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Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends an upper limit of 10% for atypia of undetermined significance (AUS). Recent data suggest that this category might be overused when the rate of cases with molecular positive results is low. As a quality metric, the AUS and positive call rates for this facility's cytology laboratory and each cytopathologist (CP) were calculated., Methods: A retrospective analysis of all thyroid cytology cases in a 4.5-year period was performed. Cases were stratified by TBSRTC, and molecular testing results were collected for indeterminate categories. The AUS rate was calculated for each CP and the laboratory. The molecular positive call rate (PCR) was calculated with and without the addition of currently negative to the positive results obtained from the ThyroSeq report., Results: A total of 7535 cases were classified as nondiagnostic, 7.6%; benign, 69%; AUS, 17.5%; follicular neoplasm/suspicious for follicular neoplasm, 1.4%; suspicious for malignancy, 0.7%; and malignant, 3.8%. The AUS rate for each CP ranged from 9.9% to 36.8%. The overall PCR was 24% (range, 13%-35.6% per CP). When including cases with currently negative results, the PCR increased to 35.5% for the cytology laboratory (range, 13%-42.6% per CP). Comparison analysis indicates a combination of overcalling benign cases and, less frequently, undercalling of higher TBSRTC category cases., Conclusions: The AUS rate in the context of PCR is a useful metric to assess cytology laboratory and cytopathologists' performance. Continuous feedback on this metric could help improve the overall quality of reporting thyroid cytology., (© 2024 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

When a solitary liver mass is identified in a dog, a fine-needle aspirate (FNA) is commonly employed to attempt to obtain a diagnosis. Little information is provided in the literature evaluating the sensitivity/specificity of FNA cytology for solitary liver masses. We hypothesized that liver lesion size nor the presence of cavitation would impact the success of cytological diagnosis. Medical records were obtained for 220 client-owned dogs. Inclusion criteria included preoperative abdominal imaging, percutaneous FNA of a solitary hepatic mass with cytologic interpretation by a board-certified pathologist, and a surgical biopsy or mass excision yielding a histopathological diagnosis. Six dogs (2.7%) experienced a complication after FNA, none considered severe. The agreement rate for correct cytologic diagnosis was 22.9% (49/220). Of the neoplastic masses 18.9% (35/185) were correctly diagnosed via cytology. The overall sensitivity was 60%, and the specificity was 68.6%. Neither institution (P = 0.16), lesion size (P = 0.88), cavitation (P = 0.34), or needle gauge (P = 0.20) had an association with correct diagnosis. This study demonstrates that, although there is a low risk of complications following FNA of a hepatic mass, overall success rate for correct cytologic diagnosis based on FNA was low compared to histopathologic diagnosis., (© 2023 by American Animal Hospital Association.)

Objectives: Despite the important role of the community in the assessment and risk stratification of patients with thyroid nodules, evidence-based data on the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) performance in community clinics is lacking. We aim to evaluate BSRTC performance of aspirations taken in community clinics compared with primary referral center., Methods: Patients who underwent thyroid surgery between 2013 and 2018 at our institution were divided according to the fine needle aspirations (FNA) settings: community FNA (cFNA) vs. institutional FNA (iFNA). Demographics, BSRTC results and final pathology were collected. Diagnostic values were calculated for BSRTC categories (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]), and were compared between the groups., Results: A total of 268 nodules were included in the study; 77% (207) cFNA and 23% (61) iFNA. Patients in the community were younger (51.7 ± 15.1 vs. 56.6 years±14.8, p = 0.03) and with less epidemiology risk factors for thyroid cancer (1.9% vs 13.1%, p < 0.001). cFNA malignancy rate for BSRTC I-VI was 0%, 6.4%, 11.8%, 32.1%, 91.6% and 93.8% respectively. Best sensitivity was found for BSRTC III-VI in both groups (88% and 83%, cFNAs and iFNAs, respectively). Overall best performance was obtained for BSRTC V-VI for both groups (cfNA: 85%, 97%, 93%, 94% and 93%; iFNAs: 81%, 100%, 100%, 87% and 91%, for sensitivity, specificity, PPV, NPV and accuracy, respectively)., Conclusions: Community-performed FNAs demonstrate acceptable BSRTC distribution and malignancy rates, comparable with a primary referral academic hospital. This supports the universality of the BSRTC 2017 and its recommendations also in the community., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Thyroid cancer, predominantly papillary thyroid carcinoma (PTC), is common, but an estimated 30% of ultrasonography-guided fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate. BRAF variation, associated with poor clinicopathological characteristics, is a useful molecular marker for diagnostics., Objective: To develop a sensitive molecular assay for BRAF V600E detection in remaining tissue of thyroid FNA biopsies to identify patients with cancer carrying a BRAF variation., Design, Setting, and Participants: This diagnostic study used tumor tissue from surgical formalin-fixed, paraffin-embedded (FFPE) specimens and residual tissue from thyroid FNA biopsies for genomic DNA extraction. FFPE specimens served as the validation set, and residual tissue from FNA biopsies served as the test set. A molecular assay was developed for accurate detection of BRAF V600E variation using locked nucleic acid (LNA) probe-based droplet digital polymerase chain reaction (dPCR), and the assay was validated by BRAF V600E immunohistochemical staining (IHC). The study was conducted between February 2019 and May 2021., Results: A total of 271 specimens, including 77 FFPE specimens (with a follow-up of 48 matched surgical specimens) and 146 residual FNA samples, were collected from 223 patients (mean [SD] age, 53.8 [15.3] years; 174 [78.0%] women; 49 [22.0%] men). The molecular assay by dPCR was first established to specifically and accurately detect and quantify wild-type BRAF and variant BRAF in DNA from human follicular thyroid carcinoma-derived FTC-133 and papillary thyroid carcinoma-derived BCPAP cells. The linearity of quantification of BRAF V600E was calculated (y = 0.7339x; R2 = 0.9996) with sensitivity at 0.02 copies/μL and reproducibility in detecting variant DNA at various dilutions(coefficient of variance in 0.3% DNA, 9.63%; coefficient of variance in 1.0% DNA, 7.41%). In validation testing, the dPCR assay and IHC staining exhibited 100% specificity in concordantly identifying BRAF V600E in PTCs (κ = 0.873; P < .001) and sensitivity of 32.0% (95% CI, 19.1% to 44.9%) in dPCR and 26.0% (95% CI, 13.1% to 38.9%) in IHC staining, with an improvement by 23.08% in dPCR compared with the IHC staining. The dPCR assay further detected BRAF V600E in 39 of 146 residual FNA specimens (26.7%). At short-term follow-up, 48 patients, including 14 of 39 patients with BRAF variation and 34 of 107 patients without BRAF variation on residual FNA specimens, underwent resection. The dPCR assay of BRAF status in the matched surgical specimens showed BRAF V600E variations in 12 patients and wild-type BRAF in 36 patients, with a high agreement to that in residual tissue of FNA specimens (κ = 0.789; P < .001). Among 14 patients with BRAF variations on residual FNA, 13 were diagnosed with PTC and 1 was diagnosed with anaplastic thyroid cancer at the thyroidectomy., Conclusions and Relevance: This diagnostic study developed a sensitive molecular assay for detection and quantification of BRAF V600E variation in residual tissue from thyroid FNA biopsies to identify patients with cancer harboring BRAF V600E in a cost-effective manner, highlighting the clinical value of molecular assay of the remaining FNA tissue in the management of thyroid nodules.

Background: Fine-needle aspiration cytology (FNAC) has become one of the most useful modalities for diagnosis and staging of lymphoma. However, diagnostic accuracy of this technique has been reported with varying results across several studies around the world. Hence, this meta-analysis was done to assess the accuracy of FNAC for lymphoma diagnosis., Methods: We conducted a systematic search for all studies reporting the diagnostic accuracy of FNAC for lymphoma in the databases of PubMed Central, MEDLINE, EMBASE, MEDLINE, SCOPUS and Cochrane library from inception till January 2021. Meta-analysis was performed using STATA software "midas" package., Results: Forty-seven studies with 7268 patients were included. The pooled sensitivity and specificity of FNAC for diagnosing lymphoma were 93% (95% CI, 90%-95%) and 97% (95% CI, 95%-98%), respectively. Likelihood ratio positive was 33.5 (95% CI, 18.5-60.7) and likelihood ratio negative was 0.07 (0.05-0.11) making the technique to occupy the left upper quadrant in LR scattergram indicating that FNAC can be used for confirmation and exclusion. There was significant heterogeneity with significant chi-square test and I 2 statistic >75%. There was significant publication bias as per Deek's test and funnel plot., Conclusion: To summarize, our study found that FNAC has a vital role as a diagnostic tool for lymphoma with higher sensitivity and specificity. Further studies assessing the accuracy of FNAC on specific types of lymphoma is required., (© 2021 Wiley Periodicals LLC.)

