Thyroid cytopathology: updates and molecular testing.

The utility of fine needle aspiration (FNA) is well described in the context of evaluating thyroid lesions. Among the various international systems of classification of thyroid cytology, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has also provided a sound framework to standardize the reporting of FNA cytology results. New molecular evidence and clinical studies demonstrated the need for revision of the nomenclature resulting in introduction of new categories, such as the noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Indeterminate thyroid cytology results pose a challenge for further management and the continued development of molecular markers may aid in the management of indeterminate thyroid lesions.

An Insight into the Utility of Sub-Categorisation of Atypia of Undetermined Significance for Risk Stratification: A Retrospective Study on an Indian Cohort with Histopathological Correlation.

BACKGROUND: Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) criterion in thyroid fine-needle aspirates (FNAs) has been a heterogeneous entity with much inter-observer variation. Sub-categorisation of AUS/FLUS has been observed to play an effective role in risk stratification. We aimed to validate AUS/FLUS sub-categorisation in correlation with the spectrum of malignancy. STUDY DESIGN: Subjects included patients with AUS/FLUS diagnosed between January 2015 and December 2016. AUS/FLUS cases were sub-categorised into those exhibiting (1) architectural atypia, (2) cytological atypia, (3) architectural and cytological atypia, (4) AUS with Hürthle cells, and (5) AUS not otherwise specified (AUS-NOS). Each sub-category was correlated with their corresponding incidence of malignancy in surgical resections. RESULT: The overall incidence of AUS/FLUS in our centre was 13% (132/1,018). On retrospective review of 117 patients with AUS/FLUS, smears with cytological atypia showed a higher incidence of malignancy (78.3%) than those with architectural atypia (75.3%). AUS/FLUS cases with both cytological and architectural atypia had a malignancy rate of 71.4%. CONCLUSION: AUS/FLUS cases with cytological atypia had a higher risk of malignancy than those with architectural atypia. The sub-categorisation of AUS/FLUS is diagnostically important for the proper risk stratification of patients.

Three-year cytohistological correlation of salivary gland FNA cytology at a tertiary center with the application of the Milan system for risk stratification.

BACKGROUND: Fine-needle aspiration (FNA) cytology of salivary glands is a well-established technique that plays a critical role in the preoperative diagnosis of lesions. A risk stratification of FNA diagnostic categories has been recently proposed to be useful in reporting. The aims of this study were to evaluate the diagnostic accuracy of salivary gland FNA and to apply the proposed Milan system for reporting salivary gland lesions. METHODS: A retrospective audit of FNA specimens of salivary gland lesions reported from 2014 to 2016 was performed. A correlation with the follow-up histopathology, wherever it was available, was performed. The aspirates were then categorized according to the Milan system as follows: nondiagnostic, nonneoplastic, atypical, benign neoplasm, neoplasm of uncertain malignant potential (NUMP), suspicious for malignancy, or positive for malignancy. Furthermore, the risk of malignancy and the risk of high-grade malignancy were calculated for all diagnostic categories. RESULTS: A total of 631 salivary gland aspirates were evaluated: 2.2% were nondiagnostic, 55.8% indicated nonneoplastic lesions, and 40.4% indicated neoplastic lesions. Histopathology was available for 94 cases (14.9%). FNA had a sensitivity of 79.4% and a specificity of 98.3% with an overall diagnostic accuracy of 91.4% for differentiating malignant tumors from benign tumors. The overall risk of malignancy was 17.4% for the nonneoplastic category, 100% for the atypical category, 7.3% for the benign neoplasm category, 50% for the NUMP category, and 96% for the positive-for-malignancy category. CONCLUSIONS: Salivary gland FNA continues to have high diagnostic accuracy and is thus helpful for guiding management. Neoplasms with classic cytomorphology are easily diagnosed; however, in difficult cases showing overlapping features, the use of the Milan system could be beneficial. Cancer Cytopathol 2017;125:767-75. © 2017 American Cancer Society.

Application of the Bethesda Classification for Thyroid Fine-Needle Aspiration: Institutional Experience and Meta-analysis.

