Case Of Follicular Thyroid Carcinoma Research Articles

Abstract 6273: GGCT expression is a useful marker for the diagnosis of follicular thyroid carcinoma

Abstract Background: Follicular thyroid carcinoma (FTC) and follicular adenoma (FA) have similar histological findings. FTC is distinct from FA based on the presence of capsular or vascular invasion in the tissues, but it is difficult to confirm the diagnosis in some cases. In this study, we aimed to establish useful molecular maker for differential diagnosis between FTC and FA. Methods: This study included FTC (n = 32), FA (n = 64), and follicular tumors of uncertain malignant potential (FT-UMP, n = 5). Invasive front tissue and tumor center tissue from 3 cases of FTC were collected using a laser microdissection system; RNA was extracted, followed by microarray analysis to examine molecules that were commonly highly expressed in the invasive front. Subsequently, immunohistochemical staining of gamma-glutamyl cyclotransferase (GGCT) was performed. For assessment of GGCT expression, the intensity of the nuclear staining was stratified using a four-tiered scale (0 to 3) and percentage of positive cells (0-100%) in the hotspot. Multiplying intensity score and percent of positive cells, an expression score ranging from 0 to 300 was calculated. The Ki-67 labeling index was examined in 20 cases of FTC, 25 cases of FA, and 4 cases of FT-UMP from the same cohort. We counted at least 2,000 tumor cells in the hot spot for the assessment of Ki-67 labeling index. Results: Microarray analysis revealed GGCT exhibited high expression levels at the invasive front of FTC. In immunohistochemical assessment, GGCT expression scores were significantly higher in FTC than in FA (118.5 ± 51.4 vs. 57.3 ± 34.7, p < 0.0001). The median Ki-67 labeling index were 3.9% (range 0.2 - 16.1) for FTC and 2.4% (range 0.3 - 7.0) for FA. FTC showed a higher Ki-67 index than FA (Wilcoxon rank sum test, p = 0.0444). With GGCT expression score, applying a cutoff value of 101.1, the distinction between FTC and FA resulted in a sensitivity of 68.8% and a specificity of 87.5% (AUC: 0.832). With Ki-67 labeling index, applying a cutoff value of 4.0%, the distinction between FTC and FA resulted in a sensitivity of 50.0% and a specificity of 80.0% (AUC: 0.677). The GGCT expression score was positively related with the Ki-67 labeling index in the FTC cases. (Spearman's ρ = 0.5293, p = 0.0164). There were no significant associations between GGCT expression scores and clinicopathological parameters, including age, gender, tumor diameter, pT stage, pN stage, pattern of capsular invasion, number of foci of vascular invasion, and the presence of distant metastasis. Conclusions: GGCT is a potential marker for differentiating FTC from FA. The GGCT expression of FTC may contribute to estimating the invasive activity and proliferative activity. Citation Format: Toshiyuki Mitsuhashi, Sachiko Ogasawara, Masamichi Nakayama, Reiichiro Kondo, Jun Akiba, Kenta Murotani, Takeharu Ono, Fumihiko Sato, Hirohito Umeno, Hirohisa Yano. GGCT expression is a useful marker for the diagnosis of follicular thyroid carcinoma [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 6273.

Identification of invasive subpopulations using spatial transcriptome analysis in thyroid follicular tumors.

Follicular tumors include follicular thyroid adenomas and carcinomas; however, it is difficult to distinguish between the two when the cytology or biopsy material is obtained from a portion of the tumor. The presence or absence of invasion in the resected material is used to differentiate between adenomas and carcinomas, which often results in the unnecessary removal of the adenomas. If nodules that may be follicular thyroid carcinomas are identified preoperatively, active surveillance of other nodules as adenomas is possible, which reduces the risk of surgical complications and the expenses incurred during medical treatment. Therefore, we aimed to identify biomarkers in the invasive subpopulation of follicular tumor cells. We performed a spatial transcriptome analysis of a case of follicular thyroid carcinoma and examined the dynamics of CD74 expression in 36 cases. We identified a subpopulation in a region close to the invasive area, and this subpopulation expressed high levels of CD74. Immunohistochemically, CD74 was highly expressed in the invasive and peripheral areas of the tumor. Although high CD74 expression has been reported in papillary and anaplastic thyroid carcinomas, it has not been analyzed in follicular thyroid carcinomas. Furthermore, the heterogeneity of CD74 expression in thyroid tumors has not yet been reported. The CD74-positive subpopulation identified in this study may be useful in predicting invasion of follicular thyroid carcinomas.