Background: Recently the International Academy of Cytology (IAC) introduced a new reporting system for breast fine-needle aspiration cytology that classifies cytologic diagnoses into five-categories: (I) insufficient material, (II) benign, (III) atypical, (IV) suspicious of malignancy, and (V) malignant. The current study was undertaken to categorize the breast lesions utilizing the newly proposed IAC Yokohama classification system and evaluate the risk of malignancy (ROM) for respective categories and the diagnostic yield of this technique., Methods: All FNAs of breast lesions over 2.5 years were categorized retrospectively using the newly proposed IAC Yokohama reporting system. The ROM was calculated along with sensitivity, specificity, positive and negative predictive value, diagnostic accuracy, false positive, and false-negative rate using the histological diagnosis as the gold standard., Results: The 512 cases were distributed as follows: Category I (insufficient material) 7.4%, Category II (benign) 74%, Category III (atypical) 5.7%, Category IV(suspicious) 1.4%, and Category V (malignant) 11.5%. Histopathological correlation was available in 285 (55.7%) cases. The respective ROM calculated was 33.3%, 0.5%, 13.3%, 83.3%, and 100% for Category I-V. The Sensitivity, Specificity, Positive and Negative Predictive Value, and Diagnostic accuracy were 95%, 99.5%, 98.27%, 98.6, and 98.5% respectively., Conclusions: Despite previous attempts to establish a standardized diagnostic terminology, there has been a lack of a single internationally approved standardized reporting system allowing substantial diagnostic clarity and incorporating distinct diagnostic categories, each linked with a specific ROM and recommended management. This System also provides enhanced communication between pathologists and attending clinicians for the benefit of the patient., (© 2021 Wiley Periodicals LLC.)

Objective: Fine needle aspiration (FNA) cytology has been successfully utilized in the preoperative diagnosis of oral masses. Lymphoma involving other sites has also been diagnosed frequently on FNA. Oral cavity lymphoma (OL) is rare and is clinically indistinguishable from other lesions of the mouth. A complete excision of these may be difficult. Our experience with FNA diagnosis of 11 OLs along with histopathological correlation is reported herein in a tertiary health care setting., Methods: In this retrospective study, clinico pathological characteristics of patients with final diagnosis of non-Hodgkin's lymphoma (NHL) were reviewed over a 7 year period. Routine cytological giemsa staining was performed in all cases along with immunocytochemistry (ICC) wherever possible. The gold standard for diagnosis of NHL was based on: (1) Histopathology and immunohistochemistry and/or (2) Flow cytometry (FC)., Results: A total of 11 cases were diagnosed as NHL. All showed B cell immunophenotype. Two of them were diagnosed as follicular lymphoma on histopathology. Male to female ratio was 7:4 and ranged in age from 37 to 70 years. The most common site was tonsillar fossa (N = 5), followed by hard palate (N = 3), soft palate (N = 2), and buccal mucosa (N = 1). Size ranged from 1 to 6 cm., Conclusions: Diagnosis of OLs may be hampered by its rarity and difficulties in obtaining sufficient cellularity in oral FNA but there is need for immediate and accurate diagnostic procedures, including immunohistochemical analysis to avoid delay in treatment. FNA along with ICC helps in early diagnosis of this rare entity and can also provide sample for FC., (© 2021 Wiley Periodicals LLC.)

Background: Milan system for reporting salivary gland cytopathology (MSRSGC) was proposed to provide a standardized reporting system for salivary gland fine needle aspiration biopsies. Modified Menghini type semi-automatic aspiration biopsy needles provide small tissue fragments (STFs), as well as cellular smears, and immunohistochemical and molecular studies can be performed using the STFs., Aims: We aimed to evaluate the contribution of STFs and ancillary techniques to pre-operative diagnosis of salivary gland lesions., Materials and Methods: In this study, smears of 287 cases with histopathological correlation were re-reviewed and assigned to one of the MSRSGC categories. In the second step, histopathological and immunohistochemical findings in STFs were evaluated together with cytological findings. Final diagnoses were obtained with the inclusion of flow cytometry (FC) results when available. Risk of malignancy (ROM) was calculated for each diagnostic category., Results: In the evaluation based on smears, a specific diagnosis could be obtained in 64.8% of the cases. ROMs were 0% for nondiagnostic (ND), 5.6% for non-neoplastic (NN), 55% for atypia of undetermined significance (AUS), 0.6% for benign neoplasm (BN), 27.8% for salivary gland neoplasm of uncertain malignant potential (SUMP), and 100% for suspicious for malignancy (SFM) and malignant (M) categories. With the addition of histopathological and immunohistochemical findings and FC results, a specific diagnosis could be obtained in 75.2% of the cases. ROMs were 0% for ND, 4.5% for NN, 53.8% for AUS, 0.6% for BN, 0% for SUMP, and 100% for SFM/M categories., Conclusions: STFs contribute correct categorization of salivary gland lesions. The major contribution of ancillary methods is in the SUMP category., (© 2021 Wiley Periodicals LLC.)

Background: Fine-needle aspiration cytology (FNAC) is an established technique for preoperative diagnosis of salivary gland lesions; however, lack of a uniform reporting system has been a handicap. The main aims of this study were to evaluate the utility of the - "The Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC) and ascertain the risk of malignancy (ROM) for each category., Methods: All salivary gland FNACs over 5 years (January 2014-December 2018) were reviewed and assigned a diagnostic category from the MSRSGC. Clinical data were taken from Cytology records. Cytodiagnosis was correlated with histopathology wherever available and ROM was calculated., Results: A total of 120 salivary gland FNACs were studied. Age ranged between 5 and 85 years, male:female ratio was 2:1 and parotid was the commonest gland aspirated. Cases were reclassified as I non-diagnostic (2.5%), II non-neoplastic (15%), III atypia of uncertain significance-AUS (1.7%), IV A neoplasm benign (50%), IV B neoplasm of uncertain malignant potential (12.5%), V suspicious for malignancy (5%), and VI malignant (13.3%). Follow-up was available in 70 (58.3%) cases. The sensitivity, specificity, negative predictive value, and positive predictive value were 92.3%, 100%, 100%, and 98.27% respectively. ROM was non-neoplastic (0%), AUS (50%), neoplasm benign (0%), neoplasm of uncertain malignant potential (28.6%), suspicious for malignancy (100%), and malignant (100%)., Conclusion: Salivary gland FNAC is a reliable diagnostic tool and the "Milan system" will further increase FNA reliability, help risk stratification, and improve patient care., (© 2021 Wiley Periodicals LLC.)

Background: This study aims to assess in our institutional experience the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of salivary gland masses (SGM) according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and to an in-house system., Methods: The study included 189 FNACs conducted between January 2011 and December 2019. The FNACs, classified according to the in-house system, were reclassified according the MSRSGC. Taking histopathology as gold standard, the measures of diagnostic accuracy of FNAC were determined for suspicion for malignancy (SFM) and malignant categories., Results: According to the in house system, FNAC diagnoses were classified as: 23 (12.2%) non-diagnostic (ND), 23 (12.2%) non-neoplastic (NN), 119 (62.9%) benign neoplasm (BN), 10 (5.2%) indefinite neoplasm (IN), 2 (1.1%) SFM, and 12 (6.4%) malignant (M). Based on the MSRSGC, there were 3 (1.5%) cases of atypia of undetermined significance (AUS) and 7 (3.7%) neoplasms of uncertain malignant potential (SUMP). The number of ND, NN, BN, SFM, and M cases were identical in the two systems. For both systems, the sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy for malignancy diagnosis were 77.8%, 100%, 100%, 97.6%, and 97.8%, respectively., Conclusion: According to the MSRGC and to our in-house reporting system, FNAC is an accurate technique for the diagnosis of malignant salivary tumors with excellent specificity and good sensitivity. However, MSRGC has the advantage of standardization of salivary gland cytology reporting., (© 2020 Wiley Periodicals LLC.)

Objective: Sternocleidomastoid tumor of infancy (SCMI) is a rare, benign self-limiting condition which occurs in the perinatal period. The goal of our study is to highlight clinicoradiological and cytopathological findings in these cases., Material and Methods: A study was done at a tertiary level hospital, from January 2016 to December 2019. Thirteen cases were studied, out of which 11 were clinically suspected cases of SCMI tumor and two cases were clinically suspected as cervical lymph node tuberculosis which were finally diagnosed as SCMI on fine needle aspiration cytology (FNAC) evaluation. Drs. N. K., S. Z., S. S. K., and S. R. independently reviewed the original diagnosis. Clinical, ultrasonographical, and cytopathological features are highlighted along with follow-up of the cases., Results: There were a total of 13 cases, out of which 11 cases were neonates and two cases were more than 1 month of age (2 months and 2.5 months). Male: female ratio was 10:3 and swelling was present more commonly on the right side of the neck. Ultrasonography predominantly showed non-cystic, bulky, and heterogenous echotexture of the sternocleidomastoid muscle. Smears were moderately cellular showing mainly singly scattered oval to spindle shaped fibroblasts along with degenerating and regenerating muscle fibers., Conclusion: FNAC along with adequate clinic-radiological correlation aids in early and reliable diagnosis and can help curtail complications., (© 2020 Wiley Periodicals LLC.)

