Should Core Needle Biopsy be Used in the Evaluation of Thyroid Nodules?

Fine needle aspiration (FNA) is the first choice in thyroid nodules suspected of harboring malignancy on sonography in routine practice. However, sampling with core needle biopsy (CNB) is also being used, especially in cases with repeated nondiagnostic/indeterminate diagnoses. The aim of this study was the retrospective evaluation of CNB samples. A total of 604 thyroid CNB samples registered in the Department of Pathology at Bezmialem Foundation University Medical Faculty within the 1-year period between June 2014 and June 2015 were re-evaluated by correlation with previous FNA and later resection results. CNB was divided into diagnostic groups of insufficient, malignant, suspicious for malignancy, no evidence of malignancy/benign, atypia of uncertain significance (AUS)/follicular lesions of uncertain significance (FLUS), and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN). Among the 604 cases, 15 cases (2.48 %) were classified as malignant and 9 cases (1.49 %) as suspicious for malignancy. No evidence of malignancy was seen in 512 cases (84.76 %). There were 26 (4.3 %) cases in the AUS/FLUS-FN/SFN group, and the sample was inadequate in 42 cases (6.95 %). Resection was performed for 17 of the cases classified as malignant or suspicious for malignancy, and all were found to be malignant. There were also 10 resected cases with a diagnosis of no evidence of malignancy, and all were found to be benign. We think that sampling with CNB may be useful especially in repeating inadequate biopsies or cases diagnosed with AUS/FLUS that have hesitations regarding clinical management. Larger series including comparisons with FNA and resection results are required.     

Cytological results of ultrasound-guided fine-needle aspiration cytology for thyroid nodules: emphasis on correlation with sonographic findings

Purpose

To compare the cytological results of ultrasound-guided fine-needle aspiration (US-FNA) cytology of thyroid nodules to sonographic findings and determine whether US findings are helpful in the interpretation of cytological results.

Materials and Methods

Among the thyroid nodules that underwent US-FNA cytology, we included the 819 nodules which had a conclusive diagnosis. Final diagnosis was based on pathology from surgery, repeated FNA cytology or follow-up of more than one year. Cytological results were divided into five groups: benign, indeterminate (follicular or Hurthle cell neoplasm), suspicious for malignancy, malignant, and inadequate. US findings were categorized as benign or suspicious. Cytological results and US categories were analyzed.

Results

Final diagnosis was concluded upon in 819 nodules based on pathology (n=311), repeated FNA cytology (n=204) and follow-up (n=304), of which 634 were benign and 185 were malignant. There were 560 benign nodules, 141 malignant nodules, 49 nodules with inadequate results, 21 with indeterminate results, and 48 that were suspicious for malignancy. The positive and negative predictive values of the US categories were 59.1% and 97.0%, and those of the cytological results were 93.7% and 98.9%. The US categories were significantly correlated with final diagnosis in the benign (p=0.014) and suspicious for malignancy (p<0.001) cytological result groups, but not in the inadequate and indeterminate cytological results groups. The false positive and negative rates of cytological results were 1.9% and 3.2%.

Conclusion

Sonographic findings can be useful when used alongside cytological results, especially in nodules with cytological results that are benign or suspicious for malignancy.     

Thyroid Cancers with Benign-Looking Sonographic Features Have Different Lymph Node Metastatic Risk and Histologic Subtypes According to Nodule Size

A decision to perform fine needle aspiration (FNA) on thyroid nodules mainly depends on sonographic features. We investigated if lymph node metastasis (LNM) risk differed by tumor size of thyroid cancers without suspicious sonographic features. Three hundred sixty patients with thyroid cancers with benign looking sonographic features were grouped by nodule size on ultrasonography (US) (≤ or >1 cm). The clinicopathologic parameters were compared between the groups. A multivariate analysis was performed to discover the independent factors predicting the presence of LNM. The nodules greater than 10 mm on US (n?=?157) demonstrated a larger tumor size on histology (17.9?±?14.5 vs. 5.6?±?2.4 mm, P?P?P?P?=?0.007). A multivariate analysis revealed that classical PTC, extrathyroidal extension, and the US nodule size >10 mm were independent predictive factors of LNM after adjusting for age, sex, TSH level, and multifocality. Thyroid cancers larger than 10 mm with benign US features are more likely to be nonclassical PTC than those with smaller diameters. The larger ones also have an increased risk of LNM in classical PTC. These cases require a more aggressive approach to FNA.     