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

PurposeRAS mutations represent common driver alterations in thyroid cancer. They can be found in benign, low-risk and malignant thyroid tumors with follicular architecture, which are often diagnosed as indeterminate nodules on preoperative cytology. Therefore, the detection of RAS mutations in preoperative setting has a suboptimal predictive value for malignancy. In this study, we investigated differentially expressed microRNA (miRNA) in benign and malignant thyroid tumors with follicular architecture carrying mutations in RAS genes.MethodsTotal RNA was purified from 60 RAS-mutant follicular-patterned thyroid tumors, including follicular adenoma (FA), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), papillary and follicular thyroid carcinoma cases (PTC, FTC); 22 RAS-negative FAs were used as controls. The expression analysis of 798 miRNAs was performed by digital counting (nCounter nanoString platform).ResultsComparing RAS-mutant and RAS-negative FAs, 12 miRNAs showed significant deregulation, which was likely related to the oncogenic effects of RAS mutations. Twenty-two miRNAs were differentially expressed in RAS-mutant benign versus malignant tumors. Considering the tumor type, 24 miRNAs were deregulated in PTC, 19 in NIFTP, and seven in FTC and compared to FA group; among these, miR-146b-5p, miR-144-3p, and miR-451a showed consistent deregulation in all the comparisons with the highest fold change.ConclusionsThe miRNA expression analysis of follicular-patterned thyroid tumors demonstrated that RAS mutations influences miRNA profile in benign tumors. In addition, several miRNAs showed a histotype-specific deregulation and could discriminate between RAS-mutant benign and RAS-mutant malignant thyroid lesions, thus deserving further investigation as potential diagnostic markers.

Follicular thyroid carcinoma detected in ⁶⁸Ga-PSMA PET/CT imaging. Case report.

Introduction: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein located on the cell membrane, initially discovered in prostate cells, and highly expressed in the cells and metastases of prostate carcinoma. 68Ga-PSMA PET/CT is a molecular imaging technique widely used in the algorithm of this pathology. PSMA expression has been observed in several malignancies, usually incidentally. We report a case of follicular thyroid carcinoma detected in ⁶⁸Ga-PSMA PET/CT. To our knowledge, only 3 cases have been reported in the literature to date. Clinical findings: Patient with a history of prostate cancer adenocarcinoma, who after initial treatment, presented biochemical recurrence. A Ga68-PSMA PET/CT was performed, showing uptake of the radiopharmaceutical in the left thyroid lobe. Interventions: The patient was evaluated by the head and neck specialty, taken to total thyroidectomy plus central dissection. The pathology report confirms a follicular thyroid carcinoma. Conclusion: Ga68-PSMA PET/CT is a molecular image with high diagnostic performance in prostate cancer, however, its uptake in other solid tumors is well established, so attention should be paid to these uptakes, since the the vast majority may be related to another type of primary tumor. This is an example of PSMA uptake in follicular carcinoma of the thyroid.

A rare case of follicular thyroid carcinoma with metastasis to the scalp

A rare case of follicular thyroid carcinoma with metastasis to the scalp

The Prognostic Impact of Extent of Vascular Invasion in Follicular Thyroid Carcinoma.

