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(a) FNAC thyroid showing follicular cells arranged in sheets with few showing Hurthle cell and degenerative change (H and E stain x200); (b and c) Smears show few nuclei showing intra nuclear inclusions (black arrow) but features not sufficient enough to be diagnosed as papillary carcinoma. Case was diagnosed as category AUS/FLUS of BSRTC (b: H and E stain ×200, c: May–Grunwald–Giemsa; ×400); (d) Histopathological examination of same case showed papillary carcinoma (H and E stain x200) d c
Source publication
Introduction: Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) of Bethesda system for reporting thyroid cytopathology has emerged as most controversial category due to its heterogeneity and inconsistent usage. Initially associated risk of malignancy was estimated to be about 5–15%, but eventually di...
Context in source publication
Context 1
... The category III or AUS\FLUS diagnosis was rendered when there was predominance of micro follicles and\or oncocytes in paucicellular smear or in the presence of air drying or clotting artefact and thus not otherwise fulfilling the criteria of "follicular neoplasm\ suspicious of follicular neoplasm" [ Figure 1]. In addition, the category III was also diagnosed when there were same nuclei showing features suspicious of papillary carcinoma in otherwise hyperplastic or colloid nodule [ Figure 2] or there were presence of atypical lymphoid cells. The risk factors for surgical intervention were worrisome radiological and clinical features including age, size, margins, and ultrasonography features of hypoechogenicity, hypervascularity, and calcification. ...
Similar publications
Molecular testing has a potential to improve the management of patients with indeterminate thyroid nodules considered for surgery. This study examined the influence of molecular tests on the treatment of indeterminate nodules, particularly the differences between Western and Asian countries. Electronic databases including PubMed and Web of Science...
Background
This study aims to determine the clinical value of contrast enhanced ultrasound (CEUS) for fine-needle aspiration (FNA) of high inadequate risky thyroid nodules.
Methods
During April 2018 and April 2021, consecutive 3748 thyroid nodules underwent FNA were retrospectively analyzed. CEUS guided FNA (CEUS-FNA) was applied in 115 nodules wi...
Objective: To determine the risk of malignancy of Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) indeterminate Thyroid Nodules (Bethesda III, IV and V) by combining cytologic (TSBRTC) and Thyroid Imaging Reporting and Data Systems (TI-RADS) ultrasonographic features based on final histopathology. Methods:Design: Retrospective review o...
Objective
Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) is a safe and effective method of screening malignant thyroid nodules such as papillary thyroid carcinoma. However, not much data are available regarding the diagnostic efficacy of US-FNAB for papillary thyroid microcarcinoma (≤10 mm in diameter). We aim to compare the diagnostic e...
Citations
... We accomplished the study in a tertiary-care center where patients were referred with increased chances of malignancy. We observed FVPC was the most common malignant diagnosis on histopathology in category III and category IV subjected to surgery, similar to a study by Chandra et al. [10] and Godoi et al. [11] A provisional goal of limiting AUS/FLUS interpretations to approximately 7% of all thyroid FNA interpretations was proposed in the previous edition of the TBSRTC atlas. The incidence of AUS/FLUS diagnoses in this study is comparable to the suggested rate of 7% by TBSRTC, indicating that the results are similar to its objective. ...
Thyroid fine-needle aspiration cytology (FNAC) has gained significance as a quick, safe, and relatively
simple method to differentiate malignant from benign thyroid nodules and is regarded as the gold-standard first-line
diagnostic test in the evaluation of thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology
(TBSRTC) established a standardized, category-based reporting system for thyroid FNAC with each category having
an implied cancer risk. However, the optimal management of thyroid nodules in the Bethesda III and IV categories
is controversial, given the variable malignancy rates.
... Thirteencases (16.9%) within this category had a follow-up surgery and the ROM was 30.8%. In comparison, the malignancy rates of this category were ranged from15.9% to 29%, [20,22,30,31]. Chakravarthy et al., [28], and Chirayath et al., [29] demonstrated much higher malignancy rates of 69% and 54.6% respectively. ...
