Tall Cell Variant Of Papillary Thyroid Carcinoma Research Articles

Abstract 6277: Tall cell variant papillary thyroid carcinoma from Middle Eastern patients have worse outcome than classical papillary thyroid carcinoma using propensity score matching

Abstract The tall cell variant of Papillary Thyroid Carcinoma (TCV-PTC) is the most common aggressive variant of PTC. The impact of TCV-PTC on patients’ prognosis still remains controversial. Moreover, the clinico-pathological and prognostic effect of TCV-PTC from Middle Eastern ethnicity remains unexplored. We aimed to study TCV-PTC in comparison to classical PTC in Middle Eastern patients and their impact on prognosis. We performed a retrospective cohort study of tall cell variant (TCV-PTC) and classic variant of papillary thyroid carcinoma (CV-PTC) after post-surgical radioactive iodine therapy. We used the propensity score matching (1:3 matching ratio) to account for differences between recipients of TCV-PTC vs CV-PTC. Univariate and multivariate analysis were performed to assess the independent factors for persistent/recurrent disease. Kaplan-Meier curve analyses were used to compare disease-free survival (DFS). In total, 174 (16.3%) patients with TCV-PTC and 891 (83.7%) patients with CV-PTC were included. After propensity score matching, 174 pairs of patients were selected (TCV-PTC, n = 174; CV-PTC, n = 522). In the matched analysis, higher proportions of TCV-PTC experienced persistent/recurrent disease compared with CV-PTC (25.7% vs 31.4%; p = 0.0119). In multivariate analyses of clinical and tumor characteristics, histological type of TCV-PTC (odds ratio, 2.09; 95% confidence interval, 1.28-3.40; p = 0.0031) was associated with increased risk of persistent/recurrent disease. The five-year DFS rates for the TCV-PTC and CV-PTC groups were 48.5% and 73.1%, respectively. The Kaplan- Meier analysis indicated that the TCV-PTC group (p < 0.0001) had shorter DFS. In conclusion, when other clinico-pathological factors were similar, this propensity score matched analysis showed that histological subtype TCV-PTC is by itself an independent predictive marker of persistent/recurrent disease in Middle Eastern patients. Therefore, individualized therapeutic approaches might be needed for this aggressive PTC subtype. Citation Format: Khawla S. Al-Kuraya, Sandeep K. Parvathareddy, Abdul K. Siraj, Saeeda O. Ahmed, Nabil Siraj, Manal Manakhan, Hassan Aldossari. Tall cell variant papillary thyroid carcinoma from Middle Eastern patients have worse outcome than classical papillary thyroid carcinoma using propensity score matching [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6277.

SAT575 Can We Miss Diagnosis Of Tall Cell Variant Papillary Thyroid Carcinoma?

Abstract Disclosure: J. Huynh: None. A. Makawi: None. G. Elshimy: None. Introduction Large thyroid nodules have a high rate of evolving into malignancy. Fine needle aspiration biopsy (FNAB) is a key diagnostic tool with a caveat of a high false-negative rate for cancer detection ranging from 0.7 to 13%. Key to maximizing the odds of a successful FNAB are the utilization of ultrasound (US) guidance, visualization of the needle tip, preprocedural consideration of the size of the target nodule, and expertise of the cytopathologist. Case presentation 40-year-old African American female who presented to endocrinology clinic given concern for a large left-side thyroid nodule with tracheal deviation seen on a CT scan of the chest. The US revealed a large left hypoechoic, spongiform nodule >5cm with grade 2 vascularity with no calcification measuring 5.1 x 4.3 cm. The thyroid labs were within normal range and she denied any compressive symptoms. FNAB of the nodule showed benign colloid. Given the large size of the nodule, we recommended surgical resection but the patient declined and preferred conservative management. Five months later, she started to experience dysphagia with positional neck pain and shortness of breath. Due to the progression of the compressive signs, the patient opted for left thyroidectomy which revealed multifocal papillary thyroid carcinoma (PTC) tall cell variant (TCV) with the largest foci of 1.7 cm with extrathyroidal extension and vascular invasion. She then underwent completion thyroidectomy followed by postoperative radioactive iodine ablation later on as the second surgery pathology was also consistent with PTC with metastasis to the lymph nodes. She was treated with levothyroxine with the goal to suppress TSH. Postoperatively, the patient is being monitored with biochemical testing and imaging for recurrence given the aggressive nature of her disease. Discussion There is a positive correlation between nodule size and false negative results (FNR). FNR for malignancy is known to be higher in nodules larger than 4cm. Patients with large thyroid nodules causing compressive signs should undergo resection regardless of the FNAB result. This patient had a benign FNAB initially which was misleading as the pathology of thyroidectomy was consistent with TCV PTC, a more aggressive variant. TCV PTC usually presents in larger nodules and with a higher rate of extrathyroidal extension and metastasis compared to classic. The prognosis is poorer with TCV, even without an extranodal extension. This patient received appropriate treatment with total thyroidectomy, THR therapy, sequential imaging, and biochemical testing for recurrence. A key takeaway here is that FNABs may not always reflect accurate histology of the whole lesion with larger nodules having a higher tendency for inadequate sampling. Key to successful biopsy and reducing FNAB false-negative results is an experienced radiologist, a cytopathologist familiar with these tumors, and US guidance. Presentation: Saturday, June 17, 2023

