Diagnosis Of Thyroid Carcinoma Research Articles

Comprehensive Review of the Imaging Recommendations for Diagnosis, Staging, and Management of Thyroid Carcinoma.

Thyroid cancer is the most common head and neck cancer (HNC) in the world. In this article, we comprehensively cover baseline, posttreatment, and follow-up imaging recommendations for thyroid carcinomas along with the eighth edition of the tumor, node, metastasis (TNM) staging system proposed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). We include characterization and risk stratification of thyroid nodules on ultrasound (US) proposed by various international bodies. Management guidelines (depending upon the type of thyroid carcinoma) based on the international consensus recommendations (mainly by the American Thyroid Association) are also extensively covered in this article, including the role of a radioiodine scan. The management of recurrent disease is also briefly elucidated in this article. In addition, we cover the risk factors and etiopathogenesis of thyroid carcinoma along with the non-imaging diagnostic workup essential for thyroid carcinoma management, including the significance of genetic mutations. US is the diagnostic imaging modality of choice, with US-guided fine needle aspiration (FNA) being the procedure of choice for tissue diagnosis. The roles of computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) in thyroid carcinoma staging are also specified. Through this article, we aim to provide a comprehensive reference guide for the radiologists and the clinicians in the pursuit of optimal care for patients with thyroid carcinoma.

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.

Sodium iodide symporter immunolabelling as a predictor of clinical iodide uptake in canine thyroid carcinoma: A preliminary study.

Thyroid follicular tumours may take up iodide via the sodium-iodide symporter. Knowledge of iodide uptake could then allow treatment with I-131 in dogs with high-risk tumours. The objective of this study was to determine the relationship between clinically detectable iodide uptake (as determined by scintigraphy and/or thyroxine concentrations) and sodium iodide symporter immunohistochemical labelling on histologically fixed thyroid tumours. Nineteen dogs were identified who were diagnosed with thyroid carcinoma and underwent surgery from November 2017 to July 2021. All had recorded thyroid hormone concentrations and were hyperthyroid and/or underwent preoperative nuclear imaging using planar scintigraphy (technetium-99m or I-123), or I-124 PET-CT. All dogs subsequently underwent surgery to remove the thyroid mass. Twenty-two tumours were submitted for histopathologic analysis immediately following surgery, which confirmed a diagnosis of thyroid carcinoma for each tumour. Images and/or thyroid hormone concentrations were reviewed for the included cases, and tumours were sorted into an avid/functional group (group 1) and a non-avid/functional group (group 2). The tumour tissues were re-examined histologically using sodium iodide symporter (NIS) immunohistochemistry (IHC). Group 1 contained 15 avid/functional tumours. Twelve of these tumours had membranous NIS IHC labelling. Group 2 contained 7 non-avid tumours. One of these tumours had membranous NIS IHC labelling. This resulted in an overall sensitivity and specificity for identification of avid/functional tumours with membranous NIS of 80.0% and 85.7%, respectively. NIS IHC may predict ion trapping in canine follicular thyroid tumours. Further studies using iodide-based imaging are warranted to better determine the clinical utility of this diagnostic modality.

Thyroid Cancer With Cutaneous Metastases.

Objectives: Thyroid carcinoma with cutaneous metastases is a rare clinical finding. Cutaneous metastases from thyroid carcinoma have been associated with a poor prognosis, but these data are limited to case reports. The exact mechanism of cutaneous metastases from thyroid carcinoma is not clear. Our study aims to report the demographic, clinical, and histologic findings of patients with cutaneous metastases from thyroid carcinoma. Methods: A review was conducted using the Medline/PubMed, Cochrane, and Scopus databases to review literature from inception to May 2023. Data extracted included patient age at diagnosis of cutaneous metastases, patient sex, thyroid carcinoma histotype, location of metastases, the time interval between diagnoses of thyroid carcinoma and cutaneous metastases, and overall survival (OS) from the time of cutaneous metastases. Results: One hundred thirty-six patients were identified and 75 were female. The most common types of thyroid carcinoma with cutaneous metastases were papillary (47.79%), followed by follicular (30.15%), and medullary (11.03%). In addition, 11 cases of anaplastic carcinoma, 2 cases of oncocytic carcinoma, and 2 cases of poorly differentiated thyroid carcinoma were reported. The average age at diagnosis of cutaneous metastases was 63.13 years, and the average time interval between the diagnoses of primary thyroid carcinoma and cutaneous metastases was 48.27 months. The most common location of metastases was the scalp (n = 48). Other common locations included the neck, chest, and face. The OS after diagnosis of metastases was only available in 34 patients with an average of 13.07 months. Of these 34 cases, 10 were medullary, 10 were papillary, 9 were anaplastic, and 5 had follicular carcinoma. Conclusions: This study represents an up-to-date review of the cases of thyroid carcinoma with cutaneous metastases. While cutaneous metastasis remains a rare finding, one needs a high index of suspicion, and their presence portends a poor prognosis.

