Photoacoustic detection of follicular thyroid carcinoma using targeted Nano-Au-Tripods

Follicular thyroid carcinoma(FTC)is the second most common form of thyroid malignancy,and it is associated with more aggressive growth and worse long-term survival outcomes relative to papillary thyroid carcinoma(PTC).Reliable approaches to preoperative FTC detection,however,remain to be established.Herein,a targeted Affibody-Au-Tripod nanoprobe was developed and successfully utilized to facilitate the targeted photoacoustic imaging(PAI)of epidermal growth factor receptor(EGFR)-positive cells and tumors.These Affibody-Au-Tripods were found to be highly sensitive and specific for cells expressing EGFR when used as a PA contrast agent in vitro,and studies conducted in an FTC-133 subcutaneous tumor model system in mice further revealed that these Affibody-Au-Tripods were able to specifically target these EGFR-expressing tumors while providing a strong photoacoustic signal in vivo.Importantly,these nanoprobes exhibited negligible cytotoxicity and robust chemical and physical stability,making Affibody-Au-Tripods promising candidates for targeted PAI-based FTC diagnosis.In addition,these nanoprobes have the potential to facilitate the individualized treatment of patients harboring EGFRpositive tumors.

A Surgical Case of Bilateral Pulmonary Metastases from Thyroid Follicular Cancer

An 80-year-old woman underwent a bilateral lung resection for metastases originating from follicular thyroid cancer. The resection was performed 30 years after right hemithyroidectomy to remove the follicular adenoma. Chest X-ray revealed a 30-mm mass shadow in the right lower lung filed. Chest computed tomography revealed a 32-mm mass shadow in right lung segment 10 (S10) and a 15-mm nodular shadow in left S10. Another partial lung resection of left S10 and a right lower lobectomy were performed 3 months later. Although rarely performed, resection of bilateral pulmonary metastases arising from follicular thyroid cancer was conducted for this patient.

Thyroid follicular renal cell carcinoma excluding thyroid metastases:A case report

BACKGROUND Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years.It has attracted attention because of its unique histology,immunophenotype,and clinical characteristics.It has a very low incidence,and the number of case reports available for review is limited.Moreover,a thyroid mass with type of tumour is rare.CASE SUMMARY We report a case of a renal mass with a bilateral thyroid mass that was accidentally discovered in a 60-year-old man during physical examination.B-mode ultrasound showed a hypoechoic mass in the middle and lower parenchyma of the right kidney,and computed tomography showed an iso-density shadow tumour in the right kidney.Contrast agents had a significant continuous enhancement effect on the tumour,and the enhancement was not uniform.After partial nephrectomy,pathological analysis was performed to rule out the possibility that the renal tumour was caused by thyroid tumour metastasis.Needle biopsy of the thyroid tumour confirmed that the renal cell carcinoma was not related to the thyroid tumour.The patient was alive at the last postoperative follow-up.CONCLUSION This is the third published case in which thyroid tumour biopsy was performed to confirm that thyroid follicular renal cell carcinoma is not thyroid related.

The Utility of Fine-Needle Aspiration in the Diagnosis and Management of Follicular Thyroid Neoplasms:One Institution’s 10-Year Experience

Background: Classical teaching dictates that follicular adenoma (FA) can be distinguished from follicular carcinoma (FC) based on histologic features only. We retrospectively reviewed our institution’s 10-year experience in the use of fine-needle aspiration (FNA) to diagnose follicular thyroid neoplasms. Methods: Patients who had FNA of a thyroid neoplasm from 2000 to 2010 were reviewed. Diagnoses of FA, FC, or follicular neoplasm-not otherwise specified (NOS) were included. Cytopathological results were correlated with surgical pathology. Results: Of 138 patients, 65% underwent surgery. FNA diagnosis for FA had a sensitivity of 50% and specificity of 71%. 25% of patients with an FNA diagnosis of FA were found to have cancer after surgical specimen examination. FNA diagnosis for FC had a sensitivity of 60% and specificity of 94%. Conclusions: FNA has a low sensitivity for diagnosing FA. Surgical pathology remains the gold standard for differentiating follicular carcinoma from adenoma.

