Atypia Of Unknown Significance Research Articles

Cytodiagnosis of pleural effusions according to the International System for Reporting Serous Fluid Cytopathology: retrospective analysis of oncological dispensary experience

BACKGROUND: The International Serous Fluid Cytopathology Reporting System (TIS RSFC) was proposed in 2020 to standardize cytological reports and include information on perceived risk of malignancy in reports. It is necessary to analyze the use of TIS RSFC to determine the principles of rational practical implementation and possible improvement of this classification.
 AIM: To assess the possibility and results of the application of TIS RSFC (2020) in the cytodiagnosis of pleural effusions using the organizational technologies and resources of a regional oncological dispensary.
 METHODS: This observational, retrospective, crossover study carried out a comparative analysis of reports following cytological examination of pleural effusion with clinical and anamnestic information, histological, immunohistochemical results of 1507 patients of the Altai Regional Oncological Dispensary (Barnaul) from 2019 to 2021. The microscope slides were prepared by the traditional smear method, as well as by liquid cytology methods. Papanicolaou and Pappenheim staining methods were used. In certain cases, immunocytochemical tests were performed additionally.
 RESULTS: The following numbers of cytological reports corresponding to the TIS RSFC categories were formulated: non-diagnostic material, C I — 11 (0.7%); absence of malignant tumor cells, C II — 946 (62.8%); atypia of unknown significance, C III — 61 (4.0%); suspicion of a malignant process, C IV — 13 (0.9%); malignant process, C V — 476 (31.6%). Within category C V there were 37 (7.8%) cases of the primary tumor — mesothelioma; 398 (83.6%) cases of metastatic tumors, including 41 (8.6%) cases of non-epithelial tumors. Immunocytochemical tests of pleural fluid were performed in 273 (18.1%) cases. Risk of malignancy was 9.1% (1/11) for C I; 1.2% (11/946) — for C II; 59.0% (36/61) — for C III; 84.6% (11/13) — for C IV, and 100% — (476/476) for C V. Cytodiagnosis with immunocytochemistry in unclear cases was characterized by a sensitivity of 92.5%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 88.5%, and an accuracy of 96.6%.
 CONCLUSIONS: The application of TIS RSFC (2020) in cytological tests of pleural fluid does not cause difficulties for specialists in cytological laboratory. If the required diagnostic accuracy of cytological tests is available, this system makes it possible to characterize the risk of malignancy and thus guide the oncologist in the case management. The liquid-based cytology and the addition of traditional cytological techniques with immunocytochemical tests increase the cytodiagnostic sensitivity.

Application of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in reporting serous effusion: A retrospective study.

In order to develop uniform diagnostic standards and reporting terminology, the International Academy of Cytology and the American Society of Cytopathology have recommended the establishment of the International System for Reporting Serous Fluid Cytopathology (ISRSFC). ISRSFC has 5 diagnostic categories: non-diagnostic (ND), negative for malignancy (NFM), atypia of unknown significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). So far, very few studies have evaluated the risk of malignancy (ROM) and performance characteristics (sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy) of different categories. The purpose of this study was to reclassify serous effusions based on the ISRSFC and to assess their ROM and performance characteristics. All serous effusions from January 2017 to December 2022 were categorized according to the ISRSFC. Using histopathological diagnosis as the gold standard, the ROM and performance characteristics were calculated for each group. Finally, a total of 2103 serous effusion specimens were analyzed. After reclassification, 9 (0.4%) cases were classified as ND, 547 (26%) as NFM, 94 (4.5%) as AUS, 386 (18.4%) as SFM, and 1067 (50.7%) as MAL. The ROMs for ND, NFM, AUS, SFM and MAL were calculated to be 50%, 24.9%, 36.8%, 89.0%, and 100%, respectively. As an easy-to-grasp reporting system, ISRSFC provides a consistent standard for better communication between physicians and pathologists.