CONTEXT: -Fine-needle aspiration (FNA) biopsies have been an important component in the preoperative evaluation of thyroid nodules. Until the introduction of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) in 2008, individual institutions had developed their own diagnostic categories. The BSRTC proposed 6 categories in an attempt to standardize reporting of thyroid FNA. OBJECTIVE: -To present a 15-year experience of thyroid FNA at one institution, including data before and after introduction of the BSRTC. The risk of malignancy is compared with the meta-analysis of high-quality published data. DATA SOURCES: -Data sources were PubMed, a manual search of references, and institutional data. CONCLUSIONS: -The diagnostic categories developed at our institution were similar to those proposed by the BSRTC, with best fit into the 6 categories easily accomplished and reported in the final 2 years of the study. Significant differences were noted in the frequencies of cases in diagnostic categories Benign (II; P = .003), Suspicious for follicular neoplasm/Follicular neoplasm (IV; P < .001), and Malignant (VI; P = .003) after the introduction of the BSRTC. Eighteen published articles met the criteria for inclusion in the meta-analysis. The risk of malignancy in each category in our institution was similar to that determined in the meta-analysis, except for Insufficient for diagnosis (I; 20% versus 9%-14%). Meta-analysis showed an overlapping 95% CI of risk of malignancy between Atypia of undetermined significance/Follicular lesion of undetermined significance (III; 11%-23%) and Suspicious for follicular neoplasm/Follicular neoplasm (IV; 20%-29%), suggesting similar risks of malignancy. The use of newer molecular tests for these indeterminate cases may further refine risk assessment.

Aspectos actuales del carcinoma bien diferenciado de tiroides / Present-day aspects of Carcinoma well told apart of the thyroid

El carcinoma de tiroides ha aumentado su incidencia en los últimos años. Su diagnóstico rápido y consiguiente tratamiento son necesarios para una mayor sobrevida del paciente. El ultrasonido aun es la prueba diagnóstica de mayor utilidad. La biopsia por aspiración por aguja fina guiada por ultrasonido ha permitido disminuir los falsos negativos, así como incrementar la eficacia y sensibilidad de esta prueba. La cirugía es la mejor opción curativa que tiene la enfermedad, su extensión es aun controversial. El tratamiento en equipo multidisciplinario ha hecho avanzar en ello y optimizar el tiempo de diagnóstico, los mÚtodos, así como el tipo de tratamiento a utilizar(AU)

Thyroidal carcinoma incidence has increased over recent years. Quick diagnosis and arranged treatment are necessary for the patients improved survival. Ultrasound continues to be the diagnostic test of greater usefulness. Ultrasound-guided aspiration biopsy has decreases the false-negative results, as well as this tests efficacy and sensibility have increased. Surgery is the best healing choice against the disease, though its extension is even controversial. Treatment by multidisciplinary teams has prospered it optimized diagnosis time and methods, as well as the type of treatment to use(AU)

Reducing indeterminate thyroid FNAs.

BACKGROUND: The Bethesda System recommends limiting the percentage of cases diagnosed as indeterminate in thyroid fine-needle aspirations (TFNAs). However, studies are lacking that document how to decrease the rate of indeterminate TFNAs and its effects. METHODS: The authors modified the Bethesda criteria to reduce the rate of indeterminate TFNAs ("atypical cells of undetermined significance" and "suspicious for a follicular/Hurthle cell neoplasm") by reassigning cases that may have been categorized as indeterminate to "suspicious for papillary carcinoma" or "favor benign" for an 18-month period and correlated this with histologic follow-up. RESULTS: The indeterminate rate decreased from 14.4% (Bethesda) to 8.2% (modified Bethesda; P < .001). There was no significant difference in the risk of malignancy for the 2 groups (23.6% vs 17.3%, respectively; chi-square P = .39). There were 6 false-positive diagnoses in the Bethesda group compared with none in the modified Bethesda group (P = .06). In the Bethesda group, but not in the modified Bethesda group, the indeterminate rate was correlated with the overall rate of malignant and suspicious for papillary carcinoma diagnoses. CONCLUSIONS: Modifying the Bethesda criteria can decrease indeterminate TFNAs diagnoses without a significant decrease in the risk of malignancy. The modified Bethesda criteria, but not the Bethesda criteria, are independent of the malignancy rate.

[Up-to-date experience with the international classification system Bethesda 2010 for thyroid fine-needle aspirate: a review]. / Prehled dosavadních zkuseností s mezinárodní klasifikací tenkojehlové aspiracní cytologie stítné zlázy Bethesda 2010.