Trefoil Factor 3 (TFF3) mRNA Expression Level in Follicular Thyroid Tumors Using Formalin-Fixed, Paraffin-Embedded (FFPE) Blocks

Background: Differential diagnosis of follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) is often difficult since presence or absence of capsular/vascular invasion can not be determined by preoperative fine needle aspiration cytology, and may not be judged unanimously on permanent sections even among experienced pathologists. Determination of molecular-genetic factors such as trefoil factor 3 (TFF3) mRNA in the follicular thyroid tumors may be useful aid to improve the accuracy of diagnosis, though it is considered to be unstable and relatively low concentrated genetic substance. Purpose of our study is to investigate expression level of TFF3 mRNA of thyroid follicular tumors using formalin-fixed, paraffin-embedded (FFPE) tissue. Methods: Study population included FFPE sections from 19 FTC cases, 20 FTA cases, 11 adenomatous goiter (G) cases and 12 samples of normal thyroid tissue (N) adjacent to thyroid tumors. RNeasy FFPE kit was used for extraction of total RNA. Purification and concentration values were determined by spectrophotometer. Extracted RNA was used for cDNA synthesis in reverse transcription. Synthesized cDNA subsequently proceeded for relative quantification of TFF3 mRNA by RT-qPCR using TFF3 primers. Glyceroldehyde-3-phosphate dehydrogenase (GAPDH) and hypoxanthin phosphorobosyltransferase1 (HPRT1) were used as control genes. The mean and standard deviation of TFF3 mRNA expression level were analyzed by software Multiplate RQ. Results: Extraction by the FFPE kit yielded high concentration of RNA in all cases. Purification values were 1.8 in average. Concentration values were significantly higher in FTC and FTA relative to G and N tissues, possibly due to high density of thyrocytes in the samples. Relative quantification of TFF3 mRNA expression level showed broad ranges both in FTC and FTA, while the analyses in G and N tissues indicated narrow ranges. Conclusion: FFPE tissues from thyroid follicular tumors can be used for measurement of unstable and low concentrated genetic substances such as TFF3 mRNA. Its diagnostic value yet remains to be determined.

Therapeutic challenges in metastatic follicular thyroid cancer occurring in pregnancy:A case report

BACKGROUND Hormones could play a role in the evolution of follicular thyroid cancer(FTC)for which we discuss an unusual presentation of FTC occurring during pregnancy.CASE SUMMARY A pregnant woman was admitted with FTC metastasis resulting in a gluteal mass.Preoperative abdominal computed tomography revealed liver metastasis for which the patient underwent total thyroidectomy and liver resection,oral radioiodine therapy and radiotherapy,followed by embolization of the pelvic mass.The patient died of cerebral hemorrhage 16 mo after the initial diagnosis.CONCLUSION Human chorionic gonadotropin and estrogen stimulation might have a role in cancer growth,especially during pregnancy.FTC management aims to stop disease progression and overcome hormonal imbalances after thyroidectomy thus reducing fetal complications.It is still under debate whether it is possible to combine optimal timing for treatment to ensure the best possible outcome with reduction of fetal complications and risk of cancer growth.

Progress in the Pathologic Diagnosis of Borderline Follicular Thyroid Tumor

With the progress of science and technology as well as the development of ultrasound technology,more and more thyroid tumors have been found.Follicular tumor is one of the most common thyroid tumors,but borderline follicular tumors are relatively rare.At present,the diagnosis of borderline follicular thyroid tumor is unclear prior to surgery,and it is difficult to identify in frozen section or even conventional section.In order to effectively improve the diagnostic sensitivity and specificity of borderline follicular thyroid tumor,this paper summarizes the new WHO(World Health Organization)classification of borderline follicular thyroid tumor along with diagnostic methods,including clinical fine needle aspiration cytology,histopathology,and molecular biology,and reviews the research progress.

