Fine-needle Aspiration Cytopathology Research Articles

RAPID ON-SITE EVALUATION AND MICRONUCLEUS SCORING IN BREAST LESIONS FINE NEEDLE ASPIRATION CYTOPATHOLOGY BY NEW IAC YOKOHAMA SYSTEM OF REPORTING

Objective: The objective of the study is to report all fine needle aspiration cytopathology (FNAC) cases of lump breast as per New Yokohama classification 2016, to highlight the importance of rapid onsite evaluation (ROSE) in breast cytology at the time of FNAC, and to assess the relationship between micronucleus (MN) scoring and various breast lesions in cytology. Methods: The study was conducted on 70 patients with breast lumps in the Department of Pathology in Government Medical College, Patiala, and comprised evaluation of ROSE and MN scoring in breast FNAC by the use of New Yokohama system of reporting. Results: On ROSE, 11 out of 70 patients were categorized under category I according to the Yokohama system of reporting and on the same sitting with repeat FNAC after performing the ROSE; nine cases were upgraded for cytological reporting and two remained in category I. According to as per the International Academy of Cytology (IAC) Yokohama system of reporting (2016) cases were categorized as category I – 2 (2.9%), category II – 46 (65.7%), category III – 7 (10.1%), category IV – 5 (7.1%), and category V – 10 (14.2%). In MN scoring, MN with the highest score of 14–17/1000 epithelial cells was in category V (malignant), and the lowest score was 0–1/1000 epithelial cells in category II (benign). Conclusion: ROSE is an easy, safe, and cost-effective method. IAC Yokohama system for reporting (2016) provides a comprehensive way of categorizing various breast lesions on FNAC with clinical correlation. MN score is a good biomarker in differentiating benign, atypical, and malignant breast lesions.

Stepwise analysis of thyroid diagnostic modalities with genomic imprinting detection.

The current preoperative malignancy risk evaluation for thyroid nodules involves stepwise diagnostic modalities including ultrasonography, thyroid function serology and fine-needle aspiration (FNA) cytopathology, respectively. We aimed to substantiate the stepwise contributions of each diagnostic step and additionally investigate the diagnostic significance of quantitative chromogenic imprinted gene in-situ hybridization (QCIGISH)-an adjunctive molecular test based on epigenetic imprinting alterations. A total of 114 cytopathologically-diagnosed and histopathologically-confirmed thyroid nodules with complete ultrasonographic and serological examination records were evaluated using QCIGISH in the study. Logistic regression models for thyroid malignancy prediction were developed with the stepwise addition of each diagnostic modality and the contribution of each step evaluated in terms of discrimination performance and goodness-of-fit. From the baseline model using ultrasonography [area under the receiver operating characteristics curve (AUROC): 0.79; 95% confidence interval (CI): 0.71-0.86], significant improvements in thyroid malignancy discrimination were observed with the stepwise addition of thyroid function serology (AUROC: 0.82; 95% CI: 0.74-0.90; P=0.23) and FNA cytopathology (AUROC: 0.88; 95% CI: 0.81-0.94; P=0.02), respectively. The inclusion of QCIGISH as an adjunctive molecular test further advanced the preceding model's diagnostic performance (AUROC: 0.95; 95% CI: 0.91-1.00, P=0.007). Our study demonstrated the significant stepwise diagnostic contributions of standard clinical assessments in the malignancy risk stratification of thyroid nodules. However, the addition of molecular imprinting detection further enabled a more accurate and definitive preoperative evaluation especially for morphologically indeterminate thyroid nodules and cases with potentially discordant results among standard modalities.

Comparison of Fine-Needle Aspiration Cytopathology with Histopathological Examination of the Thyroid Gland in Patients Undergoing Elective Thyroid Surgery: Do We Still Need Fine-Needle Aspiration Cytopathology?

Background: The thyroid gland is responsible for various functions, but it is susceptible to pathologies. The gold standard for preliminarily diagnosing thyroid abnormalities is fine-needle aspiration cytology (FNAC), although it has some limitations; thus, postoperative histopathological examination confirms the diagnosis. The aim of the present study was to compare preoperative FNAC results with postoperative histopathological examination. Methods: This study is a retrospective study based on FNAC and postoperative histopathology examination, which were compared and analyzed. Results: This study included 344 patients between 18 and 86 years old (mean age: 53.06 ± 13.89), comprising 274 females and 70 males (mean ages 52.72 ± 13.86 and 54.39 ± 14.05, respectively) with a 3.9:1 female-to-male ratio. Statistical significance between the FNAC and histopathology results was observed (p = 0.0000), and 86 (25.00%) patients were found to have been diagnosed incorrectly based on FNAC. The sensitivity of FNAC was 92.31%, and its specificity was 82.08%, with positive and negative predictive values of 68.57% and 96.08%, respectively. Conclusions: Due to many factors, FNAC may lead to over- or under-diagnosis, increasing the chances of complications associated with the selected treatment. However, we do not have any other more accurate tools; therefore, FNAC should still remain as the gold standard of preliminary examination.