Prioritizing parotid gland surgery: A call for the implementation of the MSRSGC classification.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is developed to aid diagnosis and management of salivary gland tumors. This study evaluates the time-to-treatment initiation (TTI) for parotid gland tumors in the Netherlands and relates these to the MSRSGC classification. Subsequently, the use of the MSRSGC in the Netherlands is evaluated. Data regarding fine-needle aspiration cytology (FNAC) and histopathological resections of the parotid were gathered from the Dutch nationwide pathology data bank (PALGA). The TTI was calculated for each MSRSGC category and type of treating center. FNACs performed from 2018 to 2021 were gathered from PALGA to estimate how frequently the MSRSGC classification was applied. Median TTI in days were 86 for nondiagnostic (MSRSGC I), 75 for nonneoplastic (MSRSGC II), 65 for atypia of unknown significance (AUS) (MSRSGC III), 89 for benign (MSRSGC IVa), 52 for salivary gland neoplasm of unknown malignant potential (SUMP) (MSRSGC IVb), 31 for suspected malignant (MSRSGC V), and 30 for malignant (MSRSGC VI) categories. Significant variation in the TTI between the types of treating centers was found for the nondiagnostic, nonneoplastic, AUS, SUMP, and suspected malignant categories. In the first 3 years after the introduction of the MSRSGC, the pathologist stated the MSRSGC classification in 6.4% of all reports. The median TTI for most categories is long, and there is significant interhospital variation in TTI. Preoperative risk stratification and treatment prioritization in parotid gland surgery in the Netherlands should be improved. The MSRSGC could contribute to this. Until 2021, the MSRSGS classification was implemented on a limited scale in the Netherlands.

Targeted Next-Generation Sequencing of Flat Urothelial Lesions Reveals Putative Pathobiological Pathways, Potential Biomarkers, and Rational Therapeutic Targets

Flat urothelial lesions are controversial diagnostic and prognostic urologic entities whose importance relies mainly on their ability to progress to muscle-invasive tumors via urothelial carcinoma in situ (CIS). However, the carcinogenetic progression of preneoplastic flat urothelial lesions is not well established. Moreover, predictive biomarkers and therapeutic targets of the highly recurrent and aggressive urothelial CIS lesion are lacking. Using a targeted next-generation sequencing (NGS) panel of 17 genes directly involved in bladder cancer pathogenesis, we investigated alterations of genes and pathways with clinical and carcinogenic implications on 119 samples of flat urothelium, including normal urothelium (n = 7), reactive atypia (n = 10), atypia of unknown significance ( n = 34), dysplasia ( n = 23), and CIS (n = 45). The majority of the flat lesions were tumor-associated but grossly/microscopically or temporally separated from the main tumor. Mutations were compared across flat lesions and concerning the concomitant urothelial tumor. Associations between genomic mutations and recurrence after intravesical bacillus Calmette–Guerin treatment were estimated with Cox regression analysis. TERT promoter mutations were highly prevalent in intraurothelial lesions but not in the normal or reactive urothelium, suggesting that it is a critical driver mutation in urothelial tumorigenesis. We found that synchronous atypia of unknown significance-dysplasia-CIS lesions without concomitant papillary urothelial carcinomas had a similar genomic profile that differed from atypia of unknown significance-dysplasia lesions associated with papillary urothelial carcinomas, which harbored significantly more FGFR3, ARID1A, and PIK3CA mutations. KRAS G12C and ERBB2 S310F/Y mutations were exclusively detected in CIS and were associated with recurrence after bacillus Calmette–Guerin treatment (P = .0006 and P = .01, respectively). This targeted NGS study revealed critical mutations involved in the carcinogenetic progression of flat lesions with putative pathobiological pathways. Importantly, KRAS G12C and ERBB2 S310F/Y mutations were identified as potential prognostic and therapeutic biomarkers for urothelial carcinoma.

Could double stain for p53/CK20 be a useful diagnostic tool for the appropriate classification of flat urothelial lesions?

BackgroundThe differential diagnosis between flat urothelial lesions [reactive urothelial atypia (RUA), atypia of unknown significance (AUS), urothelial dysplasia (UD) and carcinoma in situ (CIS)] has relevant prognostic and therapeutic implications. This crucial distinction could be very challenging but it is currently performed on hematoxylin and eosin (H&E) slides, with a great amount of partially discordant and/or not conclusive findings of the potential adjunctive role of immunohistochemistry. Herein, we tested double staining (DS) for p53/CK20 to verify if p53(+) cells, CK20(+) cells and double-positive cells (DPCs) are differentially expressed among these lesions and if p53/CK20 could be a useful tool in this diagnostic setting. MethodsWe tested 50, 9, 36 and 29 consecutive and retrospectively enrolled cases of RUA, AUS, UD and CIS, respectively. p53(+) cells, CK20(+) cells and DPCs were evaluated and compared by adopting the appropriate statistic tests (Mann-Whitney U and Kruskal-Wallis tests). ResultsWe found that p53(+) cells (p = 0.000), CK20(+) cells (p = 0.000) and DPCs (p = 0.000) showed statistically significant differences among the different flat urothelial lesions. Besides, when dichotomized, both CIS and RUA are easily differentiable from their histological mimickers adopting all these markers; by contrast, AUS and UD did not reach statistically significant differences able to differentiate them from each other [p53(+) cells, p = 0.123; CK20(+) cells, p = 0.567; DPCs, p = 0.409], except if compared to CIS [AUS VS CIS: p53(+) cells, p = 0.013; CK20(+) cells, p = 0.000; DPCs, p = 0.000; UD vs CIS: p53(+) cells, p = 0.000; CK20(+) cells, p = 0.000; DPCs, p = 0.000]. Conclusionsp53(+) cells, CK20(+) cells and DPCs are differently expressed by flat urothelial lesions and p53/CK20 could be a time- and money-saving tool for the appropriate management of these lesions if applied to a routine scenario.