Case Report of a Clear-Cell Variant of Follicular Thyroid Carcinoma

Clear-cell variants of follicular carcinoma are rare subtypes of thyroid cancer. There is no unified view of the histopathological features of clear cell variants, but follicular carcinomas composed predominantly of clear cells are distinguished from clear cell variants. In clinical practice, it is important to determine whether clear cell variants arise primarily from the thyroid gland or are thyroid metastases of other clear cell carcinomas, such as renal cell carcinoma. We present a case in which a patient with initially suspected anaplastic thyroid carcinoma due to a rapidly progressive anterior neck mass was diagnosed with a clear cell variant of follicular carcinoma after a tissue biopsy. The patient was treated with lenvatinib, then his performance status improved, and he was discharged from the hospital. On day 188 after discharge, a contrast-enhanced computed tomography (CECT) scan of the neck showed further shrinkage of the tumor. However, a CECT scan of the chest revealed multiple lung metastases. On day 233 after discharge, the patient developed severe pneumonia resulting from tracheal rupture due to intratumoral necrosis. It was difficult to decide whether lenvatinib should have been discontinued or reduced when lung metastasis appeared. It is necessary to accumulate additional cases to make informed decisions about continuing lenvatinib therapy.

Difference between papillary and follicular thyroid carcinoma outcomes:an experience from Egyptian institution

Objective: Differentiated thyroid carcinomas(DTCs) are classified into papillary thyroid carcinoma(PTC) and follicular thyroid carcinoma(FTC). DTCs are analyzed as a single group in clinical studies that investigated the prognostic factors and prognosis of these malignancies. However, the biological behaviors of these carcinomas significantly differ. In the present study, we aimed to detect differences in the outcomes between PTC and FTC in Mansoura University Hospital in Egypt. Methods: A total of 558 patients with histologically proven thyroid carcinomas from January 2003 to December 2012 were retrospectively enrolled. The clinical and pathological data of patients were reviewed. Results: Large primary tumor size, lymph node involvement, extrathyroid extension, and distant metastasis were significant poor prognostic factors for overall survival(OS) in old PTC patients. Cox hazard analysis showed that the patient's age, extra thyroid extension, and distant metastasis were the only independent prognostic factors. In FTC patients, only the distant metastasis and degree of tumor invasion were significant poor prognostic factors in OS univariate analysis. However, these factors were nonsignificant in multivariate analysis. The 10-year OS rates were 97% and 89% for PTC and FTC, respectively(P=0.003). The 10-year disease-free survival(DFS) rates were 77.2% in PTC vs. 65% in FTC(P=0.179). Conclusion: The significant prognostic factors vary between the two types of DTCs. Therefore, PTC and FTC patients need to be analyzed and reported independently. PTC survival is widely and significantly affected by age, extrathyroid extension, and distant metastasis. By contrast, these factors were nonsignificant in FTC, which showed poorer survival than PTC.

3D Gray Level Co-Occurrence Matrix Based Classification of Favor Benign and Borderline Types in Follicular Neoplasm Images

Since the efficiency of treatment of thyroid disorder depends on the risk of malignancy, indeterminate follicular neoplasm (FN) images should be classified. The diagnosis process has been done by visual interpretation of experienced pathologists. However, it is difficult to separate the favor benign from borderline types. Thus, this paper presents a classification approach based on 3D nuclei model to classify favor benign and borderline types of follicular thyroid adenoma (FTA) in cytological specimens. The proposed method utilized 3D gray level co-occurrence matrix (GLCM) and random forest classifier. It was applied to 22 data sets of FN images. Furthermore, the use of 3D GLCM was compared with 2D GLCM to evaluate the classification results. From experimental results, the proposed system achieved 95.45% of the classification. The use of 3D GLCM was better than 2D GLCM according to the accuracy of classification. Consequently, the proposed method probably helps a pathologist as a prescreening tool.