Integration of ultrasound-based radiomics with clinical features for predicting cervical lymph node metastasis in postoperative patients with differentiated thyroid carcinoma.

The primary objective was to establish a radiomics model utilizing longitudinal +cross-sectional ultrasound (US) images of lymph nodes (LNs) to predict cervical lymph node metastasis (CLNM) following differentiated thyroid carcinoma (DTC) surgery. A retrospective collection of 211 LNs from 211 postoperative DTC patients who underwent neck US with suspicious LN fine needle aspiration cytopathology findings at our institution was conducted between June 2021 and April 2023. Conventional US and clinicopathological information of patients were gathered. Based on the pathological results, patients were categorized into CLNM and non-CLNM groups. The database was randomly divided into a training cohort (n = 147) and a test cohort (n = 64) at a 7:3 ratio. The least absolute shrinkage and selection operator algorithm was applied to screen the most relevant radiomic features from the longitudinal + cross-sectional US images, and a radiomics model was constructed. Univariate and multivariate analyses were used to assess US and clinicopathological significance features. Subsequently, a combined model for predicting CLNM was constructed by integrating radiomics, conventional US, and clinicopathological features and presented as a nomogram. The area under the curves (AUCs) of the longitudinal + cross-sectional radiomics models were 0.846 and 0.801 in the training and test sets, respectively, outperforming the single longitudinal and cross-sectional models (p < 0.05). In the testing cohort, the AUC of the combined model in predicting CLNM was 0.901, surpassing that of the single US model (AUC, 0.731) and radiomics model (AUC, 0.801). The US-based radiomics model exhibits the potential to accurately predict CLNM following DTC surgery, thereby enhancing diagnostic accuracy.

Pitfalls in Thyroid Fine Needle Aspiration Cytopathology: An Approach to Atypical Findings.

Thyroid nodules are prevalent among the general population, thus imposing substantial demands upon healthcare providers to establish effective management paradigms when investigating these lesions. A pivotal component in the diagnostic process involves the cytomorphologic evaluation of fine needle aspiration (FNA) specimens extracted from the nodule under scrutiny. This examination serves the critical purpose of enabling a comprehensive assessment for the risk of either a neoplasm or malignancy, thereby providing the clinical team with the requisite information to render decisions regarding potential surgical intervention and/or a structured clinical follow-up. A subset of FNA specimens obtained from the thyroid gland present a vexing challenge for interpretation and cannot be classified based on cytomorphology as either benign or malignant and are classified as "indeterminate" for neoplasm or malignancy. The indeterminate thyroid FNA diagnosis in the third iteration of the Bethesda classification are termed as "atypia of undetermined significance" (AUS). The thyroid FNA specimens classified as "atypical" constitutes a perplexing category, necessitating considerations such as repeated cytological evaluations, supplementary molecular analyses, diagnostic lobectomy, or vigilant surveillance. This review article draws upon the most recent Bethesda classification guidelines and delineates various potential pitfalls encountered during the interpretation of atypia observed in thyroid fine needle aspiration and histopathologic counterparts. Additionally, it proffers strategic algorithms devised to effectively navigate these diagnostic challenges.

SAT571 When Two Is Too Few: Bethesda IV Pathology On Repeat Thyroid Fine Needle Aspiration

