Follicular Variant Of Papillary Carcinoma Research Articles

Encapsulated Follicular Variant of Papillary Carcinoma of Thyroid-Case Report

Encapsulated Follicular Variant of Papillary Carcinoma of Thyroid-Case Report

Role of CD10 Marker in Differentiating Malignant Thyroid Neoplasms from Benign Thyroid Lesions (Immunohistochemical & Histopathological Study).

BACKGROUND:CD10 was initially recognised as a cell–surface antigen expressed by acute lymphoblastic leukaemias, and hence it’s early designation as Common Acute Lymphoblastic Leukemia Antigen (CALLA). Also, it has been proven to be reactive in various non-lymphoid cells and tissue and different types of neoplasms.AIM:To evaluate the immunohistochemical expression of CD10 in malignant thyroid neoplasms and different benign lesions and to assess whether CD10 can be used as a malignancy marker in thyroid pathology or not.MATERIAL AND METHODS:A total of 83 archived, formalin fixed, paraffin embedded tissue blocks of 83 cases of malignant thyroid neoplasms and different benign lesions. The samples were immunohistochemically analysed for CD10 expression. A p-value of less than 0.05 was considered statistically significant.RESULTS:CD10 was expressed in 91% of the studied malignant thyroid neoplasms and 58% of benign thyroid lesions. It was expressed in 26 of 28 (92.9%) conventional papillary carcinomas, ten of 10 (100%) follicular variants of papillary carcinoma, seven of nine (77.8%) minimally invasive follicular carcinomas, two of three (66.7%) widely invasive follicular carcinomas, and seven of 7 (100%) undifferentiated carcinomas, seven of 11 (66.7%) adenomatous nodules and eight of 15 (53.3%) follicular adenomas. No statistically significant correlations were detected between CD10 expression and patients’ age, sex, lymph node metastasis, tumour stage and capsular invasion.CONCLUSION:CD10 shows strong sensitivity (91.2%) and moderate specificity (42.3%) in the diagnosis of malignancy overall and shows strong sensitivity (86.4%) and moderate specificity (42.3%) in the diagnosis of malignancy in the follicular-patterned lesions. So, CD10 might be useful in differentiating malignant from benign thyroid lesions (good positive test) and in the diagnosis of follicular variant of papillary carcinoma.

Diagnostic value of HBME-1, CK19, Galectin 3, and CD56 in the subtypes of follicular variant of papillary thyroid carcinoma.

Our aim is to explore differences in Hector Battifora mesothelial-1 (HBME-1), cytokeratin-19 (CK19), Galectin-3 (Gal-3), and CD56 expression in infiltrative follicular variants of papillary carcinoma (IFVPTC) and encapsulated follicular variants of papillary carcinoma (EFVPTC) and to provide clues for distinguishing the two subtypes preoperatively. Tissue microarrays from 100 EFVPTC (45 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 55 invasive EFVPTCs), 43 IFVPTCs, and 64 follicular neoplasms (FN) were immunostained with HBME-1, CK19, Gal-3, and CD56. Each case was scored 1 point for every positive result. Immunohistochemical expression was not significantly different in invasive EFVPTC and NIFTP, except for that of HBME-1. HBME-1, CK19, Gal-3, and CD56 expression were significantly higher in IFVPTC than in EFVPTC. At the cutoff of 3 points, the score method had special diagnostic value for differentiating IFVPTC from EFVPTC and FN and for predicting lymph node metastasis. Scoring of immunohistochemistry results may be applied to core biopsy or cell blocks to assist ultrasonographic, cytologic and molecular tests in differentiating IFVPTC and EFVPTC preoperatively, possibly appropriately guiding EFVPTC preoperatively for limited operation or active surveillance.

Targeted next-generation sequencing of cancer-related genes in thyroid carcinoma: A single institution's experience.