Validation of the Milan System for Reporting Salivary Gland Cytopathology and the diagnostic accuracy of FNA cytology for submandibular gland lesions.

BackgroundThe Milan System for Salivary Gland Cytopathology (MSRSGC) is a categorical system for salivary gland fine‐needle aspiration cytopathology (FNAC) developed to aid clinicians in the management of salivary gland lesions. This classification is widely studied and validated, especially in cohorts that consist of mostly parotid gland lesions. However, only sparse literature describes the use of this classification for submandibular gland lesions in particular.MethodsAll patients in the Netherlands that underwent a submandibular gland resection between January 1, 2006, and January 1, 2017, with a FNAC before resection were identified with the use of the Dutch Pathology Registry database (PALGA). All FNAC results were retrospectively classified according to the MSRSGC. The risk of malignancy was calculated for all the MSRSGC categories. The sensitivity and specificity of the MSRSGC classification were calculated for submandibular gland FNAC.ResultsA total of 837 patients who underwent 975 FNAC aspirates from the submandibular glands were included in the analysis. Risks of malignancy for each of the MSRSGC categories were 14.4% in nondiagnostic, 4.4% in nonneoplastic, 37.0% in atypia of unknown significance, 3.9% in benign neoplasms, 40.7% in salivary gland neoplasms of unknown malignant potential, 76.2% in suspected malignant, and 91.3% in malignant cytology results. The sensitivity for diagnosing malignant submandibular gland tumors was 71.6% and specificity was 98.4%.ConclusionsThe results of the present study validate the use of this classification for submandibular gland lesions. Risks of malignancy vary according to the anatomical subsites of the salivary gland lesions.Lay Summary The risks of malignancy of the various Milan System for Salivary Gland Cytopathology (MSRSGC) categories vary according to the anatomical subsite of the salivary gland lesion.The proposed management techniques of the MSRSGC are valid for use with submandibular gland lesions.

Application of the International System for Reporting Serous Fluid Cytopathology with Cytohistological Correlation and Risk of Malignancy Assessment.

The International System for Reporting Serous Fluid Cytopathology (TIS) classifies serous effusions into five categories: non-diagnostic (ND), negative for malignancy (NFM), atypia of unknown significance (AUS), suspicious for malignancy (SFM) and malignant (MAL). The main objectives of this classification comprise the establishment of a universal code of communication between cytopathologists and clinicians and histopathologists, as well as between different laboratories worldwide, paving the way for the setting of clinical management guidelines based on the risk of malignancy assessment for each diagnostic category. We retrieved the total number of pleural and peritoneal effusion cases of our department for the three-year time period between 2018 and 2020, yielding a total of 528 and 500 cases, respectively. We then proceeded to reclassify each specimen according to TIS guidelines and calculate the risk of malignancy (ROM) for each category by searching each patients’ histology records, medical history and clinical follow-up. For pleural effusions, 3 (0.57%) cases were classified as ND, 430 (81.44%) cases as NFM, 15 (2.84%) as AUS, 15 (2.84%) as SFM and 65 (12.31%) as MAL. ROM amounted to 0%, 5.3%, 33.33%, 93.33% and 100% for each category, respectively. As far as peritoneal effusions are concerned, 6 (1.2%) were categorized as ND with ROM estimated at 16.66%, 347 (69.4%) as NFM (ROM = 9%), 13 (2.6%) as AUS (ROM = 38.46%), 12 (2.4%) as SFM (ROM = 83.33%) and 122 (24.4%) as MAL (ROM = 100%). Our results underline the utility of the current classification, both as a means of communication between doctors of different specialties and as general guidelines for the further clinical management of patients.