Abstract Disclosure: C.M. Godar: None. A.J. Spiro: None. M.K. Shakir: None. T.D. Hoang: None. Background: The 2015 American Thyroid Association Guidelines for Adult Patients with Thyroid Nodules provide a strong recommendation against routine ultrasound surveillance of thyroid nodules for which two benign fine needle aspiration (FNA) cytology results have been previously obtained. Strict adherence to these guidelines may hinder detection of malignancy, especially in large nodules where there is potential to miss heterogeneous pathology based on sampling technique. Clinical Case: A 36-year-old female was evaluated for surveillance of a large non-toxic multinodular goiter. Thyroid ultrasound demonstrated a dominant right thyroid nodule greater than 7 centimeters in size. The patient had undergone FNA of this nodule in 2014 and 2019 with Bethesda II (benign) cytopathology results. A chest x-ray showed tracheal deviation without evidence of narrowing. She noted a sensation of neck pressure without dysphagia or shortness of breath. She denied fatigue, heat or cold intolerance, hand tremor, or pretibial myxedema. She denied a family history of thyroid cancer or any history of neck irradiation. Due to new compressive symptoms a repeat FNA was performed. Three passes were performed with adequate samples, and the final FNA cytopathology demonstrated a Hurthle cell oncocytic-type follicular neoplasm with Bethesda IV classification. The sample was submitted for ThyGeNEXTTM and ThyraMIRv2TM molecular testing, which returned with NRAS q61R mutation of moderate-to-high risk of malignancy (65-75%). The patient was subsequently referred for total thyroidectomy with pending surgery date. Discussion: The current ATA guidelines offer a cost-effective surveillance strategy for the vast majority of patients with thyroid nodules. False negative FNA results are rare and are reported to occur in about 1% of cases1. As in this vignette, it is reasonable to perform an additional FNA after two consecutive Bethesda II results in nodules with clinically significant growth, new compressive symptoms, or if there is concern for incomplete sampling in nodules of large size. During an FNA, care should be taken to gently move the needle at various angles to capture follicular cells from different areas within a nodule. Large nodules should be sampled via multiple, separate skin entry points when feasible. Judicious use of repeat FNA along with these sampling techniques may help to prevent under-diagnosis in nodules containing multifocal areas of heterogeneous pathology. Reference: 1) Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S, Attard M, Lamartina L, Nicolucci A, Filetti S. 2015. The natural history of benign thyroid nodules. JAMA 313:926-935 Presentation: Saturday, June 17, 2023

SAT522 Validating Molecular Testing As An Adjunct To Fine Needle Aspiration In Pediatric Thyroid Malignancy

Abstract Disclosure: A. Aekka: None. N. Arva: None. M. Raval: None. J. Rastatter: None. S.D. Finkelstein: Employee; Self; Interpace Biosciences. J. Levine: Employee; Self; Interpace Biosciences. J. Josefson: None. The standard diagnostic approach for thyroid malignancy includes evaluation of cytopathology derived from thyroid fine needle aspiration (FNA). Nearly 40% of pediatric cases have indeterminate FNA results, and there is no clear consensus regarding the management of these cases. Molecular analysis is beneficial in increasing diagnostic yield and informing treatment stratification in adults, although its use remains limited in pediatrics. This study sought to assess the validity of next-generation sequencing mutational analysis and microRNA (miRNA)-based risk classification of FNA cytopathology derived from a single-center cohort of pediatric patients. The study hypothesized that molecular analyses improve diagnostic performance of FNA for children with thyroid cancer. Interpace Diagnostics’ validated multiplatform tool comprised of ThyGeNEXT (mutational panel capturing 10 oncogene sequence variants and 38 fusions) and ThyraMIR (miRNA risk classifier including 11 miRNA markers) was utilized for this study. Multiplatform testing was performed on 27 archived FNA thyroid samples collected from patients ages 7-20 years (mean age 14.1 years, 78% female). Molecular results were compared with final surgical pathology or repeat FNA results to determine validity. Surgical pathology confirmed papillary thyroid carcinoma in 14 patients and benign pathology in 6 patients. Repeat FNA confirmed benign pathology in 2 patients. Surgical pathology or repeat FNA was unavailable for 5 cases, all of which had benign initial cytopathology. The most common mutational finding was BRAF_V600E (6/14) followed by RET-PTC fusions (3/14). MiRNA findings were as follows: 16 high-risk expression profiles, 3 low-risk expression profiles, and 8 negative profiles. The validation analysis included 22 samples that had corresponding surgical or repeat FNA results. All cases of malignancy demonstrated high-risk miRNA profiles and all benign cases demonstrated negative or low-risk miRNA profiles. Multiplatform molecular testing demonstrated 100% sensitivity, 87.5% specificity, 93.3% positive predictive value, and 100% negative predictive value in detecting malignant versus benign pathology in our population. Molecular analyses appear to be a valid adjunct to FNA in pediatric thyroid cancer evaluation. Incorporation of molecular diagnostics advances precision medicine in pediatric thyroid care and may better inform presurgical treatment stratification, mitigate risks associated with unnecessary procedures, and ultimately improve outcomes for children and adolescents with thyroid nodules. Presentation Date: Saturday, June 17, 2023

B-392 Standardization of Nucleic acid Extraction Method From Thyroid Fine Needle Aspiration (FNA) Cells on Stained and Fixed Slides for Next-Generation Sequencing Protocols

