Cervical Lymph Node Features Predictive of Suboptimal Adequacy During Ultrasound-Guided Fine-Needle Aspiration in Thyroid Cancer Patients.

PURPOSE: To determine the rate of cytologic and diagnostic adequacy and identify features associated with suboptimal tissue sampling in ultrasound-guided fine-needle aspiration (US-FNA) of suspected nodal disease in thyroid cancer patients. METHODS: A single-institution pathology database was queried for lymph node FNA reports in thyroid cancer patients from 2014 to 2019. Charts were reviewed for demographics, body mass index (BMI), prior thyroidectomy, cancer type, and subsequent surgery. Ultrasound images were retrospectively reviewed for location, size, depth from skin, cystic components, macrocalcification, echogenic foci, and internal vascularity score. Pathology reports were categorized as cellular and diagnostic, hypocellular/acellular but diagnostic with abnormal cells or thyroglobulin levels, or hypocellular and nondiagnostic. Correlation and multivariate regression analyses were performed. RESULTS: Initial query yielded 552 lesions in 343 subjects. Following exclusion, 377 lesions in 255 subjects were included. Mean patient age was 48.5 years (14-90), BMI 28.5, and 66.7% female and 33.3% male. The majority (95.3%) had papillary thyroid carcinoma (PTC); and 65.5% had prior thyroidectomy. 17.7% of lesions were hypocellular/acellular (suboptimal), and 5.6% nondiagnostic. Patient factors had no association (P >.05). Right-sidedness and hypovascularity were associated with hypocellularity (P <.05). Higher long/short-axis ratio and cystic foci were weakly associated. On multivariate analysis, right-sidedness (odds ratio [OR] 1.99; confidence interval [CI] 1.10-3.57) and lower vascularity score (OR 0.54; CI 0.39-0.73) were predictive of suboptimal sampling. CONCLUSION: US-FNA has high diagnostic yield and cellular sample rate. Lesion size had no effect. Right-sidedness and lower vascularity scores were predictive of suboptimal tissue. Identifying these features and expected sample adequacy rates can inform management decisions for thyroid cancer patients with cervical lymphadenopathy.

Disseminated Legionella micdadei infection in a liver transplant patient presenting as pulmonary nodules and a laryngeal lesion.

We report a liver transplant patient with disseminated Legionella micdadei infection with pulmonary, laryngeal, and suspected muscle involvement. This organism, which stains weakly acid-fast, primarily affects immunocompromised patients. The diagnosis is difficult to make; in this case, the organism was identified via molecular diagnostics on laryngeal and pulmonary biopsy tissue.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a review for pathologists.

The rising incidence of papillary thyroid carcinoma is linked in part to inclusion of noninvasive follicular variant of papillary thyroid carcinoma. Despite its designation as carcinoma, noninvasive follicular variant of papillary thyroid carcinoma appears to be exceptionally indolent, often over treated by current treatment practices. Additionally, criteria for diagnosis have historically been subjective and challenging. Recently, an international multidisciplinary collaborative group performed a clinicopathologic survey of such cases with extended follow-up and concluded based on the outcome data that a revision in nomenclature was warranted, proposing 'Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).' This monograph is a synopsis and guide for pathologists on NIFTP and focuses on histologic features, including inclusion and exclusion criteria used to define NIFTP, as well as grossing guidelines, reporting practices, and potential diagnostic limitations.

Squamous differentiation in papillary thyroid carcinoma: a rare feature of aggressive disease.