Incidental Papillary Thyroid Carcinoma: Diagnostic Findings in a Series of 287 Carcinomas

The recent increase in the detection of papillary thyroid carcinoma (PTC) has been influenced by the finding of incidental tumours. To this group, carcinomas measuring less than 1 cm (the so-called microcarcinomas) as well as those above 1 cm belong. Analyzing a case series from our own experience, this paper focuses on the current pre-operative diagnostic challenges that can lead to PTC incidental discovery. For this retrospective study, 287 patients with a PTC diagnosis were selected. For each, the following variables were analysed: sex, age, ultrasound (US) appearance, number of thyroid nodules, PTC size, PTC variants and presence of other associated pathology. Pre-operative fine needle aspiration (FNA) results were classified according to the five-tiered SIAPEC system. For 281 patients, the US-guided FNA results were available. Cytohistological correlation was evaluated in terms of FNA sensitivity and false negative rate. An incidental PTC was found in 45.2 % of patients. The majority of these were due to unsuccessful US detection of malignant nodules (103 cases); incorrect cytological diagnosis was responsible for the other 24 cases. The most powerful clinical confounding factors were: multinodular background versus single nodule presentations (p?p?2 cm) due to tumour heterogeneity. Although with limitations related to the tumour’s intrinsic features and the thyroid background, US-guided FNA, especially if performed by a dedicated multidisciplinary team, is a powerful diagnostic tool for detecting malignant thyroid nodules. To the state of the art, we propose a practical clinical-pathological cut-off for this procedure, setting it at 5 mm.     

Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules

Indeterminate cytology results increase the number of repetitive procedure and unnecessary surgery. This study was designed to find useful and simple predictive tools to differentiate malignant thyroid nodules from indeterminate nodules. We retrospectively enrolled 164 patients who had undergone thyroid surgery as a result of indeterminate cytology in the National Cancer Center. We reviewed patients' age at diagnosis, sex, preoperative biochemical markers such as thyroglobulin (Tg), anti-Tg antibody, free T4 and TSH level, and sonographical and pathological findings, which were subjected to statistical analysis. We found several clinical and sonographical predictive factors that showed significant differences. Young age, male, preoperative high Tg level, and hypoechoic nodule on sonography all increased cancer probability significantly in multivariate analysis. With a cut-off value of 187.5 ng/mL Tg, sensitivity and specificity were 54.8% and 90.1%, respectively (AUC 0.748, P < 0.001). In the case of nodule size > 1.7 cm, elevated serum Tg predicts the risk of malignancy; especially Tg > 70 ng/mL (odds ratio 3.245, 95% confidence interval 1.115-9.450, P = 0.038). Preoperative Tg levels had very high specificity in predicting thyroid cancer in case of suspicious follicular neoplasm. Therefore, Tg levels may be a useful marker for differentiating thyroid cancer from benign thyroid nodules in the cytological diagnosis of indeterminate nodules.     

Follicular Variant of Papillary Thyroid Carcinoma: Accuracy of FNA Diagnosis and Implications for Patient Management

Follicular variant of papillary thyroid carcinoma (FVPTC) creates a continuous diagnostic dilemma among pathologists because of the paucity of nuclear changes of papillary carcinoma and overlapping features with benign and other neoplastic follicular lesions. Current guidelines for the management of thyroid nodules recommend surgery for confirmed PTC, suspicious for PTC, and follicular neoplasm cases, while further immediate diagnostic studies or treatment are not routinely required if the nodule is benign on cytology. This study is designed to determine the accuracy of cytology in the diagnosis of FVPTC, based on the Bethesda classification system, and determine the implications for patient management based on the current recommendation. Based on a retrospective review of cytologic diagnoses between January 2008 and December 2011, thyroid fine needle aspiration (FNA) cytology specimens with subsequent surgical intervention and a final diagnosis of FVPTC were selected. The cytologic diagnoses were compared with the final diagnoses, and the percentage of cases contributing to the final diagnosis of FVPTC was calculated for each diagnostic category. Triage efficiency and diagnostic accuracy were calculated. One hundred and fifty-two cases with histologic confirmation of FVPTC were identified (representing 128 patients—101 female, 27 male). All patients had undergone either lobectomy with completion thyroidectomy or total thyroidectomy. The cytologic diagnosis of “positive for malignancy” accounted for only 27 % of the final histologic diagnosis of FVPTC, while suspicious for carcinoma, follicular neoplasm, follicular lesion of undetermined significance, and benign accounted for 11, 23, 23, and 16 % of the final diagnosis of FVPTC, respectively. Only 18 % of the 55 cases tested were positive for BRAF mutation. The subtle nuclear features of FVPTC pose challenges for an accurate diagnosis. Therefore, a better approach is to triage these cases for surgical intervention and/or further evaluation of the particular nodule. Our triage efficacy for FVPTC was 84 %; however, the diagnostic accuracy of PTC was 38 %. A negative diagnosis on FNA has diagnostic and management implications for up to 16 % of cases because they may have no further immediate diagnostic studies or treatment. BRAF mutation analysis provides minimal effect on diagnostic accuracy.     