Abstract Background Thyroid Fine Needle Aspiration (FNA) cytopathology is the best method for histological classification of thyroid nodules. However, between 20%–30% of thyroid nodules show indeterminate classification and are often referred for surgery due to the malignancy risk. Post-surgical histological reports indicate that 84% of these cases are benign, highlighting a high rate of unnecessary surgeries. In this sense, molecular approaches using next-generation sequencing (NGS) have been useful to confirm benignity or malignancy. As important as the choice of a powerful methodology to evaluate different genes simultaneously such as NGS, is the standardization of nucleic acid extraction methods to allow sufficient quality recovery of these molecules. Pre-analytical steps involved in FNA slide preparation include fixation and stain methods that contribute to the low quality and poor recovery of nucleic acid, representing a great challenge to NGS analysis. Thus, this work aims to describe a standardization of nucleic acid extraction method from FNA slides for NGS protocols. Methodology Nucleic acid isolation from 30 FNA samples collected between 2016–2022 were performed by Trizol or RecoverAll kits, according to the manufacturer’s instructions (ThermoScientific). Initially, cells’ slides were counted in an optical microscope, considering cell clusters &amp;gt;10 (equivalent to 1 counter unit). Before extractions with Trizol, the slides were submerged in xylene for 15 min. For RecoverAll extractions, the varnished slides were previously exposed to dry ice for 5 min, while the slides containing coverslip were also exposed to dry ice and submerged in xylene for 15 min. In all cases, the slides were hydrated before scraping and then extracted. Subsequently, the extraction of whole slides and split slides was tested. To split slides, one-half of the slide was separated for RNA extraction, while the remaining half was for DNA extraction. Then, the DNA/RNA were quantified using the Qubit™ 4 Fluorometer equipment (ThermoScientific) and concentrated using Amicon® Ultra filters (Millipore). Results The DNA and RNA quantifications range from 0.0720–1.77 ng/µL and 0.508–7.43 ng/µL, respectively. Among samples, 12% (DNA) and 62.5% (RNA) presented concentration below the quantification limit (too low). Four samples extracted with Trizol did not obtain recovery of nucleic acid and this methodology was discontinued. The use of Amicon® filter improved all samples’ yield. The number of thyroid cell clusters was not proportional to the amount of DNA/RNA recovered. The split slides showed worst RNA/DNA recovery, being ideal to use at least two slides for each patient since co-extraction using the RecoverAll kit was not possible. Conclusion The isolations of nucleic acid from FNA slides are essential to performing subsequent molecular tests, such as NGS. However, specific protocols for nucleic acid extraction from FNA slides are hardly found in the literature. This work showed the combination of methodologies that allowed the scraping of material from FNA slides by exposure to dry ice in samples with varnish or coverslip. The nucleic acid recovery capacity described for this type of sample indicates a way of possibilities to improve the FNA extraction methodology.

Detailed fine needle aspiration cytopathology findings of noninvasive follicular thyroid neoplasm with papillary-like nuclear features with nuclear grading correlated to that of biopsy and Bethesda category and systematic review.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses diagnostic challenge in fine needle aspiration cytopathology (FNAC). We aimed first to document our FNAC Bethesda categories (BCs) for all of our NIFTPs and compare our findings with those in the literature with series containing at least 14 cases each. Cases with final histopathological diagnoses of NIFTP and their preoperative FNAC were retrieved from 2006 to 2022 and our cytopathological BCs were documented. Then the slides were re-reviewed in a blinded manner for detailed classification and the results of both the BCs and blinded reclassification were compared with series in the literature for both BCs and detailed cytopathological review of the cases. Thyroid FNACs of 43 out of 86 patients with final NIFTP diagnoses were obtained. Females composed 72.1% (F/M: 31/12); mean age and mean tumor diameter was 47.6 (19-72 years) and 23.4 mm (7-60 mm), respectively. Totally 81.4% (35/43) were classified in the "indeterminate" diagnostic categories; namely 44.2% (19/43) were reported as atypia of undetermined significance (AUS; BC III), 20.9% (9/43) were follicular neoplasm (FN; BC IV), and 16.3% (7/43) were suspicious for malignancy (SM; BC V). No patient was diagnosed as positive for malignancy (BC VI), preoperatively. Detailed cytomorphologic reevaluation revealed heterogeneous cytopathologic findings and nuclear grade (especially nuclear enlargement, membrane irregularity and elongation) significantly increased with respect to BCs. Systematic review confirmed extremely heterogeneous cytomorphologic nature of NIFTP. NIFTPs were categorized most frequently as AUS, followed by FN and SM on FNAC. Our re-review were not able to specify features solely unique to NIFTP alone but may distinguish these cases from classic papillary thyroid carcinoma.

Degenerative atypia in benign thyroid nodules: a potential diagnostic pitfall on fine-needle aspiration.