Solid Cell Nests Hyperplasia (Ultimobranchial Body Remnants) of the Thyroid: A Pitfall

Abstract Introduction/Objective Solid cell nests (SCN) are small epithelial cell nests interspersed within thyroid parenchyma, resembling squamous/transitional epithelium. SCNs, which are ultimobranchial remnants, are popularly considered pluripotent stem-cells responsible for developing follicular and C-cells. While SCNs are not an uncommon incidental findings in thyroid, solid cell nest hyperplasia is rare. SCNs are often mistaken for benign entities such as C-cell hyperplasia (CCH) or malignant lesions such as papillary thyroid carcinoma (PTC), metastatic squamous cell carcinoma, or medullary thyroid microcarcinoma (MTC). Methods/Case Report To reiterate this diagnostic dilemma, we present a case of a 57-year-old male with a six-year history of Hashimoto thyroiditis and multiple bilateral thyroid nodules. Ultrasonography revealed two nodules, one in each lobe, measuring 2.0x1.9x1.8cm(right) and 1.6x1.5x1.5cm(left). Both were solid, hypoechoic nodules with smooth margins and no echogenic foci. Fine-needle aspiration of right nodule was suspicious for follicular neoplasm, Hürthle- cell type, and the left nodule was atypia of unknown significance. Right-hemithyroidectomy specimen revealed follicular adenoma and oncocytic adenomatous nodules in a background of florid lymphocytic thyroiditis (Hashimoto). In two blocks, small solid nests of cells were identified, largest focus measuring 0.5 cm. The cells were polygonal to epithelioid with moderate amphophilic cytoplasm. Nuclei were centrally located, irregular to oval with occasional grooves. While nests had a squamoid appearance, they did not have intercellular bridges. Although nuclear grooves and evenly dispersed chromatin and chromocenters were noted, they lacked optical clearing or intra-nuclear inclusions characteristic for PTC. Thus, excluding these two possibilities, primary diagnostic considerations were SCN versus CCH. Immunohistochemical analysis showed cells positive for P63 and CK5/6 and negative for PAX-8, TTF-1, thyroglobulin, CEA, and calcitonin. Results (if a Case Study enter NA) NA Conclusion If wrongly diagnosed as CCH, patients may be placed in a high-risk category for possible development of MTC. It is, thus, necessary to be aware of SCN, which can occasionally become hyperplastic, to prevent misdiagnosis.

Cytohistological Correlation in Pleural Effusions Based on the International System for Reporting Serous Fluid Cytopathology.

The International System for Reporting Serous Fluid Cytology (TIS) was recently developed. Given its novelty, most studies looking into the risk of malignancy (ROM) of serous effusion diagnostic categories were published before the development of TIS. We searched the database of our department for pleural effusions diagnosed in the last five years, excluding those without a corresponding pleural biopsy. Cases were reviewed and reclassified according to the TIS. A cytohistological correlation was performed. In total, 350 pleural effusion specimens with one or more corresponding pleural biopsies were included. After reclassification, 5 (1.43%) were nondiagnostic (ND), 253 (72.29%) were negative for malignancy (NFM), 7 (2.00%) had atypia of unknown significance (AUS), 14 (4.00%) were suspicious for malignancy (SFM), and 71 (20.57%) were malignant (MAL). Calculated ROM was 40% for ND, 20.16% for NFM, 42.86% for AUS, 78.57% for SFM, and 100% for MAL. Effusion cytology sensitivity and specificity were 60.29% and 98.56%, respectively. This is the first publication looking into the cytohistological correlation of a retrospective cohort of pleural effusions based on the TIS. We add to the body of data regarding the ROM for TIS categories, highlighting areas of potential future research.

O31: CORRELATION BETWEEN THYROID FINE NEEDLE ASPIRATION CYTOLOGY (FNAC) SCORES AND CANCER INCIDENCE ON FINAL HISTOPATHOLOGY – A MULTI-CENTRE RETROSPECTIVE ANALYSIS

Abstract Introduction Fine Needle Aspiration Cytology (FNAC) is the best diagnostic tool for evaluating thyroid nodules pre-operatively. The Bethesda System for Reporting Thyroid Cyto-pathology (TBSRTC) in America and THY classification in Europe are standardized reporting systems for thyroid FNAC specimens using six categories. As compared to the first edition in 2009, a second edition of TBSRTC published in 2017 has revised risk of malignancy (ROM) for these categories, with focus on atypia of unknown significance (Thy3A) upgraded to 10-30% from previously 5-15%, and suspicion for follicular neoplasm (Thy3F) 25-40% from previous 15-30%. Method A three-year audit of thyroid surgeries performed in two high volume thyroid institutions from January 2016 to September 2019, was performed retrospectively. The FNAs were performed by thyroid specialist radiologists with a cytopathology technician in attendance for rapid on-site evaluation and reported as per TBSRTC and Thy classification, by a Consultant Cyto-pathologist from a single institution. Result A total of 702 patients were examined. There were 552 patients who had corresponding FNAC prior to surgery (mean age 53.6 years, females 79%). The rates of malignancy were, Thy1: 9.3%, Thy2: 4.6%, Thy3A: 10.8%, Thy3F: 28.7%, Thy4: 82.3% and Thy5: 100%. The main types of thyroid malignancy were Papillary (73.6%), Follicular (14.1%), Medullary (4%), Anaplastic (4.7%) and others (3.6%). Conclusion Pre-operative diagnosis of thyroid nodules using TBSRTC was comparable and the criteria helped avoid misinterpretation of results. Our results were comparable with the risk of malignancy in 2009 edition of TBSRTC, as compared to the 2017 revision. Take-home message Pre-operative diagnosis of thyroid nodules using The Bethesda System for Reporting Thyroid Cyto-pathology (TBSRTC) was comparable and the criteria helped avoid misinterpretation of results. Our results were comparable with the risk of malignancy in 2009 edition of TBSRTC, as compared to the 2017 revision.

