A NOVEL DEFINITION OF EXTRATHYROIDAL INVASION FOR PATIENTS WITH PAPILLARY THYROID CARCINOMA

Abstract Purpose Recent diagnostic criteria updates of the tall cell variant of papillary thyroid carcinoma (TCPTC) by the World Health Organization (WHO) have determined the inclusion of tumours with 30-49% of tall cells. However, the impact of tall cell percentage on papillary thyroid carcinoma (PTC) patients’ prognosis is still debated. We aimed to evaluate whether tall cell percentage affects patients’ outcome in the absence of aggressive features. Methods Rates of aggressive features, recurrence-free survival (RFS) and distant RFS (DRFS) (5-year median follow-up) were compared among tumours with less than 30%, 30-49% and at least 50% of tall cells. We also evaluated the impact of the new tall cell cut-off on patient management. Results Overall, 3092 tumours (15.7% of all PTC) were collected: 792 PTC had less than 30%, 503 had 30-49%, and 1797 had 50% or more tall cell areas. With the new definition of WHO, the number of TCPTC increased by 28%. There were no differences in recurrence rates according to tall cell percentage. The coexistence of BRAF and TERT promoter mutations predicted a worse RFS. Considering the new definition of TCPTC, the level of risk according to the American Thyroid Association increased from low to intermediate in 4.2% of cases. However, the recurrence rate within this subgroup was comparable to low-risk. Conclusions TCPTC and PTC with tall cell areas can be considered as a unique group with similar recurrence risk. However, whenever aggressive features are absent, tumors have a low risk of recurrence independently of tall cell percentage.

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Association between the expression of four upregulated miRNAs and extrathyroidal invasion in papillary thyroid carcinoma

OncoTargets and Therapy ◽

10.2147/ott.s43014 ◽

2013 ◽

pp. 281 ◽

Cited By ~ 49

Author(s):

Wang ◽

Hao Zhang ◽

Liang He ◽

Wenwu Dong ◽

Jing Li ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Papillary Thyroid ◽

Extrathyroidal Invasion

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IRAK1, a Target of miR-146b, Reduces Cell Aggressiveness of Human Papillary Thyroid Carcinoma

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-2276 ◽

2016 ◽

Vol 101 (11) ◽

pp. 4357-4366 ◽

Cited By ~ 16

Author(s):

Chen-Kai Chou ◽

Shun-Yu Chi ◽

Cai-Hua Huang ◽

Fong-Fu Chou ◽

Chao-Cheng Huang ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Reporter Gene ◽

Target Gene ◽

Mrna Level ◽

Advanced Tumor Stage ◽

Papillary Thyroid ◽

Extrathyroidal Invasion ◽

Advanced Tumor ◽

Reporter Gene Assays

Context: MicroRNA (miR)-146b is overexpressed in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal invasion, advanced tumor stage, and poor prognosis. However, the underlying mechanism of miR-146b in relation to its oncogenic behavior in PTC and its putative targets remain unknown. Objective: The purpose was to investigate IL-1 receptor-associated kinase 1 (IRAK1) as the potential miR-146b target gene and its involvement in PTC. Design: We used genome-wide microarray, computational analysis, and 3′ UTR reporter gene assays to identify IRAK1 as a miR-146b target gene. In vitro gain/loss-of-function experiments were further performed to determine the effects of IRAK1 on proliferation, colony formation, and wound-healing in PTC cancer cell lines. Expression levels of miR-146b and IRAK1 of 50 cases of PTC and its adjacent normal thyroid specimens were assessed via qRT-PCR. Results: Microarray expression profile revealed that the mRNA level of IRAK1 gene was down-regulated by miR-146b. The 3′ UTR of IRAK1 mRNA was found to be a molecular target of miR-146b posttranscriptional repression in BCPAP cells by reporter gene assays. MiR-146b promoted the migration and proliferation of PTC cells by down-regulating IRAK1 expression, whereas restoration of IRAK1 expression reversed this effect. In addition, the expression of IRAK1 mRNA was significantly lower in PTC clinical tissue samples than normal adjacent thyroid specimens and showed a strong inverse correlation with the expression of miR-146b in PTC specimens. Conclusion: Our results demonstrated that IRAK1 is a direct target of miR-146b and has functional roles to inhibit various aggressive PTC cell activities. In conjunction with current therapeutic regimens, targeting the miR-146b-IRAK1 axis may provide a potential approach for PTC management.