Benign (B) follicular lesions of the thyroid are among the most encountered specimens on fine needle aspiration (FNA). Although FNA and The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) remain highly accurate, minimally invasive and robust tools in triaging thyroid nodules, false positive (FP) diagnoses may still occur. Endocrine-type degenerative atypia can cause diagnoses of suspicious for malignancy (SFM) or malignant (M), resulting in overtreatment and exposure to undue surgical risk in patients. We performed a multi-institutional retrospective clinicopathologic correlation of benign thyroid nodules with degenerative atypia on FNA. Review of cytologic material was conducted to identify potential cytomorphologic features which may have prompted these diagnoses. Among 342 patients with benign thyroid nodules harboring degenerative atypia, 123 had available preceding FNA cytopathology. TBSRTC nondiagnostic, B, atypia of undetermined significance, follicular neoplasm, SFM, and M, comprised 3.3%, 49.6%, 30.1%, 13.0%, 2.4%, and 1.6% of cases. Among patients with FP diagnoses (SFM and M), 100% underwent total thyroidectomy, and 40.0% underwent additional neck lymph node dissections. Among remaining patients, 61.0%, 39.0%, and 0% underwent lobectomy, thyroidectomy, and lymph node dissection. The number of patients who underwent total thyroidectomy was significantly different (P = 0.03) between those with FP nodules and those without. We demonstrate that 4.1% of nodules harboring endocrine-type degenerative atypia may be given FP diagnoses on initial FNA. Such atypia may be indistinguishable from that of Graves' Disease, dyshormonogenic goiter, and radiation therapy. FP diagnoses of degenerative atypia can expose patients to undue surgical procedures and risks.

US of thyroid nodules: can AI-assisted diagnostic system compete with fine needle aspiration?

Artificial intelligence (AI) systems can diagnose thyroid nodules with similar or better performance than radiologists. Little is known about how this performance compares with that achieved through fine needle aspiration (FNA). This study aims to compare the diagnostic yields of FNA cytopathology alone and combined with BRAFV600E mutation analysis and an AI diagnostic system. The ultrasound images of 637 thyroid nodules were collected in three hospitals. The diagnostic efficacies of an AI diagnostic system, FNA-based cytopathology, and BRAFV600E mutation analysis were evaluated in terms of sensitivity, specificity, accuracy, and the κ coefficient with respect to the gold standard, defined by postsurgical pathology and consistent benign outcomes from two combined FNA and mutation analysis examinations performed with a half-year interval. The malignancy threshold for the AI system was selected according to the Youden index from a retrospective cohort of 346 nodules and then applied to a prospective cohort of 291 nodules. The combination of FNA cytopathology according to the Bethesda criteria and BRAFV600E mutation analysis showed no significant difference from the AI system in terms of accuracy for either cohort in our multicenter study. In addition, for 45 included indeterminate Bethesda category III and IV nodules, the accuracy, sensitivity, and specificity of the AI system were 84.44%, 95.45%, and 73.91%, respectively. The AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with BRAFV600E mutation analysis. Given its advantages in terms of operability, time efficiency, non-invasiveness, and the wide availability of ultrasonography, it provides a new alternative for thyroid nodule diagnosis. Thyroid ultrasonic artificial intelligence shows statistically equivalent performance for thyroid nodule diagnosis to FNA cytopathology combined with BRAFV600E mutation analysis. It can be widely applied in hospitals and clinics to assist radiologists in thyroid nodule screening and is expected to reduce the need for relatively invasive FNA biopsies. • In a retrospective cohort of 346 nodules, the evaluated artificial intelligence (AI) system did not significantly differ from fine needle aspiration (FNA) cytopathology alone and combined with gene mutation analysis in accuracy. • In a prospective multicenter cohort of 291 nodules, the accuracy of the AI diagnostic system was not significantly different from that of FNA cytopathology either alone or combined with gene mutation analysis. • For 45 indeterminate Bethesda category III and IV nodules, the AI system did not perform significantly differently from BRAFV600E mutation analysis.

Fine Needle Aspiration Cytopathology of Thymoma and Thymic Carcinoma: A Brief Review

Fine Needle Aspiration Cytopathology of Thymoma and Thymic Carcinoma: A Brief Review

Evaluation of Fine Needle Aspiration Cytopathology in Salivary Gland Tumors under Milan System: Challenges, Misdiagnosis Rates, and Clinical Recommendations.

