Consecutive Fine-needle Aspiration Research Articles

Non-invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) Lowers the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology Diagnostic Categories.

Background:The introduction of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has been shown to decrease the risk of malignancy (ROM) in The Bethesda System for Reporting Thyroid Cytopathology. This knowledge may alter the management of patients with thyroid nodules.Objectives:To correlate cytological diagnosis with histological diagnosis for establishing the ROM of all Bethesda system categories after the introduction of NIFTP.Methods:This was a retrospective cohort study. All consecutive fine-needle aspiration cytology (FNAC) specimens collected from January 1, 2013, to December 31, 2017, at King Abdullah Medical City, Jeddah, Saudi Arabia, were assessed, and patients who underwent surgical excision of thyroid nodules were further analyzed. The ROM and overall ROM for each Bethesda category were calculated with and without considering NIFTP as a malignant tumor.Results:Overall, 1066 FNAC specimens were collected, of which 281 had a surgical correlation. Our cases included 18 (6.4%) non-diagnostic (ND), 109 (38.8%) benign, 28 (9.9%) atypia/follicular lesion of undetermined significance (AUS/FLUS), 39 (13.8%) follicular neoplasm or suspicion for follicular neoplasm (FN/SFN), 20 (7.1%) suspicion for malignancy (SM), and 67 (23.8%) malignant (POM) cases. After considering NIFTP diagnosis on resection specimens, the ROM decreased as follows: ND, 38.8% to 27.7% (P = 0.2388); benign, 21.1% to 11.9% (P = 0.0343); AUS/FLUS, 50% to 39.2% (P = 0.2089); FN/SFN, 53.8% to 33.3% (P = 0.0336); SM, 85% to 75% (P = 0.2147); POM, 95.5% to 88% (P = 0.0582).Conclusion:The introduction of NIFTP would significantly decrease the ROM of thyroid FNAC in both benign and FN/SFN categories of the Bethesda system.

Prevalence and Spectrum of DICER1Mutations in Adult-Onset Thyroid Nodules

Abstract Context: DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Objective: Determine 1) the prevalence of DICER1 hotspot mutations in thyroid nodules; 2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; 3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Design: Population-based study of 14,993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot-positive cases, we selected 61, matched to DICER1 hotspot-negative nodules. We performed full sequencing of all exons and exon-intron boundaries of DICER1. Setting: Commercial and university-based laboratories in the United States and Canada Results: Among 14,993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot-positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot-negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot-negative nodules (32/61) than in DICER1 hotspot-positive nodules (4/59) (p<0.0001). Conclusions: DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer-related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.

Prevalence and Spectrum of DICER1 Mutations in Adult-onset Thyroid Nodules with Indeterminate Cytology.

DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Determine (1) the prevalence of DICER1 hotspot mutations in thyroid nodules; (2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; (3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Population-based study of 14 993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot-positive cases, we selected 61, matched to DICER1 hotspot-negative nodules. We performed full sequencing of all exons and exon-intron boundaries of DICER1. Commercial and university-based laboratories in the United States and Canada. Among 14 993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot-positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot-negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot-negative nodules (32/61) than in DICER1 hotspot--positive nodules (4/59) (P < .0001). DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer-related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.

The value of repeating fine-needle aspiration for thyroid nodules.

BACKGROUND: Fine-needle aspiration (FNA) is an invaluable technique used in the evaluation of thyroid nodules.OBJECTIVES: Evaluate the concordance of results for consecutive FNA readings.DESIGN: Retrospective, descriptive.SETTINGS: Two tertiary care centers.METHODS: Demographics were collected along with every FNA result and final pathology results for all patients (aged 9-90 years old) who underwent thyroid surgery from 2010 to 2017. The Bethesda system was used for cytology. Agreement levels were calculated and compared with final pathology.SAMPLE SIZE: Of 1237 initially included, 1134 had at least one FNA performed with results available for review.RESULTS: For the 1134 patients, demographic and clinical data were collection and a comparison was made between the three FNA results; the highest agreement was between FNA 2 and 3 (53.6%); however, the kappa value was consistently low for all comparisons, indicating a poor level of agreement overall. Also, the risk of malignancy was higher in this study than in the 2017 Bethesda system for reporting thyroid cytopathology in FNA cytology categories I and II.CONCLUSION: Repeating FNA biopsies yield different results every time; hence, there is a low level of agreement. The clinical decision should therefore include other important risk factors. Prospective studies could help shed more light on this topic.LIMITATIONS: Retrospective design.CONFLICT OF INTEREST: None.