Background: Classification of thyroid follicular neoplasms can be challenging for pathologists. Introduction of noninvasive follicular thyroid neoplasms with papillary-like nuclear features, the utilization of immunohistochemistry, and molecular analysis are all thought to be valuable diagnostic adjuncts. Our aim was to determine whether interobserver variability for follicular neoplasms has improved since the application of these adjuncts., Methods: One representative section from a cohort of follicular neoplasms previously proven difficult for pathologists were examined independently by 7 pathologists and assigned to 1 of 3 diagnostic categories (benign, neoplasms with papillary-like nuclear features, or malignant). This process was carried out separately 3 times: (1) after viewing hematoxylin and eosin stain slides, (2) hematoxylin and eosin stain in conjunction with immunohistochemistry, and (3) hematoxylin and eosin stain/immunohistochemistry in conjunction with molecular analysis. The interobserver variability and overall agreement were then calculated using the free-marginal kappa coefficient., Results: Agreement on hematoxylin and eosin stain was 57%, with a kappa coefficient of 0.36 (minimal agreement). The agreement improved slightly with the application of immunohistochemistry (kappa coefficient = 0.49 [weak agreement] and a percentage agreement 67%). The level of agreement decreased slightly after the addition of molecular analysis (kappa coefficient = 0.43 [weak agreement] and percentage agreement 62%)., Conclusion: Despite attempts to standardize the diagnostic criteria for neoplasms with papillary-like nuclear features and the utilization immunohistochemistry and molecular analysis, attaining pathologic consensus for difficult follicular neoplasms of the thyroid remains a challenge., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Thyroid nodules are common in adults, but only some of them are malignant. Ultrasound-guided fine-needle aspiration (FNA) is widely applied as a reliable and minimally invasive technique for evaluating thyroid nodules. However, the scarcity of FNA biopsy specimens poses a challenge to molecular diagnosis. This study aimed to evaluate the feasibility of FNA washout precipitation specimens as an effective supplement to the thyroid genetic test. Methods: A total of 115 patients with thyroid nodules were enrolled in our study. The BRAF V600E mutation status was detected in all FNA washout precipitation specimens and biopsy formalin-fixed paraffin-embedded (FFPE) specimens using an amplification refractory mutation system PCR (ARMS-PCR). All patients underwent cytological diagnoses; 79 patients also underwent surgery for histopathological analysis. Results: All the 115 samples were successfully analyzed using both FNA washout precipitation and biopsy FFPE specimens. The results showed that the BRAF V600E status detected in 96 FNA washout precipitation specimens were consistent with that in FNA biopsy FFPE specimens, including 41 BRAF V600E positive and 55 BRAF V600E negative, achieving a concordance rate of 84.4% (kappa  =  0.689). Furthermore, the BRAF V600E mutation status using FNA washout precipitation specimens provided a 100.0% positive predictive value for diagnosing papillary thyroid carcinoma in patients with The Bethesda system for reporting thyroid cytopathology (TBSRTC) V. Besides, the BRAF V600E mutation status was positive in 90.9% (10/11) FNA washout precipitation specimens from patients with capsule invasion, achieving a higher overall sensitivity of 100.0%, compared with 57.1% of FNA washout precipitation specimens from patients without capsule invasion. Conclusion: These results suggested that FNA washout precipitation specimens might be a valuable supplementary sample type for detecting the BRAF V600E mutation in patients with thyroid nodules, especially with thyroid capsule invasion.

Cytologic diagnosis of thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma (FACHAC) is challenging due to cytomorphologic features that overlap with other follicular-patterned lesions. This study was designed to analyze diagnostic categories (DCs) of preoperative fine needle aspiration cytology (FNAC) of histologically proven thyroid FACHACs to evaluate under- or misdiagnoses in FNAC and elucidate potential causes for such phenomena. A total of 104 thyroid nodules with preoperative FNAC which were diagnosed as FACHAC in resection specimens were included in this study. Of these, 66 cases had also undergone thyroid core needle biopsy (CNB); FNAC and CNB DCs were compared in these cases. Various cytologic and histologic parameters were compared between the nodules with different FNAC DCs. After a review of FNAC slides, DCs were re-assigned in 20 (19.2%) out of the 104 cases. Of the 66 cases with CNB diagnoses which were mostly classified as lower DCs in FNAC, 31 (47.0%) were diagnosed as suspicious for a follicular neoplasm in CNB. Cases which were underdiagnosed in FNACs were associated with lower cellularity, predominant macrofollicular pattern, absence of microfollicles arranged in trabecular pattern, and absence of transgressing vessels in cytology smears. High cellularity, microfollicles arranged in trabecular pattern, nucleolar prominence, and large cell dysplasia were more frequently found in malignancy than in benign neoplasm. In conclusion, thyroid FACHACs seem to be under- and misdiagnosed in preoperative FNAC. Innate characteristics of the nodules were associated with under-diagnosis as well as the quality of the FNAC specimens. Certain cytomorphologic features can be helpful in differentiating malignancy among FACHACs., Competing Interests: The authors have declared that no competing interests exist.

Background: Thyroglobulin washout of fine needle aspiration (FNA-Tg) has proved to be useful in detecting lymph node metastases from papillary thyroid cancer; however, the influences of thyroid gland, Hashimoto thyroiditis, serum thyroglobulin (Tg) and anti-TG antibody on the diagnostic performance of FNA-Tg are controversial. Patients & methods: We retrospectively collected the FNA-Tg results of 176 preoperative or postoperative patients (356 lymph nodes) who finally were diagnosed with papillary thyroid cancer. The diagnostic abilities of FNA-Tg were evaluated and compared under different circumstances. Results: The diagnostic performance of FNA-Tg was uninfluenced irrespective of the status of thyroid gland or serum anti-TG antibody. However, high serum Tg was positively correlated with FNA-Tg (Exp(B) = 1.57; 95% CI: 1.209-2.309; p = 0.001). Conclusion: FNA-Tg was an excellent diagnostic tool, but it should be interpreted with caution only if serum Tg is higher than 10 ng/ml.

Introduction: The aim of this study was to perform an audit of oral and maxillofacial specimens submitted for cytological diagnosis to verify the importance of this complementary examination., Methods: A retrospective analysis of our institutional cytopathology database was performed over an 18-year period. Clinical information and cytological data were collected. Associations between independent variables and outcomes were assessed using the Pearson χ 2 test or Fisher's test, with a 5% significance level. When available, the histological diagnosis was compared with cytological diagnosis to identify the percentage of agreement and the specificity, sensitivity and accuracy of cytology in identifying malignant neoplasms., Results: A total of 1082 cases were identified, which included 65 different cytological diagnoses. Exfoliative cytology (EC) was performed in 312 cases (29.1%) and fine needle aspiration cytology (FNAC) in 770 cases (70.9%). EC was mainly employed to diagnose oral infectious diseases (P < 0.001) and FNAC to diagnose neoplasms, cystic, reactive and miscellaneous lesions (P < 0.001). Cell-block was performed in 555 FNAC cases (51.3%). Panoptic, Papanicolaou and haematoxylin-eosin staining were performed in FNAC and periodic acid-Schiff in EC (P < 0.001). In 211 cases (19.5%), the histological diagnosis was available and the percentage agreement with the cytological diagnosis was 41.2%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy to identify malignant neoplasms were 84.6%, 100%, 100%, 77.8% and 90.0%, respectively., Conclusions: EC was mainly performed for diagnosis of infectious diseases and FNAC for diagnosis of salivary gland tumours, odontogenic lesions, reactive lesions and cervical metastasis., (© 2020 John Wiley & Sons Ltd.)

