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Backgruound: The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups., Methods: In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed., Results: The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery., Conclusion: Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.

Introduction: Securing a well-established mouse model is important in identifying and validating new therapeutic targets for immuno-oncology. The C57BL/6 mouse is one of the most fully characterised immune system of any animal and provides powerful platform for immuno-oncology discovery. An orthotopic tumor model has been established using TBP3743 (murine anaplastic thyroid cancer [ATC]) cells in B6129SF1 hybrid mice, this model has limited data on tumor immunology than C57BL/6 inbred mice. This study aimed to establish a novel orthotopic ATC model in C57BL/6 mice and characterize the tumor microenvironment focusing immunity in the model., Methods: Adapted TBP3743 cells were generated via in vivo serial passaging in C57BL/6 mice. Subsequently, the following orthotopic tumor models were established via intrathyroidal injection: B6129SF1 mice injected with original TBP3743 cells (original/129), B6129SF1 mice injected with adapted cells (adapted/129), and C57BL/6 mice injected with adapted cells (adapted/B6)., Results: The adapted TBP3743 cells de-differentiated but exhibited cell morphology, viability, and migration/invasion potential comparable with those of original cells in vitro . The adapted/129 contained a higher Ki-67 + cell fraction than the original/129. RNA sequencing data of orthotopic tumors revealed enhanced oncogenic properties in the adapted/129 compared with those in the original/129. In contrast, the orthotopic tumors grown in the adapted/B6 were smaller, with a lower Ki-67 + cell fraction than those in the adapted/129. However, the oncogenic properties of the tumors within the adapted/B6 and adapted/129 were similar. Immune-related pathways were enriched in the adapted/B6 compared with those in the adapted/129. Flow cytometric analysis of the orthotopic tumors revealed higher cytotoxic CD8 + T cell and monocytic-myeloid-derived suppressor cell fractions in the adapted/B6 compared with the adapted/129. The estimated CD8 + and CD4 + cell fractions in the adapted/B6 were similar to those in human ATCs but negligible in the original/B6., Conclusion: A novel orthotopic tumor model of ATC was established in C57BL/6 mice. Compared with the original B6129SF1 murine model, the novel model exhibited more aggressive tumor cell behaviours and strong immune responses. We expect that this novel model contributes to the understanding tumor microenvironment and provides the platform for drug development., Competing Interests: SC is a co-founder of Cellus, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Shin, Kim, Ha, Won, Kim, Park, Parangi, Cho and Lee.)

BACKGROUNDMolecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory (131I-refractory) PTC.METHODSPTC samples from 106 pediatric patients (age range: 4.3-19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983-March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison.RESULTSWe identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAFV600E in 41 patients, TERTC228T in 2 patients [1 of whom had a coexisting BRAFV600E], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAFV600E PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients <10 years of age) had lower expression of thyroid differentiation genes, including SLC5A5, than did adult fusion PTCs. Two girls with progressive 131I-refractory lung metastases harboring a TPR-NTRK1 or CCDC6-RET fusion oncogene received fusion-targeted therapy; larotrectinib and selpercatinib decreased the size of the tumor and restored 125I radioiodine uptake. The girl with the CCDC6-RET fusion oncogene received 131I therapy combined with selpercatinib, resulting in a tumor response. In vitro 125I uptake and 131I clonogenic assays showed that larotrectinib inhibited tumor growth and restored radioiodine avidity.CONCLUSIONSIn pediatric patients with fusion oncogene PTC who have 131I-refractory advanced disease, selective fusion-directed therapy may restore radioiodine avidity and lead to a dramatic tumor response, underscoring the importance of molecular testing in pediatric patients with PTC.FUNDINGThe Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4012417 and 2019R1A2C2084332); the Korean Ministry of Health and Welfare (H14C1277); the Ministry of Education (2020R1A6A1A03047972); and the SNUH Research Fund (04-2015-0830).TRIAL REGISTRATIONTwo patients received fusion-targeted therapy with larotrectinib (NCT02576431; NAVIGATE) or selpercatinib (LOXO-RET-18018).

Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAF V600E and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.