Outcomes of the Tall-Cell Variant of Papillary Thyroid Carcinoma in Patients with Different Ages: A 17-Year Mono-Institutional Experience

The tall-cell variant of papillary thyroid carcinoma (TCPTC) is the most common aggressive variant of papillary thyroid carcinoma (PTC) and typically occurs in older patients. In this study, we analyzed retrospectively the largest mono-institutional series of PTCs with tall-cell features (989 patients) over a 17-year period, re-evaluating tumors based on age at presentation and outcomes in different age groups. We divided patients into three age groups following different criteria (the criterion from the American Joint Committee on Cancer Tumor Node Metastasis (AJCC TNM) guidelines, criterion for the statistical division into tertiles and adolescent/post-adolescent criterion) to analyze the clinicopathological characteristics in different age groups, especially in terms of recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). We obtained three main results: 1. the population is distributed among the different age groups, and therefore, this type of cancer is not exclusively found among those of an older age; 2. in the RFS analysis, we can see a higher probability of local recurrence in the younger and older groups and, unexpectedly, a lower probability of local recurrence in the "median age" group; and 3. in the DRFS analysis, we can observe a higher probability of distant recurrence in older patients. From a molecular perspective, no significant differences in the mutational status of BRAF were detected according to different age groups, while mutations in the TERT promoter were exclusively present in older patients of all age groups, highlighting the potential prognostic implications of TERT promoter mutations in PTCs. In conclusion, the results of this series confirm that TC morphology alone in PTCs does not have the same negative prognostic significance in the younger population as in the older population. The reason for these different outcomes remains unclear and needs further studies.

Tall cell variant papillary thyroid carcinoma impacts disease-free survival at the 10 % cut-point on multivariate analysis

IntroductionThe diagnosis of tall cell variant papillary thyroid carcinoma (TCV-PTC) corresponds to the feature of “aggressive histology” within the framework of the American Thyroid Association (ATA) Risk of Recurrence (ROR) guidelines. Using the current World Health Organization (WHO) definition for TCV-PTC (tall cells with height at least twice the width, distribution ≥ 30 %), we examined the impact of this diagnosis on disease-free survival (DFS). MethodsThe study cohort consisted of 347 patients treated for primary papillary thyroid carcinoma (PTC). Current ATA guidelines were followed for the extent of surgery and the administration of adjuvant radioiodine therapy. Clinical surveillance included ultrasound examination and biochemical parameters according to ATA standards. The outcome was measured as time from surgery to first disease recurrence (DR) versus time from surgery until the last documented disease-free encounter (no evidence of disease, NED). Disease-free patients with fewer than 6 months of follow-up were excluded from this cohort. Structural recurrences are documented by histology or cytology whereas biochemical recurrences are documented by rising serum thyroglobulin in the absence of structural disease. All slides on all patients were examined by two pathologists with the substantial interobserver agreement (Kappa = 73 %). The primary tumors are categorically classified either as (1) TCV-PTC (definition above), (2) Papillary thyroid carcinoma with tall cell features (PTC-TCF) (≥ 10 % < 30 % tall cells), or (3) Control (< 10 % tall cells). Tumor size is categorized as either (1) ≤ 10 mm, (2) 11–29 mm, or (3) ≥ 30 mm. Degree of ETE is categorized as either intrathyroidal, microscopic ETE, histologic spread to strap muscles, or pT4 disease. Results185 patients are classified as TCV-PTC (≥ 30 % tall cells), 62 as PTC-TCF (≥ 10 % < 30 % tall cells), and 100 as control group (< 10 % tall cells). TCV-PTC is associated with ≥ 30 mm size (p = .0246) and invasion of strap muscles and/or pT4 (p = .0325). There was no relationship between TCV-PTC and aggressive lymph node (ALN) status defined by ATA. Overall follow-up ranged from two months (one patient death) to 203 months (mean 40.8, median 33.0). DR occurred in 61 patients (mean 31.4 months, range 0 –184, 59 structural recurrences, 2 biochemical recurrences). Three models for TCV-PTC were examined: Model 1 - Tall cells ≥ 10% versus control, Model 2 - TCV-PTC versus TCF-PTC versus control, and Model 3 - TCV-PTC versus control. Kaplan Meier curves demonstrated decreased DFS with ALN status (p = .0001), ETE (p = .0295), and TCV-PTC (Model 1, p = .041). On multivariate analysis, TCV-PTC (Model 1) remained significantly predictive when adjusted for ALN (p = .0059). ETE dropped out of the model. ConclusionTCV-PTC is significantly associated with larger tumors and a greater degree of ETE. The diagnosis of TCV-PTC significantly impacts DFS at the 10 % cut-point on multivariate analysis.