Objective: Focal thyroid incidentaloma (TI) occurs in a 2% of 18 F-FDG PET/CT and about one-third of TIs is cancer. Due to the lack of evidence on the optimal management of TI, current guidelines suggest performing fine-needle aspiration cytology (FNA). The study aim was to evaluate the reliability of ACR-TIRADS, EU-TIRADS, and K-TIRADS in indicating FNA in TIs., Design: We retrospectively reviewed 18 F-FDG PET/CT TIs recorded during the period 2016-2019. Enrolled were TIs with histologic outcome and autonomous nodules. Cases with uncertain matching between 18 F-FDG PET/CT, US/scintiscan and histology were excluded., Results: Eighty TIs at 18 F-FDG PET/CT (median size 17 mm, median SUVmax 7.85) were included; a 26.2% was cancer. The percentage of nodules classified as high risk according to ACR-TIRADS, EU-TIRADS, and K-TIRADS was 20%, 30%, and 29.8%, respectively. The cancer prevalence in high-risk class was 56.2%, 66.7%, and 65.2% in ACR-TIRADS, EU-TIRADS, and K-TIRADS, respectively. ACR-TIRADS had the lowest number of cases with FNA indication (48%) and the K-TIRADS, the highest one (75%). Evaluating the reliability of the three systems in indicating FNA, we found a 100% sensitivity and NPV for EU-TIRADS and K-TIRADS; while all the three systems showed poor specificity and PPV., Conclusion: All TIRADSs were reliable to stratify the risk of cancer in focal TI. Comparing their reliability in indicating FNA, we found a good performance of EU-TIRADS and K-TIRADS. Considering the high cancer percentage expected in this setting of patients, those TIRADS with higher propensity to indicate FNA should be preferred.

Introduction: In the UK, guidelines from the Royal College of Pathologists (RCPath) facilitate consistent and reproducible reporting and classification of fine needle aspiration cytology (FNAC) thyroid specimens. The aim was to audit our department against RCPath guidelines to refine and improve our reporting process., Methods: Two-cycle retrospective observational audit of all patients undergoing thyroid FNAC over a 2-year period (1 year for each cycle). Final histology was correlated. The positive predictive value (PPV) for malignant neoplastic lesions was calculated; for Thy1, Thy1c, Thy2 and Thy2c all cases without final histology were assumed to be benign, while for Thy3a, Thy3f, Thy4 and Thy5 samples the PPV calculation was based only on those cytology samples with corresponding histology. False positive and false negative cases were reviewed., Results: In total, 288 cytology samples were included in the first cycle; 96 (33.3%) had corresponding histology. There were 287 samples included in the second cycle; 119 (41.5%) had follow-up histology. The rate of non-diagnostic samples (Thy1/1c) decreased from 39.6% to 30.0%. The PPV for malignant neoplastic lesions was Thy1/1c 2.6%, Thy2/2c 0.0%, Thy3a 40.0%, Thy3f 19.4%, Thy4 75.0%, Thy5 100.0% (first cycle); Thy1/1c 4.7%, Thy2/2c 0.7%, Thy3a 13.3%, Thy3f, 7.7%, Thy4, 50.0%, Thy5 100.0% (second cycle)., Conclusions: Our department was able to reduce the rate of non-diagnostic FNAC samples and improve the diagnostic accuracy of FNAC. Auditing local outcomes helps refine and improve the reporting process. Review of false positive and false negative cases helps examine potential pitfalls of cytology., (© 2020 John Wiley & Sons Ltd.)

Background: Previously, fine-needle aspiration biopsy was recommended for any thyroid nodule >1.0 cm in size. In 2015, the American Thyroid Association (ATA) introduced a pattern-based approach for biopsy recommendations based on size and ultrasound (US) characteristics. In 2016, the American College of Radiology (ACR) published the Thyroid Imaging Reporting and Data System, using a point-based system that assesses risk of US characteristics., Methods: This study aims to compare recommendations for thyroid nodule biopsy between the ATA and ACR systems and identify outcomes of nodules with discordant recommendations (DRs). US characteristics, fine-needle aspiration biopsy, and surgical pathology results were evaluated for all patients with >1.0 cm thyroid nodules treated at a single tertiary-care institution from 2010 to 2018., Results: Inclusion criteria were met by 1100 nodules from 687 patients; 42.8% (n = 471) had DR between the ATA and ACR guidelines. All (100%) DR nodules were not recommended for biopsy by ACR, though 53% were recommended to have follow-up. A majority (79%) of DR nodules were recommended for biopsy by ATA, with the remaining 21% recommended for follow-up. Among surgically excised DR nodules (n = 292), 10.3% (n = 30) nodules were found to be malignant, with the vast majority (90.3%) being well-differentiated carcinoma. Among malignant nodules, the ACR would not have recommended biopsy or follow-up for 26.7% (n = 8)., Conclusions: The ACR classification system is more restrictive compared with the ATA system for recommending thyroid nodule biopsy. This discrepancy could result in confusion for clinicians and delay in diagnosis or therapy for patients with thyroid cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Classification schemes for reporting thyroid cytology of fine needle aspiration (FNA) of thyroid nodules are largely used in clinical practice, but the level of inter-observer agreement among cytopathologists is poorly acknowledged. The present study aimed to explore the inter-observer agreement among the experienced authors of the 2014 Italian Consensus for Classification and Reporting of Thyroid Cytology (ICCRTC). A stratified randomization was performed in order to obtain a sample homogeneously distributed and representative of all ICCRTC classes. Four high-experience raters were randomly selected among the extensors of the Italian consensus. They independently reviewed 60 FNA samples blindly of the initial cytological report and clinical features. Their overall agreement was evaluated according to Fleiss' kappa. The overall inter-observer agreement was moderate (κ 0.46). Specifically, a good agreement was found when the samples were consistent for malignancy (TIR5) or were not adequate for diagnosis (TIR1) (κ 0.67 and κ 0.73, respectively). A moderate agreement was present for suspicious-for-malignant category (TIR4), and a fair agreement was recorded in the two intermediate ones (TIR3A and TIR3B) (κ 0.36 and κ 0.35, respectively). For clinical purposes, the agreement was good (κ 0.74) in differentiating cases with surgical indication (TIR4/TIR5) from those in which surgery is not essential or requires limited extension (TIR3B/TIR3A/TIR2). In conclusion, the present study confirms the reliability of ICCRTC. These data represent a reference for cytopathologists using this system and are useful for the practice of clinicians and surgeons.

Background: Indeterminate thyroid nodules are diagnosed in up to 30% of fine-needle aspirations and the risk of malignancy in these cases are highly variable. Consequently, managing these nodules has been a challenge. While a diagnostic thyroidectomy would help clarify the pathology, there is the risk of developing surgical-related complications for a procedure that may not have been necessary and associated high costs. Genomic testing of indeterminate thyroid nodules may help better guide management., Methods: We present an unbiased comprehensive review of available molecular testing for classifying indeterminate thyroid nodules, as well as their strengths and limitations, with the objective to allow practitioners to choose the best testing modality for their patients., Results: Molecular testing of these nodules provided a platform to help distinguish benign versus malignant nodules, providing more confidence to rule in or rule out the likelihood of thyroid cancer in indeterminate nodules., Conclusion: Genomic testing has evolved to more comprehensive panels to better stratify indeterminate nodules, including Hürthle cell neoplasms and noninvasive follicular neoplasm with papillary-like nuclear features. Understanding the methodology of each available test improves patient care and reduces unnecessary costs., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Introduction: Fine-needle aspiration cytology (FNAC) is an important diagnostic tool used preoperatively for the diagnosis of parotid lump. Mucoepidermoid carcinoma comprises 5-10% of all salivary gland tumours. It poses a diagnostic challenge on FNAC with high false negative rate. The objective of this study was to evaluate the discordance between cytology/FNAC and histopathology in patients with mucoepidermoid carcinoma., Material and Methods: A cross-sectional study was conducted from 1 January 2010 to 31 December 2014. Patients aged 18 years and above with FNAC or histopathology suggestive of mucoepidermoid carcinoma were identified. FNAC when compared with histology (gold standard) was classified into true positive (presence of mucoepidermoid carcinoma correctly diagnosed on FNAC), true negative (absence of mucoepidermoid carcinoma correctly diagnosed on FNAC), false positive (FNAC incorrectly diagnosed mucoepidermoid carcinoma), false negative (FNAC failed to diagnose mucoepidermoid carcinoma)., Results: A total of 16 patients fulfilled our eligibility criteria. Seven cytological samples were true positive (ie correctly diagnosed mucoepidermoid carcinoma by FNAC), eight cytological specimens were false negative (ie could not pick up mucoepidermoid carcinoma on FNAC). One case was false positive on cytology (ie diagnosed mucoepidermoid carcinoma on FNAC but was reported to be Warthin's tumour on histopathology) and none were true negative., Conclusion: FNAC is not reliable for diagnosis of mucoepidermoid carcinoma. More than 50% of our patients had discordant results between cytology and histology. We recommend a high index of suspicion for mucoepidermoid carcinoma given the poor yield of cytology.

