53BP1 expression as a biomarker to differentiate thyroid follicular tumors

We have previously reported that the expression of p53-binding protein 1 (53BP1) in nuclear foci (NF), a marker reflecting DNA damage response (DDR), detected using immunofluorescence (IF) is useful to estimate the malignant potency of diverse cancers. In this prospective study, we clarified the impact of 53BP1 expression via IF as a biomarker to differentiate thyroid follicular tumors (FTs) with liquid-based cytology (LBC). A total of 183 consecutively obtained-LBC samples, which were preoperatively suspected as FTs, were analyzed. Before histological diagnosis, the type of 53BP1 immunoreactivity in LBC was classified as follows: low DDR type, one or two NF; high DDR type, three or more NF; large foci type, larger than 1.0 μm; abnormal type, intense nuclear staining. Among the 183 cases, 136 cases were postoperatively diagnosed as FTs, including adenomatous goiter (AG, n = 30), follicular adenoma (FA, n = 60), FT-uncertain malignant potency (FT-UMP, n = 18), and follicular carcinoma (FC, n = 28), and 47 cases were diagnosed as tumors other than FTs or technically inadequate materials. Total 136 FT cases were collated with the type of 53BP1 immunoreactivity in LBC. The mean incidence expressing abnormal 53BP1 expression was significantly higher in FC than FA (9.5% vs 2.6%, P-value < 0.001). When adopting 4.3% as a cut-off value to distinguish FC from FA, the sensitivity, specificity, positive predictive value, and negative predictive value were 89.3, 83.3, 71.4, and 94.3%, respectively. Therefore, IF analysis of 53BP1 expression can be employed as a novel technique to diagnose FTs and to distinguish between different types of FTs using LBC.

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Periostin Expression and Its Roles in Benign and Malignant Thyroid Nodules: an Immunohistochemical Study of 105 Cases

10.21203/rs.3.rs-202219/v1 ◽

2021 ◽

Author(s):

Kimihide Kusafuka ◽

Masaru Yamashita ◽

Tomohiro Iwasaki ◽

Chinatsu Tsuchiya ◽

Aki Kubota ◽

...

Keyword(s):

Thyroid Nodules ◽

Expression Patterns ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Undifferentiated Carcinoma ◽

Thyroid Tumors ◽

Tumor Invasiveness ◽

Adenomatous Goiter ◽

Extracellular Matrix Molecule ◽

Poorly Differentiated

Abstract Background. Thyroid tumors are often difficult to histopathologically diagnose, especially follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, is related to tumor invasiveness. We aimed to elucidate the role of PON in thyroid tumors.Method. We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions. Results. PAC and MIC exhibited stromal PON deposition, especially in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC demonstrated quite strong PON expression.Except for it, we could not find any significantly histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it demonstrated strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, especially at the invasive front.Conclusions. PON plays a role in the invasion of thyroid carcinomas, especially PAC and UCa, whereas it acts as a barrier against the growth of tumor cells in FA and minimally invasive FC.

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Afirma Testing in Thyroid Nodules with Indeterminate Cytology: A single Medical Institute Experience

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.207 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S94-S95

Author(s):

Z Yang ◽

T Zhang ◽

L Layfield ◽

M Esebua

Keyword(s):

Predictive Value ◽

Thyroid Nodules ◽

False Negative ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Medical Institute ◽