The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was introduced in thyroid fine needle aspiration cytology (FNAC) in 2010. A six-tier system is generally accepted. Bethesda categories include morphologic description, risk of malignancy and follow-up suggestions in each group. The system has its advantages and disadvantages, that are discussed. The most problematic are the categories of "Atypia of undetermined significance" or "Follicular lesion of undetermined significance" (AUS/FLUS). The group is heterogenous and overused thus far. The possibilities of its improvement are discussed. The Bethesda system does not include any prognostic and predictive markers. However, they represent the promising direction in the improved version of the BSRTC. Novel molecular methods and alternative techniques such as core needle biopsy are briefly discussed.

The microscopic complexities of C3 in breast cytology.

BACKGROUND: Fine-needle aspiration (FNA) of difficult breast lesions often results in an atypical (C3) report. The assortment of outcomes generated by C3 reports varies widely, and this has given rise to different clinical management pathways. OBJECTIVE: To identify and objectively assess microscopic features associated with atypical/C3 breast FNA cases. MATERIALS AND METHODS: A total of 230 atypical breast FNAs were subjected to a blind microscopic rescreen using a range of robust qualitative and quantitative cytological criteria including cellularity, architectural qualities, cytomorphology and background features. A logistic regression with a receiver operating characteristic (ROC) curve and the resultant forward stepwise analysis were conducted to assess the results. This statistical testing was measured against malignant, benign proliferative and benign non-proliferative outcomes. RESULTS: The malignant and benign proliferative outcomes showed a mixture of opposing protective and predictive individual cytological criteria. The stepwise analysis produced models demonstrating the best combination of individual cytological criteria for malignancy, proliferative and benign non-proliferative entities. In the malignancy model, discohesion, nuclear crowding within sheets, diminished numbers of bare bipolar nuclei and myoepithelial cells, the presence of tubules or necrosis and the absence of a cystic background were important features. The benign proliferative model suggested the same criteria but with the opposite implication and with the addition of several others, such as the presence of apocrine metaplasia, retained polarity and a speckled or coarse chromatin pattern. Age was a significant factor in malignant and proliferative outcomes. The benign non-proliferative stepwise analysis produced a model with fewer criteria (complex sheets, bare bipolar nuclei and a cystic background) limiting clinical application. CONCLUSION: Atypical/C3 breast cytology remains a legitimate reporting category. However, it is associated with a number of different histological outcomes. The incidence of the C3 category can be significantly reduced by controlling extrinsic factors and understanding the associated microscopic features.

New classification of thyroid FNAB results - a three-year observation from one clinic.

INTRODUCTION: Fine needle aspiration biopsy (FNAB) is the main examination in diagnostics of thyroid nodules. Yet, it does not allow the differentiation of follicular lesions (FL). A new classification of thyroid biopsy results (newC) might improve pre-operative diagnostics mainly due to the introduction of a new subcategory of 'follicular lesion of undetermined significance', as well as the clarification of definitions of other categories. The aim of this study was to analyse the impact of the newC on the distribution of the cytological results among main diagnostic categories and on the values of the parameters describing the effectiveness of FNAB in detecting malignancy. MATERIAL AND METHODS: 34,371 FNABs outcomes and 3,557 results of surgical follow up were analysed. The frequencies of five main diagnostic categories in two periods: before (years: 2000-2009, 24,271 FNAB) and after the newC had been introduced (years: 2010-2012, 10,100 FNAB) were compared, as well as parameters describing the biopsy effectiveness, with a special focus on FL. RESULTS: In the second analysed period, the frequency of the 'suspicious for malignancy' results was three times lower, while diagnoses of 'malignant neoplasm' were 33% more frequent and the results corresponding to FL decreased by 10%. In respect to FL, specificity of FNAB increased (22.6% vs. 57.4%), but sensitivity decreased (78.8% vs. 50.0%). In respect to other diagnostic categories considered jointly, the sensitivity of FNAB (61.2% vs. 85.7%) and PPV (57.4% vs. 77.8%) increased, and the specificity was similar (95-97%) for both periods. NPV exceeded 95% irrespective of applied classification. CONCLUSIONS: Separation of FL with low risk of malignancy affects the values of the parameters describing the effectiveness of FNAB. The improved diagnostic effectiveness of FNAB is also a consequence of epidemiological changes and better selection of thyroid lesions for biopsy.