Objective: Early disease screening and diagnosis are important for improving patient survival. Thus, identifying early predictive features of disease is necessary. This paper presents a comprehensive comparative analysis of different Machine Learning (ML) systems and reports the standard deviation of the results obtained through sampling with replacement. The research emphasises on: (a) to analyze and compare ML strategies used to predict Breast Cancer (BC) and Cardiovascular Disease (CVD) and (b) to use feature importance ranking to identify early high-risk features., Results: The Bayesian hyperparameter optimization method was more stable than the grid search and random search methods. In a BC diagnosis dataset, the Extreme Gradient Boosting (XGBoost) model had an accuracy of 94.74% and a sensitivity of 93.69%. The mean value of the cell nucleus in the Fine Needle Puncture (FNA) digital image of breast lump was identified as the most important predictive feature for BC. In a CVD dataset, the XGBoost model had an accuracy of 73.50% and a sensitivity of 69.54%. Systolic blood pressure was identified as the most important feature for CVD prediction.

There is increasing evidence showing that clinicians employ different management strategies in their use of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). In this meta-analysis, we investigated the differences in diagnosis frequency, resection rate (RR), and risk of malignancy (ROM) between Western (ie, American and European) and Asian cytopathology practices. We searched PubMed and Web of Science from January 2010 to January 2019. Proportion and 95% CIs were calculated using a random-effect model. We used independent sample t tests to compare frequencies, RR, and ROM between Western and Asian practices. We analyzed a total of 38 studies with 145,066 fine-needle aspirations. Compared with Asian practice, Western series had a significantly lower ROM in most of TBSRTC categories, whereas the RR was not statistically different. Focusing on indeterminate nodules, the RR in Western series was significantly higher (51.3% vs 37.6%; P = .048), whereas the ROM was significantly lower (25.4% vs 41.9%; P = .002) compared with those in Asian series. The addition of Asian cohorts increased ROM for most of diagnostic categories compared with the original TBSRTC. In conclusion, this study demonstrates a difference in Western and Asian thyroid cytology practice, especially regarding the indeterminate categories. Lower RR and higher ROM suggest that Asian clinicians adopt a more conservative approach, whereas immediate diagnostic surgery is favored in Western practice for indeterminate nodules. The addition of Asian series into a meta-analysis of TBSRTC altered ROM for several categories, which should be considered in future revisions of TBSRTC., (© 2019 American Cancer Society.)

Background: A peritheliomatous pattern (PP) in tumors is characterized by a sheath of viable tumor cells closely surrounding a central blood vessel. In the authors' cytology practice, such a PP has been recognized in several metastatic melanoma specimens. The aim of this study was to evaluate the frequency of a PP in cytology samples of melanoma in comparison with other tumors., Methods: Eighty archival fine-needle aspiration (FNA) cases of metastatic melanoma were compared with 65 control cases (35 poorly differentiated/metastatic carcinomas, 15 lymphomas, and 15 recurrent/metastatic/high-grade sarcomas). Cytologic findings were correlated with corresponding histologic specimens, which were available for 44 cases (55%) in the melanoma group and for 23 cases (35.38%) in the control group. All slides were examined for a PP and were semiquantitatively graded for comparison., Results: A PP was present in 51.3% of the cytologic preparations (n = 41) among the melanoma group cases, whereas in the control group, a PP was present in only 3.1% of the cases (n = 2). A PP was present in 65.9% of melanomas with available histologic sections (n = 29) and in 8.7% of tissue samples from the control group (n = 2). A PP was seen more often in cell blocks than direct smear preparations (51.3% vs 40.0%) from patients with melanoma., Conclusions: The presence of a characteristic PP can be helpful in diagnosing melanoma in FNA samples because it was present in almost half of the metastatic melanoma cases in this study and was rarely present in other tumor types. A PP is easier to recognize and more often presents in cell blocks than aspirate smears. Ancillary studies such as immunohistochemistry are helpful for excluding other entities that may exhibit a PP., (© 2020 American Cancer Society.)

Introduction: Data on the performance of cytotechnologists in assessing specimen adequacy of needle core biopsies (NCB) is scant and their role in specimen triaging for ancillary studies have not been well established., Materials and Methods: We retrospectively analyzed rapid onsite evaluation (ROSE) performed exclusively by cytotechnologists on 248 NCB and fine-needle aspiration (FNA) specimens. Overall adequacy and accuracy rates were determined by comparing to final diagnosis. We also reviewed the process of specimen allocation for ancillary testing to determine whether specimens were appropriately triaged at the time of ROSE., Results: Of the 248 cases, 222 (89.5%) were touch imprint and 26 (10.5%) were FNA smears. The overall adequacy rate was 73.4% (182 of 248). Concordance for "adequate" interpretation by ROSE with unequivocal malignant or benign diagnoses on final interpretation was 95.6%. The sensitivity, specificity, and accuracy of ROSE for a final "positive for malignancy" were 89.2% (95% CI 83.04% to 93.69%), 43.24% (95% CI 31.77% to 55.28%), and 73.87% (95% CI 67.57% to 55.28%), respectively. Cases with "positive for malignancy" on final diagnosis were "adequate" by ROSE in 89.1% (132 of 148) and "inadequate" in 10.8% (16 of 148), P < 0.0001. Ancillary tests were performed in 168 of 248 (67.7%); the majority were immunohistochemical stains for determining tumor subtype. Predictive biomarkers were performed successfully in 100% of metastatic breast cancers., Conclusions: Cytotechnologists performed at a high level of competency in providing ROSE and allocating specimens for ancillary testing, which were performed successfully in the majority of cases. Implementation of a standardized protocol for tissue management/prioritization is of paramount importance to maximize tissue preservation and minimize wastage., (Copyright © 2019 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: Differentiating parathyroid from thyroid lesions can be difficult on fine-needle aspiration (FNA) due to overlapping cytomorphologic features. While the traditional parathyroid hormone (PTH) assays can help in the distinction, these tests may be cumbersome, particularly when the lesion is unexpected clinically and a needle wash is not collected at the time of FNA. Therefore, we chose to investigate the application of immunohistochemical staining (IHC) with GATA 3 and thyroid transcription factor-1 (TTF-1) on air-dried cytology smears to distinguish parathyroid and thyroid lesions., Methods: Air-dried touch preparation (TP) slides were prepared from consecutively selected parathyroid and thyroid specimens. Thirteen FNA cases with the clinical concern for parathyroid lesions were also included in the study. IHC was performed on unstained and ultrafast Papanicolaou (UFP) stained air-dried slides., Results: On TP slides, GATA 3 expression was observed in all cases of parathyroid origin but no immunoreactivity was present in thyroid lesions. TTF-1 expression was observed in all cases of thyroid origin but not in parathyroid lesions. GATA 3 and TTF-1 expression of 13 FNA cases were consistent with the clinical impression or concurrent PTH tests., Conclusions: IHC with GATA 3 and TTF-1 on air-dried cytology smears is a simple and effective way to differentiate parathyroid vs thyroid lesions on FNA. Air-dried unstained and UFP-stained slides perform equally well with IHC, but UFP-stained slides provide the added benefit of morphologic evaluation and assessment of smear cellularity prior to IHC., (© 2019 Wiley Periodicals, Inc.)

Objectives: To evaluate the predictive performance of comb-push ultrasound shear elastography for the differentiation of reactive and metastatic axillary lymph nodes., Methods: From June 2014 through September 2018, 114 female volunteers (mean age 58.1±13.3 years; range 28-88 years) with enlarged axillary lymph nodes identified by palpation or clinical imaging were prospectively enrolled in the study. Mean, standard deviation and maximum shear wave elastography parameters from 117 lymph nodes were obtained and compared to fine needle aspiration biopsy results. Mann-Whitney U test and ROC curve analysis were performed., Results: The axillary lymph nodes were classified as reactive or metastatic based on the fine needle aspiration outcomes. A statistically significant difference between reactive and metastatic axillary lymph nodes was observed based on comb-push ultrasound shear elastography (CUSE) results (p<0.0001) from mean and maximum elasticity values. Mean elasticity showed the best separation with a ROC analysis resulting in 90.5% sensitivity, 94.4% specificity, 0.97 area under the curve, 95% positive predictive value, and 89.5% negative predictive value with a 30.2-kPa threshold., Conclusions: CUSE provided a quantifiable parameter that can be used for the assessment of enlarged axillary lymph nodes to differentiate between reactive and metastatic processes., Competing Interests: The authors do not have any financial interest in the technology used in this study. At the time of the study, Dr. Bae Hyung Kim was employed by Mayo Clinic; and to the best of my knowledge, he did not have a commercial affiliation during his appointment at Mayo Clinic and did not have a financial support in the form of salary from the commercial company, Vave Health Inc. He left Mayo Clinic in October 2018. Therefore, I confirm that Vave Health Inc. did not have any role in supporting salary, the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The UK Royal College of Pathologists Thy terminology for reporting thyroid fine-needle aspiration cytology (FNAC), first published in 2009 is used throughout the United Kingdom and Ireland, in some parts of Italy and Switzerland and elsewhere. There is no review of the literature or meta-analysis of the risk of malignancy (ROM) in the various categories of the UK Thy terminology. The goal of this study was to establish the published ROM for each Thy category and compare the results with other existing terminology systems for which similar meta-analyses are available., Methods: A comprehensive literature search of online databases was conducted in May 2019 to examine the ROMs for histologically proven nodules with preoperative FNAC classified according to the UK Thy terminology., Results: Twenty-five articles were identified that showed results of both cytology and histology. Twelve of these articles were excluded to prevent a selection bias because they showed data in just 1 Thy category. In the remaining 13 articles, the pooled ROMs were as follows: Thy1, 12% (95% confidence interval [CI], 5%-22%); Thy2, 5% (95% CI, 3%-9%); Thy3, 22% (95% CI, 18%-26%); Thy3a, 25% (95% CI, 20%-31%); Thy3f, 31% (95% CI, 24%-39%); Thy4, 79% (95% CI, 70%-87%); and Thy5, 98% (95% CI, 97%-99%)., Conclusions: This meta-analysis shows results comparable to those of meta-analyses of other internationally recognized reporting terminologies for the pooled ROMs for surgically excised nodules in the various Thy reporting categories. There is comparatively little difference (only 6%) between the pooled ROMs of Thy3a and Thy3f surgically excised nodules., (© 2019 American Cancer Society.)