The Value of Negative Diagnosis in Thyroid Fine-Needle Aspiration: a Retrospective Study with Histologic Follow-Up

The Bethesda System for reporting thyroid cytopathology (BSRTC) predicts an incidence of malignancy of less than 5% in thyroid nodules with a benign diagnosis on fine-needle aspiration (FNA). However, recent series have suggested that the true rate of malignancy might be significantly higher in this category of patients. We reviewed our experience by performing a retrospective analysis of patients with benign thyroid FNA results who underwent thyroidectomy between 2008 and 2013 at a large academic center. Information including demographics, ultrasound features, FNA diagnosis, and surgical follow-up information were recorded. Slides were reviewed on cytology-histology discrepant cases, and it was determined whether the discrepancy was due to sampling or interpretation error. A total of 802 FNA cases with a benign diagnosis and surgical follow-up were identified. FNA diagnoses included 738 cases of benign goiter and 64 cases of lymphocytic thyroiditis. On subsequent surgical resection, 144 cases were found to be neoplastic, including 117 malignant cases. False negative, defined as interpretation error and inadequate biopsy of the nodule harboring malignancy, was 6%. When cases of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were excluded from the analysis, false-negative rate was 5%. When microPTC cases were excluded, false-negative rate was 3% and was slightly less than 3% when both microPTC and NIFTP cases were excluded from the analysis. Retrospective review of neoplastic cases showed that 57% were due to sampling error and 43% were due to interpretation error. Interpretation error was more likely to occur in follicular patterned neoplasms (75%), while sampling error was more common in non-follicular variants of papillary thyroid carcinoma (non-FVPTC) (61%). With the exclusion of microPTC, interpretation errors were still more likely to occur in follicular neoplasms (79%) but there was no significant difference in sampling error between non-FVPTC (37%) and follicular patterned neoplasms (42%). Tumor size was larger in cases with interpretation error (mean = 2.3 cm) compared to cases with sampling error (mean = 1.4 cm). This study shows that the false-negative rate of thyroid FNA at our institution is not significantly above the rate suggested by the BSRTC. Interpretation errors were more likely to occur in follicular patterned neoplasms, while non-FVPTC was more frequently found in false negative cases due to inadequate sampling.     

Diagnosis of "follicular neoplasm": a gray zone in thyroid fine-needle aspiration cytology.

The thyroid fine-needle aspiration (FNA) diagnosis of "follicular neoplasm" does not differentiate between a benign and malignant tumor. Often cases diagnosed as "follicular or Hürthle-cell neoplasm" undergo surgical excision for further characterization. The aim of this study was to identify clinical features that may help in predicting malignancy in patients with an FNA diagnosis of follicular neoplasm. One hundred eighty-four cases in 167 patients were diagnosed as "follicular neoplasm" among 1,024 thyroid FNA evaluated with on-site interpretation from 1998-2000. The cases were evaluated for the following variables: histologic diagnosis, age, sex, and size of the nodule. One hundred thirty-nine patients were female, and 28 were male (age range, 23-80 yr). Among 122 patients (67%) undergoing surgical excision (lobectomy, 96; total thyroidectomy, 26), malignancy was identified in 37 cases (31%). Nonpapillary (follicular/Hürthle) carcinoma was diagnosed in 11 (9%), follicular variant of papillary carcinoma in 25, and medullary carcinoma in 1 case. The risk of malignancy was greater in males (47% vs. 29%, P < 0.0004) than females, in nodules measuring 3 cm or more (55% vs. 23%, P < 0.0001), than in nodules measuring less than 3 cm, and in patients 40 or more yr old (20% vs. 10%, P = 0.0001) than in patients younger than 40 years. The diagnosis "follicular neoplasm" is indeterminate, and the majority of cases (70% in the current study) are benign. However, clinical features, including gender, nodule size, and age, can be a part of the decision analysis in selecting patients for surgery.     

