomized 2.396 (CI: 0.916-6.264), with significant subgroup difference. OR for diagnostic accuracy was 1.326 (CI: 0.890-1977), for randomized trials 0.997 (CI: 0.593-1.977) and for non-randomized studies 1.928 (CI: 1.096-3.393), significant subgroup difference (p = 0.0467). No differences were observed for technical failures or adverse events. Heterogeneity was low, risk of bias "low" to "some concerns" for most outcomes, mostly moderate for non-randomized studies. CONCLUSION: Non-randomized studies indicated differences in favor of contrast-enhanced EUS, randomized studies showed no difference in diagnostic adequacy, accuracy or sensitivity when using CEH-EUS.

Pancreatic juice cytology for diagnosing invasive pancreatic carcinoma/high-grade pancreatic intraepithelial neoplasia without visible tumors on endoscopic ultrasound.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) with a diameter ≤10 mm and high-grade pancreatic intraepithelial neoplasia (HG-PanIN) require pre-operative diagnosis. Most cases present only indirect imaging findings without visible tumors on endoscopic ultrasound (EUS). Therefore, EUS-guided fine-needle aspiration/biopsy is not applicable. An alternative diagnostic method is pancreatic juice cytology (PJC) via endoscopic naso-pancreatic drainage (ENPD-PJC), which is not the standard practice. This study aimed to investigate ENPD-PJC for diagnosing suspected PDAC/HG-PanIN cases without visible tumors on EUS. METHODS: Data of patients with suspected PDAC/HG-PanIN without visible tumors who underwent PJC were retrospectively evaluated. One PJC sample was collected during endoscopic retrograde pancreatography (ERP-PJC), and 12 samples were collected during ENPD-PJC, 3-hourly for cytological analysis. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC positivity indicated cytologically positive samples. Patients with positive/negative PJC with follow-up for <4-years were excluded as undiagnosed cases. A non-malignant diagnosis was based on histopathological absence/stable imaging findings for ≥4-years. The primary endpoint was to demonstrate that ERP/ENPD-PJC has a higher diagnostic ability than ERP-PJC. RESULTS: Twenty-two patients with histopathologically diagnosed PDAC/HG-PanIN and 31 with a non-malignant diagnosis were enrolled. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC showed sensitivities of 36.4 %, 86.4 %, and 77.3 %, specificities of 93.5 %, 87.1 %, and 93.5 %, and accuracies of 69.8 %, 86.7 %, and 86.7 %, respectively. ERP/ENPD-PJC and ENPD-PJC demonstrated superior sensitivity and accuracy compared to ERP-PJC. A greater occurrence of positive outcomes markedly distinguished true positives from false positives. CONCLUSIONS: ERP/ENPD-PJC and ENPD-PJC had higher diagnostic accuracies for PDAC/HG-PanIN without visible tumors on EUS. ENPD-PJC is recommended for the diagnosis of these lesions.

Which Ultrasound Characteristics Predict Lymphatic Spread of Papillary Thyroid Cancer?

INTRODUCTION: The 2015 American Thyroid Association guidelines recommend lymph node mapping US in patients with definitive cytological evidence of thyroid cancer. Suspicious lymph node features on imaging including enlarged size (>1 cm in any dimension), architectural distortion, loss of fatty hilum, and microcalcifications often prompt evaluation with fine needle aspiration. There is no universally agreed upon model for determining which ultrasound characteristics most strongly correlate with metastatic disease. METHODS: A retrospective review of patients with confirmed papillary thyroid cancer (PTC) undergoing lymph node mapping ultrasound from 2013 to 2019 was performed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for each individual ultrasound characteristic as well as for characteristic combinations. RESULTS: Data from 119 lymph nodes were included. Malignant lymph nodes were more likely to be enlarged (71% versus 61%, P < 0.001) and to have each individual suspicious feature. Loss of fatty hilum had the highest sensitivity (89%) but was not specific (19%) for metastatic disease. Architectural distortion was found to have the highest specificity (87%). A combination of the four features was found to have higher specificity (97%) and PPV (88%) than any individual feature or combination of two/three features. CONCLUSIONS: A combination of four sonographic features correlates with metastatic PTC to lymph nodes and has the highest specificity and PPV for malignancy. A risk stratification model based on these features may lead to better classification of ultrasound findings in PTC patients with concern for nodal metastases.