Background: Among subtypes of follicular variant of papillary thyroid carcinoma (FVPTC), encapsulated FVPTC (EFVPTC) shows more indolent behavior than infiltrative FVPTC (IFVPTC). In particular, noninvasive EFVPTC, now designated as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), tends to have an excellent prognosis. However, it remains unclear whether the molecular pathogenesis or signature of the various forms of FVPTC is different. By massively parallel sequencing analysis, this study comprehensively characterized the transcriptional and mutational landscape of FVPTC and established correlations with phenotypic subtypes., Methods: This study included 48 FVPTCs: 17 NIFTPs, 13 invasive EFVPTCs (I-EFVPTCs), and 18 IFVPTCs. For comparison, 55 classical papillary thyroid carcinomas (cPTCs) harboring a BRAF V600E mutation, six follicular adenomas (FAs), and 15 minimally invasive follicular thyroid carcinomas (miFTCs) with RAS mutations were also included., Results: In NIFTP, the BRAF V600E mutation was not found, but RAS and other alterations were present in 64.7% and 17.6% of cases, respectively. However, in I-EFVPTC and IFVPTC, the proportions of BRAF V600E mutation (38.5% and 38.9%, respectively) and of RAS mutations (38.5% and 38.9%, respectively) or other alterations (15.4% and 16.7%, respectively) were similar. On a molecular level, RAS-mutated FVPTCs were all RAS-like except for one IFVPTC case. Transcriptomic profiles of NIFTP, I-EFVPTC, and FA/miFTC were comparable, although the profile of RAS-mutated IFVPTC was altered to activate molecular pathways involved in cell adhesion and invasion. Interestingly, 80% of BRAF V600E -mutated I-EFVPTCs were also classified as RAS-like, whereas all BRAF V600E -mutated IFVPTCs were BRAF-like and indistinguishable from cPTC. Molecular pathways associated with cell adhesion and invasion were also differentially activated in BRAF V600E -mutated IFVPTC., Conclusions: Molecular profiles of NIFTP and I-EFVPTC may be shared with FA/miFTC, while IFVPTC seems to be associated with a similar profile as cPTC. Activation of cell adhesion and invasion pathways may play a key role in the development of invasive phenotypes of FVPTC.

Background: BRAF V600E mutation is the most common somatic variant in papillary thyroid carcinoma (PTC) and is associated with aggressive prognostic factors. The conventional detection method for BRAF mutations is polymerase chain reaction followed by Sanger sequencing. Recently, an immunohistochemistry (IHC) method using a BRAF V600E -specific antibody (VE1) has been developed and widely adopted in the clinics; however, there is a lack of evidence regarding the comparability of the IHC and Sanger sequencing methods., Methods: Our institution began using the BRAF V600E IHC test in January 2013. We retrospectively analyzed 697 samples that were tested using both the IHC and sequencing methods, and evaluated their concordance., Results: BRAF mutation was detected in 90.0% (627/697) of samples using IHC and 83.4% (581/697) of samples using direct sequencing. The diagnostic parameters of IHC compared with Sanger sequencing were as follows: 100% sensitivity (581/581), 60.3% specificity (70/116), 92.7% positive predictive value (581/627), and 100% negative predictive value (70/70). No false negative results were recorded using IHC. The overall concordance rate between the two methods was 93.4% (651/697). Discordant results were found in 46 samples (6.6%), 29 of which were from cases with small tumors (< 6 mm), 8 were from cases with low tumor cellularity, and 9 were specimens yielding low-quality DNA., Conclusions: IHC using the VE1 antibody is a reliable and highly sensitive method for detecting the BRAF V600E mutation in classic PTC.

Rationale: There have been many reports of non-thyroidal lesions which can be mistaken for thyroidal lesions on ultrasound (US) examination. However, it is not known that pyriform sinus fistula (PSF) can manifest as an incidental thyroid nodule and cause serious complication on fine-needle aspiration (FNA)., Patient Concerns: We present a 34-year-old man with PSF incidentally detected on US. US examination showed hypoechoic nodule with several bright echogenic spots at the uppermost part of left thyroid gland. With the suspicion of thyroid cancer, although there would have been some morphologic changes between the 2 US examinations, FNA was performed., Diagnoses: Cytologic specimen revealed some clusters of ciliated columnar cells mixed with inflammatory and lymphoid cells. On computed tomography (CT) before FNA, there were tiny air bubbles within the thyroid nodule. Laryngoscopy revealed fistula originating from the pyriform sinus., Interventions: After FNA, he had to undergo tracheostomy and removal of abscess due to infectious complication., Outcomes: The deep neck abscesses and infections were controlled after the treatment. At 1 year after FNA, successful chemocauterization with 40% trichloracetic acid solution was performed for PSF found on laryngoscopy., Lessons: PSF can manifest as an incidental thyroid nodule mimicking thyroid cancer. Special care should be taken when FNA is planned for the nodule with air foci and morphologic changeability at the uppermost part of left thyroid gland.