Radiologic and Clinical Predictors of Malignancy in the Follicular Lesion of Undetermined Significance of the Thyroid

Various ultrasonographic characteristics of thyroid nodules have been associated with a higher likelihood of malignancy, and certain clinical features may also increase the likelihood of malignancy in patients. This study is designed to determine the ultrasonographic and clinical predictors of malignancy in the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category. A search through the cytology files at our institution was made for cases with diagnosis of AUS/FLUS. The clinical and radiologic findings were correlated with the final surgical pathology diagnosis. A total of 140 cases of AUS/FLUS with corresponding surgical intervention were identified (112 females and 28 males). There was a 79 % malignancy rate in nodules with irregular contours, compared to 51 % in nodules with regular outlines. Nodules demonstrating calcifications showed a 57 % malignancy rate, compared to 50 % in nodules without calcifications. Sixty-one percent of cases with an ultrasonographic diagnosis of indeterminate to suspicious were malignant following surgical resection. The rates of malignancy in patients with radiation exposure, symptomatic nodules, and positive family history of thyroid cancer were 22, 59, and 33 %, respectively. BRAF mutation was demonstrated in 57 % of malignant cases and in none of benign cases. No single clinical or ultrasonographic feature or combination of features is adequately sensitive or specific to identify all malignant nodules. However, a combination of solid nodules, nodules with irregular contours, symptomatic nodules, and positive BRAF mutation has high predictive value for malignancy in patients with a cytologic diagnosis of AUS/FLUS.     

Cytopathologist‐performed ultrasound‐guided fine‐needle aspiration of parathyroid lesions

The gold standard to determine the cause of primary hyperparathyroidism (PHPT) is bilateral neck exploration. As most cases are caused by parathyroid adenoma, there is a movement toward preoperative localization of the abnormal gland by ultrasound and/or Tc⁹⁹‐sestamibi scan and minimally invasive parathyroidectomy. Nonpalpable thyroid nodules are common and cannot be differentiated from parathyroid lesions by imaging alone. This study examines cytopathologist‐performed ultrasound‐guided fine‐needle aspiration (UG‐FNA) in diagnosis of parathyroid lesions. Between January 1, 2007 and December 31, 2008, seven patients with PHPT or other parathyroid lesions with one or more sonographically‐visible thyroid masses underwent cytopathologist‐performed UG‐FNA with immediate cytological evaluation (ICE). One mass was palpable and nine were nonpalpable. Three parathyroid adenomas, two benign colloid nodules, one papillary carcinoma, three parathyroid cysts, and one thyroid cyst were diagnosed. The nodules in three patients with parathyroid adenomas were identified as follicular lesion/neoplasm on ICE. Additional UG‐FNA passes were made to obtain tissue for immunohistochemistry stains, which confirmed parathyroid origin. Two of these patients had a separate benign colloid nodule and one had a thyroid cyst diagnosed by UG‐FNA. The PHPT patient with papillary carcinoma on UG‐FNA had the malignancy confirmed at surgery and a sonographically occult parathyroid adenoma. The three patients with thyroid cysts identified by radiology were suspected of being parathyroid cysts on the basis of real‐time sonographic features at the biopsy table. The clear cyst fluid obtained by UG‐FNA had markedly elevated PTH. Cytopathologist‐performed UG‐FNA can distinguish between parathyroid and thyroid nodules in patients with suspected parathyroid lesions. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

The triage efficacy of fine needle aspiration biopsy for follicular variant of papillary thyroid carcinoma using the Bethesda reporting guidelines

Diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine-needle aspiration (FNA) is challenging. In this retrospective review, we evaluated triage efficacy (i.e., potential for triggering surgical intervention) in 44 archived FNA biopsies of surgically confirmed FVPTC obtained between December 2006 and December 2008. We compared the original FNA diagnoses with reclassified diagnoses based on 2007 National Cancer Institute (NCI)/Bethesda recommendations, and reviewed FNA cytologic features. Original FNA diagnoses included colloid nodule (7%, 3/44), atypical follicular cells (5%, 2/44), follicular lesion (11%, 5/44), follicular neoplasm (16%, 7/44), suspicious for malignancy/PTC (27%, 12/44), and papillary thyroid carcinoma (34%, 15/44). Reclassified diagnoses included indeterminate (5%, 2/44), colloid nodule (7%, 3/44), atypical cells of undetermined significance [ACUS] (7%, 3/44), Hurthle cell neoplasm (2%, 1/44), follicular neoplasm (7%, 3/44), suspicious for malignancy/PTC (25%, 11/44), and PTC (48%, 21/44). Triage efficacy was 77% (34/44) for original diagnoses versus 82% (36/44) for reclassified FNA diagnoses. We frequently observed cytologic features of PTC, such as nuclear grooves and fine chromatin; conversely, intranuclear inclusions, though present in 77% cases, were scant. Our review findings suggest that lack of characteristic cytologic features of PTC,coexistence with other thyroid lesions, and small tumor size arethe major obstacles to FNA diagnosis of FVPTC. Reclassification of thyroid FNA diagnoses does not significantly improve triage efficacy. Furthermore, FNA diagnoses of follicular neoplasm and suspicious for malignancy are valuable in patients with FVPTC because they trigger triage toward surgical intervention.     

Differential Expression of a Set of Genes in Follicular and Classic Variants of Papillary Thyroid Carcinoma

Fine-needle aspiration biopsy (FNA) is currently the best initial diagnostic test for evaluation of a thyroid nodule. FNA cytology cannot discriminate between benign and malignant thyroid nodules in up to 30% of thyroid nodules. Therefore, an adjunct to FNA is needed to clarify these lesions as benign or malignant. Using differential display-polymerase chain reaction method, the gene expression differences between follicular and classic variants of papillary thyroid carcinoma (PTC) and benign thyroid nodules were evaluated in a group of 42 patients. Computational gene function analyses via Cytoscape, FuncBASE, and GeneMANIA led us to a functional network of 17 genes in which a core sub-network of five genes coexists. Although the exact mechanisms underlying in thyroid cancer biogenesis are not currently known, our data suggest that the pattern of transformation from healthy cells to cancer cells of PTC is different in follicular variant than in classic variant.     

A valuable adjunct to FNA diagnosis of papillary thyroid carcinoma: In‐house PCR assay for BRAF T1799A (V600E)

The diagnostic approach to thyroid nodules generally starts with FNA cytology. However, approximately one‐fifth of cytologic evaluations yield indeterminate cytological findings but only 20% of cases with indeterminate thyroid nodule cytology have a cancer diagnosis, emphasizing the need for an effective ancillary test based on FNA material to help prevent unnecessary surgery. Detection of BRAFV600E mutation, the genetic signature of papillary thyroid carcinoma (PTC) in FNA material provides an invaluable diagnostic adjunct to overcome the limitations of FNA cytology. There are many ways to detect V600E, such as direct DNA sequencing, allele‐specific PCR and hybridization‐based colorimetric methods. In this study, a newer simple PCR method is presented that removes requirements for sequencing special equipment and commercial kits. Two forward primers including the mutant sequence specific (F2), and one common reverse (R) primer were optimized to generate a 241 bp fragment (F1R), an internal PCR control, and a 141 bp fragment (F2R) denoting the presence of V600E. Sensitivity studies revealed that the assay is capable of detecting V600E even in 1 ng of DNA. Direct sequencing data of 241 bp F1R fragment proved the specificity of the assay. For validation studies of the sequence specific multiplex PCR assay, archival FNA slides were used in a group of thyroid lesions including PTC, follicular carcinoma, follicular adenoma, Hashimoto thyroiditis, and benign thyroid nodules. The newer PCR‐based method presented in this study is a practical, inexpensive one‐step assay to detect the BRAF T1796A mutation on FNA samples. Diagn. Cytopathol. 2011;39:424–427. © 2010 Wiley‐Liss, Inc.     