Encapsulated angioinvasive follicular thyroid carcinoma (EAFTC) is associated with an increased risk of distant metastasis and reduced survival compared to minimally invasive follicular thyroid carcinoma (MIFTC). There is controversy regarding the extent of surgery and adjuvant radioactive iodine therapy for angioinvasive follicular thyroid carcinoma when stratified by number of foci of angioinvasion. All follicular thyroid carcinoma cases from 1990-2018 were identified from a thyroid cancer database. Primary outcomes were distant metastasis-free survival (DMFS) and disease-specific survival (DSS) with factors of interest being age, gender, tumour size, treatment, foci of angioinvasion and histological subtype. A total of 292 cases were identified; 139 MIFTC, 141 EAFTC and 12 widely invasive follicular thyroid carcinoma (WIFTC). Over a follow-up period of 6.25years, DMFS was significantly reduced (p < 0.001) with 14.2% (EAFTC) and 50% of WIFTC developing metastasis. The risk of metastasis in EAFTC with ≥ 4 foci of angioinvasion was 31.7% (HR = 5.89, p = 0.004), 6.3% for EAFTC with < 4 foci of angioinvasion (HR = 1.74, p = 0.47), compared to 3.6% MIFTC. Age ≥ 50years (HR = 4.24, p = 0.005) and tumour size (HR = 1.27, p = 0.014) were significantly associated with increased risk of distant metastasis. DSS was reduced significantly (p < 0.001), with 7.8% EAFTC patients dying of disease. For EAFTC patients, DSS was 96.8% for < 4 foci and 82.6% for ≥ 4 foci of angioinvasion (p = 0.003). EAFTC is at increased risk of distant metastasis related to the extent of angioinvasion. Tumours with < 4 foci of angioinvasion should be considered for a total thyroidectomy, particularly in older patients.

High Prevalence of Gene Fusions and Copy Number Alterations in Pediatric Radiation Therapy-Induced Papillary and Follicular Thyroid Carcinomas.

Background: Childhood cancer survivors and bone marrow transplant recipients treated with radiation therapy (RT) are at increased risk for subsequent thyroid cancer. However, the genetic landscape of pediatric thyroid cancer, both primary and RT-induced, remains poorly defined, as pediatric papillary thyroid carcinoma (PTC) has been understudied compared with adults and data on pediatric follicular thyroid carcinoma (FTC) are virtually nonexistent. The objective of this study was to characterize and compare the molecular profiles of pediatric RT-induced PTC and FTC cases with primary pediatric thyroid cancers. Methods: A total of 41 differentiated thyroid carcinomas (11 RT cases and 30 primary cases) from 37 patients seen at Phoenix Children's Hospital between January 1, 2010 and December 31, 2019 were evaluated by targeted next-generation sequencing and/or BRAF immunohistochemistry. Results: Eighty-six percent (6/7) of RT-PTC harbored a gene fusion (GF) compared with 56% (14/25) of primary PTC; 14% (1/7) of RT-PTC had a single-nucleotide variant (SNV; specifically, a point mutation in the DICER1 gene) compared with 44% (11/25) of primary PTC (all of the latter had the BRAFV600E mutation). An exceedingly rare ROS1 fusion was identified in a child with RT-PTC. With respect to FTC, copy number alterations (CNAs) were seen in 75% (3/4) of RT cases compared with 40% (2/5) of primary cases. None of the RT-FTC had SNVs compared with 100% (5/5) of primary FTC. Conclusions: In children, the molecular profile of subsequent RT-induced thyroid cancers appears to differ from primary (sporadic and syndromic) cases, with a high prevalence of GFs in RT-PTC (similar to PTC occurring after the Chernobyl nuclear reactor accident) and CNAs in RT-FTC. A better understanding of the molecular mechanisms underlying these cancers may lead to more accurate diagnosis, prognosis, and treatment, as some of the genomic alterations are potentially targetable.

A Case of Solitary Metastatic Deposit in the Orbital Rim from Follicular Thyroid Cancer

Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer, following papillary carcinoma. Metastasis to the orbital rim from FTC is very rare. We recently experienced a case of FTC with metastasis to the orbital rim in a 74-year-old woman, who initially presented with a huge thyroid mass and an asymptomatic solitary orbital rim lesion. The solitary orbital rim lesion was suspected to be a separate disease entity such as lymphoma from the preoperative imaging, but bone metastasis from FTC was finally confirmed after orbital rim resection and total thyroidectomy. During follow-up, the patient presented multiple bone metastasis, so the solitary orbital rim lesion was considered a clinical sign of systemic metastasis from FTC. Therefore, we present this unique case with a review of the literature.