Background: Among follicular variant papillary thyroid carcinomas (FVPTCs), the noninvasive encapsulated subtype has an excellent prognosis. For this reason, reclassification of noninvasive encapsulated FVPTC (EFVPTC) as a new entity called "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) has been proposed, but controversy remains. To characterize noninvasive EFVPTC in an Asian population, the clinicopathologic features of each FVPTC subtype were compared in a Korean population., Methods: FVPTC patients (n = 142) who underwent thyroidectomy between 2009 and 2014, and whose tumor size was >1 cm, were included in the study. The surgical pathology of each patient was reevaluated by two independent expert pathologists., Results: The percentages of noninvasive and invasive EFVPTC and infiltrative FVPTC (IFVPTC) in the study were 30%, 31%, and 39%, respectively. There was no difference in preoperative cytological diagnosis or the extent of surgery between noninvasive and invasive EFVPTC. However, the proportion of Bethesda category IV was lower in IFVPTC (16%) than in noninvasive and invasive EFVPTC (35% and 36%, respectively). Therefore, thyroid lobectomy was more common in noninvasive or invasive EFVPTC (54% or 48%, respectively) than in IFVPTC (16%). Noninvasive EFVPTC showed lower multiplicity, extrathyroidal extension, and BRAF V600E mutation frequency (three cases; 8%) than did invasive EFVPTC, but other pathological characteristics were similar. However, IFVPTC showed significant differences in tumor size, extrathyroidal extension, lymph node metastasis, Tumor Node Metastasis stage, and American Thyroid Association high-risk category compared with noninvasive and invasive EFVPTC. In the noninvasive EFVPTC group, there were six (14%) cases with multifocality and three (7%) cases with lymph node metastasis. However, only two cases with multifocality and one case with lymph node metastasis originated from noninvasive FVPTC, while the other cases were from coexisting conventional PTCs., Conclusions: Noninvasive EFVPTC has favorable pathological features, but lymph node metastasis or BRAF V600E mutations were observed in some patients. Therefore, in order for the distinction between noninvasive EFVPTC and invasive EFVPTC to have more clinical significance, the criteria for NIFTP need to be more strictly revised.

Objective: To explore the potential preoperative ultrasonography (US) and cytopathological features to avoid total thyroidectomy in NIFTP., Context: Recently, it has been proposed that that noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) be classified as tumours, rather than cancer., Patients: A total of 142 surgically proven follicular variant papillary thyroid carcinomas (FVPTCs; 45 NIFTP, 97 non-NIFTP; mean size: 20.4±11.0 mm, range: 10.0-65.0 mm) from 142 patients were included in this study., Measurements: Three preoperative features of thyroid nodules (each US finding, US and Bethesda category) were compared in NIFTP and non-NIFTP groups. The preoperative decision-making process to avoid total thyroidectomy in NIFTP was evaluated based on combination of those features., Results: In each US finding, there was only significantly less macrocalcification in the NIFTP group than in the non-NIFTP group (8.8% [4/45] vs 32.0% [31/97], P = .006). In US category, all of the NIFTP nodules were a low or intermediate suspicion (100% [45/45]). In Bethesda category, 26.7% [12/45] of the NIFTP was diagnosed as either suspicious malignancy or malignant, which increased the risk of a total thyroidectomy. In our study, a total thyroidectomy might be avoided in all of the NIFTP cases if lobectomy was selected for the nodules classified as a low or intermediate suspicion in US, despite being classified as a suspicious malignancy or malignant by cytopathology., Conclusions: Combining the US and cytopathological results could sensitively reduce total thyroidectomy in cases of NIFTP., (© 2017 John Wiley & Sons Ltd.)