A review of the cytomorphological features of NIFTP

Follicular variant of papillary thyroid carcinoma (FVPTC), including encapsulated (E-FVPTC) and infiltrative (I-FVPTC) forms, account for approximately 30% of all PTC. These subtypes demonstrate different biological behavior and molecular profiles when compared to classical PTC. E-FVPTC has low regional recurrence and metastatic potential with a biological behavior similar to that of follicular adenoma. In 2015, a multidisciplinary panel of experts revised the diagnostic terminology for cases of noninvasive E-FVPTC to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). NIFTP was morphologically defined as a noninvasive follicular patterned neoplasm with nuclear features of PTC and scant nuclear pseudo-inclusions, specifically excluding papillary structures and psammoma bodies. The employment of NIFTP diagnostically has significantly impacted fine needle aspiration (FNA) diagnosis and the associated risk of malignancy employed in reporting thyroid FNA specimens. The emerging literature suggests specific cytomorphologic features more frequently encountered with NIFTP compared to cases of I-FVPTC. This article reviews the cytology literature regarding NIFTP and discusses the significance of this new entity in the practice of thyroid cytopathology.     

Clinical Utility of KAP-1 Expression in Thyroid Lesions

Although there are evidences of the involvement of KAP-1 in other tumors, data on differentiated thyroid carcinomas (DTC) are still lacking. We aimed to evaluate KAP-1 clinical utility in the diagnosis and prognosis of DTC. We used both visual immunohistochemistry and a semiquantitative analysis to evaluate KAP-1 expression in 230 thyroid carcinomas and 131 noncancerous thyroid nodules. There were 43 follicular carcinomas (FC) and 187 papillary thyroid carcinomas (PTC), including 130 classic (CPTC), 4 tall cells (TCPTC), and 53 follicular variants (FVPTC). Patients were followed up for 53.8?±?41 months. They were classified as free-of-disease (142 cases) or poor outcome (25 cases—10 deaths), according to their serum Tg levels and image evidences. KAP-1 was identified in 78 % PTC, 75 % TCPTC, 74 % FC, 72 % FVPTC, 55 % FA, 44 % hyperplasia, and 11 % normal thyroid tissues. A ROC analysis identified malignant nodules with 69 % sensitivity and 75 % specificity, using a cutoff of 73.19. In addition to distinguishing benign from malignant thyroid tissues (p?<?0.0001), KAP-1 expression differentiated CPTC from nodular hyperplasia (p?<?0.0001), CPTC from FA (p?=?0.0028), FVPTC from hyperplasia (p?=?0.0039), and FC from hyperplasia (p?=?0.0025). Furthermore, KAP-1 was more expressed in larger tumors (>4 cm; p?=?0.0038) and in individuals who presented recurrences/metastases (p?=?0.0130). We suggest that KAP-1 may help diagnose thyroid nodules, characterize follicular-patterned thyroid lesions, and identify individuals with poor prognosis.     

Fine‐needle aspiration of follicular patterned lesions of the thyroid: Diagnosis,management, and follow‐up according to National Cancer Institute (NCI) recommendations

The National Cancer Institute (NCI) State of the Science Conference on thyroid fine‐needle aspiration (FNA) proposed that follicular patterned lesions can be divided into two diagnostic categories; follicular lesion of undetermined significance/Atypia of undetermined significance (FLUS/AUS) and suspicious for follicular neoplasm/follicular neoplasm (SFON/FON). The former group can benefit from repeat FNA (RFNA) to achieve a more definitive diagnosis and the latter should undergo surgical excision for histologic characterization (adenoma vs. carcinoma). In this study, we report the combined experience from our institutions with thyroid FNA cases that can be placed into NCI‐designated thyroid FNA diagnostic categories for follicular patterned lesions. The case cohort comprised of 857 cases in 645 females and 212 males; 509 cases could be classified as FLUS/AUS and 348 as SFON/FON. Histologic follow‐up was available in 273/509 (54%) cases diagnosed as FLUS/AUS and 251/348 (72%) cases diagnosed as SFON/FON. RFNA was performed in 203/509 (40%) patients classified as FLUS/AUS. RFNA diagnoses were: benign (125 cases), FLUS (46 cases), SFON/FON (20 cases), suspicious for papillary carcinoma (7 cases), papillary carcinoma (3 cases) and non‐diagnostic (2 cases). The malignancy rate on surgical excision in the FLUS/AUS group was 27 and 15% with and without RFNA, respectively; and 25% in cases diagnosed as SFON/FON. RFNA is effective in managing thyroid nodules diagnosed as FLUS/AUS since the malignancy rates are different in cases with or without RFNA (27% vs. 15%). The malignancy rate (25%) in cases diagnosed as SFON/FON is similar to reported by other authors. Diagn. Cytopathol. 2010;38:731–739. © 2010 Wiley‐Liss, Inc.     