Introduction: The diagnostic performance of ultrasound-fine needle aspiration to identify thyroid nodules harbouring malignancy remains variable. The aim of this study was to determine thyroid nodule size and cytological classification as predictors of malignancy risk., Materials and Methods: We conducted a retrospective cohort analysis at an academic hospital involving 499 consecutive patients who underwent thyroid surgery between 2004 and 2015., Results: A total of 503 thyroid nodules (499 patients, 84% female; mean age 50.8 years, standard deviation, SD, 15.4 years) were analysed. Of these, 19.5% were malignant. The mean (± SD) nodule size was 3.28 ± 1.63 cm and 3.27 ± 1.54 cm for benign and malignant nodules, respectively. The odds of malignancy for thyroid nodules less than 3.0 cm was similar to those for nodules of 3.0 cm or greater (0.26 compared with 0.29; p =0.77). Overall, the sensitivity and specificity of fine-needle aspiration in this cohort were 71.4% and 100%, respectively. The overall false negative rate was 5.4%. When the cut-off of 3.0 cm was used, the false negative rate in thyroid nodules less than 3.0 cm was 0% compared with 7.0% in nodules of 3.0 cm or greater. Thus, class ( p <0.01) but not nodule size ( p =0.49), was associated with higher malignancy risk., Conclusions: Our results suggest that thyroid nodule size did not accurately predict the risk of thyroid malignancy irrespective of fine-needle aspiration cytology. Routine diagnostic thyroid lobectomy solely owing to thyroid nodule size of 3.0 cm or greater is currently not justified.

Background: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is considered an indolent neoplasm of the thyroid. Currently, this entity presents a diagnostic challenge on preoperative fine-needle aspiration (FNA) cytology., Methods: Cases of NIFTP and noninvasive encapsulated follicular variant of papillary thyroid carcinoma from January 1994 to August 2018 were retrieved from our institution's pathology databases, and their clinical and cytopathologic features were reviewed., Results: A total of 45 patients with NIFTP were identified. Thirty-nine of 45 patients had presurgical thyroid FNAs, 27 of which showed abnormal cytology (27/39). NIFTPs were most often classified in the indeterminate diagnostic categories on presurgical FNAs (78%), including suspicious for follicular neoplasm (8/27), atypia of undetermined significance (8/27) and suspicious for malignancy (5/27). Six patients had a cytologic diagnosis of papillary thyroid carcinoma (6/27) on thyroid FNAs. Fourteen out of 27 cases with abnormal FNAs had in-house cytology available for review. The most frequent cytologic features observed in NIFTPs included architectural abnormalities, such as crowded clusters (13/14), nuclear overlapping (13/14), predominance or presence of individual microfollicles (11/14), and abundant to scattered isolated cells (10/14). The papillary-like nuclear features observed included nuclear enlargement (14/14), eccentric nucleoli (13/14), nuclear membrane irregularity (12/14), pale chromatin (12/14), nuclear grooves (10/14), and elongated nuclear contour (8/14)., Conclusions: The NIFTPs were most frequently categorized as atypia of undetermined significance and suspicious for follicular neoplasm on cytology. Recognition of the architectural and nuclear features of NIFTP can be helpful in distinguishing NIFTPs from other entities, such as papillary thyroid carcinoma and follicular neoplasms., (© 2019 Wiley Periodicals, Inc.)

Background: This study was conducted to evaluate the diagnostic utility of cell block material in fine needle aspiration (FNA) of thyroid nodules., Design: A total of 242 thyroid fine need aspirations (FNAs) were performed between January 2015 and December 2015. Of those, all consecutive thyroid FNA cases with cell blocks (n = 140) from 129 patients (age: 58.9 ± 12.8 years) are included in this study. Cytology slides and cell blocks are reviewed for adequacy assessment based on the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) and then categorizing them into TBSRTC diagnostic categories. These cases are divided into two groups, combined cytology and cell block (C + CB) and cytology without cell block (C)., Results: In the first group (C + CB), a total 140 cases are categorized in TBSRTC as follows: I: 13 (9.3%) cases, II: 78 (55.7%) cases, III: 7 (5%), IV: 16 (11.4%), V: 3(2.2%) and VI: 23 (16.4%). In the second group (C), the cases are classified in TBSRTC as follows: I: 23 (16.4%) cases, II: 70 (50%), III: 7 (5%), IV: 16 (11.4%), V: 3 (2.2%) and VI: 21 (15%). Nondiagnostic rate was 7.1% lower in the first group (C + CB) as compared with second group (C) (First group: 9.3% vs second group: 16.4%, P = .0764)., Conclusions: Combined use of cytology slides and cell block decreases the nondiagnostic rate up to 7.1% as compared with cytology without cell block., (© 2019 Wiley Periodicals, Inc.)

Context.—: The College of American Pathologists periodically surveys laboratories to determine changes in cytopathology practices. We report the results of a 2016 survey concerning thyroid fine-needle aspiration (FNA)., Objective.—: To provide a cross-sectional survey of thyroid cytology practices in 2016., Design.—: In 2016, a survey was sent to 2013 laboratories participating in the College of American Pathologists Non-Gynecologic Cytology Education Program (NGC-A) requesting data from 2015-2016 on several topics relating to thyroid FNA., Results.—: A total of 878 laboratories (43.6% of 2013) replied to the survey. Radiologists performed the most thyroid FNA procedures in most laboratories (70%; 529 of 756), followed by endocrinologists (18.7%; 141 of 756), and most of these were performed under ultrasound guidance (92.1%; 699 of 759). A total of 32.6% of respondents (251 of 769) provided feedback on unsatisfactory rates for nonpathology providers who performed FNA. Intraprocedural adequacy assessment was primarily performed by attending pathologists (77.4%; 490 of 633) or cytotechnologists (28.4%; 180 of 633). Most laboratories used the Bethesda System for Reporting Thyroid Cytopathology (89.8%; 701 of 781) and performed molecular testing based on clinician request (68.1%; 184 of 270) rather than FNA diagnosis. Correlation of thyroid excisions with prior cytology results most often occurred retrospectively (38.4%; 283 of 737) and was used for pathologist interpretive quality assurance purposes., Conclusions.—: These survey results offer a snapshot of national thyroid FNA cytology practices in 2016 and indicate that standardized cytology terminology is commonly used; pathologists perform most immediate adequacy assessments for thyroid FNA; laboratories use correlation statistics to evaluate pathologists' performance; and molecular tests are increasingly requested for indeterminate interpretations, but reflex molecular testing is rare.

Context.—: Needle biopsy of diseased tissue is an essential diagnostic tool that is becoming even more important as precision medicine develops. However, the capability of this modality to efficiently provide samples adequate for diagnostic and prognostic analysis remains quite limited relative to current diagnostic needs. For physicians and patients, inadequate biopsy frequently leads to diagnostic delay, procedure duplication, or insufficient information about tumor biology leading to delay in treatment; for health systems, this results in substantial incremental costs and inefficient use of scarce specialized diagnostic resources., Objective.—: To review current needle biopsy technology, devices, and practice with a perspective to identify current limitations and opportunities for improvement in the context of advancing precision medicine., Data Sources.—: PubMed searches of fine-needle aspiration and core needle biopsy devices and similar technologies were made generally, by tissue site, and by adequacy as well as by health economics of these technologies., Conclusions.—: Needle biopsy adequacy can be improved by recognizing the importance of this diagnostic tool by promoting common criteria for needle biopsy adequacy; by optimizing needle biopsy procedural technique, technologies, clinical practice, professional education, and quality assurance; and by bundling biopsy procedure costs with downstream diagnostic modalities to provide better accountability and incentives to improve the diagnostic process.