Background: Thyroid diseases are considered the commonest endocrine disorders worldwide. Fine needle aspiration cytology (FNAC) is the mosteasy, reliable screening test in diagnosing thyroid lesions. Objectives: To determine the frequency of Bethesda system diagnostic categories and cyto-histopathological correlation of FNAC results. Material and methods: This study comprised 488 thyroid FNA smears. cyto-histopathological correlation was conducted on surgically excised cases. Results: Out of 488 of thyroid FNAC smears, thyroidectomy was done for one hundred cases. Sensitivity, specificity, PPV, NPV and accuracy of FNAC were 82.8%, 94%, 88.9%, 90.4% and 89.9% respectively. Conclusion: FNAC is a highly sensitive and specific method in diagnosing different thyroid lesions.
... The histiocytes and macrophages with foamy cytoplasm and large nucleus may cause confusion with adenocarcinoma cells on cytology and therefore should be carefully examined to avoid misdiagnosis. Chandra et al. [12,13] have also studied the cyto-histopathological correlation and discrepancy rate in thyroid and gall bladder lesions previously. ...
Objective:
Analytical and post analytical phase are integral part of total quality management system and include steps from submission of slides till reports are dispatched. The present study was conducted to analyze the analytical and post analytical phase of the ISO15189:2012 certified cytopathology laboratory. It was also intended to study the various errors which were encountered and steps taken to reduce these discrepancies.
Methods:
The study included all documents of quality program from 1 November 2014 till 31 Oct 2019 in medical institute situated in north Himalayan region of India. All the data was recorded and analyzed for analytical and post analytical phase.
Results:
The number of samples received in cytopathology lab was 21,566 with total quality errors of 5.19%. Out of these pre-analytical errors were 55%, analytical 10.5% and post analytical errors constituted 34.4%. The maximum errors detected were due to typographical errors followed by delayed turnaround time. Cyto-histopathological discordance was 10.5% in non-gynecological cases and 2.2% in gynecological cases.
Conclusion:
Analytical and post analytical phase analysis is essential to minimize the errors and improve the quality of cytopathology lab. Cyto-histopathological correlation is valuable for continuous data tracking in the cytopathology with analytical errors analysis. Maintenance of external, internal quality program, turnaround time with documentation, continuous training and communication with clinician is fundamental for quality improvement in any cytopathology lab. Acknowledgement of nonconformance with root cause analysis and sincere efforts to minimize them is the basic key for successful quality management.
... Fine needle aspiration cytology (FNAC) is an important process for diagnosing thyroid nodules and managing their treatments (1). FNAC results are categorized in six groups according to the Bethesda system for reporting thyroid cytopathology (TBSRTC) which resulted from a conference in 2007 and the first edition was published in 2010 (2,3). ...
... So a new revised edition was published in 2018 (TBSRTC II) (4,5). Clinical management of the indeterminate "gray zone" categories, especially category III or atypia of undetermined significance / follicular lesion of undetermined significance (AUS/ FLUS) is still difficult (1,(3)(4)(5). ...
... There were malignancy rates and proper managements for each category in TBSRTC and these rates were updated in TBSRTC II (2,5). Although the expected risk of malignancy (ROM) in this category is 5-15% in TBSRTC I and updated to 10-30% in TBSRTC II, variable risks of malignancy ranging from 25% to 50% were reported in different studies (1,2,(4)(5)(6)(7). For these reasons the biggest challenge for AUS /FLUS category is waiting for repeat biopsies, molecular testing or doing a diagnostic surgery for definitive diagnosis (3,5,8). ...
Aim:
To evaluate the malignancy rates of Atypia of undetermined significance /follicular lesion of undetermined significance (AUS/FLUS) cases in the light of clinical and sonographic features.
Material and methods:
The percentage of AUS/FLUS cases, second fine needle aspiration cytology (FNAC) results, cyto-histopathological correlations and risk of malignancy were analyzed.