(1) Background: Salivary gland tumors are rare in the head and neck. To determine the need and extent of surgical intervention, fine needle aspiration (FNA) is a widely accepted tool to approach salivary gland lesions. However, the FNA cytology varies between entities, while the lack of uniform terminology makes diagnosis more challenging. Since establishing the Milan system for reporting salivary gland cytopathology (MSRSGC) has become an increasingly accepted reporting standard, further examination and detailed recommendations were needed. (2) Methods: Between April 2013 and October 2021, 375 cases with FNA and salivary gland resection were retrospectively collected. All FNA specimens were reclassified according to the criteria of MSRSGC. After surgical excision, the FNA data were compared with the histological diagnosis to estimate the risk of malignancy (ROM), the risk of neoplasm (RON), and the diagnostic accuracy for each diagnostic category. (3) Results: Our cohort's distribution of ROM and RON was similar to the MSRSGC's recommendation. Carcinoma ex pleomorphic adenoma (CXPA) has the highest rate (66.7%) of misdiagnosed as a nonneoplastic lesion or benign salivary gland tumor. Pleomorphic adenoma (PA) and Warthin's tumor were the most common benign salivary gland tumors, while the cytology diagnosis of Warthin's tumor seems more challenging than PAs. (4) Conclusions: Despite the convenience and effectiveness of MSRSGC, we suggest close follow-up, re-biopsy, or surgical removal for salivary lesions even in Milan IVA-Benign for possibly missing FNA of malignancy, mixed lesions, or prevention of malignant transformation.

Fine needle aspiration cytopathology of pleomorphic dermal sarcoma.

Pleomorphic dermal sarcoma (PDS) is an uncommon cutaneous mesenchymal neoplasm. It is cytomorphologically identical to atypical fibroxanthoma (AFX), but differs due to its invasion beyond the dermis. We undertook an examination of our experience with fine needle aspiration (FNA) biopsy cytology of PDS. Our cytopathology files were searched for examples of PDS with concomitant histopathological verification. FNA biopsy smears and cell collection were performed using standard techniques. Seven cases of PDS were retrieved from four different patients (M:F, 1:1; age range: 63-88 years; mean age = 78 years). All patients (57%) presented with a primary tumour with one having an FNA biopsy of two local recurrences and a single distant metastasis. Five aspirates were from the extremities and two from the head/neck. Tumours ranged from 1.0 to 3.5 cm (mean, 2.2 cm). Specific cytological diagnoses were pleomorphic spindle/epithelioid sarcoma (3 cases), PDS (2), AFX (1), and atypical myofibroblastic lesion, query nodular fasciitis (1). Immunohistochemical (IHC) staining from FNA-generated cell blocks in two cases showed non-specific staining with vimentin in both cases; positive CD10, CD68, and INI-1 staining in one case; and smooth muscle actin expression in the other. Multiple negative stains were performed in both of these cases to exclude malignant melanoma, carcinoma, and specific forms of sarcoma. Cytopathology consisted of a mixture of spindle, epithelioid, and bizarre pleomorphic cells. Coupled with ancillary IHC stains, FNA biopsy can help recognise PDS as a sarcomatous cutaneous neoplasm, but is unable to distinguish PDS from AFX.

Utility of the Proposed Sydney System for Classification of Fine-Needle Aspiration Cytopathology of Lymph Node: A Retrospective Study at a Tertiary Care Center

Introduction: Fine-needle aspiration cytology (FNAC) is an established first-line technique for the evaluation of lymphadenopathy and, with the help of ancillary testing, can in many instances obviate the need for an open biopsy. The Sydney system was recently proposed to provide consensus guidelines for the performance, classification, and reporting of lymph node FNAC. The present study was undertaken to evaluate its utility and study the impact of rapid on-site evaluation (ROSE). Material and Methods: A retrospective analysis in which 1,500 lymph node FNACs was reviewed and assigned a diagnostic category from the Sydney system. Cyto-histopathological correlation and adequacy parameters were evaluated. Observation and Results: The cervical group of lymph nodes was the commonest group aspirated (89.7%). A total of 1,205/1,500 (80.3%) cases were category II (benign), and necrotizing granulomatous lymphadenitis was the most common pathology. The 750 cases with ROSE were subclassified as follows: 15 category I (inadequate), 629 category II (benign), 2 category III (atypia of undetermined significance), 9 category IV (suspicious for malignancy), and 95 category V (malignant). Among 750 cases without ROSE, 75 cases were in category I, 576 in category II, 3 in category III, 6 in category IV, and 90 in category V. Category I was thus significantly lower in the ROSE group compared to the non-ROSE group. Overall, the risk of malignancy was L1-0%, L2-0.20%, L3-100%, L4-92.3%, and L5-100%. Accuracy parameters revealed a sensitivity of 97.7%, specificity of 100%, PPV of 100%, NPV of 99.10%, and diagnostic accuracy of 99.54%. Discussion and Conclusion: FNAC can be used as the 1st line of treatment for lymph node pathology. ROSE can be used as an add-on to FNAC for reducing unsatisfactory rates and help triage material for ancillary testing whenever possible. The Sydney system should be implemented for achieving uniformity and reproducibility.

Childhood sarcomas: fine-needle aspiration cytopathology with an emphasis on the use of molecular studies.