Thyroid carcinoma (TC) has characteristic genetic alterations, including point mutations in proto-oncogenes and chromosomal rearrangements that vary by histologic subtype. Recent developments in next-generation sequencing (NGS) technology enable simultaneous analysis of cancer-associated genes of interest, thus improving diagnostic accuracy and allowing precise personalized treatment for human cancer. A total of 50 patients who underwent thyroidectomy between 2014 and 2016 at Hokuto Hospital were enrolled. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 24 cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina MiSeq platform. Subjects included 30 patients with papillary carcinoma (PC), two with PC tall cell variant (TVPC), two with PC follicular variant (FVPC), eight with follicular carcinoma, seven with poorly differentiated carcinoma (PDC), and one with anaplastic carcinoma (AC). The BRAF V600E mutation was present in 25 of 30 (83%) patients with PC, 2 of 2 (100%) patients with TVPC, 6 of 7 (86%) patients of PDC, and one patient with AC. PIK3CA mutations were present in 3 of 30 (delPV104P, A1046T and C420R; 10%) patients with PC and 1 of 7 (H1047R; 14%) patients with PDC. The TP53 mutation was present in 1 of 30 (R306*; 3.3%) patients with PC and 1 of 7 (Q152*; 14%) patients with PDC. The NRAS mutation was present in 1 of 2 (Q61K, 50%) patients with FVPC. Statistical analysis showed that patients without the BRAF V600E mutation had advanced pathologic T and N stages compared with those with the mutation (P=0.047 and P=0.019, respectively). The BRAF V600E mutation was not correlated with overall and disease-free survival in patients with PC. A patient with PC with a mutation in EGFR (K852Q) and the PIK3CA mutation had an aggressive course with multiple bone and lung metastases. Detection of mutations in cancer-associated genes using NGS could enhance the understanding of the clinical behavior of TC.

Well-differentiated Thyroid Carcinoma of Childhood and Adolescence- A Long Term Experience at a Single Institute

<p><strong><em>Background:</em></strong> Thyroid carcinoma is rare in childhood and adolescence. The presentation is more advanced in case of children as compared to adults. However, the prognosis for survival in children is reportedly excellent. The aim of the study was to see the outcome of patients with well differentiated thyroid carcinoma during childhood and adolescence treated at a single institute.</p><p><strong><em>Patients and methods:</em></strong> A retrospective study of 61 children and adolescent patients (age ≤18years) with well differentiated thyroid carcinoma (DTC) enrolled in the National Institute of Nuclear Medicine and Allied Sciences, Dhaka during the period of January1986 up to December 2007 was carried out. To allow for a theoretical follow up of at least 5 years the last inclusion year was 2007 and follow up was carried on up to June 2013. All patients were treated by thyroidectomy followed by radioiodine ablation therapy. Whole body scans, Tg, anti Tg Ab and neck ultrasound findings were recorded six months to one year after initial therapy to classify patients into remission, persistent or recurrent disease. Status on last follow up was noted to estimate the survival rate.</p><p><strong><em>Results:</em></strong> A total of 40 patients had papillary carcinoma, 18 had follicular variant of papillary carcinoma (FVPCT) and three had follicular carcinoma. Age range at diagnosis was nine to 18 years with a mean of 15± 2 years. The number of patients ≤10 years were five and > 10 years were 56. There were 12 males and 49 females giving a M: F ratio of about 1:4. Among the 61 patients 30 patients had lymph node metastases and two had both nodal and lung metastases at initial presentation. After one year follow up from the initial radioiodine therapy, 30 patients were in remission and 31 patients had persistent disease. Eventually recurrence occurred in five patients. Three patients died during the whole observation period and all of them were cancer related giving a cancer specific mortality ratio of 0.049%, 95% CI 0 to 0.105%. Cancer specific survival by Kaplan-Meier curve was 98.2%, 98.2% and 66% at 5, 10 and 15 years respectively.</p><p><strong><em>Conclusion:</em></strong> DTC in children and adolescent has a good prognosis in the presence of neck and distant metastases. Awareness of the patient and regular follow up with life long surveillance is essential to obtain a favorable outcome.</p><p>Bangladesh J. Nuclear Med. 20(2): 99-104, July 2017</p>