Molecular Profiling in Thyroid cancer- Using next generation sequencing to differentiate rare cases of papillary thyroid hyperplasia from papillary thyroid carcinoma

Abstract Introduction/Objective Differentiating papillary thyroid hyperplasia from papillary thyroid carcinoma is made primarily on differences in key histologic and cytomorphologic features. These include architectural features such as invasion and nuclear changes such as chromatin pallor, nuclear grooves, and intranuclear pseudoinclusions. Distinguishing between these two diagnoses is not always straightforward in a minority of cases, as papillary thyroid hyperplasia nodules can be misinterpreted as papillary thyroid carcinoma and vice versa. This is because the nuclear changes can be subtle and be induced artificially by poor or inadequate formalin fixation. Immunostains such as cytokeratin 19 (CK19), galectin-3, and HBME1 may be used to distinguish between papillary thyroid hyperplastic nodules and papillary thyroid carcinoma; however, as immunostaining results are not always definitive, other more definitive ancillary tests are sometimes utilized such as molecular testing. Methods/Case Report Thyroid cases with indeterminate diagnoses (n=6) were obtained from the archives. Such cases included papillary thyroid hyperplasia and cases with descriptive diagnoses such as well-differentiated encapsulated and low-grade papillary carcinoma. Five cases of definitive papillary thyroid carcinoma and one case of follicular thyroid carcinoma (n=6) were used as a comparison group. Next generation sequencing (NGS) assays were performed using a custom SLIMamp targeted DNA solid tumor panel (Pillar Biosciences) and a targeted multi gene RNA fusion panel (Invitae). Results (if a Case Study enter NA) All of the definitive cases of papillary thyroid carcinoma showed characteristic mutations such as BRAF V600E as well as RNA fusions such as RET/PTC while all of the indeterminate cases did not show any detectable DNA mutations or RNA fusions, confirming their benign nature. A separate case that was signed out as non-invasive follicular thyroid neoplasm with papillary-like nuclear features showed an NRAS Q61R mutation and a novel ETV1-ERG fusion. Conclusion This study demonstrates the utility of molecular testing as an adjunct to histopathological evaluation in definitive diagnosis and differentiation of papillary thyroid hyperplasia from papillary carcinoma. Next generation sequencing with targeted DNA and RNA panels will be beneficial for both known and novel variant or fusion detection in suspect cases.

Follicular Thyroid Carcinoma in a Developing Country: A 10-Year Retrospective Study.

BackgroundThe most common endocrine tumor is thyroid cancer. Follicular thyroid carcinoma (FTC) accounts for 5-10% of all thyroid cancers. Patients with FTC frequently present with more advanced diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery while radioactive iodine (RAI) therapy is the main adjuvant therapy according to the American Thyroid Association guidelines.MethodologyThis was a retrospective observational study of FTC patients aged 18 and above conducted at a tertiary care hospital in Karachi from January 01, 2010 to December 31, 2019.ResultsA total of 404 patients with thyroid carcinoma were sorted, of which 40 (10.1%) were FTC cases. Overall, 50% of the patients were in the age group of 41-60 years, and the female-to-male ratio was 1.5:1. The majority of patients (60%) presented with neck swelling, followed by bone and lung metastasis in 20% and compressive symptoms in another 20%. On fine needle aspiration cytology (FNAC), 50% had Bethesda category III-IV nodules while 10% had Bethesda category II. Overall, 50% had a total thyroidectomy while 50% had a lobectomy followed by a completion thyroidectomy. On histopathology, 23 (57.5%) patients had minimally invasive FTC while 17 (42.5%) had widely invasive FTC. A total of 17 (42.5%) patients had received RAI 30-100 mCi while 10 (25%) received more than 100 mCi.ConclusionsFTC can present with both local or metastatic symptoms. The atypical presentation of metastatic FTC should be considered, diagnosed, and managed early to limit mortality and morbidity. Ultrasound is the best diagnostic investigation of choice followed by FNAC. Surgery is the mainstay of treatment and should be followed by RAI in select cases. Thus, understanding the trend of FTC and proper planning and utilization of the resources will help developing countries in effectively treating the FTC.