Cell Adenoma ◽

Indeterminate Cytology ◽

Thyroid Fna

Abstract Introduction/Objective About 10 to 30% of thyroid fine needle aspiration (FNA) nodules have indeterminate cytology, including Bethesda III, IV, and V. Afirma Gene Expression Classifier (GEC) measuring the expression of 167 mRNA was designed to classify the indeterminate thyroid nodules into benign and suspicious categories. This study aimed to evaluate the clinical performance of the Afirma GEC testing in these indeterminate thyroid lesions. Methods Medical records of patients with indeterminate thyroid FNA results and corresponding Afirma GEC results from November 2012 to December 2019 were retrieved. Subsequent surgical follow-up results were obtained. GEC results were compared to the histologic diagnoses. Results 1. There were 77 cases with indeterminate thyroid FNA results. Cytology diagnosis included 67 Bethesda III and 10 Bethesda IV. Afirma GEC results were benign for 41 cases (53%), suspicious for 32 cases (42%), and non- diagnostic for 4 cases (5%). Twenty seven of 32 cases (84%) with suspicious GEC results had surgical follow-up which revealed 12 malignant and 15 benign histologic diagnoses. Only 11 of 41 cases (27%) with benign GEC results had surgery which showed 8 benign and 3 malignant diagnoses. Based on the data, the sensitivity of this test is 80% and specificity is 65%. Positive predictive value (PPV) is 44% and negative predictive value (NPV) is 73%. The false positive cases include 5 Hurthle cell adenoma, 4 nodular hyperplasia, 3 follicular adenoma, 2 Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFPT), and 1 lymphocytic thyroiditis. The false negative cases include 2 minimally invasive follicular carcinoma (from same patient) and 1 papillary thyroid carcinoma. Conclusion 1. We demonstrated in this study that a little more than half of the cases with indeterminate thyroid cytology had negative Afirma GEC results. 2.Afirma test has relatively low specificity (65%) and PPV (44%). The sensitivity (80%) and NPV (73%) is relatively higher but is lower than the values in most literature. This could be due to the fact that majority of the Afirma GEC negative cases in this study did not have surgical follow-up and the sample size is small. 3.Afirma GEC test is a relatively good “rule-out” molecular test for indeterminate thyroid nodules but is not a reliable “rule-in” test due to the low specificity and PPV.

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The Clinical and Pathological Presentation of Thyroid Nodules in Children and the Comparison with Adult Population: Experience of a Single Institution

International Journal of Endocrinology ◽

10.1155/2016/1256189 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Tamas Solymosi ◽

Gyula Lukacs Toth ◽

Laszlo Budai ◽

Istvan Gal

Keyword(s):

Thyroid Nodules ◽

Adult Population ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Medullary Carcinoma ◽

Adult Patients ◽

Follicular Variant ◽

Central Type ◽

Region Data ◽

Follicular Tumors

The clinical and pathological presentation of thyroid nodules among younger and adult patients was compared in an iodine-deficient (ID) region. Data of 3,010 consecutive patients younger than 20 years and 3,010 patients older than 20 years were compared. The proportion of nodular goiters (22.8% versus 39.3%), the ratio of surgically treated nodules (33.2% versus 15.2%), and the proportion of malignant nodules (4.3% versus 2.1%) among diseased patients differed significantly between the two groups (younger versus adult). Nine papillary and 1 medullary carcinoma were found among children, while 15 papillary, 2 follicular, 1 insular, 1 anaplastic, and 1 medullary carcinomas occurred among adults. The ratio of follicular adenoma to hyperplastic nodules (3 : 1 to 1 : 1.67), the proportion of follicular variant (77.8% versus 26.7%), T4 tumors (77.8% versus 33.3%), and tumors with lymph node metastasis (88.9% versus 66.7%) were significantly higher among younger papillary carcinoma patients. No malignancies occurred among spongiform and central type cysts. Similarly to iodine-sufficient regions, more nodules are malignant and carcinomas have a clinically more aggressive presentation in children in comparison with adult patients in ID. Taking the significantly greater proportion of adenomas and the lack of follicular carcinoma into account, a conservative approach has to be considered in follicular tumors among children.

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Comparison between patients with thyroid follicular tumors in the histological pattern and size of follicular lesion

Al Mustansiriyah Journal of Pharmaceutical Sciences ◽

10.32947/ajps.18.01.0359 ◽

2018 ◽

pp. 26-37

Keyword(s):

Malignant Lesion ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Histopathological Diagnosis ◽

Follicular Hyperplasia ◽

Significant Difference ◽

Paraffin Block ◽

The Difference ◽

Follicular Tumors ◽

Mixed Pattern

The main problem encountered in thyroid nodule is difficult to differentiate between a benign and malignant lesion. Differential between follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort. A total of 120 paraffin block were included in the study, 30 blocks were (FC), 30 blocks were (FVPC). 30 blocks were (FA), 30 blocks were blocks thyroid follicular hyperplasia.20 blocks endocervical epithelium.20 paraffin blocks of colonic epithelium as control. From each paraffin block, 4 slides, each of thicken were taken, stained with Hematoxylin and Eosin (H&E) for revision of histopathological diagnosis. The histological arrangement in follicular carcinoma and follicular adenoma was significant (P= 0.001) in trabecular pattern and the difference was significant (P= 0.016) in mixed pattern while no significance with microfollicular, macrofollicular and normofollicular pattern in both follicular carcinoma and adenoma. There was no significant difference in size follicular lesion among FA, FVPC and follicular hyperplasia (P> 0.05) while, the size follicular lesion in of (FC) was significantly higher from all other groups (P< 0.05).