Cytological features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

The noninvasive encapsulated follicular variant of papillary carcinoma (EFVPC) was recently renamed a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) because of its unique genetic alterations and biological behavior. The objective of this report is to help cytopathologists and cytotechnologists improve diagnostic accuracy and determine the need for cytogenetic studies during adequacy evaluation of thyroid fine-needle aspirations. Fifty-five cases of surgery-proven noninvasive EFVPC with corresponding cytology material were reviewed. These cases were collected over 17 years, from 1999 to2016. Thirty-four of 55 (61.8%) cases were diagnosed as follicular neoplasm or suspicious for follicular neoplasm on cytology. Eighty to ninety percent of cases showed scant colloid, cellular smears with small clusters of follicular cells with nuclear atypia including enlarged nuclei, oval-shaped nuclei, nuclear grooves, mild chromatin powdering, and rare nuclear pseudo-inclusions. NIFTP has unique features: cytologically similar to follicular neoplasms, and nuclear atypia falling between atypia of undetermined significance (category III) and suspicious for/and papillary thyroid carcinoma (category V/VI) (The Bethesda System for Reporting Thyroid Cytopathology).

Follicular thyroid lesions: is there a discriminatory potential in the computerized nuclear analysis?

BackgroundComputerized image analysis seems to represent a promising diagnostic possibility for thyroid tumors. Our aim was to evaluate the discriminatory diagnostic efficiency of computerized image analysis of cell nuclei from histological materials of follicular tumors.MethodsWe studied paraffin-embedded materials from 42 follicular adenomas (FA), 47 follicular variants of papillary carcinomas (FVPC) and 20 follicular carcinomas (FC) by the software ImageJ. Based on the nuclear morphometry and chromatin texture, the samples were classified as FA, FC or FVPC using the Classification and Regression Trees method.ResultsWe observed high diagnostic sensitivity and specificity rates (FVPC: 89.4% and 100%; FC: 95.0% and 92.1%; FA: 90.5 and 95.5%, respectively). When the tumors were compared by pairs (FC vs FA, FVPC vs FA), 100% of the cases were classified correctly.ConclusionThe computerized image analysis of nuclear features showed to be a useful diagnostic support tool for the histological differentiation between follicular adenomas, follicular variants of papillary carcinomas and follicular carcinomas.

TIRADS score is of limited clinical value for risk stratification of indeterminate cytological results.

Thyroid nodules with cytological indeterminate results represent a daily and recurrent issue for patient management. The primary aim of our study was to determine if TIRADS (Thyroid Imaging Reporting and Data System) could be used to stratify the malignancy risk of these nodules and to help in their clinical management. Secondary objective was to estimate if this risk stratification would change after reclassification of encapsulated non-invasive follicular variant of papillary carcinomas (FVPTC) as non-invasive follicular thyroid neoplasm (NIFTP). Single-center retrospective study of a cohort of 602 patients who were referred for ultrasound-guided fine-needle aspiration from January 2010 to December 2016 with an indeterminate cytological result and in whom histological results after surgery were available. TIRADS score was prospectively determined for all patients included. Nodules that had been classified as FVPTC were submitted to a rereading of histological report and reclassified as NIFTP when judged relevant. A table of malignancy risk crossing Bethesda and TIRADS results was built before and after this reclassification. The study included 602 cytologically indeterminate nodules. TIRADS score was positively correlated with the malignancy rate (P < 0.0001). Risk stratification with TIRADS was significant only in Bethesda V nodules (P = 0.0004). However, the risk of malignancy in this Bethesda V category was always above 45%, whatever the TIRADS score. For a clinician facing an indeterminate cytological result for a thyroid nodule, return to TIRADS score is of limited value in most conditions to rule in or rule out malignancy and to guide subsequent management of patients.

