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.

Expanding the Spectrum of BRAF Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre.

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. BRAF alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of BRAF non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. BRAF mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other BRAF non-V600E alterations. BRAF non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that BRAF non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that BRAF non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the BRAF mutations were concomitant with other molecular alterations, such as TERT promoter mutation.

Rare Columnar Cell Variant Papillary Thyroid Carcinoma with Metastasis to Pancreas and Lungs at Initial Presentation: A Case Report and Review of Literature

AbstractPapillary thyroid cancer (PTC) is the most common endocrine malignancy, accounting for 85% of differentiated thyroid cancers. A small percentage of PTC variants are considered more aggressive, such as the tall cell variant associated with the V600E mutation in the BRAF gene and the rarer columnar variant, which is described in only 0.2% of cases and has a poor prognosis. Although locoregional metastases to neck lymph nodes are common, distant metastases of PTC are rare at presentation with only 5 to 7% reported in the literature. We present a very rare case of columnar cell variant PTC with synchronous metastasis to the lungs and indolent focus in the pancreas at initial diagnosis, which has never been reported in the literature. Our patient presented with non-radioactive iodine (RAI) responsive PTC with diffuse metastases to the lungs and one synchronous focal metastatic lesion in the pancreas. After multidisciplinary discussions, pancreatectomy/metastasectomy was deferred due to the disseminated PTC with multiple metastases to the lungs, lack of pancreas-related symptoms in the patient, and inherent complication risks. The patient was treated with systemic therapy using a tyrosine kinase inhibitor (lenvatinib), which is the standard of care for non-RAI responsive PTC and showed a complete radiologic resolution of the pancreatic lesion, however, with partial yet nonprogressive metastatic disease in the lungs.

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.

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.

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

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.

Tall Cell Variant Papillary Thyroid Carcinoma in Saudi Patients: A clinicopathological and Outcomes Analysis.

Objectives:To evaluate the clinicopathological features and treatment outcomes of papillary thyroid carcinoma tall cell variant (PTC-TCV) in Saudi population.Methods:This retrospective study were medical records of 776 treated PTC patients between December 2007 and 2015, at King Fahad Medical City and King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia was probed for PTC-TCV. Total 42 (5.4%) patients were found to have PTC-TCV, which were investigated for demographic, symptoms, histopathological features, and treatment outcomes locoregional control (LRC), distant metastasis control (DMC), disease free survival (DFS), and overall survival (OS) rates.Results:Mean age of cohort was 52.3 years (range: 46-80), with female predominance (73.8%). Mean tumor size was 3.62 cm (range: 0.4-10). Rates of LVSI (59.5%), positive pathological lymph nodes (66.7%), multifocality (42.9%) and extrathyroidal extension, (45.3%). Median follow-up was 37.4 months (range: 6-60). Local recurrence rate were seen in 6/42 (14.2%) patients and 8/42 (19%) developed distant metastasis. The 5 year rates of LRC (82.3%), DMC (77.8%), DFS (69.2%), and OS (86.7%) multivariate analysis showed PTC-TVC as an important independent prognosticator (odds ratio: 4.2; 95% confidence interval: 1.79-7.3; p=0.03)Conclusion:Papillary thyroid carcinoma tall cell variant is associated with aggressive biological behavior.

Prognostic Factors in Papillary Microcarcinoma with Emphasis on Histologic Subtyping: A Clinicopathologic Study of 148 Cases

There continues to be controversy regarding which clinicopathological features confer a higher risk of adverse outcome in papillary microcarcinomas (PMC). The aim of this study was to assess the prognostic value of a meticulous histologic examination in PMC. All papillary thyroid carcinoma <1 cm in size without associated larger thyroid carcinomas, identified between 1977 and 2002, were categorized as PMC and subjected to a meticulous histopathologic examination by 2 thyroid pathologists. 148 PMC patients fulfilled the inclusion criteria. Within PMC, young age, male sex, tumor multicentricity, extrathyroidal extension, and infiltrative and larger tumor (≥0.5 cm) correlated with the presence of >1 cm metastatic node (MN) or >3 MN at presentation (p<0.05). With a median follow-up of 9.9 years, only 1 (0.7%) of 134 PMC patients died of thyroid carcinomas and 3 (2.2%) had recurrences in the neck. The patient who died had harbored a poorly differentiated carcinoma in his MN. The presence of MN and especially a large MN (>1 cm) correlated with worse recurrence-free survival (p=0.005 and p<0.0001, respectively). Except for one, all individuals with clinically adverse outcomes had >1 cm MN. Patients whose MNs were predominantly composed of poorly differentiated carcinoma or tall cell variant papillary thyroid carcinoma had a significant shorter recurrence-free survival (p<0.0001). Only 1 of 80 radioactive iodine-naïve PMC patients with absent or small MN (≤1 cm) had recurrence with a median follow-up of 9.2 years. (i) The size and histotype of the MN are predictors of outcome in PMC and should be recorded. (ii) The very rare PMC patients who suffer recurrence or even die of disease have usually aggressive histopathologic features at presentation. (iii) PMC patients with nodal disease that is small or absent at presentation are at a very low risk of recurrence and may be spared radioactive iodine therapy.