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Tall cell variant: An aggressive form of papillary thyroid carcinoma

Otolaryngology ◽

10.1067/mhn.2000.100755 ◽

2000 ◽

Vol 122 (3) ◽

pp. 352-357 ◽

Cited By ~ 4

Author(s):

Stephen Prendiville ◽

Kenneth D. Burman ◽

Matthew D. Ringel ◽

Barry M. Shmookler ◽

Ziad E. Deeb ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Distant Metastases ◽

Control Group ◽

Papillary Thyroid ◽

Tall Cell Variant ◽

Extrathyroidal Invasion ◽

Tall Cell ◽

Cell Variant

Twenty-four cases of the tall cell variant (TCV), a subset of papillary thyroid carcinoma, were identified in a group of 624 patients with thyroid cancer. All pathology specimens were reviewed, and each patient's carcinoma was categorized according to characteristics on presentation, local recurrence, distant metastases, follow-up, and tumor-related mortality. The TCV group was compared with a historical control group (Mazzaferri and Jhiang: 1355 patients). The TCV group had a statistically higher percentage of stage 3 and 4 carcinoma, extrathyroidal invasion, and tumor size less than 1.5 cm than the control group. There was no statistical relationship between age greater than 50 years and stage in the TCV group. No relationship could be found between TCV histology and recurrence or mortality. These findings, combined with those of studies that link stage on presentation to poor outcomes, have led to our conclusion that TCV is an aggressive malignancy warranting appropriate treatment and close follow-up.

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Tall Cell Variant: An Aggressive Form of Papillary Thyroid Carcinoma

Otolaryngology ◽

10.1016/s0194-5998(00)70047-7 ◽

2000 ◽

Vol 122 (3) ◽

pp. 352-357 ◽

Cited By ~ 68

Author(s):

Stephen Prendiville ◽

Kenneth D. Burman ◽

Matthew D. Ringel ◽

Barry M. Shmookler ◽

Ziad E. Deeb ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Distant Metastases ◽

Control Group ◽

Papillary Thyroid ◽

Tall Cell Variant ◽

Extrathyroidal Invasion ◽

Tall Cell ◽

Cell Variant

Twenty-four cases of the tall cell variant (TCV), a subset of papillary thyroid carcinoma, were identified in a group of 624 patients with thyroid cancer. All pathology specimens were reviewed, and each patient's carcinoma was categorized according to characteristics on presentation, local recurrence, distant metastases, follow-up, and tumor-related mortality. The TCV group was compared with a historical control group (Mazzaferri and Jhiang: 1355 patients). The TCV group had a statistically higher percentage of stage 3 and 4 carcinoma, extrathyroidal invasion, and tumor size less than 1.5 cm than the control group. There was no statistical relationship between age greater than 50 years and stage in the TCV group. No relationship could be found between TCV histology and recurrence or mortality. These findings, combined with those of studies that link stage on presentation to poor outcomes, have led to our conclusion that TCV is an aggressive malignancy warranting appropriate treatment and close follow-up.