BACKGROUND: Papillary thyroid carcinoma with squamous differentiation (PTC-SD) is a poorly understood pathologic finding of unknown clinical significance. Selected case reports have suggested that PTC-SD is an aggressive tumor with a poor prognosis. Here we present the largest case series of PTC-SD reported in the United States. MATERIALS AND METHODS: The cancer registry at our tertiary care referral center was reviewed to identify all patients from 1995-2015 who had been diagnosed with PTC-SD on initial total thyroidectomy or lymph node dissection for recurrent disease. All cases were reviewed by an endocrine pathologist to confirm the diagnosis. Patient demographic, pathology, and outcomes data were collected and reviewed. RESULTS: During the study period, ten patients were diagnosed with PTC-SD, six in the primary tumor at the time of initial surgery, and four in lymph node metastases during surgery for recurrent disease. The median age at diagnosis was 56 y and half of the patients were male. Aggressive features such as multifocality (67%), extrathyroidal extension (67%), positive margin (89%), lymph node metastases (80%), and extranodal extension (60%) were far more prominent than is typically seen in classic PTC. Long-term follow-up (median 56.5 mo) demonstrated high rates of locoregional recurrence (60%), pulmonary metastases (30%), and mortality (10%). CONCLUSIONS: Squamous differentiation is a rare finding in PTC that is associated with aggressive pathologic features and poor long-term outcomes. This phenomenon may represent a step in progression toward dedifferentiation; thus, patients with PTC-SD should have close, life-long surveillance and should be treated according to evidence-based guidelines for high-risk thyroid cancers.

Microscopic Positive Tumor Margin Does Not Increase the Risk of Recurrence in Patients with T1-T2 Well-Differentiated Thyroid Cancer.

BACKGROUND: Incomplete surgical resection with gross positive tumor margin increases the risk of recurrence in patients with well-differentiated thyroid cancer (WDTC); however, it is not clear whether a microscopic positive margin found only on final pathology has similar implications on patient outcomes. METHODS: We conducted a single-institution retrospective review of all patients undergoing total thyroidectomy for T1-T2 WDTC (January 2000-January 2010). Factors that may influence the risk of locoregional recurrence or distant metastasis were evaluated by univariate and multivariate analysis. RESULTS: Of 1000 consecutive patients undergoing surgical resection for WDTC, 684 T1-T2 cancers were included. Mean age was 46 years and 81 % were women. Of this total cohort, 78 (11 %) patients had microscopic positive margins. Radioactive iodine (RAI) was administered in 47/78 (60 %) patients with positive margins versus 312/606 (51 %) patients without positive margins. After a mean follow-up of 46 months, 53 (8 %) patients developed recurrent disease (1 local and 52 nodal). On multivariate analysis, nodal metastases (N1, odds ratio [OR] 7.7) and contralateral multifocality (OR 3.7) were independent risk factors for recurrent disease. A microscopic positive margin was not a risk factor for recurrence. CONCLUSIONS: A microscopic positive margin found only on final pathological analysis does not increase the risk of recurrence in T1-T2 WDTC. Clinicians should interpret such pathology findings accordingly when considering further surveillance and treatment decisions such as the use of RAI ablation.

Seven years of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Rate of Acceptance and Variation of Diagnostic Approaches Across Different Continents.

CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

Molecular Profiling of 50 734 Bethesda III-VI Thyroid Nodules by ThyroSeq v3: Implications for Personalized Management.

CONTEXT: Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine needle aspiration (FNA) samples has not been reported. OBJECTIVE: To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules. METHODS: This retrospective analysis of FNA samples, tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier at UPMC Molecular and Genomic Pathology laboratory, analyzed the prevalence of diagnostic, prognostic, and targetable genetic alterations in a total of 50 734 BCIII-VI nodules from 48 225 patients. RESULTS: Among 50 734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alterations. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.9% of cases. CONCLUSION: In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutations and targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.

Retroperitoneal duodenal perforation due to COVID-19: An extremely rare case report.