Detection of PAX8/PPAR fusion gene by FISH Technique in follicular thyroid lesions

The main problem established by a discovery of a thyroid nodule is to discriminate between a benign and malignant lesion. Differential diagnosis between follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort.The purpose of the study was to detect PAX8/PPAR G gene rearrangement by fluorescent in situ hybridization (FISH) technique,the present study is the first time in Iraq used this technique to detect fusion gene in follicular thyroid lesions,follicular carcinoma (FC) follicular variant papillary of carcinoma (FVPC), follicular adenoma (FA) and follicular hyperplasia. 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. The clinicopathological parameters were obtained from patients’ admission case sheets and pathology reports (age,gender). The description of measures regarding fluorescent instu hybridization of PAX8/ PPAR G fusion gene there was significantly highest in follicular carcinoma,followed by follicular variant of papillary carcinoma,then follicular adenoma and lastly by follicular hyperplasia The area under the curve for all three markers was &gt;0.8.The p-value was highly significant for all three markers (P&lt;0.001). Cutoff values that predict malignant thyroid follicles lesion were as following: score of &gt;1 for Galectin-3 marker,score of &gt;2 for HBME-1 marker and number of positive cells per 50 of &gt;13 (&gt;26%) for PAX8 /PPAR G fusion gene marker. The sensitivities for the three markers were 100.00 %,90.00 % and 66.67 %,respectively,whereas the specificities were 88.30 %,98.33 % and 100.00 % respectively.

The Relationship between Clinic Pathological Characteristics and Follicular Thyroid Lesion

Study was done in the period between (2015-2017) in biology department in college of Education for pure science /Ibn Al-Haitham at Baghdad University and in Pathology department /college of medicine at Al-Nahrain University.The study was retrospectively designed.The clinicopathological parameters were obtained from patients’ admission case sheets and pathology reports (age, gender).The presents study included 120 patients having thyroid nodules, classified according to results of histopathology into 4 groups, 30 patients within each; the first group included patients with follicular adenoma, the second group included patients with follicular carcinoma, the third group included patients with follicular variant of papillary carcinoma (FVPC) and the last group included patients with follicular hyperplasia.The ratio of male to female in case with follicular carcinoma was 1:4,in case with follicular variant of papillary was 1:2.33, in case with follicular adenoma was 1:5 and in case with follicular hyperplasia.

Ultrasound-guided Fine-needle Aspiration Cytology along with Clinical and Radiological Features in Predicting Thyroid Malignancy in Nodules ≥1 cm.

Aims and Objectives:The aim of the study is to examine the adequacy and accuracy of ultrasound-guided fine-needle aspiration cytology (US-FNAC) in thyroid nodules ≥1 cm and to analyze the clinical, sonological, and cytological features in predicting thyroid malignancy.Materials and Methods:US-FNAC was done on 290 patients from December 2013 to December 2014 by the radiologist. The Thyroid Imaging Reporting and Data System (TIRADS) was used to record the sonological features. FNAC samples were reported by a dedicated cytopathologist. Accuracy was calculated by comparing US-FNAC, clinical features and ultrasound (US) features for those who had final histopathology till April 2017.Results:The adequacy of US-FNAC in this study was 80.2%. Thyroidectomy was performed in 128/290 (44.1%). The sensitivity and specificity of US-FNAC in this study is 83.9 and 76.3%, respectively, with a positive predictive value of 85.2%, negative predictive value of 74.4%, and an accuracy of 81% in predicting malignancy in thyroid nodules ≥1 cm. The malignancy rate in benign FNAC sample was 25% (10/40), and was 69% (8/13) in those with a follicular lesion of undetermined significance (FLUS). Around 80% of benign and 89% of FLUS had follicular variant of papillary carcinoma of thyroid (FVPTC). US-FNAC, a high TIRADS score, and US features such as marked hypoechogenicity, taller than wide, irregular margins, microcalcification, and clinical features, such as hard in consistency and significant cervical lymph nodes, were important in predicting malignancy (P < 0.001).Conclusions:The accuracy of US-FNAC in this study is 81%. The US-FNAC, a high TIRADS score, a hard thyroid nodule, and significant cervical lymph nodes are important in predicting malignancy. The accuracy rate in benign and atypia undetermined significance categories needs to improve in this study. Further research to help in decreasing false negative rates of FVPTC will help in increasing the accuracy of US-FNAC in the present study.