The advent of the first electric driven EUS-guided 17 gauge core needle biopsy - A pilot study on subepithelial lesions.

BACKGROUND AND AIMS: This pilot study aimed to evaluate safety and tissue sampling from subepithelial lesions (SEL) in the upper gastrointestinal tract with a novel electric motor driven endoscopic ultrasonography (EUS)-guided 17-gauge (G) size core needle biopsy (CNB) instrument. METHODS: An investigator-led prospective open label, performance and safety control study, including seven patients (female n = 4, median 71 y, range 28-75) with a determined SEL (median size 30 mm, range 17-150 mm) in the upper digestive tract (stomach n = 6, duodenum n = 1) were eligible and later followed up 14 days after index procedure. All investigations were completed according to protocol with three FNB 22-G passes with four fanning strokes and two EndoDrill® 17-G passes with three fanning strokes. RESULTS: Quality of samples as 'visible pieces' (>5 mm): FNB (n = 5/7) (fragmented/blood imbibed n = 1, poor tissue quantity n = 1) compared with 17-G CNB (n = 7/7). Histological result which led to final diagnosis (leiomyoma n = 2, adenocarcinoma n = 1, schwannoma n = 1, neuroendocrine tumour n = 1, desmoid tumour n = 1 and gastrointestinal stromal tumour (GIST) n = 1) could be obtained with the 17-G CNB instrument in all seven patients. FNB technique reached correct diagnosis in six patients. No serious adverse event were recorded. CONCLUSIONS: By using an electric driven 17-G biopsy device, a true cylinder of core tissue can be obtained in one single puncture from the area of interest reducing the need for a second sampling. The absolute benefit of EUS-guided CNB is that the sample can be handled and histologically prepared in the same manner as standard percutaneous core needle sample, e.g., breast and prostate cancer.

Comparison of Breast Fine-Needle Aspiration Cytology and Tissue Sampling for High-Throughput Proteomic Analysis and Cancer Biomarker Detection.

INTRODUCTION: Fine-needle aspiration cytology (FNAC) specimens are widely utilized for the diagnosis and molecular testing of various cancers. We performed a comparative proteomic analysis of three different sample types, including breast FNAC, core needle biopsy (CNB), and surgical resection tissues. Our goal was to evaluate the suitability of FNAC for in-depth proteomic analysis and for identifying potential therapeutic biomarkers in breast cancer. METHODS: High-throughput proteomic analysis was conducted on matched FNAC, CNB, and surgical resection tissue samples obtained from breast cancer patients. The protein identification, including currently established or promising therapeutic targets, was compared among the three different sample types. Gene Ontology (GO) enrichment analysis was also performed on all matched samples. RESULTS: Compared to tissue samples, FNAC testing revealed a comparable number of proteins (7,179 in FNAC; 7,196 in CNB; and 7,190 in resection samples). Around 85% of proteins were mutually identified in all sample types. FNAC, along with CNB, showed a positive correlation between the number of enrolled tumor cells and identified proteins. In the GO analysis, the FNAC samples demonstrated a higher number of genes for each pathway and GO terms than tissue samples. CCND1, CDK6, HER2, and IGF1R were found in higher quantities in the FNAC compared to tissue samples, while TUBB2A was only detected in the former. CONCLUSION: FNAC is suitable for high-throughput proteomic analysis, in addition to an emerging source that could be used to identify and quantify novel cancer biomarkers.

Endoscopic Ultrasound-Guided Tissue Acquisition Using Fork-Tip Needle for Subepithelial Lesions: A Single-Center Validation Study.