BRAF V600E as an accurate marker to complement fine needle aspiration (FNA) cytology in the guidance of thyroid surgery in the Chinese population: evidence from over 1000 consecutive FNAs with follow-up.

Currently, several commercial molecular tests have been developed for reclassifying thyroid nodules with indeterminate fine needle aspiration cytology. These tests are quite expensive and not available in China. Previous studies demonstrated a very high prevalence of the BRAF V600E mutation in Asian people. A high incidence may result in a robust sensitivity. We conducted this study to determine the prevalence of BRAF V600E mutation and its ability to reclassify cytologically indeterminate thyroid nodules in the Chinese population. Between January 2016 and October 2018, consecutive patients who underwent a fine needle aspiration procedure and agreed to provide materials for molecular analysis in our hospital were recruited in this study. All were followed up until they had a thyroidectomy and a final pathological diagnosis or until January 2019 (those did not have surgery). A total of 1960 patients were included in this study. Until January 2019, 1240 patients underwent surgery. Using histopathological diagnosis as a gold standard, the overall sensitivity and specificity of the BRAF V600E mutational analysis for the discrimination of benign nodules from cancer in thyroid fine needle aspiration samples were 83.3% (81.0-85.3%) and 96.0% (77.7-99.8%), respectively, with an area under the ROC curve of 0.90 (95% CI 0.85-0.95, P<0.001). Among cases with indeterminate cytology, BRAF-positive cases were showing malignancy in the final pathology, and BRAF-negative cases were showing safer to be followed up. The BRAF V600E mutation is highly prevalent in the Chinese population and can accurately complement cytopathology in the guidance of thyroid surgery.Mini-abstract: The BRAF V600E mutation has both high specificity and sensitivity to predict thyroid malignancy in the Chinese population. It can accurately complement cytopathology in the guidance of thyroid surgery.

Interobserver Agreement for the International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology

Background: A number of guidelines have been developed to improve standardization of the terminology and criteria for cytologic specimens obtained from the thyroid, pancreas, lung, and salivary glands. A major goal of these guidelines is to improve reproducibility and understanding of the reporting of diagnostic results among cytopathologists and between cytopathologists and clinicians. The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology (IAC YSRB) is the most recent of these guidelines. The value of this system is, in part, dependent upon interobserver reproducibility. Design: Ninety consecutive fine-needle aspiration biopsies (FNAB) of the breast, performed over a 6-year period, were independently evaluated by 4 board-certified pathologists blinded to the original diagnoses. The 5 diagnostic categories used were those of the IAC YSRB according to published criteria for these categories. Observed agreement and chance corrected agreement (Fliess κ) were calculated. Differences in κ values were evaluated using the T statistic of Gwent. Statistical calculations were performed using STATA v16.0 (STATA Corp., College Station, TX, USA). Results: Overall agreement between observers was good. Observed unweighted agreement was 69% and weighted agreement was 91%. The majority of diagnoses were concordant (68.6%). Conclusions: Interobserver agreement of 4 cytopathologists was good using the 5 categories of the IAC YRSB (69%). Agreement was greater among pathologists with more years of experience. The IAC YSRB system appears to provide greater agreement among viewers than guidelines for cytologic specimens obtained from some other body sites (salivary gland and lung). Most discrepancies were only by a single category, with only 22/113 (19%) differing by more than one category.

Endoscopic ultrasound and fine-needle aspiration for the detection of residual nodal disease after neoadjuvant chemoradiotherapy for esophageal cancer.

Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) are potential tools for the detection of residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. This study investigated yield of EUS and FNA for detection of malignant lymph nodes (LNs) after nCRT. This was a post hoc analysis of the preSANO trial. EUS was performed 10 - 12 weeks after nCRT. 18F-fluorodeoxyglucose positron emission tomography - computed tomography (18F-FDG PET-CT) was used to guide targeting of suspicious LNs. Consecutive FNA sampling was performed for suspicious LNs identified on EUS and/or PET-CT. EUS nodal staging was compared with histopathological examination of the resection specimen. The primary outcome was the proportion of correctly identified patients with malignant LNs by radial EUS. 101 consecutive patients were included: 79 patients had no malignant LNs, of whom 62 were classified correctly by EUS (specificity 78 %); 22 patients had malignant LNs, of whom 11 were identified (sensitivity 50 %). Six of these patients had ≥ 1 suspicious LN not fulfilling EUS criteria (round, hypoechogenic, > 5 mm). Malignant LNs in falsely negative patients were predominantly located at distal LN stations. Specificity and sensitivity of conclusive FNA outcomes were 100 % (7/7) and 75 % (3/4), respectively. FNA outcome was uncertain in eight patients, half of whom appeared to have malignant LNs. EUS only detected 50 % of patients with malignant LNs 10 - 12 weeks after nCRT. To optimize sensitivity and minimize the risk of missing residual disease, FNA of LNs should be performed even in cases of low endosonographic suspicion.

Molecular Testing of Nodules with a Suspicious or Malignant Cytologic Diagnosis in the Setting of Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP).

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor characterized by frequent RAS mutations and an absence of the BRAF V600E mutation commonly seen in classical papillary thyroid carcinoma (cPTC). The ability to differentiate potential NIFTP/follicular variant of papillary thyroid carcinoma (FVPTC) from cPTC at the time of fine-needle aspiration (FNA) can facilitate conservative management of NIFTP. The aim of the current study was to investigate how molecular testing may add to cytologic assessment in the pre-operative differentiation of potential NIFTP/FVPTC and cPTC. We had previously evaluated cytologists' ability to prospectively distinguish potential NIFTP/FVPTC from cPTC in a cohort of 56 consecutive FNAs diagnosed as malignant or suspicious for malignancy. We utilized this cohort to perform molecular analysis. Detected molecular abnormalities were stratified into two groups: (1) those supporting malignancy and (2) those supporting a diagnosis of potential NIFTP/FVPTC. The cytologists' characterization of cases and the detected molecular alterations were correlated with the final histologic diagnoses. Molecular testing was performed in 52 (93%) of the 56 cases. For the 37 cases cytologists favored to be cPTC, 31 (84%) had a molecular result that supported malignancy (28 BRAF V600E mutations, 2 NTRK1 fusions, 1 AGK-BRAF fusion). For the 8 cases that were favored to be NIFTP/FVPTC by cytologists, 7 (88%) had a molecular result that supported conservative management (1 NRAS mutation, 6 wild-type result). Seven cases were designated as cytomorphologically indeterminate for NIFTP/FVPTC or cPTC, of which 6 (86%) had a molecular result that would have aided in the pre-operative assessment of potential NIFTP/FVPTC or cPTC/malignancy. These included 3 BRAF V600E mutations in nodules that were cPTC on resection, an HRAS mutation, and a wild-type result in the 2 nodules that were NIFTP, and a TERT promoter mutation along with an NRAS mutation in a poorly differentiated thyroid carcinoma. For nodules with an FNA diagnosis of suspicious for malignancy or malignant, cytologists can differentiate most cases of potential NIFTP/FVPTC from cPTC. However, molecular testing may be valuable for a subset of cases, especially those that are indeterminate for potential NIFTP/FVPTC versus cPTC based on cytologic features alone.

Fine-needle Aspiration of Thyroid Nodules: Is it Worth Repeating?