In children and adolescents, most sarcoma subtypes have a simple karyotype with a single genetic alteration; cytologic findings combined with ancillary testing can lead to a specific diagnosis. The goal of this study was to review the use of fine-needle aspiration in conjunction with immunohistochemistry and molecular studies as a part of an integrated, multidisciplinary diagnostic workup for bone and soft tissue sarcomas in this population. We searched for cases aged ≤18 years old with a malignant bone or soft tissue tumor that had corresponding cytology specimens from 3 institutions. Clinical data, cytologic findings and diagnoses, histologic diagnoses, and ancillary testing were documented. Of 99 cases, 55% were male with a mean age of 12 years. Ninety-four cases (95%) had a specific histologic diagnosis, and 84 cases (85%) were primary neoplasms. Ninety-four cases (95%) had a malignant cytologic diagnosis, and 71 cases (72%) had a specific cytologic diagnosis concordant with the histologic diagnosis. Among primary tumors with a specific histologic diagnosis, a specific cytologic diagnosis was made in 63 cases (79%). After excluding osteosarcoma, 74% of the tumors (n = 50) had molecular studies. Specific genetic alterations supporting a definitive diagnosis were found in 42 cases (84%), the majority of which were demonstrated using Fluorescence In Situ Hybridization (n = 33, 79%). We found that fine-needle aspiration in conjunction with core needle biopsy, immunohistochemistry, and molecular studies allowed cytopathologists to accurately classify sarcomas in a pediatric age group.

Accuracy of fine‐needle aspiration cytopathology to differentiate malignant and benign thyroid nodules with ≥4 cm diameter: A retrospective study

Thyroid nodules (TN) are commonly present in the general population and are usually pathologically benign. An initial diagnosis with fine-needle aspiration (FNA) cytopathology could help clinical decision-making with fewer complications. As the previous studies suggest surgical procedures for >4cm TNs, we aimed to investigate the accuracy of preoperative FNA cytology to predict malignancy risk in these nodules in a sample of the Iranian population. Patients with ≥4cm TNs who had preoperative FNA cytology, underwent nodulectomy and had a histopathological report were included. Each patient's preoperative demographic, ultrasonographic, and cytology data were gathered. After surgery, resected samples were assessed pathologically and diagnosed as benign or malignant. Finally, data were analyzed to evaluate the presurgical accuracy of the FNA cytology. We identified 41 (51.25%) patients with malignant legions among our study population (N= 80). The pathology reports were indeterminate in 3 patients with follicular neoplasm. Bethesda scores were substantially higher in patients with malignancy. The sensitivity, specificity, and false-negative rate of FNA cytology reports using the Bethesda system were 73.7%, 74.2%, and 26.3%, respectively. There was no association between malignancy and TNs' size, neither their volume nor their highest diameter. FNA cytology is not as sensitive and specific in nodules>4cm as in smaller ones. However, it can still be used alongside other diagnostic procedures in malignancy screening. Clinicians should make more complex decisions considering various influential factors to avoid missing malignant lesions and reduce diverse probable complications of highly invasive diagnostic surgery. Further prospective research on >4cm TNs and their multiple features' association with malignancy is required for more precise judgment.

The clinical significance of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category 5 thyroid nodules: Not as risky as we think?

BackgroundAlthough the prevalence of thyroid nodules is high, few prove to be malignant. Based on sonographic features, the American College of Radiology Thyroid Imaging Reporting and Data System categorizes malignancy risk of thyroid nodules with associated management recommendations for each category level. Malignancy rates among nodules with a highly suspicious Thyroid Imaging Reporting and Data System category 5 warrant examination in the context of additional risk stratification tools, including cytopathology and molecular testing. MethodsAll patients who underwent fine-needle aspiration biopsy for Thyroid Imaging Reporting and Data System category 5 nodules from January 2018 to September 2021 in a large integrated academic health system were reviewed. Using the Bethesda System for Reporting Thyroid Cytopathology, categories V and VI were set as malignant. Molecular testing (ThyroSeq version 3; Rye Brook, NY) yielding ≥50% risk of malignancy was deemed positive and correlated with surgical pathology. ResultsA total of 496 Thyroid Imaging Reporting and Data System category 5 nodules were identified. On fine-needle aspiration cytopathology, 61 (12.3%) were malignant. The breakdown included Bethesda System for Reporting Thyroid Cytopathology I, 15 (3%); II, 362 (73%); III, 52 (10.5%); IV, 5 (1%); V, 6 (1.3%); and VI, 55 (11.1%). Of Bethesda System for Reporting Thyroid Cytopathology III/IV nodules with molecular testing (n = 53), 24.5% yielded positive results. In total, 42 (8.5%) nodules underwent surgical resection, most of which were Bethesda System for Reporting Thyroid Cytopathology VI (n = 26, 61.9%). Of excised nodules, 33 (78.6%) nodules were malignant, 6 (14.3%) benign, and 3 (7.1%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features. All Thyroid Imaging Reporting and Data System category 5 nodules with malignant cytology (Bethesda System for Reporting Thyroid Cytopathology V/VI) that underwent surgery were malignant on histopathology. On average, the total Thyroid Imaging Reporting and Data System points were higher in malignant nodules compared with benign (9.3 vs 7.3; P = .015). Moreover, benign nodules more frequently received Thyroid Imaging Reporting and Data System points when the radiologist was unable to determine composition or echogenicity (33% vs 3% among malignant nodules; P = .01). ConclusionThyroid Imaging Reporting and Data System category 5 designation in thyroid nodules is associated with a lower risk of malignancy than previously reported. Benign and malignant nodules with Thyroid Imaging Reporting and Data System category 5 designation have discrepancies in certain Thyroid Imaging Reporting and Data System characteristics and individual points assigned, which may offer an opportunity for quality improvement and standardization measures in ultrasound reporting practices.