The Role of Ultrasound-Guided Fine-Needle Aspiration of Thyroid Bed Lesions and Clinical Predictors of Recurrent Papillary Thyroid Carcinoma.

Fine-needle aspiration (FNA) of thyroid bed lesions after thyroidectomy is challenging to evaluate. We determined the sensitivity, specificity, and positive and negative predicative value of thyroid bed FNA (TB-FNA) for detecting local recurrence of thyroid carcinoma. A retrospective search was conducted for TB-FNAs from patients with a prior thyroid resection and subsequent ipsilateral FNA from the thyroid bed. Clinical and pathologic data were retrieved from the medical record. Patients were ultimately classified as "malignant" or "benign" based on the worst pathology identified and follow-up available. Forty-two cases were included, and the prior thyroidectomy pathology included 36 papillary thyroid carcinomas, two follicular carcinomas, one medullary carcinoma, and three benign cases. TB-FNA was adequate in 38 (90.5%) cases and interpreted as positive for malignancy (n = 22; 52.4%), suspicious for follicular neoplasm (n = 3; 7.1%), atypia of unknown significance (n = 2; 4.8%), and benign (n = 10; 23.8%). Twenty-seven patients had histologic follow-up, and 24 (87.5%) showed recurrent malignancy. The cytology sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 96%, 100%, 100%, 92.3%, and 97.4%, respectively, for identification of recurrent malignancy. Most TB-FNA cases ultimately were diagnosed with malignancy on follow-up, although there may be sampling bias, as not all clinically benign cases had surgical follow-up.

Need for Completion Thyroidectomy in Patients Undergoing Lobectomy for Indeterminate and High-Risk Nodules: Impact of Intra-Operative Findings and Final Pathology.

Current guidelines increasingly suggest the use of thyroid lobectomy for indeterminate (Bethesda 3 and 4) and high-risk (Bethesda 5 and 6) thyroid nodules; however, the clinical reality is often very different. The aim of this study was to determine the rate of completion thyroidectomy (CTx) for indeterminate and high-risk thyroid nodules which are pre-operatively classified as suitable for unilateral resection (lobe eligible) based on current guidelines. Seven hundred consecutive patients with thyroid nodules and FNA cytology over four years (2015-2018) were reviewed. Distribution of the dominant nodules by Bethesda was: non-diagnostic 3.9%, benign 28.1%, atypia of unknown significance 19.0%, follicular neoplasm 23.6%, suspicious for malignancy 6.1% and malignancy 19.3%. Of 298 indeterminate nodules, 68.8% (205/298) had relative but independent indications for a total thyroidectomy (TTx) and the remainder were candidates for lobectomy. For these lobe eligible patients, the overall risk of ultimately needing a TTx was 19.4% (18/93), comprising 4.3% (4/93) from intra-operative findings and 15.7% (14/89) from final pathology. Similarly, of 170 high-risk nodules, 63.5% (108/170) had upfront indications for a TTx and the remaining 62 nodules were lobe eligible. Of the patients taken to the operating room for a lobectomy, 21.0% (13/62) were upgraded to a TTx intra-operatively and 26.5% (13/49) post-operatively. The lobe success rate for indeterminate nodules was 25.2% and for high-risk nodules was 21.2%. The rate of CTx, or the proportion of patients needing a second operation was 15.7% (14/89) and 26.5% (13/49), respectively. In counselling a patient for surgery, the risk of needing a more radical initial procedure or second surgery needs to be accurately explained. There are three points of care that can influence operative strategy, pre-operatively by way of high-risk clinical factors, intra-operatively via anatomical findings and post-operatively in response to unrecognized pathological features. Additionally, the patient's personal value judgment and level of risk aversion should be taken into consideration.