The fine-needle aspiration has a significant role in assessing the malignancy risk of thyroid nodules. There is uncertainty regarding the value of repeat fine-needle aspiration in benign nodules. This study aims to evaluate the concordance of results in consecutive fine-needle aspiration and to study the relevance of repetition in benign results. Retrospective study of the 4800 thyroid nodules fine-needle aspiration held in Instituto de Patologia e Imunologia Molecular da Universidade do Porto between January 1, 2014 and May 2, 2016. Of the initial sample, we selected the repeated fine-needle aspiration on the same nodule. The first fine-needle aspiration result of the 309 nodules underwent revaluation was non-diagnostic in 103 (33.3%), benign in 120 (38.8%) and atypia/follicular lesion of undetermined significance in 86 (27.8%). The agreement between the first and second fine-needle aspiration was significantly higher in cases with an initial benign result (benign: 85.8%, non-diagnostic: 27.2% and atypia/follicular lesion of undetermined significance: 17.4%, p < 0.005). The fine-needle aspiration repeating motifs in initially benign nodules (n = 78) were repetition suggestion in 58, nodule growth in 17 and suspicious ultrasonographic features in 3. The fine-needle aspiration repetition in nodules with initial non-diagnostic and atypia/follicular lesion of undetermined significance result changed the initial diagnosis in a significant proportion of patients, modifying their therapeutic approach. The high concordance of results in initially benign nodules makes fine-needle aspiration repetition not cost-effective in most cases. The fine-needle aspiration should be repeated when the initial cytology result is non-diagnostic or atypia/follicular lesion of undetermined significance.

Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology.

Recent discussions have focused on redefining noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC) as a neoplasm rather than a carcinoma. This study assesses the potential impact of such a reclassification on the implied risk of malignancy (ROM) for the diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The study consisted of consecutive fine-needle aspiration biopsy (FNAB) cases collected between January 1, 2013 and June 30, 2014 from 5 academic institutions. Demographic information, cytology diagnoses, and surgical pathology follow-up were recorded. The ROM was calculated with and without NI-FVPTC and was presented as a range: all cases (ie, overall risk of malignancy [OROM]) versus those with surgical follow-up only. The FNAB cohort consisted of 6943 thyroid nodules representing 5179 women and 1409 men with an average age of 54 years (range, 9-94 years). The combined average ROM and OROM for the diagnostic categories of TBSRTC were as follows: nondiagnostic, 4.4% to 25.3%; benign, 0.9% to 9.3%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 12.1% to 31.2%; follicular neoplasm (FN), 21.8% to 33.2%; suspicious for malignancy (SM), 62.1% to 82.6%; and malignant, 75.9% to 99.1%. The impact of reclassifying NI-FVPTC on the ROM and OROM was most pronounced and statistically significant in the 3 indeterminate categories: the AUS/FLUS category had a decrease of 5.2% to 13.6%, the FN category had a decrease of 9.9% to 15.1%, and the SM category had a decrease of 17.6% to 23.4% (P < .05), whereas the benign and malignant categories had decreases of 0.3% to 3.5% and 2.5% to 3.3%, respectfully. The trend of the effect on the ROM and OROM was similar for all 5 institutions. The results from this multi-institutional cohort indicate that the reclassification of NI-FVPTC will have a significant impact on the ROM for the 3 indeterminate categories of TBSRTC.

Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology.