Does noninvasive follicular thyroid neoplasm with papillary-like nuclear features have distinctive features on sonography?

The noninvasive encapsulated follicular variant of papillary carcinoma (nEFVPTC) has recently been reclassified to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)," removing this entity from the malignant category. This re-categorization has had major implications for clinical management. NIFTP has overlapping cytohistologic features with papillary thyroid carcinoma (PTC) and with follicular adenomas (FA), but sonographic data comparing NIFTP to PTC and FA is lacking. Our study examines the sonographic features of NIFTP as compared with PTC and FA. Ultrasound scans and Doppler blood flow from subjects who had pre-surgical sonograms and fine needle aspiration biopsies with final surgical pathology diagnoses of NIFTP/nEFVPTC, classical PTC, and FA between 01/2013-08/2016 were assessed. Sonographic and Doppler features as well as Bethesda System (TBS) diagnoses were recorded and analyzed. 40 NIFTP, 58 classical PTC, and 23 FA cases were included. The most common NIFTP pre-surgical TBS cytology diagnosis was Atypia of Undetermined Significance (AUS/FLUS) (40%). NIFTP cases predominantly displayed wider-than-tall shape (100%), smooth borders (75%), occurrence in multinodular glands (82.5%), heterogeneous echogenicity (50%), both perinodular and intranodular Doppler flow patterns (70%), minimal Doppler flow grade (62.5%), and no calcifications (90%). Our study demonstrates that NIFTP, PTC, and FA display several distinguishing and overlapping sonographic and Doppler features. Sonographic features appear to complement cytology findings and may help raise pre-operative concern for NIFTP in the proper clinical setting, potentially leading to a more conservative management approach.

Large (≥3cm) thyroid nodules with benign cytology: Can Thyroid Imaging Reporting and Data System (TIRADS) help predict false-negative cytology?

BackgroundThere is controversy about the accuracy of the fine-needle aspiration (FNA) cytology results in large sized thyroid nodules. Our aim was to evaluate the false-negative rate of FNA for large thyroid nodules and the usefulness of the Thyroid Imaging Reporting and Data System (TIRADS) in predicting false-negative cytology for large thyroid nodules with benign cytology.Methods632 thyroid nodules larger than or equal to 3cm in size with subsequent benign cytology on US-guided FNA were included. US features of internal composition, echogenicity, margin, calcifications, and shape were evaluated, and nodules were classified according to TIRADS. TIRADS category 3 included nodules without any of the following suspicious features:solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. Category 4a, 4b, 4c, and 5 were assigned to nodules showing one, two, three or four, or five suspicious US features, respectively. US features associated with malignancy for these lesions were analyzed and malignancy risk according to TIRADS was calculated.ResultsOf the 632 lesions, 23 lesions(3.6%) were malignant and 609(96.4%) were benign, suggesting a 3.6% false-negative rate for FNA cytology. Of the 23 malignant lesions, final pathology was mainly follicular carcinoma minimally invasive(65.2%, 15/23) and the follicular variant of papillary carcinoma(26.1%, 6/23). The malignancy risks of categories 3, 4a, 4b, and 4c nodules were 0.9%, 4.6%, 10.0%, and 11.8%, respectively.ConclusionLarge thyroid nodules with benign cytology had a relatively high false-negative risk of 3.6% and TIRADS was helpful in predicting false-negative cytology for these lesions.

Abstract 5639: Diagnosing indeterminate thyroid nodules: combining next generation sequencing and gene expression analysis