Well-Differentiated Thyroid Cancer: Who Should Get Postoperative Radiation?

The mainstay of treatment of well-differentiated thyroid cancer (WDTC) is surgery followed by adjuvant radioactive iodine therapy. Postoperative radiation therapy (PORT) is rarely used. The aim of our study was to report our experience of patients with WDTC who were selected to receive PORT. After Institutional Review Board approval, patients who received PORT were identified from a departmental database of 6259 patients with WDTC treated with primary surgery from 1986 to 2015. We carried out propensity matching to compare outcomes with a cohort of patients who did not receive PORT. The main outcome of interest was central neck recurrence-free probability (CNRFP), while secondary outcomes were lateral neck recurrence-free probability (LNRFP), disease-specific survival (DSS), and overall survival (OS). From 6259 patients, 32 (0.5%) patients with a median age of 65.2 years received PORT. Tall-cell variant papillary thyroid carcinoma was the most common pathology (45%). Patients who received PORT had no difference in CNRFP compared with patients treated without PORT (10-year CNRFP 88% vs. 73%; p=0.18). Furthermore, patients who received PORT had superior LNRFP (10-year LNRFP 100% vs. 62%; p=0.001) compared with the no-PORT cohort. Despite this, patients who received PORT had similar DSS (71% PORT vs. 75% no-PORT) and OS (65% PORT vs. 58% no-PORT group) as the no-PORT cohort. Our data show that select patients who received PORT had improved locoregional recurrence-free probability; however, this did not translate into improved DSS and OS. At our institution, we recommend the use of PORT only in highly selected patients with locally advanced primary tumors who are deemed to have a high risk of central neck recurrence for which salvage surgery would result in unacceptable risk to the airway.

Limitations of fine-needle aspiration and core needle biopsies in the diagnosis of tall cell variant of papillary thyroid carcinoma.

The tall cell variant papillary thyroid carcinoma (TCV-PTC) shows aggressive behaviour. Thus far, the diagnosis of TCV-PTC can only be confirmed using the postoperative specimen. This study aims to evaluate whether fine-needle aspiration (FNA) or core needle biopsy (CNB) could diagnose TCV-PTC preoperatively. This is a retrospective cohort study. We included adult patients diagnosed with TCV-PTC or PTC with tall cell features (TCF) at final surgical pathology between January 2015 and December 2018. Preoperative histology was reviewed for six cytomorphologic features suggesting TCV-PTC in FNA or the percentage of tall cells in the CNB specimen. The postoperative pathology was also reviewed to confirm the percentage of tall cells. A total of 119 patients were included in this study; 35 (29%) patients with PTC with TCF served as controls. The most frequent cytomorphological feature in FNA samples of TCV-PTC was tall columnar cells, including single tombstone-like cells (70%). Among 43 TCV-PTC evaluated by FNA, 3 FNA (7%) revealed the absence of any of the six cytomorphologic features suggesting TCV-PTC. When we defined 30% of tall cells in CNB specimens as a cutoff suggesting TCV-PTC, only 16 (41%) TCV-PTCs could be preoperatively detected, and 3 (7%) TCV-PTCs did not have any tall cells. The proportion of tall cells was not associated with the postoperative percentage of tall cells. Both cytomorphologic features in FNA and the percentage of tall cells in CNB present limitations for use as accurate preoperative diagnostic tools of TCV-PTC.

Tall Cell Histology – Comparison of T1 Tall Cell Variant and Classical Papillary Thyroid Carcinoma