Background: Fine needle aspiration (FNA) cytology has been widely used in the preoperative evaluation of salivary gland lesions. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a tiered risk-stratification scheme designed to standardize reporting and facilitate decision making. We aimed to clarify the validity and diagnostic utility of the MSRSGC-based classification of salivary gland lesions., Methods: A total of 1020 salivary gland FNA specimens were retrieved between 2008 and 2017, with histologic follow-up data available for 349 specimens. Within the present retrospective study, each specimen with follow-up data was reclassified according to the MSRSGC diagnostic categories: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), and malignant. The risk of malignancy (ROM) was calculated based on the histologic follow-up data., Results: The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the MSRSGC-based classification of the malignant potential of salivary gland lesions were 80.1%, 70.4%, 99.2%, 90.5%, and 96.7%, respectively. The ROM calculated for specimens assigned to the nondiagnostic, nonneoplastic, AUS, benign neoplasm, SUMP, SM, and malignant categories were 8.6%, 15.4%, 36.8%, 2.6%, 32.3%, 71.4%, and 100%, respectively., Conclusion: The present results confirm the validity and diagnostic utility of MSRSGC, supporting its use in clinical practice to help devise adequate management strategies for salivary gland lesions., (© 2019 Wiley Periodicals, Inc.)

Background: Hürthle cell lesions often pose diagnostic challenges, despite their common occurrence on thyroid fine-needle aspiration cytology (FNAC). The associated molecular alterations are also not well understood. Therefore, our study aimed to delineate the molecular profile of Hürthle cell lesions classified as Bethesda Categories III or IV (atypia of undetermined significance (AUS) or suspicious for follicular neoplasm (SFN)) on FNAC and to correlate this molecular profile with surgical resection findings., Methods: This study consisted of 188 Hürthle cell lesions with indeterminate cytology and ThyroSeq® v2/v3 molecular testing results. Surgical follow-up was available for 33 cases., Results: The majority of indeterminate Hürthle cell lesions had negative ThyroSeq® results (61%) and were benign on available surgical follow-up. The most prevalent mutations involved the RAS gene (21%), which were associated with benign lesions, non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and malignancy. The remaining mutations involved less than 18% of the cases, including PAX8/PPARG (3.7%), TSHR (3.7%), EIF1AX (2.7%), MET (2.1%), PTEN (1.6%), clonal copy number alteration (1.6%), TERT (1.1%), and 0.5% each of GNAS, PIK3CA, and TP53 mutations. On follow-up, 45% were benign, 24% were NIFTP, and 30% were malignant. The malignant cases had different molecular alterations., Conclusion: No single molecular alteration defines cytologically indeterminate Hürthle cell lesions; the majority of cases have low-risk or no molecular alterations and are benign on follow-up. These findings suggest that molecular testing may be useful, but is not definitive, in determining which cases may be managed conservatively; additional studies are needed to fully determine the negative predictive value in ruling out malignancy., (© 2019 Wiley Periodicals, Inc.)

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates., (© 2019 Wiley Periodicals, Inc.)

The risk of malignancy for some diagnoses in thyroid fine-needle aspirations is higher than the actual risk of clinical progression. Other measures of prognosis may be helpful in managing patients with indeterminate thyroid fine-needle aspiration diagnoses. We estimated the risk of death due to disease (RDDD) for well-differentiated thyroid carcinoma using a series of over 15 000 aspirates with over 2000 excisions and data from the SEER database. RDDD was low (1.3% or less for all categories). The RDDD of some indeterminate thyroid aspirates was higher than for malignant aspirates. The RDDD may provide additional information for patients and clinicians seeking to manage patients with indeterminate thyroid fine-needle aspirates., (© 2019 Wiley Periodicals, Inc.)

Background: India, being a developing country, harbors the third largest human immunodeficiency virus (HIV)-infected population in the world, and HIV-associated lymphadenopathy is commonly encountered. HIV lymphadenopathy is more commonly generalized and pathology ranges from reactive lymphoid hyperplasia to infections like tuberculosis to neoplasms such as lymphoma and Kaposi sarcoma. The study intended to assess the utility of fine-needle aspiration (FNA) cytology in HIV lymphadenopathy., Materials and Methods: A retrospective FNA slide review of HIV-infected cases with lymphadenopathy received over a period of 2 years in the cytopathology department was performed. The clinicopathological characteristics, absolute lymphocyte count (ALC), and CD4 counts were analyzed., Results: Seventy-nine lymph node aspirates were received from HIV patients over 2 years. The mean age at presentation was 39 years with a male:female ratio of 2.4:1. Cervical lymph nodes (62%) were more commonly affected. Tuberculous lymphadenitis was the commonest lesion (41.8%), followed by reactive lymphadenitis (24%), nonspecific granulomatous lymphadenitis (14%), suppurative lymphadenitis (8%), cryptococcal lymphadenitis (2%), lymphoma (9%), and metastasis (1%)., Conclusion: Lymph node FNA in HIV/AIDS is not only useful in identifying those cases that require further evaluation, but also aids in categorizing various etiologies such as opportunistic infections, non-neoplastic, and neoplastic lesions. FNA is a less expensive, expeditious minimally invasive method for an early diagnosis that abets in deciding the treatment strategy, thus curtailing the associated morbidity and mortality., (© 2019 Wiley Periodicals, Inc.)

A re-named diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) likely impacts the prevalence of thyroid cancer and risk of malignancy in populations based on the established Bethesda System of Reporting Thyroid Cytopathology (TBSRTC). This study was done to investigate the prevalence and cytological distribution of NIFTP. PRISMA guided systematic review was done from a database search of Pubmed, EMBASE, and Medline using the search terms "non-invasive follicular thyroid neoplasm with papillary-like nuclear features", "non-invasive follicular variant of papillary carcinoma", "niftp", and "Bethesda" until November 2018. Original articles with surgically proven diagnoses of NIFTP using strict NIFTP criteria were included. Twenty-nine studies with 1563 cases of NIFTP were included. The pooled prevalence of NIFTP in cases which would be classified previously as the follicular variant of papillary thyroid cancer (FVPTC) and papillary thyroid cancer (PTC) were 43.5% (95% CI 33.5-54.0%) and 4.4% (95% CI 2.0-9.0%) respectively. The pooled TBSRTC distribution of cases diagnosed as NIFTP was: from the non-diagnostic category 3.6% (95% CI 2.4-5.3%), benign 10.0% (95% CI 7.2-13.6%), AUS/FLUS 34.2% (95% CI 28.2-40.8%), FN/SFN 22.7% (95% CI 17.2-29.4%), suspicious for malignancy 22.4% (95% CI 17.7-27.9%), and malignant 7.5% (95% CI 4.2-12.9%). While a significant reduction in FVPTC prevalence is anticipated, a modest reduction of PTC prevalence is also expected with adoption of the NIFTP terminology that would be distributed mainly among lesions classified as indeterminate thyroid nodules. Further studies are needed to identify unique clinical characteristics of these lesions preoperatively.

Background: This retrospective study evaluated and compared the diagnostic accuracy and suitability of tissue specimens for advanced molecular diagnostic testing obtained via 2 different techniques for percutaneous biopsy of primary and metastatic liver tumors., Patients and Methods: Samples from 137 patients with liver masses who underwent concurrent fine-needle aspiration biopsy with cell block (FNAB-CB) and core needle biopsy (CNB) at 2 hospitals were assessed for diagnostic accuracy, tumor fraction, and tumor cellularity. A subset of FNAB-CBs, that were deemed to have less or equal tumor cellularity compared with CNBs, had level sections performed and were reassessed for tumor cellularity., Results: Diagnostic accuracy was 96% for FNAB and 93% for CNB (P=.267). In FNAB-CBs, tumor fraction was significantly higher than in CNB samples (67% vs 36%; P<.0001), whereas nontumor components were significantly lower (stromal component, 7% vs 29%; P<.0001; background benign hepatocytes, 25% vs 36%; P=.003). Additionally, in 44% of cases, FNAB-CB tumor cellularity was equal to or greater than that of the concurrent CNB., Conclusions: In the current age of personalized medicine, a minimally invasive, safe approach to obtaining adequate tissue for myriad molecular testing is paramount. We have shown that FNAB sampling is diagnostically accurate and produces higher tumor fractions than CNB. Thus, FNAB should be strongly considered as an initial sampling modality, especially for patients in whom molecular tests will determine management.