BACKGROUND: The cutoff value for stereomicroscopic on-site evaluation (SOSE) in endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high diagnostic sensitivity when a Franseen needle is employed for upper gastrointestinal subepithelial lesions (SELs) (stereomicroscopically visible white core [SVWC] ≥ 4 mm). AIM: We aimed to determine whether high diagnostic sensitivity could be obtained when EUS-TA was performed using a Fork-tip needle. METHODS: Twenty-one patients were prospectively registered. Patients underwent EUS-TA using a Fork-tip needle for upper gastrointestinal SELs at Kitasato University Hospital between January and November 2022. Punctures were made twice using the needle, and SOSE was conducted for each specimen. Blood and physical examination were performed to assess adverse events. Pathological diagnosis was made using hematoxylin and eosin-stained sections and immunohistochemical staining. Statistical comparisons were completed using Fisher's exact tests. RESULTS: The diagnostic rate of EUS-TA was 100% (21/21 cases). The final diagnosis was gastrointestinal stromal tumor in 17 (81.0%) and leiomyoma in 4 (19.0%) patients. SOSE was conducted on all 42 punctures, and the tissue sampling rate was 100% (42/42 punctures). Specimens with SVWC ≥ 4 mm were collected in 97.6% punctures (41/42 punctures) and the diagnostic sensitivity for these specimens was 100% (41/41 punctures), which is significantly higher (p < 0.0238) compared to the absence of cutoff value (diagnostic sensitivity of 0%). No EUS-TA-related adverse events occurred. CONCLUSIONS: EUS-TA combined with SOSE for upper gastrointestinal SEL using a fork-tip needle had a high diagnostic rate, and the cutoff value of SVWC ≥ 4 mm had high diagnostic sensitivity.

Accuracy and diagnostic performance of the Bethesda system for reporting thyroid cytopathology in a tertiary endocrine surgical referral center in Belgium.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology is a commonly used classification for fine needle aspiration (FNA) cytology of suspicious thyroid nodules. The risk of malignancy (ROM) for each category has recently been analyzed in three international databases. This paper compares the diagnostic performance of the Bethesda classification in a high-volume referral center in Belgium. METHODS: All consecutive thyroid procedures were registered in a prospective database from January 2010 till August 2022. Patient and surgical characteristics, preoperative Bethesda categories, and postoperative pathology results were analyzed. RESULTS: Out of 2219 consecutive thyroid procedures, 1226 patients underwent preoperative FNA. Papillary thyroid cancer was the most prevalent malignancy (N = 119, 70.4%), followed by follicular (N = 17, 10.1%) and medullary thyroid cancer (N = 15, 8.9%). Micropapillary thyroid cancer was incidentally found in 46 (3.8%) patients. Bethesda categories I, II, III, IV, V, and VI, respectively, represented 250 (20.4%; ROM 4.4%), 546 (44.5%; ROM 3.8%), 96 (7.8%; ROM 20.8%), 231 (18.8%; ROM 15.2%), 62 (5.1%; ROM 72.6%), and 41 (3.3%; ROM 90.2%) patients. Overall ROM was 13.8%. An negative predictive value (NPV) of 96.2% was found. Overall specificity was 64.2% with a positive predictive value (PPV) of 31.9%. Diagnostic accuracy was 67.8%. Compared to international databases (CESQIP, EUROCRINE, and UKRETS), ROM in this study appeared lower for Bethesda category IV (15.2 vs. 26.7% and p = 0.612). CONCLUSION: Despite being validated in numerous studies, ROM based on preoperative FNA cytology classified according to the Bethesda classification may vary among surgical centers and countries as this study reveals a higher NPV and lower PPV.

Effect of Music Therapy on Pain During Thyroid Fine Needle Aspiration Biopsy; A Randomized Controlled Clinical Trial.

INTRODUCTION: High-resolution ultrasonography devices have led to the increased detection of thyroid nodules and the need for fine-needle aspiration biopsy (FNAB). However, FNAB is an invasive procedure that can cause discomfort and pain. Music therapy has been used for centuries to alleviate pain, and our clinical trial was conducted to investigate its impact on pain scores during thyroid FNAB. MATERIALS AND METHODS: We conducted a randomized, controlled clinical trial, including adult patients undergoing thyroid FNAB. We evaluated the nonpharmacological intervention of listening to music before and during thyroid FNAB. We used a slow, nonlyrical, flowing melody with a tempo of 60 to 80 beats per minute as a therapeutic intervention for managing anxiety and pain. It had low tones, minimal percussion, and a volume of around 60 dB. The Beck Anxiety Inventory and Visual Pain Scale were used. RESULTS: The study included 529 patients assigned to either the music group (n = 258, 48.7%) or the control group (n = 271, 51.2%). The patients were categorized into subgroups based on either a single nodule (73.63%) or multiple nodules (24.18%). When all patients or single nodule and multiple data are examined separately, the intervention group showed statistically significantly lower pain scores than the control group. CONCLUSION: Our study is among the first on this topic and the largest in the available literature to demonstrate that listening to music during FNAB significantly reduces pain and anxiety. Music therapy is an effective, safe, and noninvasive intervention that can improve patient care and reduce distress and pain.