Rates of thyroid malignancy by FNA diagnostic category.

BACKGROUND: Fine needle aspiration (FNA) of thyroid nodules is a cornerstone of surgical decision making in thyroid cancer. The most widely utilized system for reporting thyroid FNA results is the Bethesda System, which includes predicted malignancy rates for each FNA category. To date there have been few studies to determine whether these predictions are widely applicable. METHODS: All thyroid FNA results at the Queen Elizabeth II Health Science Centre from 2006-2010 were included in this study. The results were tabulated by FNA category and the health records were reviewed to determine whether the patient went on to have surgery and the result of surgical histopathology. Rates of malignancy were calculated and compared to published values. RESULTS: A total of 1491 thyroid FNAs were included in the study, representing 1117 individual patients with available health records. The majority of these FNAs were Benign, but the proportion of Unsatisfactory FNAs was higher than predicted while Malignant and Suspicious for Malignancy were lower than predicted. Surgery was performed on 388 patients and 110 were positive for malignancy (28%). The malignancy rate for each FNA category was higher than predicted based on literature values. CONCLUSIONS: The proportions of FNA diagnoses and the rates of malignancy for each FNA category at our institution were not consistent with predicted values. It is important for clinicians to base their surgical recommendations on institution specific malignancy rates, not solely on literature values.

The interobserver reproducibility of thyroid cytopathology using Bethesda Reporting System: analysis of 200 cases.

OBJECTIVE: To determine interobserver reproducibility of thyroid cytopathology in cases of thyroid fine needle aspirates. METHODS: The retrospective, descriptive study, was conducted at the Foundation University Medical College, Islamabad, using cases related to period between 2009 and 2011. A total of 200 cases of fine-needle aspirations were retrieved from the archives. Three histopathologists independently categorised them into 6 groups according to Bethesda reporting system guidelines without looking at previous reports. Kappa statistics were used for analysis of the results on SPSS 17. RESULTS: Of the 200 patients, 194 (97%) were females and 6 (3%) were males. The overall mean age of patients was 46 +/- 20 years. Kappa value calculated for observer-1 and observer-2 was 0.735; for observer-1 and observer-3, 0.841; and for observer-2 and observer-3, 0.838, showing substantial interobserver agreement. Histopathological correlation was available, for 39 (19.5%). Of these cases, 5 (13%) were 'non-diagnostic, 20 (51%) 'benign, 2 (5%) 'atypia of undetermined significance/follicular lesion of undetermined significance, 6 (15%) 'follicular neoplasm, 1 (3%) 'suspicious for malignancy, and 5 (13%) 'malignant. CONCLUSIONS: Good overall interoberver agreement was found, but discordance was seen when certain categories were analysed separately.

Stereotactic breast biopsy: comparison of histologic underestimation rates with 11- and 9-gauge vacuum-assisted breast biopsy.

OBJECTIVE: The purpose of this study was to compare histologic underestimations at stereotactic 11- and 9-gauge vacuum-assisted breast biopsy. MATERIALS AND METHODS: The reports of 1,223 consecutive stereotactic vacuum-assisted breast biopsies were retrospectively reviewed. An 11-gauge device was used to perform 828 and a 9-gauge device to perform 395 biopsies. The pathologic results were reviewed for all cases. Biopsy results of atypical ductal hyperplasia and ductal carcinoma in situ were compared with the pathologic results after surgical excision. Underestimation was defined as the need to upgrade atypical ductal hyperplasia to ductal carcinoma in situ or invasive carcinoma at surgery and to upgrade ductal carcinoma in situ to invasive carcinoma. Statistical significance was determined with the chi-square test and 95% CI. RESULTS: In the 11-gauge group, 12 (26%) of 46 cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ and one (2%) of the cases to invasive carcinoma. In the 9-gauge group, six (22%) of 27 cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ and two (7%) of the cases to invasive carcinoma. In the 11-gauge group, 35 (28.7%) of 122 cases of ductal carcinoma in situ were upgraded to invasive carcinoma. In the 9-gauge group, 10 (23%) of 44 cases of ductal carcinoma in situ were upgraded to invasive carcinoma. CONCLUSION: There was no statistically significant difference between 11-gauge biopsy and 9-gauge biopsy in underestimation of atypical ductal hyperplasia and ductal carcinoma in situ.