Fine needle aspiration cytopathology of eccrine spiradenoma.

Eccrine spiradenoma (ES) is a rare benign cutaneous adnexal tumor. The aim of our study was to discuss the clinical presentation, cytomorphologic features, and differential diagnosis of a series of 3 cases of ES diagnosed by fine needle aspiration (FNA). The pathology databases were searched for cases of ES diagnosed by FNA and confirmed by follow-up surgical excision. FNA smears, cell blocks, and histologic sections were examined. Three cases of ES that had presented as a soft tissue mass from 3 patients were reviewed. The sites included the left forearm, left leg, and left ankle. Cytology smears showed the presence of hypercellular 3-dimensional dense cell clusters and smaller loose cell aggregates, single cells, and bare nuclei. Most cells had round to oval nuclei, scant cytoplasm, and indistinct cell borders. A second population of cells had more spindled nuclei and were often dispersed as single cells. Scattered lymphocytes were present. Two cases showed the presence of pseudo-rosettes composed of hyaline globules of basement membrane-like material with a surrounding row of basaloid cells. None of the cases showed cytologic atypia, necrosis, or mitoses. Immunohistochemistry was used in 2 cases and showed positive staining with myoepithelial markers (smooth muscle actin, calponin, S100, and CK5). The cytology diagnoses were ES, basaloid cutaneous adnexal neoplasm, and suspicious for ES. FNA cytopathology of ES demonstrated banal basaloid and spindle cells, lymphocytes, and infrequent metachromatic-stained hyaline globules. A specific diagnosis requires immunohistochemistry testing to avoid confusion with other cutaneous basaloid neoplasms.

Ultrasound-Guided Fine Needle Aspiration of Deep Thyroid Nodule: Is There a Correlation between the Nodule's Depth and Nondiagnostic Results?

Objective To evaluate whether thyroid nodule depth correlates with nondiagnostic results in ultrasound-guided fine needle aspiration cytopathology. Background Many factors correlate with nondiagnostic ultrasound-guided fine needle aspiration cytology (FNAC) results, including older age, macrocalcification, small-sized nodules, aspirin medication, and cystic portion in more than 50% of the thyroid nodules. However, there are few studies which have examined whether there is a relationship between the depth of nodules and the percentage of nondiagnostic results in cytology (Bethesda category I). We conducted this study in order to investigate if such a correlation exists. Materials and Methods FNAC was performed on 283 thyroid nodules between January 2019 and December 2020. Cytological analyses of the nodules were reviewed and sorted as nondiagnostic and diagnostic according to the Bethesda score. Patient files and ultra sound (US) scans were reviewed for clinical information (such as age, sex, and ethnic group) and sonographic features of nodules (such as depth, size, cystic portion, type of calcification, and echogenicity) and were compared between the nondiagnostic and diagnostic nodule results. The depth of a nodule was calculated as the shortest distance from the skin to the most superficial border of the nodule in the axial plane, using our medical center's computer program, which allows reviewing all saved shots of the US scan. Results Age, sex, and ethnicity were not significantly different between the nondiagnostic group and the diagnostic group (p > 0.05). Nodule diameter, cystic portion, calcification, and echogenicity were also not associated with the frequency of nondiagnostic results. The depth of nodules ≥9 mm was correlated with nondiagnostic US-guided FNA cytological results (OR = 2.55, p=0.018). Conclusions Deep thyroid nodules correlated with nondiagnostic US-guided FNA cytological results. Further studies are needed for optimizing the approach to deep thyroid nodules in order to improve the efficacy of FNA in deep thyroid nodules.