Neoadjuvant Chemotherapy in 16 Patients with Locally Advanced Papillary Thyroid Carcinoma

It is believed that chemotherapy (ChT) is ineffective in papillary thyroid carcinoma (PTC). The aim of our retrospective chart review was to find out if neoadjuvant ChT before thyroid surgery had any effect on the size of primary tumors in patients with PTC. The study included 16 patients (13 women, 3 men; median age 63.5 years) with PTC, who were treated with neoadjuvant ChT from 1988 to 2005. Poorly differentiated PTC, classical PTC, a follicular variant of PTC, and a Hürthle cell variant of PTC were diagnosed in 5, 5, 3, and 3 cases, respectively. The mean tumor diameter was 9.67 cm. Seven patients had a pT4 tumor. Regional and distant metastases were detected in 10 and 7 patients, respectively. ChT consisted of vinblastine in 11 cases, vinblastine with adriamycin in 2 cases, and other schedules in 3 cases. Four patients were also treated with preoperative external irradiation. Altogether, 40 cycles of ChT were given. After ChT, the tumor size decreased in all 16 patients: by >50% in 7 (44%) patients and by <50% in 9 patients. R0, R1, and R2 resection was performed in 2, 10, and 4 cases, respectively. The median survival time of our patients was 88 months. Six patients are still alive; two died of causes not related to carcinoma, while eight patients died of PTC. Neoadjuvant ChT before thyroid surgery may be effective in patients with locally advanced PTC. After neoadjuvant ChT, in 44% of patients, the tumor size decreased by >50%.

Correlation between thyroid-stimulating hormone-peroxiredoxin1 signaling pathway and invasion of papillary thyroid carcinoma

In order to assess the significance of thyroid-stimulating hormone receptor (TSHR), peroxiredoxin1 (Prx1), thioredoxin1 (Trx1), hypoxia inducible factor-1 (HIF-1)alpha in invasion and metastasis of papillary thyroid carcinoma (PTC). The 34 paraffin-embedded specimen of classical PTC, 39 of tall cell variant of PTC and normal thyroid tissues adjacent to cancer operated in Tianjin Cancer Hospital from 2003 to 2007 were tested. The expressions of TSHR, Prx1, Trx1, HIF-1alpha in the specimen were assayed by immunohistochemical staining. The correlation between the 4 factors (TSHR, Prx1, Trx1, HIF-1alpha) and clinical features of PTC such as gender, age, tumor size, invasion, lymph node metastasis, histological type and T stage were studied. The rates of immuno-positive staining Prx1, Trx1 and HIF-1alpha in PTC were higher than the normal thyroid tissues adjacent to cancer with significant difference respectively (chi2 were 5.49, 6.16 and 40.48, P<0.05). The positive expression rate of TSHR in PTC was lower than the normal thyroid tissues adjacent to cancer (chi2=15.70, P<0.05), in tall cell variant of PTC was lower than classical PTC (chi2=4.24, P<0.05). The positive expression rates of Prx1, Trx1 and HIF-1alpha in PTC with local invasion, with lymph node metastasis, in tall cell variant and in stage T3-T4 were higher than PTC without local invasion, without metastasis, in classical variant and in stage T1-T2 with significant difference respectively (P<0.05). There were correlation between the expressions of Prx1 and Trx1, Trx1 and HIF-1alpha (r1 were 0.664 and 0.652, P<0.05). The high expressions of Prx1, Trx1 and HIF-1alpha were related to invasion and lymph node metastasis in PTC. TSH may promote the development of thyroid carcinoma by TSH-Prx1-Trx1-HIF-1 signaling pathway.

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases.

Five cases of a hitherto undescribed breast tumor having histologic features similar to those of the tall cell variant papillary thyroid carcinoma are described. They were composed of columnar mitochondrion-rich to oxyphilic cells arranged in nests, papillae, and follicle-like structures. In addition, the neoplastic cells showed numerous nuclear grooves and, in two cases, nuclear pseudo-inclusions. None of the patients had previous concomitant or subsequent evidence of a thyroid tumor. Immunohistochemistry further excluded a metastasis from the thyroid in the four cases tested, as they were consistently thyroglobulin and thyroid transcription factor 1 negative.