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Chest x-ray or CT for COVID-19 pneumonia? Comparative study in a simulated triage setting

European Respiratory Journal ◽

10.1183/13993003.04188-2020 ◽

2021 ◽

pp. 2004188

Author(s):

Nicola Sverzellati ◽

Christopher J Ryerson ◽

Gianluca Milanese ◽

Elisabetta A Renzoni ◽

Annalisa Volpi ◽

...

Keyword(s):

Predictive Value ◽

Diagnostic Tools ◽

Clinical Decisions ◽

First Line ◽

Diagnosis And Prognosis ◽

Chest X Ray ◽

Sensitivity Specificity ◽

Triage Algorithm ◽

The Impact ◽

Extent Of Disease

Introduction:for the management of patients referred to respiratory triage during the early stages of the SARS-CoV-2 pandemic, either chest radiograph (CXR) or computed tomography (CT) were used as first-line diagnostic tools. The aim of this study was to compare the impact on triage, diagnosis and prognosis of patients with suspected COVID-19 when clinical decisions are derived from reconstructed CXR or from CT.Methods:we reconstructed CXR (r-CXR) from high-resolution CT (HRCT) scan. Five clinical observers independently reviewed clinical charts of 300 subjects with suspected COVID-19 pneumonia, integrated with either r-CXR or HRCT report in two consecutive blinded and randomised sessions: clinical decisions were recorded for each session. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and prognostic value were compared between r-CXR and HRCT. The best radiological integration was also examined to develop an optimised respiratory triage algorithm.Results:interobserver agreement was fair (Kendall's W=0.365; p<0.001) by r-CXR-based protocol and good (Kendall's W=0.654; p<0.001) by CT-based protocol. NPV assisted by r-CXR (31.4%) was lower than that of HRCT (77.9%). In case of indeterminate or typical radiological appearence for COVID-19 pneumonia, extent of disease on r-CXR or HRCT were the only two imaging variables that were similarly linked to mortality by adjusted multivariable modelsConclusions:the present findings suggest that clinical triage is safely assisted by CXR. An integrated algorithm using first-line CXR and contingent use of HRCT can help optimise management and prognostication of COVID-19.

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Evaluation of initial shockable rhythm as an indicator of short no-flow time in cardiac arrest: a national registry study

Emergency Medicine Journal ◽

10.1136/emermed-2021-211823 ◽

2022 ◽

pp. emermed-2021-211823

Author(s):

Keita Shibahashi ◽

Kazuhiro Sugiyama ◽

Takuto Ishida ◽

Yuichi Hamabe

Keyword(s):

Cardiac Arrest ◽

Positive Predictive Value ◽

Predictive Value ◽

Cardiac Rhythm ◽

Flow Time ◽

Lower Probability ◽

Time Duration ◽

Predictive Values ◽

Sensitivity Specificity ◽

The Impact

BackgroundThe duration from collapse to initiation of cardiopulmonary resuscitation (no-flow time) is one of the most important determinants of outcomes after out-of-hospital cardiac arrest (OHCA). Initial shockable cardiac rhythm (ventricular fibrillation or ventricular tachycardia) is reported to be a marker of short no-flow time; however, there is conflicting evidence regarding the impact of initial shockable cardiac rhythm on treatment decisions. We investigated the association between initial shockable cardiac rhythm and the no-flow time and evaluated whether initial shockable cardiac rhythm can be a marker of short no-flow time in patients with OHCA.MethodsPatients aged 18 years and older experiencing OHCA between 2010 and 2016 were selected from a nationwide population-based Japanese database. The association between the no-flow time duration and initial shockable cardiac rhythm was evaluated. Diagnostic accuracy was evaluated using the sensitivity, specificity and positive predictive value.ResultsA total of 177 634 patients were eligible for the analysis. The median age was 77 years (58.3%, men). Initial shockable cardiac rhythm was recorded in 11.8% of the patients. No-flow time duration was significantly associated with lower probability of initial shockable cardiac rhythm, with an adjusted OR of 0.97 (95% CI 0.96 to 0.97) per additional minute. The sensitivity, specificity and positive predictive value of initial shockable cardiac rhythm to identify a no-flow time of <5 min were 0.12 (95% CI 0.12 to 0.12), 0.88 (95% CI 0.88 to 0.89) and 0.35 (95% CI 0.34 to 0.35), respectively. The positive predictive values were 0.90, 0.95 and 0.99 with no-flow times of 15, 18 and 28 min, respectively.ConclusionsAlthough there was a significant association between initial shockable cardiac rhythm and no-flow time duration, initial shockable cardiac rhythm was not reliable when solely used as a surrogate of a short no-flow time duration after OHCA.