Results:
113 out of 1461 thyroid FNAC samples (7.7%) were diagnosed as AUS/FLUS and included in the study. Seventy three out of 113 cases (64.6 %) underwent repeat biopsies or surgery. From 45 cases repeat biopsies were taken and 28 had thyroidectomy or lobectomy. There was a significant relation between nodule size and underwent surgery or repeat FNAC (p=0.036). Malignancy rate was 24.6% for cases which had any managements. The malignancy rates were higher in AUS/FLUS cases with cytological atypia (28.8%). After surgery the most common malignancy was papillary thyroid carcinoma, followed by follicular carcinoma.
Conclusion:
The risk of malignancy of AUS/FLUS cases is quite high because of the heterogeneity of the group. The sub-classification of this category according to cytological or/and architecture atypia may be more useful in predicting malignancy risk. Further larger studies with ancillary techniques including molecular analysis may be more useful in determining the malignancy risk and appropriate management of this heterogeneous category.
... Fine needle aspiration cytology (FNAC) is an important process for diagnosing thyroid nodules and managing their treatments (1). FNAC results are categorized in six groups according to the Bethesda system for reporting thyroid cytopathology (TBSRTC) which resulted from a conference in 2007 and the first edition was published in 2010 (2,3). ...
... So a new revised edition was published in 2018 (TBSRTC II) (4,5). Clinical management of the indeterminate "gray zone" categories, especially category III or atypia of undetermined significance / follicular lesion of undetermined significance (AUS/ FLUS) is still difficult (1,(3)(4)(5). ...
... There were malignancy rates and proper managements for each category in TBSRTC and these rates were updated in TBSRTC II (2,5). Although the expected risk of malignancy (ROM) in this category is 5-15% in TBSRTC I and updated to 10-30% in TBSRTC II, variable risks of malignancy ranging from 25% to 50% were reported in different studies (1,2,(4)(5)(6)(7). For these reasons the biggest challenge for AUS /FLUS category is waiting for repeat biopsies, molecular testing or doing a diagnostic surgery for definitive diagnosis (3,5,8). ...
Aim. To evaluate the malignancy rates of Atypia of undetermined significance /follicular lesion of undetermined significance (AUS/FLUS) cases in the light of clinical and sonographic features. Material and Methods. The percentage of AUS/ FLUS cases, second fine needle aspiration cytology (FNAC) results, cyto-histopathological correlations and risk of malignancy were analyzed. Results. 113 out of 1461 thyroid FNAC samples (7.7%) were diagnosed as AUS/FLUS and included in the study. Seventy three out of 113 cases (64.6 %) underwent repeat biopsies or surgery. From 45 cases repeat biopsies were taken and 28 had thyroidectomy or lobectomy. There was a significant relation between nodule size and underwent surgery or repeat FNAC (p=0.036). Malignancy rate was 24.6% for cases which had any managements. The malignancy rates were higher in AUS/FLUS cases with cytological atypia (28.8%). After surgery the most common malignancy was papillary thyroid carcinoma, followed by follicular carcinoma. Conclusion. The risk of malignancy of AUS/ FLUS cases is quite high because of the heterogeneity of the group. The sub-classification of this category according to cytological or/and architecture atypia may be more useful in predicting malignancy risk. Further larger studies with ancillary techniques including molecular analysis may be more useful in determining the malignancy risk and appropriate management of this heterogeneous category.
... In our study, 100 (55.6%) of our cases underwent surgical resection due to presence of clinical and radiological risk factors. This proportion is similar to the management done in other studies [12,14]. ...
... More importantly, however, the high incidence of malignancy can be explained by the referral bias in our study as it was conducted in a tertiary center where cases with suspicious thyroid nodules would be referred from most centers in the region. Previous literature demonstrates a variable rate of malignancy in this category, ranging from a rate as low as 6%, as estimated by the BSRTC, to a rate as high as 69% in other studies [3,14,15]. Local data of 2 studies demonstrated around 18% prevalence of malignancy in Bethesda III (6 out of 32 cases) [16] and 20% when UK classification is used and intermediate thyroid nodules were analyzed [17]. ...