Operative indications of follicular type tumors,based on Japanese clinical guidelines

AIM: To investigate the accuracy of preoperative examinations in follicular type tumors, we re-evaluate results of our operative cases.METHODS: Cases are follicular neoplasms in 36 patients, which are more than 30 mm in diameter and underwent surgery in our hospital in 2005-2006. These cases had been suspected of malignancy on one or more of the preoperative examinations, including ultrasound(US), thallium-technecium(Tl-Tc) scinitigram,computed tomography(CT), or fine needle aspiration biopsy(FNA) examinations. Concern about operative procedure, lobectomy plus sentinel lymph node biopsy(SNB) was performed in all 36 follicular tumors at the first surgery. Because we can diagnose a suspected follicular tumor as carcinoma and can change the operative procedure intra-operatively, when the metastasis of lymph nodes, outside of the thyroid, is found. The operative procedure was changed from lobectomy to total thyroidectomy plus lymph nodes dissection(centralcomponent), when the SNB has metastasis. All thirty six cases were obtained to track the prognosis until 2012, for 6-7 years follow up periods.RESULTS: The final pathological results are 3 cases of follicular carcinoma, 6 cases of papillary carcinoma, 1 case of papillary carcinoma follicular type, 1 case of malignant lymphoma, 16 cases of follicular adenoma, and 9 cases of adenomatous goiter. The malignant tumor were observed in 11/36(30.6%) cases. All six papillary carcinomas were less than 20 mm, and present with follicular adenoma and adenomatous goiter, which have more than 40 mm diameter. In physical examination, tumor size of 36 cases of follicular neoplasm is more than 30 mm all at the time of surgery. The tumors were palpable somewhat stiff, such as no cystic component in 34 cases. Occasional dyspnea, dysphagia, and cough was accompanied in all 36 cases. The true ratio of correct diagnosis of preoperative US, Tl-Tc scinitigram, CT, and FNA were 17/36(47.2%), 16/36(44.4%), 24/36(66.7%), 21/36(58.3%), respectively. In 11 malignant cases, there was one SNB positive case(one lymph node metastasis in 3 SNB: 1/3). This case was changed the operative procedure from lobectomy to total thyroidectomy plus lymph node dissection(central component). There is other lymph nodes metastasis in dissected lymph nodes(4/15). For the remaining malignant 10 cases, the observations were selected without additional resection, because surgical margins and SN were negative in postoperative pathology results at the first operation. No recurrence and metastasis are allowed in 11 malignant cases, up to 7 years after post-operation. Over all, the more than 30 mm in diameter follicular neoplasms, which were suspected the malignancy in the one and more preoperative examinations, are present the malignancy by pathological diagnosis in 11/36(30.6%) cases after surgery. The non SNB metastasis cases had no symptoms of lymph nodes metastasis up to 7 years after post-operation.CONCLUSION: We think that more than 30 mm in diameter follicular neoplasms are considered as candidates of surgery from our results.

Core needle biopsy for thyroid nodules assessment-a new horizon?

Ultrasound-guided fine-needle aspiration is the standard for evaluating thyroid nodules with a high safety profile and a relatively low number of non-diagnostic cytological findings.Nevertheless,this diagnostic method traditionally has its weak points.Several diagnostic categories such as BethesdaⅠ,ⅢandⅣare not reliable for thyroid carcinoma risk assessment.Recent advancements in a core needle biopsy made it possible to use this tool as a new method for thyroid nodules evaluation.The main feature of this method is the use of thin needles(18-21G)and guns with an automatic trigger mechanism.The histological material collected with the use of a core needle biopsy is usually superior to cytological.Therefore,the core needle biopsy can be used as a complementary technique to a standard fine needle aspiration in difficult and dubious cases of thyroid neoplasia with uncertain malignant potential.

Evaluation with low-dose dual-phase helical computed tomography of patients with thyroid lesions