<h3>Purpose/Objective(s)</h3> Tall cell histology in papillary thyroid carcinoma (PTC) is considered intermediate risk on ATA guidelines. However, it is unclear if patients with T1 tumors with tall cell histology require aggressive treatment. The objective of our study was to compare pathology and outcomes of patients with tall cell histology with that of classical PTC in T1 disease. <h3>Materials/Methods</h3> The study cohort was selected from our departmental database of differentiated thyroid cancers treated surgically between 1985 and 2015 (n=6,259). PTC cases demonstrating ≥30% tall cells were considered as tall cell variant (TCV). All T1 classical PTC and TCV were identified. Patient and tumor characteristics were compared between groups by Fisher exact test, chi-squared test or two sample t test. Survival and recurrence outcomes were compared using the log-rank test and Kaplan-Meier method. <h3>Results</h3> There were 712 TCV and 2,354 classical PTC patients with T1 tumors. Total thyroidectomy and lobectomy were done in 622 and 90 TCV patients compared to 1883 and 471 classical PTC patients. Central neck dissection was done in 140 TCV and 420 classical PTC patients. Lateral neck dissection was done in 89 TCV and 323 PTC patients. 208 and 87 TCV patients were N1a and N1b compared to 385 and 306 classical PTC patients. There was no significant difference between TCV and classical PTC in gender, age >55 years and vascular invasion. Compared to classical PTC, TCV cases were significantly more likely to demonstrate microscopic extrathyroidal extension (p<0.01), multifocality (p<0.01), larger size (mean 1.30cm in tall cell and 1.15cm in classical PTC) (p=0.02), less encapsulation (p<0.01) and treatment with radioactive iodine (p<0.01). Rates of central nodal disease were significantly higher in TCV cases (p<0.01), but there was no significant difference in rates of lateral nodal disease (p=0.61). There was no significant difference in overall survival (p=0.73), disease-specific survival (p=0.69) or locoregional recurrence (p=0.08). Of those that underwent lobectomy only, there was no significant difference in locoregional recurrence between classical PTC and TCV cases (p=0.79). For TCV cases only, there was no significant difference in locoregional recurrence between those that underwent lobectomy compared to those that had total thyroidecomy (p=0.08). <h3>Conclusion</h3> Despite having a higher rate of microscopic extrathyroidal extension and regional metastases, patients with T1 tall cell tumors have similar oncologic outcomes to patients with classical PTC.

What is the difference between the tall cell variant and the classic type of papillary thyroid carcinoma on ultrasonography?

PurposeThe prevalence of the tall cell variant of papillary thyroid carcinoma (TCVPTC), which has a poor prognosis, has increased as its definition has been modified. We sought to investigate whether TCVPTC is different from the classic type on ultrasonography (US).MethodsThis study included 46 consecutive TCVPTC patients and 92 classic papillary thyroid carcinoma (PTC) patients who were confirmed surgically at the authors’ institution. The US findings and pathologic reports of these patients were retrospectively reviewed. US features based on the Korean Thyroid Imaging Reporting and Data System, preoperative US suspicion for lymph node metastasis, and the presence of capsular location were evaluated.ResultsUnivariable and multivariable analyses identified that TCVPTC showed more frequent irregular tumor margin (odds ratio [OR], 6.62; 95% confidence interval [CI], 1.46 to 30.09; P=0.014) and capsular location (OR, 4.63; 95% CI, 1.49 to 14.41; P=0.008) than classic PTC. Capsular location was an independent predictor of TCVPTC for tumors less than or equal to 1.5 cm in size (OR, 4.23; 95% CI, 1.12 to 15.92; P=0.033). Irregular margin was an independent predictor of TCVPTC for tumors larger than 1.5 cm (OR, 10.46; 95% CI, 1.16 to 94.48; P=0.037). Extrathyroidal extension was not significantly different between the two groups.ConclusionThe two key features of TCVPTC on US are frequent capsular location for tumors less than or equal to 1.5 cm in size and the higher likelihood of an irregular margin for tumors larger than 1.5 cm.

Synchronous lateral lymph node metastases from papillary and follicular thyroid carcinoma: case report and review of the literature

BackgroundFollicular thyroid carcinomas (FTCs) rarely metastasize to regional lymph nodes, and descriptions of synchronous lateral lymph node metastases of FTC and papillary thyroid carcinoma (PTC) are lacking.Case PresentationWe describe a 43-year-old female with a preoperative cytology indicating a right-sided PTC with lateral lymph node metastases. She underwent a total thyroidectomy and central and lateral lymph node dissection, and histopathology confirmed a multifocal tall cell variant PTC together with a 12 mm minimally invasive FTC in the ipsilateral lobe. While the central compartment demonstrated metastatic PTC, the lateral compartment contained PTC metastases alongside a 15 mm large follicular-patterned mass in a separate lymph node. As the cells lacked PTC associated nuclear changes, the possibility of a lateral lymph node metastasis of FTC was considered, with the possibility of ectopic thyroid tissue as a differential diagnosis. By utilizing next-generation sequencing, a Q61R NRAS mutation was pinpointed, thus proving the tissue as tumorous. The patient underwent radioiodine treatment and is currently monitored following a negative whole-body scan.ConclusionsThis is probably the first case report of a patient with co-existing lateral lymph node PTC and FTC metastases. Consulting previous publications, there is currently a gap of knowledge in terms of how patients with regional FTC metastases should be followed-up and treated, especially when co-occurring with spread high-risk PTC subtypes. Moreover, what guides a seemingly indolent FTC to spread via the lymphatic system remains to be defined from a molecular standpoint.