Introduction and importance: Gastrointestinal (GI) symptoms are the most common extrapulmonary presentation of coronavirus disease 2019 (COVID-19) infection. GI perforation may be an unusual manifestation of COVID-19 infection. Case presentation: We report a 45-year-old man who presented with acute abdominal pain without any respiratory symptoms to our emergency department. Investigations revealed retroperitoneal duodenal perforation and fibrotic changes in lung bases. Laboratory findings demonstrated a positive polymerase chain reaction (PCR) test for COVID-19 and mild leukocytosis. Clinical discussion: COVID-19 related perforation of the retroperitoneal part of the duodenum is extremely rare, and to the best of our knowledge, this is the first reported case. With increasing COVID-19 infection, we might see more cases of GI perforation. In the era of COVID-19 pandemic, any abdominal signs and symptoms should alert the clinicians to consider COVID-19 diagnosis in the differential. Conclusion: Conservative management with close monitoring, antibiotic therapy and serial examinations were completely successful. The patient's general condition improved, and he was discharged on day 7 of hospitalization.

Non-Iodine-Avid Disease Is Highly Prevalent in Distant Metastatic Differentiated Thyroid Cancer With Papillary Histology.

CONTEXT: Patients with radioactive iodine (RAI) refractory metastatic differentiated thyroid cancer (DTC) have poor prognosis. Early identification of RAI refractoriness may improve care. OBJECTIVE: This work aimed to characterize DTC patients with distant metastases (DM) at diagnosis who presented with non-iodine-avid disease. METHODS: Retrospective analyses of DTC patients with DM at diagnosis who presented between 2012 and 2020 were performed. Iodine uptake in DM was correlated with tumor histology and mutational profile. The difference in uptake between BRAFV600E-like (BVL) and RAS-like (RL) cancers based on insights from The Cancer Genome Atlas was evaluated. RESULTS: Among 78 patients, 48.7% had negative uptake in DM on the first posttherapy scan. Negative scans were highly prevalent in papillary thyroid carcinoma (PTC) with papillary architecture, PTC with BRAFV600E mutation, and PTC with both BRAFV600E and TERT promoter mutations (71.1%, 80.9%, and 100%, respectively). BVL and RL tumors exhibited distinct uptake patterns with negative scan prevalence of 76.9% and 14.3% (P = .005). Multivariate logistical regression confirmed high odds of negative uptake in BVL tumors with either BVL mutations or papillary architecture, 19.8 (95% CI, 2.72-144), and low odds of negative uptake in RL tumors with either RL mutations or follicular architecture, 0.048 (95% CI, 0.006-0.344), after adjusting for age, sex, race, RAI preparation method, bone metastases, and RAI dose. Patients with negative scans were significantly older (62.4 vs 47.0 years, P = .03). CONCLUSION: Among DTC patients with DM at diagnosis, non-iodine-avid disease is highly prevalent in patients with BVL cancers, particularly with BRAFV600E and TERT promoter mutations, and is associated with an older age. Better strategies are needed to improve RAI treatment response for these patients.

B1 Vitamin Deficiency After Bariatric Surgery, Prevalence, and Symptoms: a Systematic Review and Meta-analysis.

B1 deficiency is a very prevalent complication of bariatric surgery. This study reviews prevalence and symptoms of B1 vitamin deficiency after bariatric surgery. PubMed, Scopus, and Web of Science published were searched up to 10 Feb 2022, with the following keywords: Roux-en-Y gastric bypass, one anastomosis gastric bypass, Omega bypass, Mini bypass, Bariatric surgery OR Bariatric surgery, metabolic surgery, Weight loss surgery, Classic gastric bypass, Loop gastric bypass, Gastric Bypass, thiamine OR thiamin, beriberi, B1. A total of 11 studies examining 1494 patients were included in this meta-analysis. Twenty-seven percent of patients who underwent bariatric surgeries experience vitamin B1 deficiency. Thiamine supplements should be prescribed for the patients for the rest of their lives, and also standard post-surgery follow-ups are necessary in terms of monitoring dietary factors.

Higher rate of BRAF mutation in papillary thyroid cancer over time: a single-institution study.