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Diagnostic Accuracy of Fine Needle Aspiration in Thyroid Nodules Arising in Patients with Graves Disease

Acta Cytologica ◽

10.1159/000464094 ◽

2017 ◽

Vol 61 (2) ◽

pp. 117-124 ◽

Cited By ~ 4

Author(s):

Jen-Fan Hang ◽

Mohammed T. Lilo ◽

Justin A. Bishop ◽

Syed Z. Ali

Keyword(s):

Predictive Value ◽

Thyroid Nodules ◽

Follicular Adenoma ◽

Clinical Information ◽

Needle Aspiration ◽

Follicular Neoplasm ◽

Graves Disease ◽

Fine Needle ◽

Cellular Atypia ◽

Sensitivity Specificity

Objective: Cytopathologic interpretation in Graves disease (GD) is considered challenging due to significant cellular atypia. Study Design: We retrospectively identified 55 fine needle aspirations (FNAs) from 43 patients with GD that subsequently underwent thyroidectomy from 1995 to 2016. Results: There were 5 patients with papillary thyroid carcinoma (PTC) and 4 with follicular adenoma (FA). Of the 5 patients with PTC, FNA was interpreted as PTC in 3, atypia of undetermined significance (AUS) in 1, and adenomatoid nodule (AN) in 1 (with a 0.5-cm incidental microcarcinoma). Of the 4 patients with FA, FNA was interpreted as follicular neoplasm (FN) in 2, AUS in 1, and AN in 1. Of the 46 nonneoplastic nodules, FNA was interpreted as nondiagnostic in 2, benign in 26, AUS in 15, FN in 1, and suspicious for PTC in 2. None was diagnosed as malignant. The sensitivity, specificity, positive predictive value, and negative predictive value of PTC diagnosis in FNA were 60, 100, 100, and 96.2%, respectively. Conclusion: FNA is a useful tool for identifying neoplastic nodules arising in GD. However, cytologic atypia often leads to indeterminate diagnoses (18/46, 39.1%). Awareness of clinical information regarding prior treatment for GD may be helpful to avoid overinterpretation.

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The influence of successfully completed triage courses and work experience of advanced emergency medical technicians on their perception of patient disposition

Australasian Journal of Paramedicine ◽

10.33151/ajp.17.724 ◽

2020 ◽

Vol 17 ◽

Author(s):

Javad Mozafari ◽

Mohammad Afzalimoghaddam ◽

Mohammad Taghi Talebian ◽

Maryam Bahreini ◽

Esmaeil Mohammadnejad

Keyword(s):

Emergency Medicine ◽

Predictive Value ◽

Work Experience ◽

Emergency Medical Technicians ◽

Lead Author ◽

Patient Disposition ◽

Emergency Medical ◽

Sensitivity Specificity ◽

A Prospective Study ◽

The Impact

Introduction This study assessed the impact of various one-day workshops and the work experience of advanced emergency medical technicians (AEMTs) on their prediction of patient disposition. Methods We conducted a prospective study on 267 patient transport missions to the emergency department. During the study, convenience sampling was used in all the clinical shifts of the lead author. The AEMTs completed the questionnaires, which comprised of the number of successfully completed workshops; other training courses; work experience and their perception of the patient’s disposition. The latter was compared to the ultimate disposition of patients determined by emergency medicine specialists. Results The respective figures for sensitivity, specificity, positive predictive value and negative predictive value were 86%, 80%, 33% and 66% on predicting patient disposition for AEMTs who passed fewer workshops; and 79%, 76%, 34% and 96% for the participants with less than 4 years’ work experience. The Kappa coefficient for the agreement between AEMTs’ prediction and ultimate patient disposition was 0.387. Conclusion The number of triage courses was not positively effective in the prediction of patient disposition by AEMTs; the number of years of work experience did not make a difference either. The AEMTs were fair in their prediction of patient disposition in comparison with the emergency medicine specialists.