Comparison of Fine Needle Aspiration Cytology in Thyroid Lesions using The Bethesda System for Reporting Thyroid Cytopathology with Ultrasonography using Thyroid Imaging Reporting and Data System

Introduction: Thyroid nodule is a common presentation. The estimated prevalence of thyroid nodules is 4-7% by clinical examination and 50-60% on ultrasonographic (USG) evaluation. Most are benign without any symptoms or cosmetic concerns. Only around 5% are found to be malignant. Methods: This prospective study evaluated a total of 54 patients with thyroid lesions presenting to Otorhinolaryngology, Surgery and Internal Medicine out-patient departments of a tertiary hospital for a period of nine months. The thyroid lesions were categorized into different categories using Thyroid Imaging Reporting and Data System (TIRADS) by USG and The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) by fine needle aspiration (FNA). The agreement between TIRADS and TBSRTC was evaluated using Cohen's kappa statistics. Results: By FNA, 68.5% were benign lesions whereas 7.4% were malignant. Follicular Neoplasm (FN) or Suspicious for FN and Suspicious for Malignancy category comprised 5.6% each. 1.9% of the lesions showed Atypia of Unknown Significance (AUS). 11.1% of the lesions were non-diagnostic or unsatisfactory for evaluation. Overall agreement between the cases by USG and FNA using the TIRADS and TBSRTC respectively was 77.77%. There was a substantial agreement between the diagnosis made by these systems, kappa (κ)= .633 (95% CI, 0.41 to 0.85, p<0.05). Conclusion: This study observed a substantial agreement between the diagnosis made by TIRADS on USG and TBSRTC on FNA. Our study advocates the stratification of thyroid lesions according to TIRADS so that only suspicious lesions undergo FNA.

Percutaneous Ethanol Injection for Benign Cystic and Mixed Thyroid Nodules

We aimed to determine the effect of percutaneous ethanol injection (PEI) on volume of cystic and mixed thyroid nodules, thyroid function tests (TFTs), antibody titers, and cytologic changes for 1 year. Fifty-five nodules from 53 patients with cystic and mixed properties treated with PEI were included. Nodule volumes, TFTs, and thyroid autoantibodies were analyzed at baseline, 6 months, and 12 months. Fine-needle aspiration biopsy (FNAB) was performed to PEI-treated nodules in the 12th month. Thyroid nodules were classified into three groups by structural properties (purely cystic, predominantly cystic, predominantly solid). PEI caused a volume reduction of 80.7% at 6 months and 82.1% at 12 months, without any serious complications. PEI was repeated 1.4 ± 0.4 times with a mean total ethanol amount of 3.6 ± 3.1 mL. Volume reduction in the purely cystic nodules in the 6th and 12th months after PEI was greater than the volume reductions in predominantly cystic and predominantly solid nodules. We found that smaller nodules had greater volume reductions after PEI in the 12th month. During the study, patients remained euthyroid. Antithyroglobulin levels were decreased at 12 months. None of the FNAB results were compatible with a malignant or suspicious for malignancy cytology at the 12th month. PEI is an effective means of treatment for benign cystic and mixed thyroid nodules, without any serious side effects. We can also assume that PEI is not a trigger for autoimmunity and malignancy development over the short term. anti-TG = anti-thyroglobulin; anti-TPO = anti-thyroperoxidase; AUS = atypia of unknown significance; CV = coefficient of variation; FNAB = fine-needle aspiration biopsy; fT3 = free triiodothyronine; fT4 = free thyroxine; PEI = percutaneous ethanol injection; TFT = thyroid function test; TSH = thyroid-stimulating hormone; US = ultrasonography.

THYROID MALIGNANCY RISK OF INCIDENTAL THYROID NODULES IN PATIENTS WITH NON-THYROID CANCER.

Thyroid incidentaloma is a common disorder in endocrinology practice. Current literature regarding the risk of thyroid cancer in incidentalomas found in patients with non-thyroid cancer is limited. The aim of the present study was to investigate the frequency of thyroid malignancy in thyroid incidentalomas detected in patients with non-thyroid cancer. Case control study. The database of 287 thyroid nodules from 161 patients with a history of non-thyroid cancer followed between 2008 and 2014 were retrospectively evaluated. From 287 thyroid nodules, 69.7 % had a benign final cytology. Thyroid cancer detected in one nodule while follicular neoplasia detected in 4 nodules, atypia of unknown significance (AUS) detected in 10 nodules, Hurthle cell neoplasia detected in 5 nodules and suspicious for malignancy detected in 6 nodules according to fine needle aspiration biopsy results. Metastasis of the non-thyroid cancer to the thyroid gland was detected in 4 nodules. Twenty seven nodules from 15 patients were removed with surgery. There were 3 malignant nodules found after surgery (1 papillary, 1 follicular and 1 medullary cancer). In addition to these three thyroid cancers, two patients with benign nodules had co-incidental thyroid cancer detected after surgery. Finally, 11.1 % of thyroid nodules which underwent thyroid surgery had malignant histopathology except for co-incidental and metastatic cancers. The frequency of thyroid malignancy seems not to be substantially increased in incidental thyroid nodules detected in patients with non-thyroid cancer when these patients were evaluated in nodule-based approach.