BACKGROUND: The incidence of thyroid cancer has doubled over the past decade. The reason for this dramatic increase in incidence is controversial. Some investigators have suggested that the increased incidence is because of increased detection of small primary tumors as a result of diagnostic scrutiny. Conversely, some investigators have demonstrated an increased incidence across all tumor sizes, suggesting that other factors may play a role. This study was undertaken to investigate the clinical, pathologic, and molecular changes present in papillary thyroid cancer over a 15-year period during which the incidence of papillary thyroid cancer doubled. METHODS: A total of 628 patients with conventional papillary thyroid cancer and 228 tumor samples from a single institution were analyzed from 1991 to 2005. Time-trend analyses of demographic, clinical, pathologic, and tumor genotype were performed over three 5-year time periods: group I (1991-1995), group II (1996-2000), and group III (2001-2005). RESULTS: The authors found no differences in age, sex, ethnicity, primary tumor size, rate of extrathyroidal invasion, or overall TNM cancer stage among the 3 time groups. The rate of BRAF V600E mutation was significantly higher in group III (88% BRAF V600E positive) as compared with groups I and II (51% and 43%, respectively) (P < .001). The rate of all the common somatic mutations was also significantly higher in group III (92% positive) as compared with groups I and II (68% and 64%, respectively) (P < .002). CONCLUSIONS: The rate of BRAF V600E mutation increased significantly over a 15-year period at the authors' institution. The findings suggest that a higher rate of BRAF mutation in papillary thyroid cancer may contribute to the increasing incidence of thyroid cancer.

Identification of differentially expressed microRNA in parathyroid tumors.

BACKGROUND: The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for parathyroid carcinoma. METHODS: miRNA arrays containing 825 human microRNAs with four duplicate probes per miRNA were used to profile parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples normalized to four reference normal parathyroid glands. Differentially expressed miRNA were validated by real-time quantitative TaqMan polymerase chain reaction (PCR). RESULTS: One hundred fifty-six miRNAs in parathyroid hyperplasia, 277 microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas were significantly dysregulated as compared with normal parathyroid glands [false discovery rate (FDR) < 0.05]. By supervised clustering analysis, all parathyroid carcinomas clustered together. Three miRNAs (miR-26b, miR-30b, and miR-126*) were significantly dysregulated between parathyroid carcinoma and parathyroid adenoma. Receiver-operating characteristic curve analysis showed mir-126* was the best diagnostic marker, with area under the curve of 0.776. CONCLUSIONS: Most miRNAs are downregulated in parathyroid carcinoma, while in parathyroid hyperplasia most miRNAs are upregulated. miRNA profiling shows distinct differentially expressed miRNAs by tumor type which may serve as helpful adjunct to distinguish parathyroid adenoma from carcinoma.

The spectrum of papillary thyroid carcinoma variants.

Papillary thyroid carcinoma is the most common type of thyroid malignancy. The diagnostic features of these tumors include characteristic nuclear cytology. However, many variants have been reported with different morphology and molecular profiles. Although the vast majority of papillary thyroid carcinomas have an excellent prognosis, some variants of papillary thyroid carcinoma can have a more aggressive course. With this increased attention to papillary thyroid carcinoma variants has come the need to sort out which variants are clinically important and should be recognized by practicing pathologists. The main objectives of this review article are to (1) summarize the gross and histopathologic features of papillary thyroid carcinoma; (2) provide an overview of the subtypes of papillary thyroid carcinoma and their prognosis; (3) discuss established and emerging data on the immunohistochemical findings that are helpful in differential diagnosis; and (4) summarize molecular findings and pathogenesis of these lesions.

Molecular cytopathology diagnosis of a lung neoplasm: Case report of an unusual non-small cell carcinoma with MET exon 14 skipping mutation.

Here we report the combined cytological and molecular diagnosis of a lung mass. The cytology and extensive immunohistochemistry on an endobronchial ultrasound-guided fine needle aspiration biopsy were inconclusive. By genomic profiling of the cell block material, we identified a MET exon 14 skipping mutation that indicated a lung origin and made the patient eligible for the tyrosine kinase inhibitor, crizotinib. This case is a prime example of complementing adequate aspiration and cell block processing techniques with molecular testing. Such an approach would augment the usability of fine needle aspiration biopsy, both as a diagnostic modality and as the first line to find therapeutic targets in the era of precision medicine.