Contribution of immunocytochemical stainings for galectin‐3, CD44, and HBME1 to fine‐needle aspiration cytology diagnosis of papillary thyroid carcinoma

In cytology practice some papillary thyroid carcinoma (PTC) cases have indeterminate diagnoses and overlapping cytological features with benign lesions. This study was undertaken to find out if immunocytochemistry using Galectin‐3, CD‐44 and HBME‐1 could be of help in such situations. Forty‐six cases consisting of 22 malignancy (PTC) cases, 7 suspicious of (S/O) PTC, 1 follicular neoplasm, 5 follicular lesion of undetermined significance (FLUS), and 11 benign (colloid goiter) cases diagnosed by FNA were included in this study. Staining reactions were graded in a sliding scale of –, 1+, 2+, 3+, and 4+. In an assessment of 100 cells, each cell with weak, and moderate to strong positive reaction were assigned a score of 1 and 4, respectively. Staining reaction of ≥+2 and scores >100 were considered positive. Frequency of cases with ≥+2 reaction, and scores >100 for each of Galectin‐3, CD‐44, and HBME‐1 were significantly higher in PTC or combined PTC and S/O PTC cases as compared with FLUS and benign cases taken together (P = 0.01744 to 0.00000). When the cases were compared according to histological malignant and benign diagnoses, the difference was also significant in respect of ≥+2 reaction, and scores >100 for Galectin‐3 and CD44 (P = 0.04923 to 0.00947); however, there was no significant difference, when these parameters for HBME1 were compared. Galectin 3, CD 44, and to some extent HBME 1 are useful immunocytochemical parameters with potential to support FNAC diagnosis of PTC, especially in situations with difficult differential diagnoses. Diagn. Cytopathol. 2014;42:498–505. © 2013 Wiley Periodicals, Inc.     

Correlation of fine needle aspiration cytology and frozen section biopsies in the diagnosis of thyroid nodules.

AIMS: To evaluate the correlation of fine needle aspiration (FNA) cytology and frozen section biopsy in the diagnosis of thyroid nodules. METHODS: The medical records of 662 patients who underwent FNA cytology of the thyroid and thyroid surgery were analysed. Frozen section biopsies were taken from 586 of the 662 patients. The diagnostic correlations of FNA cytology, frozen section, and both FNA cytology and frozen section with definitive histological assessment were evaluated. RESULTS: Among the 662 patients who received FNA cytology, there were 356 cases (53.8%) diagnosed as benign, 114 cases (17.2%) as malignant, 148 cases (22.4%) as indeterminate, and 44 cases (6.6%) as unsatisfactory. The positive predictive value for the detection of malignancy by FNA cytology was 92.1% and the negative predictive value was 95.2%. The incidence of malignancy in the indeterminate cytological diagnosis was 23%. The diagnosis from frozen sections was benign in 445 cases (75.9%), malignant in 134 cases (22.9%), and deferred in 7 cases (1.2%). By frozen section, the positive and negative predictive values were 97% and 95.5%, respectively. Diagnostic accuracy up to 98% was achieved when FNA cytology and frozen section diagnoses were in agreement. No false positives were observed when FNA cytology and frozen sections were both positive for malignancy. When FNA cytology and frozen section diagnoses were discordant, frozen section showed a higher accuracy (78.9%) than FNA cytology (21.1%). In the face of an indeterminate or unsatisfactory cytological diagnosis, the diagnostic accuracy of frozen sections reached 92.6%. CONCLUSIONS: The results confirm that FNA cytology is a useful tool in the initial evaluation of thyroid nodules. Intraoperative frozen section is a valuable procedure to confirm the cytological diagnosis and identify malignancy in patients with indeterminate or unsatisfactory cytological diagnosis. With reliance on frozen sections as an intraoperative guide of thyroid surgery, the possibility of unnecessary extensive surgery and the need for the second operation are considerably lower.     