Bethesda Categorization of Thyroid Nodule Cytology and Prediction of Thyroid Cancer Type and Prognosis.

Since its inception, the Bethesda System for Reporting Thyroid Cytopathology (TBS) has been widely adopted. Each category conveys a risk of malignancy and recommended next steps, though it is unclear if each category also predicts the type and extent of malignancy. If so, this would greatly expand the utility of the TBS by providing prognostic information in addition to baseline cancer risk. All patients prospectively enrolled into the authors' thyroid nodule database from 1995 to 2013 with histologically proven malignancy were analyzed. The primary ultrasound-guided fine-needle aspiration cytology (AUS, atypia of unknown significance; FN, follicular neoplasm; SUSP, suspicious; M, malignant) was correlated with the type of thyroid cancer and histological features known to impact prognosis and recurrence, including lymph node metastasis (LNM), lymphovascular invasion, and extrathyroidal extension (ETE). Primary cytology was separately correlated with higher risk malignancy. A total of 1291 malignancies were identified, with primary cytology AUS in 130 cases, FN in 241 cases, SUSP in 411 cases, and M in 509 cases. AUS, SUSP, and M cytology were progressively associated with an increasing risk of high-risk disease (p < 0.001), LNM (p < 0.001), ETE (p < 0.001), and margin positivity (p < 0.001). Notably, 71% of malignancies with AUS cytology were follicular variants of papillary thyroid cancer compared with 63% with SUSP cytology and only 20% with M cytology. In contrast, high-risk malignancies were diagnosed in only 4% with AUS cytology, but 9% and 27% with SUSP and M cytology, respectively. FN conveyed a significantly increased risk of follicular thyroid carcinoma compared with all other types (28% vs. 2%; p < 0.001). A composite endpoint of recurrence, distant metastases, and death similarly increased as cytology progressed from AUS to SUSP to M (p < 0.001). In addition to predicting cancer prevalence, the TBS also imparts important prognostic information about cancer type, variant, and risk of recurrence. These data extend the utility of TBS classification by fostering an improved understanding of the risk posed by any confirmed malignancy.

Methylation status of TSHr in well-differentiated thyroid cancer by using cytologic material.

BackgroundThe role of methylation status of the thyroid stimulating hormone receptor gene (TSHr) in the discrimination of benign and malignant thyroid nodules has already been studied using paraffin blocks and cell lines. As cytological sampling plays an important role in assessment of thyroidal nodules, we have investigated the potential clinical use of TSHr methylation status of fine needle aspiration specimens reported according to Bethesda System.MethodSixty nine patients who had both cytological and pathological diagnosis of the same nodule were selected. Four groups were composed according to cytological and pathological diagnoses: Benign (B), papillary thyroid carcinoma (PTC), atypia of unknown significance (AUS) and follicular neoplasia (FN). The latter 2 groups were further sub-classified into 2 as benign (AUS-B and FN-B) and malignant (AUS-M and FN-M) according to final pathological diagnosis. DNAs were isolated from the fine needle aspiration cytology specimens and the methylation status of TSHr promotor region was investigated by using methylation specific polymerase chain reaction.ResultsOverall, TSHr methylation was present in 58 % of cases; 71 % of malignant and 46 % of benign nodules. PTC group showed the highest TSHr methylation rate (87 %), followed by 61 % in AUS, 44 % in B, and 30 % in FN (p = 0.016). TSHr methylation rate was significantly higher in PTC group when compared to B (p = 0.013) and FN-B (p = 0.004) groups; but not in FN-M (p = 0.115) or AUS (p = 0.096) groups. All 9 cases of papillary thyroid carcinoma with lymph node metastasis showed TSHr methylation. Positive predictive value, negative predictive value, sensitivity and specificity of TSHr methylation in determination of malignancy were calculated as 60, 66, 71 and 54 %, respectively.ConclusionThe eminent ratio of TSHr methylation in well-differentiated thyroid carcinoma against benign thyroidal nodules adduced that TSHr methylation status can be utilized as a tumor marker for well-differentiated thyroid cancer; however, it has a limited value. The determination of methylation status of TSHr gene had no efficiency on decision of the malignant potential for the nodules which are cytologically classified as atypia of undetermined significance.