Background: Fine-needle aspiration (FNA) cytology is a common approach to evaluate thyroid nodules. It offers definitive diagnosis of a benign or malignant nodule in the majority of cases. However, 10–25% of nodules yield one of three indeterminate cytologic diagnoses, leading to suboptimal management of these patients. Atypia of undetermined significance/follicular lesion of undermined significance (AUS/FLUS) is a common indeterminate diagnosis, with the cancer risk ranging from 6% to 48%. This study assessed whether a multi-gene next-generation sequencing (NGS) assay can offer significant improvement in diagnosis in AUS/FLUS nodules.Methods: From May 2014 to March 2015, 465 consecutive FNA samples with the cytologic diagnosis of AUS/FLUS underwent prospective molecular testing using the ThyroSeq v2.1 panel. The panel included 14 genes analyzed for point mutations and 42 types of gene fusions occurring in thyroid cancer. In addition, eight genes were assessed for expression in order to evaluate the cell composition of FNA samples. Ninety-eight (21%) of these nodules had definitive surgical (n = 96) or nonsurgical (n = 2) follow-up and were used to determine the assay performance.Results: Among 465 AUS/FLUS nodules, three were found to be composed of parathyroid cells and 462 of thyroid follicular cells. Of the latter, 31 (6.7%) were positive for mutations. The most frequently mutated genes were NRAS and HRAS, and overall point mutations in seven different genes and five types of gene fusions were identified in these nodules. Among 98 nodules with known outcome, histologic analysis revealed 22 (22.5%) cancers. ThyroSeq v2.1 was able to classify 20/22 cancers correctly, showing a sensitivity of 90.9% [confidence interval (CI) 78.8–100], specificity of 92.1% [CI 86.0–98.2], positive predictive value of 76.9% [CI 60.7–93.1], and negative predictive value of 97.2% [CI 78.8–100], with an overall accuracy of 91.8% [CI 86.4–97.3].Conclusions: The results of the study demonstrate that the ThyroSeq v2.1 multi-gene NGS panel of molecular markers provides both high sensitivity and high specificity for cancer detection in thyroid nodules with AUS/FLUS cytology, which should allow improved management for these patients.

Evaluation of the Real-Q BRAF V600E Detection Assay in Fine-Needle Aspiration Samples of Thyroid Nodules

Recently, several molecular assays for detecting the BRAF V600E mutation in fine-needle aspiration (FNA) specimens have been developed. Herein, we tested 294 consecutive FNA samples from patients with thyroid nodules with the Real-Q BRAF V600E detection assay (Real-Q). These results were compared with an allele-specific PCR-based kit using dual-priming oligonucleotides (AS-PCR). Any discordant results between the two tests were also analyzed by mutant enrichment with 3'-modified oligonucleotide sequencing. A total of 128 cases were confirmed histologically; of these, 121 were diagnosed as papillary thyroid carcinoma (PTC). The BRAF mutation was detected by Real-Q and AS-PCR testing in 80.2% (95% CI, 71.9%-86.9%) and 76.9% (95% CI, 68.3%-84.0%), respectively, of FNA specimens with PTC. Combining the BRAF V600E molecular assays (Real-Q and AS-PCR) with cytological diagnoses of malignant and suspicious for malignant cells, the detection rates (sensitivity) of Real-Q and AS-PCR for diagnosis of PTC increased to 94.2% (95% CI, 88.4%-97.6%) and 92.6% (95% CI, 86.4%-96.5%), respectively. In conclusion, the detection of BRAF V600E mutations in PTC by Real-Q is compatible to that of AS-PCR.

Role of Fine Needle Aspiration Cytology in the Diagnosis of Skin and Superficial Soft Tissue Lesions: A Study of 510 Cases.

Diseases of the skin and superficial subcutaneous soft tissues present with a wide array of lesions ranging from nonspecific dermatoses and inflammatory lesions to frank neoplasms. Though cytopathology is an excellent diagnostic tool in routine dermatologic practice, studies relating to histopathological and cytological correlation are sparse. The aim of this study was to analyze the concordance rate between cytological and histopathological diagnosis of skin and superficial soft tissue lesions. We retrospectively studied 510 consecutive fine needle aspiration cytology findings of cases from North Bengal Medical College and Hospital and correlated their diagnoses based upon cytological and histopathological grounds. Out of the 510 cases studied, 253 were non neoplastic lesions and 257 were neoplastic. A high degree of concordance was observed (100% for malignant and 96.15% for benign lesions) when these two diagnostic modalities were compared. Histopathological correlation was possible in all malignant, 52/189 (27.51%) of benign and 27/253 (10.67%) of non-neoplastic lesions. Sensitivity and specificity of diagnoses were 95.31% and 97.6%, respectively. It can be safely concluded that fine needle aspiration cytology is a rapid, reliable and fairly accurate tool for initial triage and treatment of skin and superficial soft tissue lesions.

Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay.

Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules. The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples. In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor γ (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%). The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients.