Abstract Thyroid nodules are common in the United States and are currently diagnosed using fine needle aspiration (FNA) biopsy. FNA evaluation provides a definitive diagnosis in the majority of cases, but about 20-30% of nodules are deemed indeterminate. Targeted next generation sequencing (NGS) and gene expression analysis have been used as ancillary tests to provide additional information about the malignancy risk for indeterminate thyroid lesions. Here we develop a 31 gene NGS panel, as well as a 14 gene expression panel, and test their performance on thyroid lesions with known diagnosis. Formalin-fixed paraffin embedded tissue from 23 resected thyroid lesions (1 non-neoplastic, 3 follicular adenomas (FA), 1 medullary carcinoma (MC), 7 follicular carcinomas (FC), 7 papillary carcinomas (PC), 4 follicular variant of papillary carcinomas (FVPC)) was evaluated. Total nucleic acid extraction, NGS (31 genes including: NRAS, HRAS, KRAS, CTNNB1, PIK3CA, BRAF, RET, PTEN, AKT1, TP53, GNAS, ALK, DDR2, EGFR, ERBB2, FGFR1/2/3, GNA11, GNAQ, IDH1/2, KIT, MAP2K1, MET, MTOR, NOTCH1, PDGFRA, EPHA2, ESR1, RAC1, and ROS1) through Bio Reference Laboratories, and gene expression analysis (14 genes: KRT7, TTF-1, TG, PGK-1, CK-20, PTH, CALCA, RAP2A, PLAB, HMGA2, FN-1, GAL-3, CK19, and NIS) were performed. This assay detected mutations in 14/19 malignant lesions including 4/7 FCs (NRAS, TP53), 4/4 FVPC (BRAF, NRAS, HRAS, PTEN), 5/7 PCs (BRAF, NRAS), and 1/1 MC (RET). No mutations were detected in the non-neoplastic thyroid and 1/3 FAs contained a KRAS mutation. All three mutation-negative FCs were oncocytic variants and showed upregulation of ≥2 cancer-associated genes including FN-1, GAL-3, HMGA2, PLAB, and RAP2a. The two mutation-negative PCs showed upregulation of 4 cancer-associated genes including FN-1, CK-19, GAL-3, HMGA2, and PLAB. This upregulation was not seen in non-neoplastic thyroid and was seen in only 1 of the FAs (FN-1, GAL-3, and PLAB). This small study demonstrates that a combination of NGS and gene expression increases the assay sensitivity (100% versus 74% sensitivity) and negative predictive value (100% versus &amp;lt;45% for NGS or gene expression alone). The positive predictive value of the combined assay was 90% versus 93% for either assay alone. The addition of gene fusions will likely further improve the assay’s diagnostic capacity. In conclusion, the addition of a gene expression assay to this thyroid NGS assay allowed for identification of mutation-negative thyroid malignancies. The improved detection of malignant thyroid lesions will allow for better risk assessment for indeterminate nodules as well as improved treatment algorithms. Citation Format: Vivian L. Weiss, Robert Daber, Michael Moreau, Alisa Gaskell, Kim Ely, Alice Coogan, Thomas Stricker. Diagnosing indeterminate thyroid nodules: combining next generation sequencing and gene expression analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5639. doi:10.1158/1538-7445.AM2017-5639

Incidence and significance of true papillae in thyroid fine needle aspiration.

Whether true papillae without nuclear features of papillary carcinoma in thyroid fine needle aspirates should be diagnosed as atypia of undetermined significance (AUS) is unclear. The results of all thyroid FNAs performed from 2014-2016 with corresponding resections as well as aspirates from 2000-2016 with a diagnosis of follicular variant of papillary carcinoma or Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were reviewed. Papillae with fibrovascular cores were identified in 17 of 149 consecutive cases (11%), 3 of which had nuclear features of papillary carcinoma and were papillary carcinoma at resection. All 14 cases of papillae without nuclear features of papillary carcinoma were benign. Of 29 papillary carcinomas, papillae were identified in 8 (28%) and "swirls" were identified in 3 (10%) additional cases, all in cases of papillary carcinoma, NOS. Papillae and swirls were not identified in any cases of NIFTP (13 cases) or follicular variants of papillary carcinoma (15 cases). True papillae are relatively common. Both papillae with nuclear atypia and swirls are highly specific for papillary carcinoma, NOS and are not seen in NIFTP. True papillae with fibrovascular cores but without cytologic features of papillary carcinoma are benign and should not be diagnosed as AUS. Diagn. Cytopathol. 2017;45:689-692. © 2017 Wiley Periodicals, Inc.