A Tale of Three Cases When Thyroid Cancer Does Not Exist but Metastases Do. A Three-Case Series of Metastatic Follicular Thyroid Carcinoma

Background: Follicular and papillary thyroid carcinomas represent the majority of all malignancies of the thyroid gland. However, follicular thyroid carcinoma (FTC) is much more difficult to diagnose and manage than its papillary counterpart. Among other factors this could be explained by changing diagnostic criteria and by FTC potential for remote distant and often unpredictable metastases sites. Clinical Cases: In our high volume major academic referral center we have encountered three intriguing cases of metastatic FTC with negative surgical thyroid pathology. The first patient is a 61-year-old woman, who at age 50 was diagnosed with 5.4x3.5x4.2 cm left thyroid nodule (TN). FNAB reported hyperplastic nodule versus follicular neoplasm, subsequent surgical pathology report after lobectomy showed hyperplastic nodule. At age 58 she developed a pathological fracture of the 5th thoracic vertebra and pathology report indicated follicular carcinoma of thyroid origin. TG level at this time was 577 ng/ml. Pathology report from completion thyroidectomy again showed nodular hyperplasia, but reexamination of previously resected lobe demonstrated minimally invasive FTC. The second patient is an 83-year-old woman who at age 68 underwent lobectomy for left sided-goiter, pathology report showed benign follicular adenoma. At age 77 she was found to have right-sided skull mass which was determined to be a follicular carcinoma of thyroid origin. Pathology report from completion thyroidectomy was consistent with nodular hyperplasia. At age 82 the patient was noticed to have increased RAI uptake in thyroid bed, sternum, kidneys, and gastroesophageal junction. TG level at this time was 2214 ng/ml. The third patient is a 56-year-old woman initially diagnosed with a 3.5x2.8x2.2cm right TN at age 53. Lobectomy, performed for diagnostic and therapeutic purposes, showed benign follicular adenoma. At age 56 she developed a pathological fracture of the 3rd thoracic vertebra, follicular carcinoma of thyroid origin was shown on pathology report. TG level at this time was 1694 ng/ml. The patient underwent completion thyroidectomy demonstrating multinodular hyperplasia. Conclusion: This case series emphasizes on the pitfalls of follicular neoplasms diagnosis and management. We suggest prolonged clinical and biochemical surveillance of the patients with what appears to be follicular adenoma after lobectomy. Following serum thyroglobulin perhaps represents the most cost-effective surveillance approach of those patients.

No correlation between Galectin-3 expression and clinicopathological features of follicular thyroid carcinoma minimally invasive: study in single institution

Abstract&#x0D; Background. Galectin-3 has been suggested to involve in invasion and aggressive behaviour of several cancer. The aim of this study is to evaluate the immunoreactivity of Galectin-3 in follicular thyroid carcinoma (FTC) in an attempt to investigate its association with clinicopathology of FTC.&#x0D; Method. This study included 46 selected paraffin embedded tissue blocks from surgically resected follicular thyroid carcinoma minimally invasive, consists of 23 cases of FTC capsular invasion only and 23 cases of FTC encapsulated angioinvasive. Immunohistochemistry staining for Galectin-3 were performed on all cases. Galectin-3 protein expression was observed in the cytoplasm and the nucleus of examined tissues.&#x0D; Result. Forty-three (93.5%) samples had strong or moderate staining and 3 (6.5%) tumours had negative or weak staining. Positive immunoreactivity of Galectin-3 was found in 18/23 (78.3%) cases of FTC capsular invasion only and 20/23 (86.9%) cases of FTC encapsulated angioinvasive. The galectin-3 did not show association with the sex (p=0.345), age (p=0.200), and tumour size (p=0.767). There was no significant difference of Galectin-3 immunohistochemical expression between FTC capsular invasion only and FTC encapsulated angioinvasive (p= 0.699).&#x0D; Conclusion. No differentiation of sex, age, tumour size, and immunohistochemical expression of galectin-3 in capsular invasion only and encapsulated angioinvasive of minimally invasive FTC.