Background: This study aimed to evaluate the recurrence and survival after initial curative-intent surgery of resectable anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC)., Methods: A retrospective analysis was conducted on patients with ATC and PDTC who had been treated between 1985 and 2013. Among them, 119 patients who had undergone surgery with curative intent were included in this study. The outcome measures included the clinical response to treatment and the recurrence rates of three separate thyroid cancer groups: ATC, differentiated thyroid cancer (DTC) with anaplastic foci, and PDTC., Results: Initial remission was achieved in 100 (84.0%) patients, with higher percentages in patients with DTC with anaplastic foci (97.8%) and PDTC (96.7%) compared with ATC (60.5%). The overall recurrence rate after initial remission was 30.8% in ATC, 25.9% in PDTC, and 6.7% in DTC with anaplastic foci. Pathologic diagnosis, preexisting goiter or tumors, along with tracheal and lymphatic/vascular invasion were correlated with recurrence (p < 0.001; p = 0.001, 0.006, 0.003, and 0.016, respectively). All patients without initial remission died due to local failure, and most patients with recurrence, apart from two PDTC patients, had distant metastasis. Overall mortality after initial curative-intent surgery was 58.1% in ATC, 8.7% in DTC with anaplastic foci, and 20% in PDTC., Conclusions: The initial remission of resectable tumors was higher and the recurrence rate was lower in DTC with anaplastic foci and PDTC compared with ATC. Careful monitoring of the development of distant metastasis is necessary, especially in patients with aggressive pathology with tracheal and lymphovascular invasion.

Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are indistinguishable by preoperative diagnosis due to their similar histological features. Here we report the first RNA sequencing study of these tumors, with data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77 classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs (FVPTCs) to observe the differences in their molecular properties. Mutations in H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8-PPARG), but a high frequency of that in PTC (17.60%). The frequencies of BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC, and those of FVPTC were intermediate between miFTC and cPTC. Gene expression analysis demonstrated three molecular subtypes regardless of their histological features, including Non-BRAF-Non-RAS (NBNR), as well as BRAF-like and RAS-like. The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1, PTEN, SOS1, SPOP, and PAX8-PPARG. The transcriptome of miFTC or encapsulated FVPTC was indistinguishable from that of FA, providing a molecular explanation for the similarly indolent behavior of these tumors. We identified upregulation of genes that are related to mitochondrial biogenesis including ESRRA and PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number variations were correlated to histological and molecular characteristics. These results expanded the current molecular understanding of thyroid cancer and may lead to new diagnostic and therapeutic approaches to the disease.