Impact of the Reclassification of the Non-Invasive Follicular Variant of Papillary Carcinoma as Benign on the Malignancy Risk of the Bethesda System for Reporting Thyroid Cytopathology: A Meta-Analysis Study

Objectives: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established diagnostic categories for cytologic specimens of the thyroid. Each category was associated with an estimated risk of malignancy. Recently, the non-invasive follicular variant of papillary thyroid carcinoma has been reclassified as benign. This reclassification may alter the malignancy risk of TBSRTC diagnostic categories. Study Design: A literature search was made for all studies investigating the effect of reclassification of some non-invasive follicular variant papillary thyroid carcinomas as benign on the malignancy risk associated with TBSRTC categories. The authors calculated the malignancy risk for TBSRTC categories in a series of 315 thyroid aspirates when the non-invasive follicular variant of papillary thyroid carcinoma was considered benign. A meta-analysis of malignancy risk data for the 3 published studies and the current study was performed. Results: The meta-analysis showed that the malignancy risk was reduced for all TBSRTC categories except the “non-diagnostic” category. The reduction in malignancy risk was greatest in the categories “suspicious for malignancy” and “atypia/follicular lesion of undetermined significance.” Conclusion: A meta-analysis of all pertinent studies demonstrated that re-categorization of the non-invasive follicular variant of papillary thyroid carcinoma as benign reduces the malignancy risk in the majority of TBSRTC categories.

Importance of cytological subclassification of thyroid nodules with Bethesda category III cytology (AUS/FLUS) into architectural atypia only and nuclear atypia: A prospective study.

The objective of this study was to compare two cytological subcategories of thyroid nodules with Bethesda category III initial cytology. This was a prospective study. All patients with thyroid nodules > 1 cm were eligible and 98 patients with category III cytology were selected. Cytology was subcategorized into architectural atypia only (AA, n = 45) and nuclear atypia (NA, n = 53). All patients underwent a second fine-needle aspiration (FNA). Only patients whose second cytology was benign and ultrasonography was non-suspicious were not referred for surgery. In these patients, the nodules were considered benign. The second FNA more frequently revealed "benign cytology" in the AA subcategory (44.4% vs. 24.5% in the NA subcategory). The second cytology suggested "follicular neoplasm" or was "suspicious for follicular neoplasm" (category IV) in 5 patients (11.1%) of subcategory AA and was "suspicious for malignancy" (category V) in 13 (24.5%) of subcategory NA. Finally, malignancy was diagnosed in 15.5% of cases of subcategory AA and in 41.5% of subcategory NA. Follicular carcinoma was more frequent in subcategory AA, while classical papillary carcinoma was more frequent in subcategory NA. Excluding cases of the noninvasive encapsulated follicular variant of papillary carcinoma, malignancy was diagnosed in 11.1% of patients of subcategory AA and in 35.8% of subcategory NA. The results showed that subclassification of the Bethesda category III improves cancer risk prediction, with potential repercussions for clinical practice. Diagn. Cytopathol. 2017;45:604-607. © 2017 Wiley Periodicals, Inc.

Follicular Variant of Papillary Thyroid Carcinoma on the Basis of His-topathological and Immunohistochemical Diagnosis