Fine-needle aspiration performance during cytopathology fellowship: what do the ACGME case logs show us?

INTRODUCTION: Cytopathology fellows are required to enter their fine-needle aspiration (FNA) case numbers in an online data collection system, the Accreditation Council for Graduate Medical Education (ACGME) Case Log system. This study reviewed this data to examine trends in FNA case numbers during fellowship training. METHODS: A retrospective review of the ACGME Accreditation Data System (ADS) FNA Case Log data was performed for academic years 2006-2019. For 2006-2016, total and average numbers of FNAs performed per academic year were available. After 2016, data also included the number of programs and trainees, national averages, standard deviation, minimum, median, maximum, and percentiles for the number of FNAs performed. RESULTS: The number of FNAs documented by cytopathology fellows has gradually increased from 2006 (average 10.9) to 2013 (average 18.6) and dramatically increased in 2014 (average 38.0). Averages have remained greater than 30 FNAs documented per academic year since 2014, with some variation. However, a decline was observed in 2019, likely due to the COVID-19 pandemic. CONCLUSIONS: FNA procedures reported in the ACGME Case Log System indicate vast differences in cytopathology fellowship educational experiences and settings. After logging FNAs becoming an ACGME requirement in 2013, the average number of FNAs has been greater than 30 per year and provides some guidance for programs with respect to the number of FNAs being reported by cytopathology fellows nationally.

Excellence Available Everywhere: The Virtual Pathology Grand Rounds Experience.

OBJECTIVES: The goal is to describe the use of a virtual platform in the delivery of Virtual Pathology Grand Rounds (VPGR) and discuss the overall experience from the perspective of hosts, speakers, and participants. METHODS: Zoom was a natural choice for an online format because virtual platforms had been increasingly used to conduct meetings and medical education. VPGR hosted 14 speakers on a variety of topics, including subspecialty anatomic pathology material, digital pathology, molecular pathology, and medical education. RESULTS: There were 221 registrants and 114 participants for the first lecture, reaching a maximum of 1,268 registrants for the 12th lecture and the maximum limit of 300 participants during 3 lectures. Speakers stated that VPGR conveniently provided career-building opportunities through partnerships with host universities and remote attendance. Participants identified a lack of interpersonal communication and technical challenges as downsides. CONCLUSIONS: VPGR serves as strong proof of concept for the feasibility and demand for high-quality, remote academic pathology talks.

Multiple genetic alterations in papillary thyroid cancer are associated with younger age at presentation.

BACKGROUND: There is a significant gender and age disparity in thyroid cancer incidence and outcome. The molecular basis for these divergent clinical presentations and outcome are essentially unknown. METHODS: The primary tumor genotype in 217 patients with papillary thyroid cancer was determined for six common somatic genetic alterations (RET/PTC1, RET/PTC3, and NTRK1 rearrangements, and BRAF V600E, KRAS, and NRAS hotspot mutations) by PCR and direct sequencing, and nested PCR. Univariate and multivariate analyses were performed to determine the association of genetic changes and age, gender, and other clinicopathologic factors. RESULTS: One hundred twenty-one of the 190 conventional papillary thyroid carcinoma samples (63.7%) had at least one genetic alteration, and 27 of the samples (14.2%) had more than one alteration. In the follicular variant of papillary thyroid carcinomas, 13 of the 27 samples (48.1%) had at least one genetic alteration and three of the 27 samples (11.1%) had more than one. The presence of multiple genetic alterations was associated with younger age at diagnosis (P=0.034), mean difference of 8 y earlier. We found no significant association with the number or type of genetic alterations present by gender, tumor size, extent of tumor differentiation, multicentricity, lymph node metastasis, distant metastases, TNM stage, and the AMES risk group. The association of multiple genetic alterations and younger age were independent of tumor size, lymph node or distant metastasis, TNM stage, or AMES risk group. CONCLUSIONS: Multiple genetic alterations are more common in younger patients with papillary thyroid cancer, but there is no difference in the type or number of genetic alterations by gender. Our findings suggest that multiple genetic alterations in thyroid cancer may be associated with earlier disease initiation and or progression.

Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy.

BACKGROUND: Thyroid fine-needle aspiration (FNA) biopsy is indeterminate or suspicious in up to 30% of cases and these patients are commonly subjected to at least a diagnostic hemithyroidectomy. If malignant on histology, a completion thyroidectomy is usually performed, which may be associated with higher morbidity. To determine the clinical utility of genetic testing in thyroid FNA biopsy, we conducted a prospective clinical trial. METHODS: Four hundred seventeen patients with 455 thyroid nodules were enrolled and had genetic testing for common somatic mutations (BRAF, NRAS, KRAS) and gene rearrangements (RET/PTC1, RET/PTC3, RAS, TRK1) by PCR and direct sequencing and by nested PCR, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of genetic testing in thyroid FNA biopsy were determined based on the histologic diagnosis. RESULTS: One hundred twenty-five of 455 thyroid nodule FNA biopsies were indeterminate or suspicious on cytologic examination. Overall, 50 mutations were identified (23 BRAF, 4 RET/PTC1, 2 RET/PTC3, 21 NRAS) in the thyroid FNA biopsies. There were significantly more mutations detected in malignant thyroid nodules than in benign (P = 0.0001). For thyroid FNA biopsies that were indeterminate or suspicious, genetic testing had a sensitivity of 12%, specificity of 98%, PPV of 38%, and NPV of 65%. CONCLUSIONS: Genetic testing for somatic mutations in thyroid FNA biopsy samples is feasible and identifies a subset of malignant thyroid neoplasms that are indeterminate or suspicious on FNA biopsy. Genetic testing for common somatic genetic alterations thus could allow for more definitive initial thyroidectomy in those with positive results.

The diagnostic utility of next-generation sequencing on FNA biopsies of melanocytic uveal lesions.

BACKGROUND: Uveal melanoma is highly aggressive, and overall prognosis depends on mutation status. Fine-needle aspiration biopsies (FNABs) play an important role in obtaining fresh tissue for cytologic diagnosis and molecular studies. It has been suggested that, although FNAB usually provides high diagnostic accuracy, there may be limited cellularity, which may compromise diagnostic potential for molecular studies. FNABs of uveal melanocytic lesions were evaluated to assess sample adequacy for both cytologic evaluation and next-generation sequencing (NGS). METHODS: The authors retrospectively evaluated 36 cases of melanocytic uveal lesions from 2015 to 2018. Samples were obtained by ophthalmologist-performed FNAB and aliquoted for cytology and NGS. Various combinations of direct smears, liquid-based cytology slides, cell blocks, and immunohistochemical stains for melanocytic markers were performed. All samples were tested for molecular alterations using hybrid-capture-based NGS. RESULTS: There was sufficient material for cytologic diagnosis in 33 of 36 cases (92%), for NGS testing in 30 of 36 cases (83%), and for both cytologic diagnosis and NGS testing in 28 of 36 cases (78%). Of 7 cases that were cytologically categorized as indeterminate or diagnosed as "atypical" or "nondiagnostic," NGS testing was sufficient and diagnostic for melanoma in 5 cases. Of the cases diagnosed as melanoma on pathology, 20 cases (87%) had concordant NGS testing results, 2 lacked molecular alterations, and 1 was insufficient for testing. CONCLUSIONS: FNA sampling of melanocytic uveal lesions is adequate for both cytologic diagnosis and NGS testing. In a subset of cases in which pathologic findings were indeterminate, NGS testing results were clarifying for diagnosis. In addition, specific molecular alterations identified can aid in evaluating prognosis and guide further management.