Assessing the Frequency of Deferrable Thyroid Nodule Biopsies to De-escalate Low-Value Care.

OBJECTIVE: Thyroid nodules are common, yet fewer than 1 in 10 harbors malignancy. When present, thyroid cancer is typically indolent with excellent survival. Therefore, patients who are not candidates for thyroid cancer treatment due to comorbid disease may not require further thyroid nodule evaluation. The goal of this study was to determine the rate of deferrable thyroid nodule biopsies in patients with limited life expectancy. METHODS: We identified patients who underwent thyroid fine needle aspiration (FNA) between 2015 and 2018 at our institution. The primary outcome was the number of deferrable FNAs, defined as FNAs performed in patients who died within 2 years after biopsy. Secondary outcomes included cytologic Bethesda score, procedure costs, and final diagnosis on surgical pathology. Multivariable logistic and Cox proportional hazards regressions were used to evaluate factors associated with FNA in patients with limited life expectancy. RESULTS: A total of 2565 FNAs were performed. Most patients were female (79%), and 37 (1.5%) patients died within 2 years. Nonthyroid specialists were significantly more likely to order deferrable FNAs (odds ratio 4.13, P < .001). Of the patients who died within 2 years, most (78%) had a concomitant diagnosis of nonthyroid cancer, and 4 went on to have thyroid surgery (Bethesda scores: 3, 4, 4, and 6). Spending associated with deferrable FNAs and subsequent surgery totaled over $98 000. CONCLUSIONS: Overall, the rate of deferrable thyroid nodule biopsies was low. However, there is an opportunity to reduce low-value biopsies in patients with a concurrent nonthyroid cancer by partnering with oncology providers.

The use of telecytology for the evaluation of thyroid nodules fine-needle aspiration biopsy specimens: a systematic review.

PURPOSE: Fine needle aspiration biopsy (FNAB) is currently the gold standard for diagnosis and treatment of thyroid nodules, but the growing need for anatomic pathology services in small communities is becoming a challenge. Telecytology (TC) is defined as the electronic transmission of cytological digital images, and allows for the collection of samples, primary diagnosis, and other applications without the physical presence of a pathologist. Our aim is to systematically report, summarize, and critically analyze the most up to date applications of TC to thyroid nodules FNAB evaluation. METHODS: We performed a systematic literature review by searching PubMed, Embase, and Cochrane Library databases. Only studies published in peer-reviewed scientific journals were included. Data were extracted using the PICO framework and critically analyzed. PRISMA guidelines were applied, and the risk of bias in the included studies was assessed using the ROBINS-I tools. The methodological quality was assessed following GRADE criteria. RESULTS: We included 13 observational studies, resulting in a total of 3856 evaluated FNAB specimens. The majority of studies (63.6%) showed an excellent concordance rate of diagnosis via TC and conventional cytology. TC can be used to perform preliminary assessment of samples with a concordance rate ranging from 74 and 100%, showing a significant reduction of the non-diagnostic rate. Image quality was referred to as perfect or nearly perfect in most cases, regardless of telecytology technique. CONCLUSION: Telecytology could be a valuable implementation for thyroid FNAB evaluation both for primary diagnosis and preliminary assessment of samples.

Impact of fine-needle aspiration cytology in thyroidectomy extent and associated surgical morbidity in thyroid cancer.