Use of blue dye in sentinel lymph node biopsy: Time to reevaluate

Use of blue dye in sentinel lymph node biopsy: Time to reevaluate

Fluorescence in situ hybridization as an adjunct tool in the diagnosis of primary and metastatic renal cell carcinoma in fine needle aspiration specimens

We investigated the role of fluorescence in situ hybridization (FISH) in the diagnosis of primary renal neoplasms and lesions suspicious for metastatic renal cell carcinoma. Consecutive fine-needle aspiration biopsies (FNAB) of 39 renal masses and 41 metastatic tumours suspicious for renal cell origin were assessed with an immunohistochemical panel for CK7, RCC antigen, CD10, AMACR, PAX8, vimentin, and CD117. In addition, FISH was performed using probes for chromosomes 1p, 3p, 7, 17, X, and Y. A total of 31 of 39 primary renal masses and 33 of 41 metastatic tumors suspicious for renal origin demonstrated typical cytological and immunohistochemical (IHC) features of subtypes of renal neoplasms (40 clear cell renal cell carcinoma (RCC), 20 papillary RCC, and 4 renal oncocytomas). FISH analysis of 15 randomly selected cases each of primary and metastatic lesions revealed chromosomal abnormalities consistent with the diagnosis in 73% of these cases. Of 8 primary renal masses demonstrating atypical microscopic features and noncontributory IHC profiles, FISH was helpful in subtyping 5 (62%) of these lesions (2 clear cell RCC, 1 solid variant of oncocytic papillary RCC, 1 mixed clear cell and papillary RCC, and 1 chromophobe RCC with papillary architecture). Of 8 metastatic tumors clinically suspicious for renal cell origin and supportive, but nondiagnostic IHC, FISH revealed supportive chromosomal changes in 6 (75%) cases. In conclusion FISH analysis on FNAB material, even with limited tissue, may be contributory to the diagnosis and subtyping of RCC in diagnostically challenging biopsies.

Fine needle aspiration cytology of lesions of liver and gallbladder: An analysis of 400 consecutive aspirations.

Background:Patients presenting with mass lesions of liver and gallbladder are a common occurrence in a cancer hospital in north central part of India. Fine-needle aspiration cytology (FNAC) serves as first line of pathological investigations, but there are pros and cons involved.Aim:The main objective of the present study was to establish adequacy of the procedure and to find out diagnostic pitfalls. An attempt was made to analyze inconclusive and inadequate aspirations.Materials and Methods:A total of 400 consecutive fine-needle aspirates of liver, belonging to 328 cases over a period of 2 years, were analyzed. Hematoxylin and eosin and May-Grόnwald-Giemsa stains were used. Chi-square test was carried out to compare significant degree of difference in different kind of diagnosis.Results:Out of 400 aspirations, 289 (72.2%) were adequate, 75 (18.7%), inconclusive and 36 (9%), inadequate. Among positive aspirations the most common was metastatic adenocarcinoma, 128 (44.2%). The positive diagnosis and adequate aspirations were significantly high (P < 0.0001). Major differential diagnostic problems were: Distinguishing the poorly differentiated hepatocellular carcinoma from the metastatic adenocarcinoma; and leukemia/lymphoma from other malignant round cell tumors. Common diagnostic pitfalls were repeated aspirations from the necrotic area and aspiration of atypical, disorganized and reactive hepatocytes, adjacent to a metastasis. No complications were observed.Conclusion:FNAC can be used successfully for the diagnosis of liver and gallbladder lesions, thus avoiding open biopsy. Study indicates the potential of using FNAC in clinical intervention where the incidence of gall-bladder and liver cancer is very high and open biopsy and surgery are not an option.