Significance of Insulin-Like Growth Factor II Mrna-Binding Protein 3 (IMP3) Expression in Selected Thyroid Lesions

Background: Differentiation of benign from malignant follicular thyroid lesions remains difficult and the ability of molecular markers to differentiate between them still unclear. The aim of this study was to evaluate the usefulness of IMP3 expression to distinguish benign from malignant thyroid lesions. Methods: This is a retrospective study upon selected 57 thyroid lesions designated as; 7 cases of Hashimoto thyroiditis (HT), 10 cases of hyperplastic nodules (HN), 15 cases of follicular thyroid adenoma (FTA), 13 cases of conventional papillary thyroid carcinoma (PTC), 6 cases of follicular variant of papillary thyroid carcinoma (FV-PTC), and 6 cases of follicular thyroid carcinoma (FTC). Immunohistochemistry was applied on formalin-fixed, paraffin-embeded tissue blocks using IMP3. clinicopathological data were reviewed from patients' pathological reports and correlated with IMP3 expression. Results: IMP3 positivity was seen in1/7 cases (14.3%) of HT, 2/10 cases (20%) of HN, 4/15 cases (26.7%) of FTA, 12/13 cases of PTC, and in all (100%) FV-PTC & FTC cases. IMP3 staining was significantly increased from normal thyroid tissue up to malignant tumors (P<0.01). IMP3 showed 96% sensitivity and 78.1% specificity for malignant tumors. IMP3 expression was positively correlated with grade and tumor size in malignant cases (P<0.05). No significant correlation was found in IMP3 expression with patient age, sex, capsular invasion, lymphatic/vascular invasion, lymph node metastasis, distant metastasis and TNM stage. Conclusions: IMP3 is a potential diagnostic marker for thyroid cancer and can be a promising marker for distinguishing benign from malignant follicular patterned thyroid lesions.

SUN-488 A Coexisting of Two Different Thyroid Malignancies: A Collision Phenomenon

A Coexisting of Two Different Thyroid Malignancies: A Collision Phenomenon Introduction: Collision tumors are rare clinical entities wherein two histologically distinct tumor types occur at the same anatomic sites. Simultaneous papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) of the same thyroid is a very rare occurrence with limited clinical information. Herein, we report a case of PTC and FTC of the same thyroid lobe. Clinical case: A 79-year-old man presented to the emergency department for evaluation of left hip pain of 2-month duration. Three days before presentation, he sustained a physical trauma to the left side of his body. X-ray imaging of the left femur revealed a lytic bony lesion measuring approximately 5.2 cm x 4.2 cm at the proximal end of left femur as well as a displaced pathologic fracture of its lesser trochanter. Biopsies of the bone lytic lesion suggested metastatic follicular thyroid carcinoma. CT of the neck revealed an enlarged thyroid with a cystic lesion as well as 2 nodules in the left lobe of thyroid gland. Total thyroidectomy was performed. Histopathology revealed 2 separate primary malignancies of PTC and FTC. Following diagnosis, laboratory test results showed TSH 2.6 uIU/mL (reference range, 0.2–4), anti-thyroglobulin antibody (anti Tg) < 1.0 IU/mL (reference range, 0.0–0.9), calcitonin 8.4 pg/mL (reference range, 0–8.4), and CEA 1.1 ng/mL (reference range, 0.0–3.0). The patient was placed on thyroid hormone replacement therapy and was treated with external beam radiation to his bone metastasis. He was scheduled for later further thyroid ablation. In his follow-up visit, three months later, he reported no pain on ambulation. Discussion: For each type of thyroid malignancy, several genes have been identified. However, to date, no common gene mutation responsible for the pathogenesis of the different tumor types has been determined. For instance, point mutations of the RAS oncogene are found in about 40% of thyroid neoplasms (N-RAS, H-RAS, and K-RAS, in order of decreasing frequency) including both PTC and FTC. No single theory can completely explain the pathogenesis of these tumors in all cases, and so, with the present level of understanding of the disease, a combination of theories must be accepted. Management of collision tumors of the thyroid gland is usually complex owing to the presence of dual pathology in the tumor tissues and given the fact that literature on this condition is scarce. Generally, the treatment needs to be individualized. Conclusion: Most likely, a rare phenomenon of simultaneous mutation of different genes can give birth to contemporary different thyroidal neoplasms.