Evaluation of ITGA3 as a Biomarker of Progression and Recurrence in Papillary Thyroid Carcinoma.

ObjectiveTo investigate the expression of ITGA3 and its association with clinical outcomes in papillary thyroid carcinoma (PTC).MethodsThe expression level, association with clinicopathologic characteristics, co-expressed genes, signaling pathways of ITGA3 in thyroid cancer were comprehensively analyzed using bioinformatics analysis through multiple public gene databases. PTC specimens and cell lines were used to verify the results of bioinformatics analysis.ResultsData mining based on the Oncomine database revealed that ITGA3 expression in classical PTC and tall cell variant PTC was much higher than that in normal thyroid tissue except the follicular variant PTC. Analysis based on The Cancer Genome Atlas (TCGA) database showed that the expression of ITGA3 varies greatly in pathological stages, pathological types, tumor invasion stages, and lymph node metastasis stages of thyroid carcinoma. High expression level of ITGA3 was correlated with tumor regional invasion and lymph node metastasis. Multivariate analysis using logistic regression model showed that high expression of ITGA3 was a risk factor that associated with PTC recurrence and lymph node metastasis. Survival analysis showed that patients with high expression of ITGA3 in PTC had a poorer relapse-free survival (RFS) than patients with low expression of ITGA3 (P < 0.05). Immunohistochemistry experiments showed that the expression of ITGA3 in recurrent thyroid cancer tissues was stronger than that in no-recurrent thyroid cancer tissues (P < 0.05). Knockdown of ITGA3 by sh-RNA in PTC cell lines suppresses cell viability and invasive and migrating capacity.ConclusionITGA3 is overexpressed in PTC, especially in those with higher tumor invasion grades and lymph node metastasis, and was associated with recurrence and poor RFS of PTC. High expression of ITGA3 may have the potential role of predicting PTC recurrence and lymph node metastasis.

Primary Squamous Cell Carcinoma of the Thyroid Coexisting with Tall Cell Variant Papillary Thyroid Carcinoma: Report of Two Cases

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare and aggressive neoplasm of the thyroid, usually presenting with a rapidly growing mass. In order to diagnose a tumor as PSCCT, tumor should entirely consist of cells with squamous differentiation without any evidence of other types of carcinomas. Tall cell variant papillary thyroid carcinoma (TCVPTC) is an aggressive variant of papillary thyroid carcinoma, composed of cells that are two-three times as tall as they are wide. We report two cases of PSCCT coexisting with TCVPTC. In the literature, there are less than 50 cases showing coexistence of PSCCT and TCVPTC. In all these cases, apart from the ones in which pure squamous cell carcinoma (SCC) is seen as a recurrence of TCVPTC, SCC and TCVPTC areas were intermingled. The 2 cases we report here are unique in the way that PSCCT and TCVPTC are seen concurrently in these patients but they are separate tumors, not admixed with each other.

BRAF V600E mutation and correlation with clinicopathologic features in radioactive iodine refractory papillary thyroid carcinoma

Objective: To define the rate of BRAF V600E mutation in radioactive iodine (RAI) refractory papillary thyroid carcinoma (PTC). The correlation BRAF V600E mutation with some clinicopathologic features in RAI refractory PTC. Subject and method: 92 patients with RAI refractory PTC were operated recurrent lesions at 108 Military Central Hospital from 9/2009 to 3/2018. Recurrent lesions were evaluated histopathological characteristics, immunohistochemical staining with BRAF V600E (Ventana, Roche), BRAF V600E gene test by real-time PCR. Evaluating the status of mutated BRAF V600E and correlate with some clinicopathologic features. Result: Average age: 47.1 ± 15.6 (12 - 81); the rate of BRAF V600E mutation accounted for 80.4%; the average age of unmutated BRAF V600E RAI refractory PTC group (40.2 ± 17.2) was lower than the group of BRAF V600E mutation (48.5 ± 14.9) (p=0.042); BRAF V600E mutation in early-stage disease (I - II) had a higher rate than ones in advanced disease (II-IV); similarly, this gene mutation occurred more frequent in the group received more than 600mCi cumulative dose of RAI compared with the group received less than 600mCi cumulative dose. There was no correlation of BRAF V600E mutation with age, tumor size, lymph node, distant metastasis. BRAF V600E mutation in tall cell variant of PTC was seen more frequently than other variants and it was also seen in cases of extracapsular lymph node invasion. There was no relationship between the existence of mutated BRAF V600E with vessel invasion and calcification. Conclusion: The rate of BRAF V600E mutation in RAI refractory PTC is high, accounting for 80.4%. It correlates with some clinicopathologic characteristics such as disease stage, cumulative dose of radioactive iodine, tall cell variant of PTC; no correlation of BRAF V600E mutation with age, tumor size, lymph node and distant metastasis, extracapsular lymph node invasion