Endocrinologist-Performed Ultrasound-Guided Fine Needle Aspiration of Thyroid Nodules in Toronto

Radiologists traditionally perform ultrasound-guided fine needle aspiration (FNA) of thyroid nodules in Canada, with selection of nodules for FNA based primarily on nodule size. Most updated international guidelines for thyroid nodule management, however, recommend a consideration of medical history and sonographic features to delineate nodule/s for FNA. This is a retrospective analysis of FNAs performed by an endocrinologist in 3 centres of the Greater Toronto Area (Malton, Oakville and Thornhill). The study dataset includes 585 consecutive FNAs performed among 504 patients, with all specimens reported by a single cytopathologist. Cytology was reported as benign in 75%, malignant or suspicious in 5%, atypia in 3%, follicular neoplasm in 2% and nondiagnostic in 16% samples. Malignancy rate (suspicious/malignant cytology) was positively associated with male gender, age, radiation history and sonographic features (hypoechogenecity, irregular borders, microcalcifications and intranodular vascularity). Endocrinologist documented that high suspicion on FNA encounter was most predictive for malignancy. Nodule size (range 7 mm to 7.4 cm) was not associated with either malignancy or nondiagnostic rates. Eight percent sufficiency was observed on repeat FNAs among subjects with previous FNAs performed at other facilities (n=162), with 6% malignancy rate for previous nondiagnostic cytology reports; 20% malignancy rate for previous cytology reported as atypia. A combination of medical history and sonographic features documented by an endocrinologist yields a greater prediction of malignancy rates vs. the commonly used size criteria for selecting thyroid nodules for FNA in Canada. Overall, FNA sufficiency and malignancy rates in this Toronto-based study are consistent with published global literature.

Nondiagnostic fine-needle aspirations of the thyroid: is the risk of malignancy higher?

BackgroundNondiagnostic fine-needle aspirations (FNAs) pose a dilemma in the management of patients with thyroid nodules. In most cases, these patients undergo either repeat FNA or surgical resection. However, a significant number of patients will only be observed, assuming that the risk of malignancy is low. Therefore, the purpose of this study was to determine whether the risk of malignancy is higher in patients with thyroid nodules and nondiagnostic FNAs. MethodsWe reviewed reports from 4286 consecutive FNA biopsies performed on patients with thyroid nodules at our institution between 2002 and 2010. We divided FNAs into two categories: diagnostic and nondiagnostic. We collected demographic, follow-up, and pathology data from both groups and then analyzed them with analysis of variance and chi-square tests. ResultsOf the 4286 FNAs, 259 were classified as nondiagnostic (6%). We saw no significant differences in age or gender between patients with diagnostic versus nondiagnostic FNAs. Of the patients with nondiagnostic FNAs, 62 underwent diagnostic thyroidectomy (24%), 74 had a repeat FNA (29%), and 123 had observation only (47%); thus, 136 patients had a cytologic or pathologic diagnosis. Patients with nondiagnostic FNAs had a significantly higher rate of all types of thyroid cancer, compared with those with diagnostic FNAs (12% versus 5%, respectively; P < 0.001). Impressively, the chance of papillary thyroid cancer was twofold higher in patients with nondiagnostic FNAs. ConclusionsThe percentage of nondiagnostic FNA at our institution during this period (6%) was relatively low. However, the incidence of malignancy in these patients was significantly higher. Therefore, we recommend that patients with thyroid nodules and nondiagnostic FNAs undergo either repeat biopsy or diagnostic thyroidectomy.

Molecular Diagnostics of Melanoma Fine-Needle Aspirates

Patients with advanced-stage melanoma harboring a BRAF mutation are candidates for BRAF inhibition as a therapeutic strategy. The use of fine-needle aspiration (FNA) to diagnose metastatic melanoma is increasing. Studies examining the predictive value of BRAF mutation analysis on melanoma FNAs via correlation with follow-up excision findings are lacking. We examined 37 consecutive FNA cases of metastatic melanoma in which the aspirated lesion was subsequently excised. DNA was purified from Diff-Quik-stained FNA smears and tissue blocks from corresponding excisions in parallel. BRAF mutation status was successfully obtained from both specimen types in 34 (92%) of 37 cases. BRAF mutations were detected in 12 (35%) of 34 cases-11 V600E and 1 V600K. Results of BRAF mutational analysis were concordant in all 34 FNA smear/tissue excision pairs. Thus, melanoma FNA for molecular diagnostics represents a rapid, minimally invasive, and effective management strategy in this era of precision medicine.