Introduction: Bethesda classification of thyroid nodules cytology is an agreed upon method of classifying thyroid nodules according to risk of malignancy. Among them, Bethesda class III (Atypia of Undetermined Significance, AUS) has been a topic of great controversy. The reported estimated risk of malignancy associated with it varies in different studies. Our study investigates the associated incidence of malignancy in a single tertiary center in UAE. Methodology: Data were retrospectively collected over a 10-year period from January 2009 till December 2018 for cytology diagnosis of AUS. Patient charts were reviewed for method of management. Surgical and histopathology records were reviewed to compare findings on cytology versus histopathology. Results: A total of 180 cases were diagnosed Bethesda III (AUS) with a mean age of 45.09 ± 14.7 years. One hundred cases (55.6%) of them underwent surgical resection, and histopathological diagnosis was obtained. Among the operated cases, 46 were benign and 54 were malignant. Papillary thyroid cancer was the most common malignancy, seen in 39 (72.2%) of cases, and follicular cancer was the second most common, seen in 13 (24.1%) cases. Conclusion: The findings highlighted in our study suggest a higher incidence of malignancy in Bethesda III category than previously reported. It also puts in question the utility and benefit behind keeping a time gap and repeating FNA as previously recommended.
... Patients with TN were classified according to cytological analysis of Bethesda system (thy2, n=13; thy4, n =33; thy5, n=18; thy6, n=21). They had median and IQR of 21 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), 72 (30- ...
... We focused only on investigating Bethesda IV TC not Bethesda III. Bethesda III categories of TC is heterogenous group includes atypia (nuclear or cytoplasmic) of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) and majority of its malignancy cases are follicular variant of PTC which also involved different entities thus thy3 needs a distinct study (28). On the other hand, FTC represents 28.8% of Bethesda IV malignant lesions while only 2.4% of malignant lesion of category III (29). ...
Background
Cell-free DNA integrity (cfDI) has a promising role in the differentiation between malignant and benign tumors, but little data were reported in thyroid cancer (TC). This study aimed to explore its diagnostic role in TC mainly Bethesda IV.
Methods
cfDI was evaluated by quantitative real-time PCR using two primer sets to identify cfDNAs Alu83 and Alu244. Blood samples were collected from patients with thyroid nodules {n=85; 60 thyroid carcinomas [18 papillary (PTC), 21 follicular (FTC), 21 medullary (MTC)] and 25 benign thyroid nodule (BTN)} before fine needle aspiration cytology and surgical treatment as well as from 25 autoimmune thyroid disease (ATD) and 25 healthy subjects (HS).
Results
cfDNA Alu244 concentration ≥ 6.95 ng/dl and cfDI ≥ 0.3 are excellent sensitive and specific tests in discriminating TC with cytological indeterminate thyroid nodule (Bethesda IV) from studied control groups (BTN, ATD and HS). Levels of both cfDNA Alu83 and Alu244 were decreased while cfDI was increased significantly in MTC compared to FTC and PTC with non-significant difference between the latter subgroups. Significant positive correlation was observed between both cfDNA Alu83 and Alu244 with T-Classification of TNM staging and capsular invasion among PTC and FTC patients, and between cfDI with Bethesda categories. Additionally, ATD had significant higher cfDNA Alu83 and lower cfDI than HS.
Conclusion
Our study supports the utility of cfDI as non-invasive molecular biomarker in TC being correlated to Bethesda cytology and histopathology. Tumor size and capsular invasion were correlated to quantitative cfDNA among PTC and FTC.
... 8 A study reported surgical confirmed malignancy rate of 28.5% among patients with AUS / FLUS nodules. 19 However, the present study showed a higher malignancy rate of 60 % (14 out of 23), which is very high compared to other studies. This may be either due to overuse of this category or due to inclusion of incidental carcinoma. ...
... Each category has a list of criteria which aids in making a diagnosis and has a defined range of implied cancer risk. (6) The category III in the Bethesda system is the "Atypia of undetermined significance/Follicular lesion of undetermined significance (AUS/FLUS) category and it accounts for 7-18 % of the thyroid diagnosis. (7) This category encompasses all specimen which contain cells with architectural and/or nuclear atypia that is not sufficient to be classified as suspicious for follicular neoplasm, suspicious for malignancy, or malignant. ...