We evaluate the gray-scale ultrasonographic characteristics that differentiate between nodular hyperplasia (NH) and neoplastic follicular-patterned lesions (NFPLs) of the thyroid gland. Ultrasonographic features of 750 patients with 832 thyroid nodules (NH, n = 361; or NFPLs, follicular adenoma, n = 123; follicular carcinoma, n = 159; and follicular variant papillary carcinoma, n = 189) were analyzed. Except for echogenicity, over two-thirds of the cases of NH and NFPLs share the ultrasonographic characteristics of solid internal content, a well-defined smooth margin and round-to-ovoid shape. Independent predictors for NH were non-solid internal content (sensitivity 27.1%, specificity 90.2%), isoechogenicity (sensitivity 69.5%, specificity 63.5%) and an ill-defined margin (sensitivity 18.8%, specificity 94.5%). Independent predictors for NFPLs were hypoechogenicity (sensitivity 60.5%, specificity 70.4%), marked hypoechogenicity (sensitivity 2.8%, specificity 99.4%) and taller-than-wide shape (sensitivity 6.6%, specificity 98.1%). Although NH and NFPLs commonly share ultrasonographic characteristics, non-solid internal content and ill-defined margin are specific to NH and marked hypoechogenicity and taller-than-wide shape are specific to NFPLs., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Recent reports suggest that mutations in the promoter of the gene encoding telomerase reverse transcriptase (TERT) affect thyroid cancer outcomes., Methods: In all, 551 patients with differentiated thyroid cancer (DTC) enrolled in this study. The median follow-up duration was 4.8 years (interquartile range, 3.4-10.6 years)., Results: TERT promoter mutations were detected in 25 DTCs (4.5%): 2.8% in neither BRAF-mutated nor RAS-mutated tumors, 4.8% in BRAF-mutated tumors, and 11.3% in RAS-mutated tumors. Moreover, they were frequently observed in American Thyroid Association (ATA) high-risk and TNM stage III/IV groups (9.1% and 12.9%, respectively). The coexistence of BRAF or RAS with TERT promoter mutations increased aggressive clinicopathologic features, recurrence (hazard ratio [HR] for BRAF, 4.64; 95% confidence interval [CI], 1.42-15.18; HR for RAS, 5.36; 95% CI, 1.20-24.02), and mortality (HR for BRAF, 15.13; 95% CI, 1.55-148.23; HR for RAS, 14.75; 95% CI, 1.30-167.00), even after adjustments for the age at diagnosis and sex, although the significance was lost after additional adjustments for pathologic characteristics. Furthermore, TERT promoter mutations significantly increased the risk of both recurrence and mortality in the ATA high-risk (HR for recurrence, 5.79; 95% CI, 2.07-16.18; HR for mortality, 16.16; 95% CI, 2.10-124.15) and TNM stage III/IV groups (HR for recurrence, 3.60; 95% CI, 1.19-10.85; HR for mortality, 9.06; 95% CI, 2.09-39.26)., Conclusions: The coexistence of BRAF or RAS mutations enhanced the prognostic effects of TERT promoter mutations. Furthermore, TERT promoter mutations strengthened the predictions of mortality and recurrence by the ATA and TNM staging systems, particularly for high-risk patients with DTC. Cancer 2016;122:1370-1379. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: The purpose of this study was to evaluate the factors associated with diagnostic accuracy of preoperative fine-needle aspiration (FNA) for follicular variant papillary thyroid carcinoma (FVPTC)., Methods: The patients with FVPTC who underwent thyroidectomy were divided into 2 groups: "group A" (Bethesda category II, III, or IV) versus "group B" (category V or VI)., Results: A total of 225 patients (117 in group A and 108 in group B) were included. Group B was associated with older age, malignant ultrasonographic features, smaller tumor size, extrathyroidal extension, higher stage, and B-type Raf (BRAF)(V600E) mutation compared with group A. In multivariable analysis, malignant ultrasonographic features and tumor size ≤3.0 cm were independent predictive factors for group B., Conclusion: FVPTCs >3.0 cm are unlikely to be diagnosed as category V or VI. Clinicians should keep FVPTC in mind and consider diagnostic lobectomy for the nodules regardless of FNA or ultrasonographic findings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1467-E1471, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: This study aimed to analyze the temporal changes of the clinicopathologic characteristics, and the long-term outcomes, of various types of anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC)., Methods: A retrospective analysis was conducted on patients with ATC and PDTC who were treated from 1985 to 2013. The outcome measures included the clinical response to treatment and the survival rates of three separate thyroid cancer groups: ATC, PDTC, and differentiated thyroid cancer (DTC) with anaplastic foci., Results: The five-year disease-specific survival rate was significantly higher, both in DTC with anaplastic foci and in PTDC (81.3% and 65.8%, respectively), than it was in ATC (14.3%; p < 0.001). The proportion of cases of DTC with anaplastic foci has been increasing over time, while that of ATC has decreased. The survival rate was found to be significantly higher in resectable tumors (71.4% and 26.5%, respectively; p < 0 .001). In ATC, external beam radiation therapy showed longer survival rates than did surgery-based treatment in unresectable tumors (19.2 vs. 7.7 months, p = 0.006). Adjuvant treatment with external beam radiation or radioactive iodine increased survival duration in PDTC and in DTC with anaplastic foci. Lymphatic invasion was the most significant postoperative prognosticator in ATC (p = 0.013)., Conclusions: The choice of treatment of ATC and PDTC could be modified according to resectability and lymphatic invasion of the cancer.