Objectives: (1) To compare the American College of Radiology (ACR) thyroid imaging reporting and data system (TIRADS) and American Thyroid Association (ATA) guidelines for thyroid nodules with regard to diagnostic performance and effectiveness at reducing the number of fine-needle aspiration (FNA) biopsies and to preliminarily discuss the reasons for the differences and (2) to compare the diagnostic performance of the two guidelines in the subgroup of nodules <1 cm in diameter., Materials and Methods: In the present study, 1000 thyroid nodules in 894 consecutive patients with final diagnoses were included; these thyroid nodules were investigated via FNA biopsies in our hospital. The ultrasound (US) features of the thyroid nodules were reviewed and stratified according to the categories defined by the ACR TIRADS and ATA guidelines., Results: Compared with the ACR TIRADS guidelines, the ATA guidelines had a higher sensitivity (93.4% (P < 0.001)) and a larger negative predictive value (NPV) (85.3% (P= 0.034)). Compared with the ATA guidelines, the ACR TIRADS guidelines had a higher specificity (66.0% (P < 0.001)), a greater PPV (73.6% (P= 0.001)), and greater accuracy (75.5% (P= 0.017)). Compared with the ATA guidelines, the ACR TIRADS guidelines resulted in significantly fewer unnecessary FNA biopsies (P= 0.007)., Conclusions: This study suggests that both the ACR TIRADS and ATA guidelines have unique strengths with regard to their diagnostic performance. In terms of reducing the number of FNA biopsies, the ACR TIRADS guidelines were superior to the ATA guidelines.

Introduction The prevalence of thyroid nodules is 4-7% in adults. Although less than 5% of nodules in adults are malignant, most nodules are non-neoplastic or benign. Fine needle aspiration (FNA) is a diagnostic technique for evaluation of non-toxic nodules, which has been widely accepted. Its primary objective is the patient triage in order to identify those who need surgery and aid in the decision of the appropriate surgical procedures. Materials and Methods This retrospective study was conducted on 116 patients who underwent thyroidectomy in Semnan's Kowsar Hospital during 2011-2018 in Iran. The data were recorded before and after the surgery in the checklist. The data were compared and the sensitivity, specificity and diagnostic accuracy of FNA were calculated. Data were analyzed by SPSS software (version 18.0) and analyzed by Chi-Square test and Independent Samples test. Results The sensitivity of FNA was 96.9%; its specificity was 81.7%; its positive predictive value (PPV) was 73.8%; its negative predictive value (NPV) was 98%; and its diagnostic accuracy was 86.9%. For the nodules smaller than 4 cm, FNA was calculated with higher sensitivity, specificity, PPV, NPV, and diagnostic accuracy compared to nodules larger than 4 cm. Conclusion FNA is a reliable screening method for preoperative assessment that can accurately detect malignant cases from benign cases, especially if the size of the nodule is smaller than 4 cm.

Introduction: The second edition of The Bethesda System for Reporting Thyroid Cytopathology has incorporated the recent change in nomenclature, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), with an anticipated change in the risk of malignancy (ROM). We examined our institutional experience in the incidence of NIFTP and the change in the ROM in The Bethesda System for Reporting Thyroid Cytopathology., Materials and Methods: A computerized search was performed from January 2013 to August 2017 for all thyroid fine needle aspirations (FNAs), the corresponding surgical resection specimens, and clinical follow-up data. All thyroid specimens reported as follicular variant of papillary thyroid carcinoma were reviewed and reclassified, and all NIFTP diagnoses from April 2016 to August 2017 were identified. The ROM for each category was calculated before and after the change and analyzed for significance., Results: A total of 4500 thyroid FNA cases were collected. Of these, 479 cases had surgical resection specimens available and 36 cases had been diagnosed as NIFTP. Of these, 22 had been previously diagnosed as FVPT. Of 27 cases of NIFTP, 14 and 13 were atypia of undetermined significance/follicular lesion of undetermined significance and follicular neoplasm/suspicious for follicular neoplasm, respectively. A reduction in the ROM was observed in these 2 categories (P = 0.03 and P = 0.04, respectively)., Conclusions: In our institution, NIFTP has accounted for 13% of all malignant thyroid neoplasms since the change in nomenclature. Although the ROM was decreased in the affected categories, with absolute statistically significant decreases in ROM of 15% and 16.2% for category III and IV, respectively, the overall ROM change was marginal., (Copyright © 2019 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Background: Fine-needle aspiration (FNA) of superficial and deep-seated lesions has been used with high sensitivity and specificity in the diagnosis of neoplastic and nonneoplastic lesions. However, literature of FNA in posttransplant patients is sparse, especially in postliver transplant. We undertook a retrospective study to evaluate the utility of FNA in the clinical management of post liver transplant patients., Methods: We searched our institution's surgical/cytologic databases (November1993-February2016) to identify liver transplant cases and FNA procedures performed on allograft liver recipients. Institutional IRB approval was obtained for this study., Results: 886 liver allograft recipients were reviewed, 41(5%) of which were transplanted for hepatocellular carcinoma. 62/886(7%) underwent an FNA procedure. 39males and 23females included with mean age of 58years. Mean time between transplant and FNA was 34months. 21/62(34%) were malignant neoplasms, most common malignancy was adenocarcinoma: 8cases(3lung,3pancreas,1colon,1cholangiocarcinoma)and 8cases of transplanted hepatocellular carcinoma patients had recurrence, 6 in the allograft liver and 1case each of metastasis to the iliac bone and periportal lymph node. 3cases were squamous-cell carcinoma (2lung and 1scalp). 2cases were posttransplant lymphoproliferative disorders. 34/62(55%) cases were benign aspirates from various organs (8lung,6liver,5pancreas,4breast,3thyroid,3lymph-nodes and 1case each of salivary gland, bile-duct,intraabdominal,abdominal wall,and oral cavity) 0.6/62(10%) cases were inflammatory. 22cases had histologic correlation: 5true-positives,16true-negatives,1false-negative (a patient with parotid mucoepidermoid carcinoma whose FNA diagnosis was sialadenitis), and no false-positive. The sensitivity was 83% and the specificity was 100%. The positive predictive value was 100% and the negative predictive value was 94%., Conclusions: This review shows that 40/62(65%) of the aspirates were benign lesions, indicating that a conservative approach is recommended in the clinical management of these patients, especially since the interval between transplant and FNA was on average 34months. FNA is a safe, minimally invasive method to follow-up these patients., (© 2018 Wiley Periodicals, Inc.)

Objective: Rapid on-site evaluation (ROSE) is a technique beneficial in determining the adequacy of the samples, thereby increasing the diagnostic yield, useful in triage of specimens for ancillary studies and can also help determine a preliminary diagnosis in emergency cases. The different rapid stains for on-site evaluation described in the literature are diff quik, toluidine blue (TB), brilliant cresyl blue (BCB), ultra-fast Pap stains, and rapid hematoxylin and eosin (H&E). This study was undertaken as there is sparse literature regarding the best and the most cost-effective rapid stain., Method: Fine needle aspiration samples from 200 patients with palpable swellings in easily accessible regions were taken. Smears stained by rapid and routine stains were assessed based on four parameters, with provisional diagnosis on the rapid stained smears. A comparative analysis of the advantages and disadvantages of the rapid stains was carried out with appropriate statistical tests with the routinely stained smears as gold standard., Results: There was adequate material in 100% of ROSE smears. rapid pap stained smears showed well preserved cytoplasmic details, nuclear details, and background details. The time taken was least with TB and BCB being 5 s each. The most cost-effective was found to be TB., Conclusions: We conclude that TB is the most cost-effective, quick, least labor-intensive, and reliable rapid stain for ROSE especially in resource-poor settings., (© 2018 Wiley Periodicals, Inc.)

Background: Head and neck masses are a common presentation in daily practice and can be challenging to both clinicians and cytopathologists. Fine needle aspiration cytology (FNAC) is a widely used method for the diagnosis of head and neck masses. The aim of the study was to assess our institutional experience of the accuracy of FNAC in the diagnosis of head and neck masses., Methods: A total of 1262 FNACs were conducted from January 2013 to December 2016 and subdivided into benign and malignant categories. The thyroid and salivary glands FNACs were classified according to the Bethesda System for Reporting Thyroid cytopathology and to the Milan System for Reporting Salivary Gland Cytopathology respectively. The measures of diagnostic accuracy of FNAC were determined taking histology as a gold standard., Results: A total of 7 false negative (FN) and 6 false positive (FP) FNACs were identified. Overall sensitivity and specificity of FNAC for a malignant diagnosis were 92% and 94.4%, respectively. Accuracy of FNACs of head and neck masses was 93.5% for all sites. The salivary gland group had the highest rate of FN (2.8%). All FP were reported in the thyroid group. These cases were cytologically classified suspicious for malignancy (n = 3) and papillary carcinoma (n = 3) and proved to be lymphocytic thyroiditis on final histology. Among the most common locations, cytology of lymph nodes provided the best sensitivity (98.2%). Salivary glands as well as lymph nodes had the best specificity (100%)., Conclusion: FNAC of head and neck masses has a high accuracy allowing a correct therapeutic management. However, this accuracy depends on the anatomic location of the mass., (© 2018 Wiley Periodicals, Inc.)