Mutation profile of the tall cell variant of papillary thyroid carcinoma: analysis of 5 cases using wide-panel next-generation sequencing

The study objective is to analyze the mutation profile of the tall cell variant (TCV) of papillary thyroid carcinoma (PTC).Materials and methods. The main inclusion criteria according to the WHO classification (2017) was PTC composed of at least 30 % of tall cells. Genetic examination was conducted using the FoundationOne CDx assay (USA) with median depth of coverage of &gt;500x. This study included 5 patients (1 man and 4 women) with a mean age of 52.6 years (range: 48-56 years). The tumor size varied between 0.4 x 0.5 cm and 11.0 x 9.0 cm. All patients have undergone surgical treatment: hemithyroidectomy for patient No. 1 with a small tumor (pT1b); thyroidectomy for patient No. 2 (pT3b); extensive thyroidectomy with the removal of paratracheal tissue for patients No. 3, 4, and 5 (No. 3 - pT3bN0; No. 4 - pT3bN1b; No. 5 - pT3bN1b). Three out of the five patients also had adenomatous goiter. The mean follow-up time was 3.4 to 5.2 years.Results. Tumors in all patients were characterized by low mutational load (0 to 4 mutations per 1 million nucleotides (megabase)) and no microsatellite instability. All study participants were found to have p.V600E mutation in the BRAF gene; two patients had c.-124C&gt;T mutation in the promoter region of the TERT gene. All patients carried mutations with unknown clinical significance: p.V562I in the EPHB1 gene (in 2 patients); mutations in the genes AR, CREBBP, EP300, ERCC4, FLT1, IKBKE, JAK2, MAF, MLL2, MST1R, MYC, MYCL1, NTRK2, TSC2 (each mutation registered in one patient). One individual with the largest tumor and the most aggressive disease was found to have amplifications of the BTG2, MAP3K1, SMAD2, and TBX3 genes.Conclusion. In 5 patients analyzed in this study, the mutation profile of TCV PTC was characterized by low mutational load, no microsatellite instability, and presence of p.V600E mutation in the BRAF gene in all cases. Some patients also had c.-124C&gt;T mutation in the TERT gene and p.V562I mutation in the EPHB1 gene.

SUN-487 A Case of Type 2 Anaplastic Spindle Cell Squamous Cancer

Background: Papillary thyroid carcinoma (PTC) is generally considered a relatively slow-growing, indolent cancer; however, an important subset of these cancers known as the tall cell variant (TCV), portend a more aggressive prognosis. TCV PTC is characterized by cells, which are at least twice as tall as they are wide. Patients diagnosed with TCV PTC fare worse than those with the classic variant. A less common thyroid cancer, spindle cell squamous cell carcinoma (SCSC), may arise as a primary tumor, but rarely also alongside or from a previous TCV PTC (1). It may also occur as a component of an anaplastic thyroid cancer, the most aggressive and rarest thyroid malignancy. There are three main types of anaplastic SCSC arising from TCV PTC based on histological characteristics: Type 1 is defined by the presence of both TCV and SCSC within the initial resection; type 2 refers to when the SCSC arises as a recurrence or metastasis in patients with a known history of TCV PTC; type 3 occurs when SCSC presents as a primary laryngeal SCC in patients with or without a known history of TCV. We report a case of type 2 anaplastic SCSC. Clinical Case: A 76 yr old man with hx of invasive TCV PTC (diagnosed 2011) s/p total thyroidectomy with b/l neck dissection and laryngectomy, as well as 200 mci of I-131 (in 2012), returns to clinic in 2019, with worsening unexplained weight loss (> 20 lbs). He had been lost to follow-up since 2015. Now, chest CT showed a new, necrotic, left lower lobe mass obstructing the bronchus, as well as bony erosion of the right clavicle and manubrium. Bronchoscopy of the mass was performed, and pathology was consistent with metastatic anaplastic thyroid cancer with squamous nests. Immunohistochemistry was positive for PAX-8, p40, p63 and negative for TTF-1, Napsin A, TG and PDL-1. The endobronchial tumor tissue was compared to the prior resection specimen from 2011, showing morphologic similarity to the squamoid nests. In retrospect, these nests likely represented small foci of anaplastic thyroid cancer arising in association with TCV PTC. The positive staining for PAX-8 and lack of expression for TTF-1 and Napsin A supports this interpretation and is evidence against a primary pulmonary squamous cell carcinoma. Next Gen Sequencing was positive for BRAF V600E mutation, which allowed us to offer BRAF inhibitor and MEK inhibitor therapy. Unfortunately, due to patient’s non-adherence to therapy and follow-up clinic visits, we are not able to assess his response. Conclusion: This is a case of the rarely described type 2 anaplastic SCSC and is an example of the very poor prognosis associated with TCV PTC. It is a reminder that this variant of PTC should be treated more aggressively from the time it is first identified on biopsy. Reference: (1) Gopal PP et al. The variable presentations of anaplastic spindle cell squamous carcinoma associated with tall cell variant of papillary thyroid carcinoma. Thyroid. 2011;21(5):493–499.