GABPA-dependent down-regulation of DICER1 in follicular thyroid tumours.

Mutations in the miRNA enzyme gene DICER1 have been reported in several endocrine malignancies and is associated with the rare tumour-predisposing DICER1 syndrome. DICER1 mutations have been reported in subsets of follicular thyroid carcinoma (FTC), but the role of DICER1 in follicular thyroid tumorigenesis has not been extensively studied. In this study, we investigate the role of DICER1 in 168 follicular thyroid tumours and in an FTC cell line. We found rare DICER1 mutations in paediatric FTC cases and a general DICER1 down-regulation in FTCs visualized both on mRNA and protein level, especially pronounced in Hürthle cell carcinoma (HuCC). The down-regulation was also evident in follicular thyroid adenomas (FTAs), suggesting a potential early step in tumorigenesis. The expression of DICER1 was lower in FTCs of older patients in which TERT promoter mutations are more frequent. In FTCs, DICER1 down-regulation was not caused by gene copy number loss but significantly correlated to expression of the transcription factor GABPA in clinical cases. GABPA was found to bind to the DICER1 promoter and regulate DICER1 expression in vitro, as GABPA depletion in FTC cell lines reduced DICER1 expression. This in turn stimulated cell proliferation and affected the miRNA machinery, evident by altered miRNA expression. To conclude, we show that GABPA directly regulates DICER1 in FTC, acting as a tumour suppressor and displaying down-regulation in clinical samples. We also show reduced expression of DICER1 in benign and malignant follicular thyroid tumours, suggesting a potentially early tumorigenic role of this gene aberrancy.

Overexpression of mir-129-1, miR-146b, mir-183, and mir-197 in follicular thyroid carcinoma and adenoma tissues

Follicular thyroid carcinoma (FTC) is responsible for approximately 10% of thyroid malignancies. Since this type of malignancy indicates no capsular and vascular invasions, adenoma and follicular carcinoma of thyroid are not distinguishable. It has been proved that microRNAs, which regulate approximately 30% of coding proteins, have an association with follicular thyroid adenoma (FTA) and carcinoma of the thyroid. Therefore, the aim of this study was to assess the expression of some miRNAs for detecting the most appropriate miRNA as potential biomarker in the diagnosis of FTA and FTC patients. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression levels of miR-129-1, miR-146b,-183 and miR-197 in 48 cases (16 FTC, 16 FTA and 16 hyperplasia/multinodular goiter (MNG) cases). The significance of miRNA differential expression levels among groups were assessed using Multivariate test by Statistical Package for Science Software (SPSS v.20) and Graph Pad Prism v.8. Results indicated that all of the miRNAs had significant overexpression in FTC and FTA versus MNG cases, and also increased expression level in FTC in comparison with FTA, however it was not significant. The results of ROC curve analysis determined the significant overexpression and prognostic value of miR-129-1 in FTA cases and miR-146b in both FTA and FTC cases compared to MNG group. Although all of the earlier mentioned microRNAs were overexpressed in FTC and FTA cases, the ROC curve results demonstrated that miR-129-1 had agreeable AUC for FTA cases. Therefore, it seems that it's cut-off point could be helpful in distinguishing between FTA and multinodular goiter cases. On the other hand, although miR-146b has excellent diagnostic value in both FTA and FTC groups, it seems that this microRNA is unable to act as a specific biomarker to discriminate between FTA and FTC cases. This data need to be confirmed in a large cohort study and other biological samples such as plasma.