Background The incidence of thyroid cancer has been increasing.Our aim was to evaluate the efficacy of low-dose dualphase helical computed tomography （CT） in the characterization of thyroid lesions,and to discuss the relationship between image characteristics and their pathology.Methods One hundred and six patients with thyroid lesions underwent low-dose dual-phase helical CT after the injection of contrast material.CT scans were obtained at arterial and venous phase with delays of 25 and 65 seconds,and tube current of 60 and 120 mA,respectively.The attenuation change in the lesion between the arterial and venous phase was analyzed and categorized as ＂increased,＂ ＂decreased,＂ ＂mixed＂ or ＂no change.＂ Results Histopathologic diagnosis was obtained by surgery in 106 patients （115 lesions）.Of the 106 patients,45 had nodular goiter,5 thyroid adenoma,6 thyroiditis,and 50 papillary thyroid carcinoma （PTC） （59 lesions）.The attenuation value showed a significant difference （P ＜0.05） between the arterial and venous phase for the high attenuation area.There was statistical significant difference in terms of attenuation value in high attenuation areas at both phases and in low attenuation areas on arterial phase between nodular goiter and PTC （P ＜0.05）.However,there was no significant difference in attenuation value between adenoma and PTC.Twenty-nine cases （76.3％） of goiter manifested mixed type,3 cases （3/5） of adenoma showed decreased type,6 cases （6/6） of thyroiditis showed increased type,and 55 cases （93.2％） of PTC showed decreased type attenuation.The sensitivity,specificity for thyroid carcinoma by dual-phase CT were 94.9％ and 80.4％ respectively.The overall diagnostic accuracy for thyroid lesions by dual-phase CT was 87.8％.Conclusions The performance of dual-phase helical CT is related to the pathological structure of the lesions.The analysis of enhancement patterns by using dual-phase helical CT will be helpful in the differential diagnosis of thyroid lesions.

Hybrid model enabling highly efficient follicular segmentation in thyroid cytopathological whole slide image

Background The prevalence of thyroid cancer is growing rapidly.Early and precise diagnosis is critical in thy-roid cancer caring.An automatic thyroid cancer diagnostic tool can be valuable to achieve early detection and diagnostic consistency.Only the follicular areas in the sample contain useful information to the thyroid cancer diagnosis based on fine needle aspiration(FNA).This study aimed to develop a highly efficient accurate method for follicular cell areas segmentation(FCAS)of thyroid cytopathological whole slide images(WSIs).Methods A total of 96 cell samples from July 2017 to July 2018 were collected in one hospital in Beijing,China.Forty-three WSIs were selected and manually labeled,including 17 cases of papillary thyroid carci-noma sample and 26 cases of benign sample.Six thousand and nine hundred cropped typical image patches(available on https://github.com/bupt-ai-cz/Hybrid-Model-Enabling-Highly-Efficient-Follicular-Segmentation)of 1024×1024 pixels from 13 large WSIs were used for patch-level model training and testing and all of the 13 large WSIs were papillary thyroid carcinoma samples.Thirty testing WSIs with an average size 36,217×29,400(from 10,240×10,240 to 81,920×61,440)were used to test the effectiveness of the hybrid model.Based on the traditional semantic segmentation model deeplabv3,we constructed a hybrid segmentation architecture by adding a classification branch into the segmentation scheme to improve efficiency.Accuracy was used to measure the performance of the classification model;pixel accuracy(pAcc),mean accuracy(mAcc),mean intersection over union(mIoU),and frequency weighted intersection over union(fwIoU)were used to measure the performance of the segmentation model,respectively.Results Using this method,up to 93%WSI segmentation time was reduced by skipping the colloidal areas and the blank background areas.The average processing time of 30 WSI was 49.49 s.On the patch dataset,this hybrid model might reach pAcc=98.65%,mAcc=85.60%,mIoU=79.61%,and fwIoU=97.54%.On the WSI dataset,this model might reach pAcc=99.30%,mAcc=68.94%,mIoU=58.21%,and fwIoU=99.50%.Conclusion The proposed hybrid method might significantly improve previous solutions and achieve the superior performance of efficiency and accuracy.

Unusual Scalp Process Revealing a Thyroid Cancer: “Illustrative Case”

Background: Thyroid cancers commonly display slow evolution with local and or regional extension. The classic presentation is a painless nodule of the thyroid region in a euthyroid patient. Sometimes, the nodule is discovered only on ultrasonography. Cervical lymph node is often seen in papillary thyroid cancer due to their propensity to invade lymph node. This means that follicular thyroid cancers are more insidious. Observation: We report a painless slow-growing lesion of the scalp revealing a skull metastasis of thyroid cancer. Despite catastrophic intraoperative bleeding, a total removal was achieved. Lessons: Thus, in addition to local and regional control in the management of thyroid cancers, distant metastasis should be surgically removed to provide the best chance to prolong the patient’s survival. Moreover, neurosurgeon must be prepared to deal with massive bleeding in skull metastasis of thyroid cancer.