Background: This study was performed to determine the benefits of core needle biopsy (CNB), as compared with fine-needle aspiration (FNA), for the diagnosis of thyroid nodules with macrocalcifications., Materials and Methods: The institutional review board approved this retrospective study, and informed consent was waived. From February 2010 to March 2012, the study included 147 thyroid nodules with macrocalcification of 145 consecutive patients who underwent simultaneous FNA and CNB for each nodule. Diagnostic accuracy and inconclusive diagnoses, including nondiagnostic reading and atypia of undetermined significance or follicular lesion of undetermined significance reading were compared among FNA, CNB, and a combination of FNA and CNB (FNA/CNB) using McNemar's test; the benefits of CNB were calculated., Results: Compared to FNA, CNB and FNA/CNB showed fewer inconclusive diagnoses (FNA vs. CNB: 62/147 [42.2%] vs. 14/147 [9.5%], p<0.001; FNA vs., Fna/cnb: 62/147 [42.2%] vs. 14/147 [9.5%], p<0.001), resulting in the avoidance of repeat FNA or diagnostic surgery in 48 of 62 patients (77.4%, respectively in CNB and FNA/CNB) who would have undergone these procedures if only FNA was performed. Compared to FNA, FNA/CNB showed higher sensitivity and accuracy (sensitivity: 23/32 [71.9%] vs. 31/32 [96.9%], p=0.008; accuracy: 77/86 [89.5%] vs. 85/86 [98.8%], p=0.008), resulting in avoidance of delayed surgery in eight of nine patients (88.9%) with thyroid cancer in whom the surgery would have been missed if FNA only had been performed., Conclusion: In the workup of thyroid nodules with macrocalcification, compared with FNA alone, FNA/CNB decreases inconclusive diagnoses and increases sensitivity, thereby reducing repeated FNA procedures, diagnostic surgeries, and delayed therapeutic surgeries.

The anaplastic lymphoma kinase (ALK) gene is frequently rearranged in various types of cancer and is highly responsive to targeted therapeutics. We developed a system to detect rearrangement of ALK in a large group of Korean thyroid cancer patients. We screened 474 malignant or benign thyroid tumor cases to identify ALK fusions. Expression and translocation of the ALK gene were analyzed by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and digital multiplexed gene expression (DMGE) analysis in formalin-fixed paraffin-embedded tissues. Four cases of rearrangement of ALK were detected by IHC, and these cases were validated with FISH on 189 samples. On the other hand, DMGE analysis using Nanostring detected three out of four IHC-positive cases. Two rearrangements of ALK were striatin (STRN)-ALK fusions, which were identified by 5' RACE analysis. Rearrangements of ALK were found exclusively in v-raf murine sarcoma viral oncogene homolog B (BRAF) WT papillary carcinomas. Given the wide availability and accuracy of IHC for detecting ectopic expression of ALK in the thyroid, we suggest that IHC-based screening can be a practical method for identifying patients with ALK rearrangements in differentiated thyroid cancer., (© 2015 Society for Endocrinology.)

The aim of this study was to investigate the efficaciousness of histological tumor growth patterns in the prediction of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC). All combinations of infiltrative tumor border, lateral tubular growth, and intraglandular dissemination were assessed for their ability to predict LNM in 229 patients. In addition, we analyzed their predictive value within subgroups based on the tumor size and number of tumor nodules. Each tumor growth pattern was significantly associated with LNM, as 11 of the 12 combinations of these 3 patterns were found to be independently predictive of LNM (P < .05). Similar results were observed in both univariate and multivariate logistic regression analyses of PTCs, grouped according to the tumor size and number of tumor nodules. This study has shown that histological features suggestive of invasive tumor growth, including infiltrative tumor border and lateral tubular growth, may be used as independent predictive factors of LNM in PTC, and can improve treatment and follow-up strategies for PTC., (© 2013.)

Objectives: A panel composed of three immunomarkers, cytokeratin 19, HBME-1 and galectin-3, is recommended for improving the accuracy of diagnosing papillary thyroid carcinoma (PTC), but the results are sometimes inconsistent and difficult to interpret. We used immunocytochemistry to assess the utility of chemokine CXC ligand 12 (CXCL12) as a novel diagnostic marker for PTC employing paraffin-embedded cell blocks., Methods: We analyzed the expression of CXCL12 using immunocytochemical staining in 82 cases of thyroid lesions (47 PTCs and 35 thyroid lesions other than PTC). To determine the optimal cut-off value for the assessment of CXCL12 positivity, we used receiver operating characteristics (ROC)., Results: ROC curves showed that the optimum diagnostic cut-off was 10% (area under the curve 0.950, 95% confidence interval 0.891-1.008), with exclusive CXCL12 expression in PTC compared to other thyroid lesions (p < 0.001). In total, more than 90% of the PTCs were associated with CXCL12 immunohistochemical staining, while only up to 11.4% of thyroid lesions other than PTC were positive for CXCL12. The follicular variant PTC showed 90% CXCL12 expression compared to 10.5% positivity in follicular neoplasm., Conclusion: Our findings indicate that CXCL12 may be an effective supplementary diagnostic marker for PTC in preoperative fine-needle aspiration cytology using the cell block method.