PURPOSE: To assess the impact of fine-needle aspiration cytology (FNAC) in the extent of surgery in patients with thyroid cancer (TC) and the associated surgical morbidity in primary and completion setting. METHODS: A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing FNAC and histology reports. RESULTS: Among the 2519 cases operated for TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%). Among these, 1679 patients (72%) were female, and the median age at TC diagnosis was 52.3 years (range 18-94.6). Less than total thyroidectomy (LTT) was undertaken in 944 whereas total thyroidectomy (TT) in 1388 cases. The intermediate FNAC categories of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), as well as suspicion for follicular neoplasm (SFN) lesions were more often encountered in LTT (n = 314, 33.3%) than TT (n = 63, 4.6%), whereas FNACs suspicion for malignancy and/or malignancy were overrepresented in TT (n = 963, 69.4%). Completion thyroidectomies were undertaken in 553 patients out of 944 that initially had LTT. In 201 cases with cancer lesions > 1 cm, other than FTC (Follicular TC)/ HTC (Hürthle cell TC) subjected to primary LTT, inadequate procedures were undertaken in 81 due to absent, Bethesda I or II FNAC categories, preoperatively. Complications at completion of surgery in this particular setting were 0.5% for RLN palsy (n = 1) and 1% (n = 2) for hypoparathyroidism 6 months postoperatively. The overall postoperative complication rate was higher in primary TT vs. LTT for RLN palsy (4.8% [n = 67] vs. 2.4% [n = 23]; p = 0.003) and permanent hypoparathyroidism (6.8% [n = 95] vs. 0.8% [n = 8]; p < 0.0001). CONCLUSIONS: FNAC results appear to affect surgical planning in TC as intermediate FNAC categories lead more often to LTT. Overall, inadequate procedures necessitating completion surgery are encountered in up to 15% of TC patients subjected to LTT due to absent, inconclusive, or misleading FNAC, preoperatively. However, completion of thyroidectomy in this setting did not yield significant surgical morbidity. Primary LTT is a safer primary approach compared to TT in respect of RLN palsy and permanent hypoparathyroidism complication rates; therefore, primary TT should probably be reserved for lesions > 1 cm or even larger with suspicion for malignancy or malignant FNAC.

Diagnostic clues and pitfalls in salivary gland fine-needle aspiration cytology.

Salivary gland tumors (SGT) display morphological diversity and pose diagnostic challenges. Preoperative fine needle aspiration cytology (FNAC) is a minimally invasive and efficient diagnostic test. However, due to the limited sample size, the final diagnosis may not be established based on FNAC alone. Although cytomorphology and architecture are usually preserved on FNAC, morphologic changes specific to FNAC can complicate the diagnosis. The Milan System for Reporting Salivary Gland Cytopathology categorizes complex FNAC interpretations. Because the cytological diagnosis is closely linked to the histological diagnosis, a multidimensional approach considering the possibility of several differential diagnoses is necessary. From the standpoint of treatment, distinguishing high-grade malignancy from low-grade malignancy is more important than distinguishing malignancy from benign tumors.

Comparison of 19G FNA Versus 22G FNB Needles for Endoscopic Ultrasound-Guided Fine-Needle Sampling of Subepithelial Tumors: Is Bigger Better?

OBJECTIVES: To compare the diagnostic efficiency of 19G fine-needle aspiration (FNA) and 22G fine-needle biopsy (FNB) in endoscopic ultrasound (EUS)-guided sampling for subepithelial tumors (SETs). METHODS: The data of patients with SETs who underwent 19G FNA or 22G FNB were reviewed retrospectively in two tertiary hospitals. Tissue cores were assessed by macroscopic on-site evaluation (MOSE). Cytological or histological diagnosis were classified as definite, suspect, or no diagnosis. RESULTS: Seventy five patients (mean age: 55 years, 44 males) underwent 19G EUS-FNA (31) or 22G EUS-FNB (44). The overall diagnostic yield was 82.7%. The rate of definite cytological diagnoses was 9.7% (3/31) in 19G and 13.6% (6/44) in 22G group (x2 = 1.520, P = .468). In terms of MOSE, 19G needle, requiring only two punctures, achieved a higher good tissue core rate than 22G group (100.0% [31/31] versus 84.1% [37/44], x2 = 5.440, P = .020]). For histological diagnosis, the 19G group achieved higher definite rate than the 22G group, 93.6% (29/31) versus 65.9% (29/44) (x2 = 7.957, P = .019) on the first puncture, 90.3% (28/31) versus 63.6% (28/44) (x2 = 7.139, P = .028) on the second puncture, 96.8% (30/31) versus 70.5% (31/44) (x2 = 7.319, P = .026) on both the first and second punctures, and 96.8% (30/31) versus 72.7% (32/44) (x2 = 7.538, P = .023) on all three punctures. CONCLUSIONS: The 19G EUS-FNA requires only two punctures to achieve better tissue core quality by MOSE and yields a higher rate of histological diagnosis than 22G ProCore needle for SETs. The bigger 19G FNA needle seems to play an important role in the evaluation of SETs.