A significant increase in incidence of papillary thyroid carcinoma (PTC) has been noticed in recent decades worldwide. This is due to advances in medical surveillance, increased use of ancillary tests, and a minor component due to over diagnosis of PTC. Follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common variant of PTC and comprises about 23-41%. It is difficult to diagnose histologically when the distinctive nuclear features are either not well developed or present focally within the lesion. Several immunohistochemical markers (CD56, HMCK, GAL3, HBME-1 and CK19) either alone or combined in panels can be used to improve diagnostic accuracy. This study was aimed to differentiate FVPTC from other follicular patterned lesion of thyroid by histopathology and immunohistochemistry (IHC). A total of 50 histologically diagnosed cases of thyroid neoplasm were studied. The neoplastic cases included 40 cases of follicular variant papillary carcinoma (FVPC), 04 classic papillary carcinoma (PTC), 04 follicular carcinoma and 02 follicular adenoma. All cases were evaluated by IHC for the expression of CD56 and CK19 antibody. In case of FVPTC (n=40), 21 cases (52.5%) were CK19 positive and CD56 negative as expected. Both markers were found positive in 06 (15%) cases and CD56+ alone was found positive in 11 (27.5%) cases of FVPTC, and a finding that goes against the diagnosis of FVPTC. The histopathological slides of these cases were reviewed and findings were recorded. All cases (n=4) of classic PTC were CK19 positive and 03 (75%) cases were found CD56 negative. Diagnoses of thyroid follicular lesions are primarily based on histological and cytomorphological criteria. However, there was a subset of follicular patterned tumors like FVPTC which lack unequivocal features of malignancy. Immunohistochemistry can improve diagnostic accuracy but needs additional studies for controversial cases. It may be considered these lesions as differentiated tumor of uncertain malignant potential (WDT-UMP) to avoid the using term carcinoma. Additional studies are needed for establishing more precise morphologic criteria and for identifying useful markers for differentiating benign from borderline or malignant thyroid lesions.

Malignancy rate in thyroid nodules categorized as atypia of undetermined significance or follicular lesion of undetermined significance - An institutional experience.

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 different results have been obtained across institutions due to variable follow-ups and interpretation. The present study was conducted to evaluate the rate of malignancy along with appropriate management in this category.Materials and Methods:The study included AUS/FLUS cases diagnosed over period of 4 years on thyroid fine needle aspiration cytology (FNAC). Detailed clinical history and radiological examination were recorded along with follow-ups and management of all cases. Histopathology was available for cases which underwent surgery due to high clinical suspicion, worrisome radiological features or two consecutive AUS/FLUS reports.Results:The incidence of AUS/FLUS was 6.4% with repeat FNAC done in 39.6%, immediate surgery in 49.2% and follow-up without intervention in 11.1% cases. The overall malignancy rate was 28.5% with most common malignancy being follicular variant of papillary carcinoma (FVPC). Malignancy rate was more in cases (24.1%) which morphologically showed atypical nuclear features in comparison to architectural atypia.Conclusion:AUS/FLUS is associated with higher risk of malignancy than previously anticipated. Surgical intervention may have greater implication than repeat FNAC in appropriate management of this category. Substratification of this category according to nuclear features and architecture may be more useful in predicting malignancy risk and reducing the variability in the group.

Immunohistochemical Expression of Cytokeratin-19 in Thyroid Nodules and Its Correlation With Histopathology

Background: Thyroid neoplasms constitute the most commonly occurring endocrine tumors worldwide. They commonly occur between 30-60 years of age and affect both sexes. Papillary carcinoma is the most common malignant tumor constituting 80-85% of all the thyroid carcinomas followed by follicular carcinoma comprising 10-15%. Diagnosis becomes challenging when typical features are not seen or when overlapping features are present. In such cases immunohistochemistry can be done to make correct diagnosis. Methods: In this study we observed the immunohistochemical expression of Cytokeratin19 in 30 thyroidectomy specimens which included classic papillary carcinoma (11 cases), follicular variant of papillary carcinoma (2 cases), follicular adenoma (15 cases) and follicular carcinoma (4 cases). The study period was one year. The scoring was given from 0- 3+ based on the percentage of cells showing membrane and cytoplasmic positivity and intensity of staining. Result: The staining results of Cytokeratin19 showed diffuse and strong 3+ positivity in 8/11 cases of papillary carcinoma and its follicular variant, 2 cases showed 2+ positivity and one case with 1+ positivity. Majority of the cases of follicular adenoma (13/15 cases) and follicular carcinoma (3/4 cases) showed negative staining. Only 2 cases of follicular adenoma and 1 case of follicular carcinoma showed focal weak positivity.Conclusion: Cytokeratin19 was found to be a sensitive and specific marker in diagnosing papillary carcinoma and its follicular variant. But it does not differentiate follicular neoplasms. Hence a good panel of markers is essential in arriving at exact diagnosis of thyroid neoplasms in challenging cases. DOI: 10.21276/APALM.2017.1053