MON-266 Tall-Cell Variant Papillary Thyroid Carcinoma: Incidental Finding in a Pediatric Patient

Background: Tall cell variant papillary thyroid carcinoma (TCV) is a rare and aggressive type of thyroid cancer. It is extremely rare in children, literature reporting only a few cases with better outcomes than adults with this disease. Currently there are no specific guidelines for management in the pediatric population. Clinical Case: 16 y/o female without prior past medical history who presented with an incidental right thyroid nodule found after a bicycle accident. She was followed up 14 months later, the nodule had increased in size from 7mm to 9mm and with findings suspicious for calcifications on repeat ultrasound. Thyroid function tests were euthyroid at this time, thyroglobulin was mildly elevated above the normal range (61 ng/ml) and she denied any compressive thyroid symptoms. Physical exam only significant for slight asymmetric gland (right > left). Fine needle aspiration was performed, consistent with Bethesda V and right hemi-thyroidectomy was done. Pathology reported a Tall-Cell variant Papillary thyroid carcinoma without any lymphovascular or extra-thyroidal invasion. Due to aggressive nature of carcinoma decision was made to complete thyroidectomy after which patient was started on Levothyroxine. At 3 month follow up patient found well without any hypo/hyperthyroid symptoms. Labs showed decreasing thyroglobulin level (0.5 ng/ml). After careful discussion decision was made to closely follow patient and not proceed with immediate radioactive iodine treatment. Conclusion: We presented this case to continue to raise awareness of this rare and aggressive tumor. Additionally, from prior case reports it appears to behave differently in the pediatric population.

Anti-N-Methyl-D-Aspartate (NMDA) Encephalitis Associated with Tall-cell Variant Papillary Thyroid Carcinoma (P2.2-015)

Anti-N-Methyl-D-Aspartate (NMDA) Encephalitis Associated with Tall-cell Variant Papillary Thyroid Carcinoma (P2.2-015)

Diagnostic clues indicating tall cell variants of papillary thyroid carcinoma in fine needle aspiration.

BackgroundThe definition of tall cell variant of papillary thyroid carcinoma (TCV‐PTC) depends on the articles, and the defined cytological findings characteristic of TCV‐PTC have not yet been fully analyzed. This study aimed to establish the cytological characteristics of TCV‐PTC.MethodsWe retrospectively analyzed the smears of 19 TCV‐PTC and 50 conventional PTC (C‐PTC) cases.ResultsPalisaded pattern with the nuclei locating at the base of tall columnar carcinoma cells was seen in 94.7% of TCV‐PTCs, and the incidence was significantly higher than that of C‐PTCs (P < .0001). The palisaded pattern tended to appear at the periphery of the cell clusters. Isolated tall columnar carcinoma cells were present in 89.5% of TCV‐PTCs. The incidence was significantly higher than that of C‐PTC (P = .0001). Tombstone appearance was identified in 78.9% of TCV‐PTCs, but not in C‐PTCs. Spindle‐like carcinoma cells with tapering cytoplasmic end appeared in 68.4% and 12.0% of TCV‐PTC and C‐PTC, respectively (P < .0001). The cytoplasm of TCV‐PTC was densely stained and its cell border was distinct. Cytoplasmic elongation toward an outside of the cell clusters was observed in 89.5% of TCV‐PTCs.ConclusionIt is the most important to identify the presence of the tall columnar carcinoma cells on the cytological preparations, in order to distinguish TCV‐PTC from C‐PTC. We propose five cytological findings indicating TCV‐PTC, (1) palisaded pattern, (2) tall columnar cells with the heights of at least three times their widths, (3) tombstone appearance, (4) spindle‐like carcinoma cells, and (5) cytoplasmic elongation.

Immune Gene Signature Delineates a Subclass of Papillary Thyroid Cancer with Unfavorable Clinical Outcomes.