... This finding was similar to study done by Mosca et al and Ho et al. (8,9) The incidence of Bethesda category III lesion in the present study was 4.08% which was close to studies done by Chandra et al (6.4% ) and Garg et al (6.5 %) while other studies like Guleria et al and Ho et al show the incidence rate to be 11.7% and 8% respectively. (6,9,10,11) On follow-up, histopathology correlation showed majority of the cases as benign ( 61.9%). The most common benign lesion encountered was adenomatous hyperplasia. ...
... This finding was consistent with the findings of studies done by Guleria et al, Ho et al and Garg et al. (9,10,11) The malignancy rate of Bethesda category III lesion was calculated to be (9,10,11) The comparison with malignancy rates in other studies are given in table 5. The most common malignancy encountered was papillary carcinoma thyroid and the same was also found in the studies of Ho et al, Garg et al, Guleria et al and Chandra et al. (6,9,10,11) The BSRTC has estimated the risk of malignancy to range from 5% to15% in AUS/FLUS category and the usual recommended management is repeat FNA. (6) However, studies including the present and above-mentioned studies in table 5 have observed a higher malignancy rate in different clinical settings. ...
Background: The introduction of The Bethesda System for Reporting Thyroid Cytopathology in 2010 provided the opportunity to establish worldwide standard reporting and terminology guidelines diagnostic category in reporting of thyroid FNAC. Indeterminate lesion included in the category III are those with insufficient degree of atypia to qualify for any of the suspicious categories. This study was conducted to determine the incidence and malignancy rate of Bethesda category III thyroid lesions. Methods: A two- and half-year retrospective study was conducted in Father muller medical college. Thyroid lesion which were diagnosed as Bethesda category III on fine needle aspiration cytology during the study period were included. The cytology-histopathological correlation was done where ever available to calculate the incidence and malignancy rate of this category. Result: A total of 1397 cases underwent thyroid FNA during the study period. Out of this, 57 cases were reported as Bethesda category III lesion. The incidence rate of Bethesda category III lesions in the study was 4.08%. Twenty-one cases had histopathology correlation. The malignancy rate was found to be 38.09%. Conclusion: The Bethesda category III still remains a very challenging group with a large and varied range of diagnosis. The risk of malignancy might be higher that what is currently estimated for this category. Sub-classification of this category might help in predicting the nature of lesion better and aid patient management more accurately.
... Most, if not all, modern classification systems now include ROM for a given diagnostic category that can aid optimal patient management. Regarding quality assurance, laboratories implementing standardized classification and reporting systems are able to verify the accuracy of their diagnosis by comparing their data to established metrics (category distribution, category ratio, etc.) and other laboratories [2][3][4]. Without standardized reporting, some of the more rigorous activities associated with best practices would be impossible -activities such as data comparison, internal and external quality control, and research. Paradoxically, currently used tiered classification systems are indispensable for their refining and revision, as their strict application enabled research groups to gather more clinical data. ...
The history of classification systems and the search for a unified nomenclature in cytopathology spans several decades and expresses the preoccupation of all those involved to make cytopathology a reliable diagnostic tool and a trusted screening method. Early classification schemes, applicable to exfoliative and aspiration cytology, attempted to set some basic standards for how non-gynecological cytopathology findings should be reported. While useful in establishing some basic guidelines, these were not specific to the various fields of non-gynecologic cytopathology, often burdened with specific problems. Cytopathology has evolved tremendously in the last couple of decades, undoubtedly boosted by the emergence of various classification schemes that, more than ever, are based on evidence gathered by professionals across the globe. The benefit of classification systems and standardized nomenclature in cytopathology is to provide useful, clear, and clinically relevant information for clinicians and ultimately to provide the best patient care. Standardized reporting systems make cytopathology reports more meaningful and robust. It now became standard that these include by default elements, such as adequacy criteria, diagnostic groups, risk of malignancy (ROM), and recommendations for patient management. In this brief review, we attempted to summarize how these classification schemes emerged and how they are reshaping the landscape of diagnostic cytopathology.