甲状腺滤泡性肿瘤的诊断研究进展

甲状腺滤泡状癌(FTC)不同于甲状腺滤泡性腺瘤,其特征为细胞的异型性以及包膜和血管浸润。由于肿瘤的良恶性只能通过术后病理鉴别,绝大部分滤泡性腺瘤患者采取诊断性腺叶切除,但接受腺叶切除的患者术后绝大部分为良性,因此目前亟须寻找一种针对FTC的额外诊断补充依据。术前评估肿瘤的良恶性可减少不必要的手术伤害和短期甚至长期的药物补充治疗。未来全面了解甲状腺滤泡性肿瘤的诊断进展,可以为疾病的治疗提供新思路。

经口入路和乳晕入路腔镜手术对甲状腺恶性病变患者术后美观满意度及生活质量的影响

目的 分析经口入路和乳晕入路腔镜手术对甲状腺恶性病变患者术后美观度满意度及生活质量的影响,为甲状腺疾病患者寻求更加有效且安全美观的手术治疗方式。方法 选取2022年1月至2023年3月甲状腺恶性病变手术患者120例,按照手术入路将患者分为经口腔前庭组55例和经乳晕组65例,经口腔前庭组采用经口腔前庭入路腔镜手术治疗,经乳晕组采取乳晕入路腔镜手术方法,对比2组患者的手术相关指标、美观满意度以及治疗后生活质量水平和术后并发症发生情况。结果 2组患者手术时间、住院时间以及术后SIS评分和VHI评分差异无统计学意义(P>0.05),经口腔前庭组的手术出血量及术后引流量低于经乳晕组,且经口腔前庭组术后VAS评分显著低于经乳晕组(P<0.05);经口腔前庭组的VSS、OSAS和PSAS评分均较经乳晕组低,其美观满意度较高(P<0.05);经口腔前庭组的治疗后SF-36各维度评分均较经乳晕组高(P<0.05);2组并发症发生率差异无统计学意义(P>0.05)。结论 甲状腺恶性病变患者手术治疗中,经口腔前庭入路腔镜手术治疗相较于经乳晕入路治疗方式更具安全性,患者术中损伤及术后疼痛均较为轻微,且无瘢痕美观性更强,有助于促进患者身心状态和生活质量提升,属于安全且有效的手术治疗方法。

滤泡亚型及经典型甲状腺乳头状癌的临床特征和颈部淋巴结转移的相关因素分析

目的探讨滤泡亚型甲状腺乳头状癌(FVPTC)及经典型甲状腺乳头状癌(CPTC)的临床特征和颈部淋巴结转移(CLNM)的相关影响因素。方法回顾性分析2013-01—2022-10郑州大学第一附属医院行手术治疗并经术中和术后病理学检查确诊的116例FVPTC患者(FVPTC组)及110例CPTC患者(CPTC组)的临床资料。应用二元Logistic回归模型分析FVPTC及CPTC患者CLNM的独立影响因素。结果FVPTC组的肿瘤直径、彩超分级、BRAF基因突变率、淋巴结转移个数、甲状腺过氧化物酶抗体(TPOAb)、促甲状腺激素受体抗体(TRAB)均低于CPTC组,差异均有统计学意义(P<0.05)。FVPTC组中肿瘤大小和彩超分级是CLNM的独立危险因素,年龄是CLNM的独立保护因素。CPTC组中彩超分级是CLNM的独立危险因素,年龄是CLNM的独立保护因素。结论FVPTC的多项临床特征与CPTC存在差异,可协助鉴别诊断。肿瘤体积大、彩超分级高的年轻患者CLNM可能性较大,应采取更积极的治疗方案。

右侧卵巢甲状腺肿伴甲状腺滤泡癌1例

患者女,46岁,体检发现盆腔肿物5个月;10年前接受甲状腺手术,具体不详。查体:右附件区触及约6cm×6cm质软肿物,边界清,活动可,无明显压痛。实验室检查:甲状腺球蛋白60.58ng/ml、糖类抗原12557.29U/ml。腹部超声:右附件区5.9cm×2.8cm混合回声包块,边界清,形态规则,内见多个囊性回声团;CDFI于其内探及较丰富血流信号。