Thyroid malignancy risk of incidental thyroid nodules in patients with non-thyroid cancer

Context Thyroid incidentaloma is a common disorder in endocrinology practice. Current literature regarding the risk of thyroid cancer in incidentalomas found in patients with non-thyroid cancer is limited. Objective The aim of the present study was to investigate the frequency of thyroid malignancy in thyroid incidentalomas detected in patients with non-thyroid cancer. Design Case control study. Subjects and methods The database of 287 thyroid nodules from 161 patients with a history of non-thyroid cancer followed between 2008 and 2014 were retrospectively evaluated. Results From 287 thyroid nodules, 69.7 % had a benign final cytology. Thyroid cancer detected in one nodule while follicular neoplasia detected in 4 nodules, atypia of unknown significance (AUS) detected in 10 nodules, Hurthle cell neoplasia detected in 5 nodules and suspicious for malignancy detected in 6 nodules according to fine needle aspiration biopsy results. Metastasis of the non-thyroid cancer to the thyroid gland was detected in 4 nodules. Twenty seven nodules from 15 patients were removed with surgery. There were 3 malignant nodules found after surgery (1 papillary, 1 follicular and 1 medullary cancer). In addition to these three thyroid cancers, two patients with benign nodules had co-incidental thyroid cancer detected after surgery. Finally, 11.1 % of thyroid nodules which underwent thyroid surgery had malignant histopathology except for co-incidental and metastatic cancers. Conclusions The frequency of thyroid malignancy seems not to be substantially increased in incidental thyroid nodules detected in patients with non-thyroid cancer when these patients were evaluated in nodule-based approach.

Cytology and Molecular Results of Repeat Thyroid Nodule Aspiration Following an Initial Diagnosis of Atypia of Unknown Significance (AUS/FLUS)

s S57 Results: Of 1382 thyroid FNAs performed, 275 had cytologic diagnoses of atypical/suspicious. A total of 170 cases were sent for analysis, of which 76 (44.7%) were reported as suspicious, 85 (50%) were benign, and nine (5.2%) had insufficient material. Of the atypical cytology, 110 cases had surgery and 62 (56.3%) had Afirma testing performed with 49 (79%) classified as suspicious and 9 (14.5%) as benign. Of the 58 with malignant histology, 30 (51.7%) had Afirma testing with 24 (80%) classified as suspicious, 4 (13.3%) as benign and 2 as insufficient. There were 32/52 (61.5%) cases diagnosed as benign on histology that had Afirma testing, of which 8 (15.3%) were benign and 23 (71.8%) were suspicious. The overall false positive and negative rates were16%and 2% respectively. The positive predictive valuewas 45%and the sensitivity was 85%. Nine of the 63 patients (14%) received surgery because of indeterminate cytology despite benign Afirma results. Conclusion: Our findings suggest that the majority of patients with a benign result, no surgery were performed in these patients, which translates to better patient care and cost savings. The high false positive rate with low positive predictive value is a major limitation of this assay.

The clinical presentation and outcome of urothelial atypia on biopsy of the bladder

ObjectivesTo examine the presentation and clinical outcome of patients diagnosed with reactive urothelial atypia (RUA) or urothelial atypia of unknown significance (AUS) on tissue biopsy of the bladder. Methods and materialsWe performed a retrospective cohort study of all patients who were diagnosed with either RUA or AUS on biopsy of the bladder at our institution from November 2000 to May 2008. Excluded from the analysis were patients with a history of or a concurrent diagnosis of urothelial carcinoma. A total of 66 patients were available for final analysis. ResultsThe mean patient age at diagnosis was 63 years (range: 18–89 years). There were 46 men (70%) and 20 women (30%). The indication for cystoscopic examination included lower urinary tract symptoms in 29 (44%), gross hematuria in 17 (26%), microscopic hematuria in 12 (18%), urolithiasis in 2 (3%), and hydronephrosis in 6 (9%) patients. On biopsy, 54 (82%) had RUA and 12 (18%) had AUS. The mean follow-up was 36 months (range: 0–271 months). During this period, 37 (56%) patients underwent at least 1 additional cystoscopy with negative result. None of the 66 (0%) patients developed biopsy-proven urothelial carcinoma. ConclusionUrothelial atypia is common in men older than 60 years and often presents with either hematuria or lower urinary tract symptoms. Both RUA and AUS have a similar benign clinical course. Therefore, after diagnosis, further intervention or surveillance is unnecessary.