Does Hurthle cell lesion/neoplasm predict malignancy more than follicular lesion/neoplasm on thyroid fine‐needle aspiration?

Thyroid fine-needle aspiration (FNA) is a standard procedure for the clinical triage of thyroid nodules. The diagnosis of an adequately sampled thyroid FNA is generally grouped into three categories: benign, malignant, and indeterminate. The latter group usually includes follicular neoplasm, follicular lesion, and sometimes a more specific diagnosis such as Hurthle cell neoplasm or follicular lesion/neoplasm with Hurthle cell change. Whether a FNA diagnosis of Hurthle cell lesion/neoplasm (HLN) denotes a worse clinical outcome than follicular lesion/neoplasm (FLN) remains controversial. A cohort of 303 thyroid FNA cases with follow-up thyroidectomy in our institutes was identified, with the follow-up excision diagnosis compared to the FNA diagnosis in order to address this issue. Of this cohort, 87 cases had an FNA diagnosis of HLN while 216 cases had a diagnosis of FLN. Upon excision, the FNA diagnosis of HLN group had 14 cases of goiter/nodular hyperplasia (16%), 46 cases of adenoma (12 follicular adenoma (14%) and 34 cases of Hurthle cell adenoma (39%)), and 27 cases of carcinoma (31%, 12 papillary carcinoma and 15 Hurthle cell carcinoma). The FLN group had 74 cases of goiter/nodular hyperplasia (34.3%), 8 cases of Hashimoto thyroiditis (3.7%), 73 cases of follicular adenoma (33.8%), one case of granular cell tumor, and 60 cases of carcinoma (27.8%, 46 papillary carcinoma, 12 follicular carcinoma, and 1 Hurthle cell carcinoma and 1 parathyroid carcinoma) upon excision. There is no significant difference in predicting cancer between the two cytology diagnosis groups (HLN versus FLN, 31% versus 27.8%, P = 0.5771). When sorting all the cases by the surgical diagnosis, while comparable for age at diagnosis, the cancer group having the higher proportion of male patients than the non-cancer group (28.7% versus 16.7%, P = 0.0259). Hurthle cell carcinoma patients are typically older than patients with other cancer diagnoses (59 versus 44, P = 0.0077). Our results suggest that an FNA diagnosis of HLN does not predict more malignancy than FLN. Males and older patients with a HLN FNA diagnosis carry a higher risk of Hurthle cell carcinoma upon thyroidectomy.     

Comparison of Consecutive Results from Fine Needle Aspiration and Core Needle Biopsy in Thyroid Nodules

There are papers suggesting the complementary role of core needle biopsy (CNB) in the diagnosis of thyroid nodules. By comparing the result of CNB and fine needle aspiration (FNA) cytology performed in consecutive cases of thyroid nodules, the role of CNB was evaluated. Retrospective reviews of 2131 FNA and 275 CNB which were performed as first-line biopsy for 2406 thyroid nodules in 2187 patients were performed. The ultrasound (US) feature of thyroid nodule was classified following the risk of malignancy suggested by American Thyroid Association (ATA) guideline. Rate of unsatisfactory and cellular atypia could be decreased significantly by first-line CNB in all US group, and the nodules with highly suspicious feature showed significant decrease in inconclusive result by first-line CNB. However, increased rates of architectural and follicular neoplasm (FN) were identified in CNB group especially in intermediate and low suspicious nodules, and the first-line CNB could not decrease the inconclusive result in these US groups. The diagnostic rate of neoplasm diagnosed by surgery following the result of architectural atypia or FN was not different between FNA and CNB even with significantly higher rate in CNB group. Furthermore, the sensitivity for follicular neoplasm (21.2 vs. 61.9%) was significantly higher in CNB group. The CNB can be considered in nodules with highly suspicious feature with advantage of significantly lower inconclusive diagnostic rate than FNA group. However, significantly increased diagnosis of architectural atypia or FN in other nodules by CNB is recognized and should be evaluated in future to understand the meaning.