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Higher circular RNA_0015278 correlates with absence of extrathyroidal invasion, lower pathological tumor stages, and prolonged disease‐free survival in papillary thyroid carcinoma patients

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23819 ◽

2021 ◽

Author(s):

Huajie Ding ◽

Xiaojie Wang ◽

Huiling Liu ◽

Lei Na

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Disease Free Survival ◽

Papillary Thyroid ◽

Free Survival ◽

Extrathyroidal Invasion ◽

Tumor Stages ◽

Disease Free

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Association of BRAF V600E Mutation with Poor Clinicopathological Outcomes in 500 Consecutive Cases of Papillary Thyroid Carcinoma

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1179 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4085-4090 ◽

Cited By ~ 263

Author(s):

Cristiana Lupi ◽

Riccardo Giannini ◽

Clara Ugolini ◽

Agnese Proietti ◽

Piero Berti ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Braf Mutation ◽

Braf V600e Mutation ◽

Braf V600e ◽

Clinicopathological Parameters ◽

Papillary Thyroid ◽

Braf Mutations ◽

Tumor Capsule ◽

Extrathyroidal Invasion

Abstract Context: Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation. Objective: We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class. Design: BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples. Results: In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in three cases (0.6%), BRAF VK600–1E (0.2%) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600–3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P < 0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P < 0.00000006), and absence of tumor capsule (P < 0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation. Conclusions: Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.

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Differences in Clinicopathological Characteristics of Papillary Thyroid Carcinoma between Symptomatic and Asymptomatic Patients with Primary Hyperparathyroidism

International Journal of Endocrinology ◽

10.1155/2021/9917694 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Yuan Liu ◽

Siyi Guo ◽

Shaowei Sang ◽

Jinbo Liu ◽

Lin Qi ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Primary Hyperparathyroidism ◽

Thyroid Carcinoma ◽

Thyroid Nodules ◽

Statistical Significance ◽

Papillary Thyroid ◽

Lower Serum ◽

Thyroid Lesion ◽

Extrathyroidal Invasion ◽

Asymptomatic Patients

Background. Popularization of cervical ultrasound led to higher detection of papillary thyroid carcinoma (PTC) and primary hyperparathyroidism (PHPT), as well as increasing percentage of asymptomatic PHPT in China. Although the coexistence of PTC and PHPT has been reported, it is unknown whether the clinicopathological features of PTC differ between asymptomatic and symptomatic PHPT patients. Methods. We retrospectively reviewed the medical records of 304 PHPT patients treated in our hospital between January 2009 and July 2020, including 217 females and 87 males with the average age of 53.27 ± 13.54 years. Of the 304 patients, 181 were symptomatic PHPT patients and 123 were asymptomatic PHPT patients. We analyzed the laboratory results, postoperative pathology, and the TNM stage of PTC between asymptomatic and symptomatic PHPT patients. Results. Concurrent thyroid nodules were found in 61.51% of PHPT patients, and the prevalence of PTC in thyroidectomized PHPT patients was 29.89% in our cohort. Lower serum parathyroid hormone (PTH) ( p < 0.05 ) and calcium ( p < 0.05 ) were found in PHPT patients with PTC compared to patients with benign thyroid lesion. Compared with the symptomatic PHPT patients, the asymptomatic PHPT patients showed lower serum calcium ( p < 0.05 ), serum chlorine ( p < 0.05 ), alkaline phosphatase ( p < 0.05 ), PTH ( p < 0.05 ), and bone turnover markers ( p < 0.05 ) but higher prevalence of thyroid nodules (70.73% versus 55.24%, p < 0.05 ) and PTC (15.44% versus 3.87%, p < 0.05 ). All the PTC in symptomatic PHPT patients were papillary microcarcinoma limited to the thyroid, while 68.42% and 15.78% of the PTC in asymptomatic PHPT patients showed microscopic extrathyroidal extension and lymph node metastases, respectively. Moreover, 36.84% (7/19) of the PTC patients in asymptomatic group showed multifocality, which was much higher than 14.29% (1/7) in the symptomatic group; however, no statistical significance was found ( p = 0.24 ). Conclusions. The concomitant PTC in asymptomatic PHPT patients showed a higher rate of microscopic extrathyroidal invasion when compared to symptomatic PHPT patients. So the FNA is essential to the asymptomatic PHPT patients with suspicious thyroid nodules and once the PTC is confirmed, concurrent parathyroidectomy should be performed with thyroidectomy in asymptomatic PHPT patients.

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