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Pigment Visibility on Rectal Swabs Used To Detect Enteropathogens: a Prospective Cohort Study

Journal of Clinical Microbiology ◽

10.1128/jcm.00213-19 ◽

2019 ◽

Vol 57 (6) ◽

Cited By ~ 4

Author(s):

Jianling Xie ◽

Gillian A. M. Tarr ◽

Samina Ali ◽

Linda Chui ◽

Xiao-Li Pang ◽

...

Keyword(s):

Predictive Value ◽

Stool Specimen ◽

Pediatric Emergency ◽

Nucleic Acid Amplification ◽

Test Characteristics ◽

Telephone Advice ◽

Rectal Swabs ◽

Sensitivity Specificity ◽

Detection Characteristics ◽

The Impact

ABSTRACT Data are lacking regarding the impact of visible pigment on rectal swab diagnostic accuracy. We describe the test characteristics of rectal swabs with and without pigment in children with gastroenteritis. Between December 2014 and September 2017, children (age, <18 years) with ≥3 episodes of vomiting and/or diarrhea in a 24-h period and symptoms for <7 days were enrolled through two pediatric emergency departments and from a province-wide nursing telephone advice line in Alberta, Canada. Specimens were analyzed by employing nucleic acid amplification panels. The primary outcomes were the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the rectal swabs, with stool specimen results being used as the reference standard. An enteropathogen was detected in 76.0% (1,399/1,841) of the paired specimens. A total of 54.4% (1,001/1841) of the swabs had visible pigment. The respective enteropathogen detection characteristics of swabs with and without visible pigment were as follows: 92.2% (95% confidence interval [CI], 90.0%, 94.0%) versus 83.7% (95% CI, 80.5%, 86.4%) for sensitivity, 94.3% (95% CI, 90.5%, 96.6%) versus 91.2% (95% CI, 86.3%, 94.5%) for specificity, 97.9% (95% CI, 96.4%, 98.8%) versus 96.5% (95% CI, 94.5%, 97.8%) for PPV, and 80.9% (95% CI, 76.0%, 85.1%) versus 65.8% (95% CI, 60.0%, 71.1%) for NPV. Processing of swabs without visible pigment would increase the rate of identification of positive swabs from 50.0% (682/1,365) to 88.3% (1,205/1,365). There is a modest decrease in the reliability of a negative test on swabs without evidence of pigment, but the overall yield is significantly greater when they are not excluded from testing. Hence, rectal swabs without visible feces should not be routinely rejected from testing.

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Periostin expression and its supposed roles in benign and malignant thyroid nodules: an immunohistochemical study of 105 cases

Diagnostic Pathology ◽

10.1186/s13000-021-01146-8 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Kimihide Kusafuka ◽

Masaru Yamashita ◽

Tomohiro Iwasaki ◽

Chinatsu Tsuchiya ◽

Aki Kubota ◽

...

Keyword(s):

Thyroid Nodules ◽

Expression Patterns ◽

Follicular Adenoma ◽

Follicular Carcinoma ◽

Undifferentiated Carcinoma ◽

Thyroid Tumors ◽

Tumor Invasiveness ◽

Adenomatous Goiter ◽

Extracellular Matrix Molecule ◽

Poorly Differentiated

Abstract Background Thyroid tumors are often difficult to histopathologically diagnose, particularly follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, has been implicated in tumor invasiveness. We herein aimed to elucidate the expression status and localization of PON in thyroid tumors. Method We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions. Results Stromal PON deposition was detected in PAC and MIC, particularly in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC showed quite strong PON expression. Except for it, we could not find any significant histopathological differences between FA and FC. There were no other significant histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it showed strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, particularly at the invasive front. Conclusions PON may play a role in the invasion of thyroid carcinomas, particularly PAC and UCa, whereas it may act as a barrier to the growth of tumor cells in FA and minimally invasive FC.

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