Two Cases of Follicular Thyroid Carcinoma with Bone Metastasis Controlled by Low-Dose Lenvatinib

Two Cases of Follicular Thyroid Carcinoma with Bone Metastasis Controlled by Low-Dose Lenvatinib

Simultaneous occurrence of follicular and papillary thyroid carcinomas in same thyroid lobe: A case series of six patients from Qatar

BackgroundPapillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are the first and second most common thyroid cancers comprising about 85% and 10% of all thyroid cancers. Simultaneous occurrence of medullary and papillary thyroid cancer has been reported with various presentations, but simultaneous occurrence of FTC in addition to PTC as differentiated cancers, is an unusual event that is rarely reported. Presentation of casesWe report our experience of six rare cases of synchronous coexistence of FTC and PTC with unique features. Case 1 is 31 old Egyptian female. Case 2 is a 61 year old Sudanese male. Case 3 is a 59 year old Sudanese male. Case 4 is a 56 years old Indian female. Case 5 is a 35 years old Filipina female. Case 6 is a 52 years old Qatari female. The six cases are special in their co-occurrence of two thyroid carcinoma, consisting of histologic features of follicular thyroid carcinomas, and classical papillary thyroid carcinoma, possibly the first case series of simultaneous occurrence of these two types of thyroid cancer in the Middle East and North Africa Region. ConclusionsWe present rare cases of concurrent FTC and PTC. These six cases add more data highlighting the coincidental simultaneous coexistence of FTC and PTC. Endocrinologists and pathologists should be aware of and vigilant to this variety.

Application of Galectin-3, HBME-1, Cytokeratin-19, and CD56 in the Diagnosis of Thyroid Neoplasm

Objective: The purpose of this study was to investigate the effectiveness of immunohistochemical thyroid malignancy markers Galectin-3, HBME-1, Cytokeratin-19, and CD56 in the diagnosis of thyroid neoplasm. Methods: The study included a total of 53 cases of thyroid neoplasm on which immunohistochemical IHC staining was performed using the manual staining method. Results: The histopathological diagnosis of thyroid nodules was papillary thyroid carcinoma in 40 (75.5%), follicular thyroid carcinoma in 3 (5.7%), follicular adenoma in 8 (15.1%), medullary thyroid carcinoma in 1 (1.9%), and Hurthle cell carcinoma in 1 (1.9%). Out of 40 cases of papillary thyroid carcinoma, Galectin-3 and CK19 were positive in 36 (90%) cases while expression of HBME1 was seen in 32 (80%) papillary thyroid carcinoma cases, and 16 (40%) stained positive for CD56. For the three follicular thyroid carcinoma cases, CD56 was positive in one case, but the marker was positive in 7 out of 8 cases (87.5%) of follicular adenoma. Conclusion: Our results suggest Galectin-3 and HBME-1 are the most sensitive diagnostic markers for differentiating papillary carcinoma from follicular neoplasm.

Comparison of PTEN expression in hashimoto thyroiditis, follicular adenoma, papillary and follicular carcinomas

Aim: Thyroid malignancies account for approximately 3% of all human cancers. A loss or reduction in the expression of a tumor suppressor gene, PTEN has been observed in approximately 40% of thyroid tumors. This change in PTEN expression has been shown to be due to PTEN mutation or deletion. The aim of this study was to compare the PTEN expression among Hashimoto thyroiditis, follicular adenomas and malignant tumors originating from thyroid follicle epithelial cells. Material and Methods: 101 cases of thyroid carcinoma were studied and classified into differentiated types including 15 cases of follicular thyroid carcinomas (FTC), 28 cases of papillary thyroid carcinomas (PTC), 29 cases of follicular adenomas (FA) and 29 cases of Hashimoto thyroiditis (HT). PTEN expression in all the cases were analyzed immunohistochemically. Results: The cytoplasmic and nuclear staining intensity in Hashimoto thyroiditis showed minimal loss of PTEN expression. The nuclear and cytoplasmic staining intensity and percentage in Hashimoto thyroiditis and follicular adenomas were similar. In most of the papillary carcinoma samples, PTEN expression was lost as deduced from cytoplasmic and nuclear staining intensity. While the loss of nuclear PTEN expression was the highest in follicular carcinoma, the cytoplasmic loss was minimal. Conclusions: Loss of PTEN expression is more pronounced in papillary and follicular carcinomas than benign lesions. PTEN has been shown to play an oncogenic role in papillary and follicular carcinoma. PTEN expression loss can be used as a new biomarker in PTC and FTC cases.