Papillary thyroid carcinoma (PTC) represents a heterogeneous disease with diverse clinical outcomes highlighting a need to identify robust biomarkers with clinical relevance. We applied non-negative matrix factorization-based deconvolution to publicly available gene expression profiles of thyroid cancers in the Cancer Genome Atlas (TCGA) consortium. Among three metagene signatures identified, two signatures were enriched in canonical BRAF-like and RAS-like thyroid cancers with up-regulation of genes involved in oxidative phosphorylation and cell adhesions, respectively. The third metagene signature representing up-regulation of immune-related genes further segregated BRAF-like and RAS-like PTCs into their respective subgroups of immunoreactive (IR) and immunodeficient (ID), respectively. BRAF-IR PTCs showed enrichment of tumor infiltrating immune cells, tall cell variant PTC, and shorter recurrence-free survival compared to BRAF-ID PTCs. RAS-IR and RAS-ID PTC subtypes included majority of normal thyroid tissues and follicular variant PTC, respectively. Immunopathological features of PTC subtypes such as immune cell fraction, repertoire of T cell receptors, cytolytic activity, and expression level of immune checkpoints such as and PD-L1 and CTLA-4 were consistently observed in two different cohorts. Taken together, an immune-related metagene signature can classify PTCs into four molecular subtypes, featuring the distinct histologic type, genetic and transcriptional alterations, and potential clinical significance.

Survival of aggressive variants of papillary thyroid carcinoma in patients under 55 years old: a SEER population-based retrospective analysis.

Patients younger than 55 years of age with papillary thyroid carcinoma (PTC) have excellent survival. Diffuse sclerosing variant (DSV) and tall cell variant (TCV) of PTC are associated with aggressiveness; the survival of patients <55 years of age with these variants is still unclear. We aim to investigate the clinicopathological features and survival of these variants in the age group <55 years. All adult patients (<55 years old) with DSV, TCV and conventional PTC (CPTC) came from the Surveillance, Epidemiology, and End Results program (1988-2013). Kaplan-Meier method and log-rank test were used to analyze the survival. Prognostic factors associated with survival were analyzed by Cox multivariate regression. There were 280 DSV, 615 TCV, and 56287 CPTC in the age group <55 years. DSV and TCV were associated with multifocality, extrathyroidal extension, lymph node and distant metastasis (all p < 0.05). The 10-year disease-specific survival (DSS) of TCV was worse than CPTC (96.3 vs. 99.4%, p < 0.01), but there was no significant difference between DSV and CPTC (99.5 vs. 99.4%, p > 0.05). Cox multivariate regression showed TCV was the independent predictor of DSS (HR: 5.39, p < 0.01). In the age group <55 years, DSV and TCV are more likely to exhibit aggressive characteristics than CPTC. Patient <55 years of age with DSV have excellent survival likewise, while patients <55 years of age with TCV carry worse survival. Further investigation for the recurrence risk of patients <55 years with these variants would contribute to optimal clinical management making.

Aggressiveness of the tall cell variant of papillary thyroid carcinoma is independent of the tumor size and patient age.

The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is characterized by tall columnar cells with a height of at least three times their width. TCV usually presents at an older age, has a larger size and exhibits more extrathyroidal extension and metastases than classical PTC. The current study compared TCV with the classical and follicular variants (CaFVs) of PTC to determine if, irrespective of the age at diagnosis and tumor size, TCV is more aggressive than its classical and follicular counterparts. A total of 16 (3.66%) patients with TCV were identified in a series of 437 patients with PTC from the Clinical University Hospital (Santiago de Compostela, Spain) between 1990 and 2010. The patient clinicopathological features and B-Raf proto-oncogene (BRAF)V600E mutational status were compared with 34 cases of CaFVs of PTC matched for tumor size and patient age. The TCV series included 11 females and 5 males aged 15–74 years (median, 57 years). In total, 15 (93.8%) patients underwent total or near-total thyroidectomy, 1 underwent lobectomy and 5 (31.3%) underwent lymph node dissection. In the TCV series, the tumor size ranged from 5–45 mm (median, 19 mm). Compared with the CaFVs, the TCV of PTC exhibited a significantly higher prevalence of extrathyroidal extension [9/16 (56.3%) vs. 5/34 (14.7%) cases; P=0.007], lymph node metastases [9/16 (56.3%) vs. 9/34 (26.4%) cases; P=0.04], stage III/IV at presentation [10/16 (62.5%) vs. 7/34 (20.5%) cases; P=0.009] and BRAFV600E mutation [12/16 (80.0%) vs. 7/25 (28.0%) cases; P=0.004]. The TCV series also harbored more multifocal papillary carcinomas (50.0% vs. 26.4%), lymphovascular invasion (37.5% vs. 29.4%) and distant metastases (6.2% vs. 0.0%), as compared with the matched patient cohort. In conclusion, the TCV of PTC is frequently associated with BRAFV600E mutation and is more aggressive than the CaFVs of PTC, regardless of tumor size and patient age at diagnosis.