Thyroid nodule diagnosis: A comparative analysis of ultrasonography and fine-needle aspiration cytology

Objectives: This paper aimed to investigate the association between Ultrasonography (USG) results and fine-needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules (TNs) in private and public hospitals in Yemen. In addition, it aimed to determine the sensitivity, specificity of USG and FNAC in diagnosing thyroid nodules (TNs). Materials and Methods: The study utilized a retrospective comparative study design, analyzing medical records of patients diagnosed with TNs between June 01, 2022 and May 01, 2023, in four private and public hospitals in Yemen. USG and FNAC reports, along with demographic data were collected. The author categorized the USG findings based on the American Thyroid Association guidelines, while FNAC results were classified according to the Bethesda reporting system for thyroid cytopathology. Results: The study included 94 diverse participants with TNs. The average age was 39.96 years, with a majority of female participants (85.1%). The distribution of nodules revealed varying consistencies, sizes, and shapes. The association between USG and FNAC diagnoses showed a significant relationship (χ2 = 34.914, P < 0.001), with a high proportion of benign cases in both USG and FNAC results. Validity analysis demonstrated a sensitivity of 88.68% and a specificity of 70.73% for USG in diagnosing thyroid carcinoma. The positive predictive value was 79.66%, and the negative predictive value was 82.86%. The overall accuracy of USG compared to FNAC was 80.85%. Conclusion: This study shows USG’s potential as a diagnostic tool for TNs in Yemen. Insights improve understanding of TN diagnosis in Yemen’s healthcare settings.

Evaluation of calcitonin measurement in fine needle aspirates in the diagnosis of primary and metastatic medullary thyroid carcinoma

Serum CT represents the tumoral marker of medullary thyroid carcinoma (MTC), and is a main diagnostic tool and follow-up after treatment. Nevertheless, calcitonin levels can be elevated in a number of other situations and does not always distinguish MTC from other clinical circumstances, particularly when elevation remains moderate. Fine needle aspiration biopsy is a widely used examination for the investigation of thyroid nodules and lymph nodes, but its sensitivity for the diagnosis of MTC remains low ranging from 45% to 63%. Calcitonin measurement in fine needle aspiration wash out fluid has been reported as reliable, and is recommended by the experts of American Thyroid Association (ATA) in their 2015 consensus for the management of MTC even if its diagnostic is not standardized yet. Material and methods: Twenty patients with 45 lesions (thyroid nodule and lymph node) were included in this study; calcitonin was performed in each of them, the puncture needles were washed with 1ml of saline solution to obtain to measure Calcitonin in fine needle aspiration washout fluid. Results: After surgery 32 MTC were diagnosed on histology. Receiver operating curve (ROC curve) indicated CT in fine needle aspiration >22.99pg/ml as more accurate cut off value with a sensitivity and specificity of 96.87% and 100%. Calcitonin ratio was evaluated too, the cut off value being>0.64 with a sensitivity of 62.5% and specificity of 100%. Conclusion: Calcitonin in fine needle aspiration wash out fluid constitutes an excellent diagnostic tool of MTC with the use of 22.99pg/ml threshold.

Expression of RASSF1A, DIRAS3, and AKAP9 Genes in Thyroid Lesions: Implications for Differential Diagnosis and Prognosis of Thyroid Carcinomas.

Thyroid carcinoma is the primary endocrine malignancy worldwide. The preoperative examination of thyroid tissue lesion is often unclear. Approximately 25% of thyroid cancers cannot be diagnosed definitively without post-surgery histopathological examination. The assessment of diagnostic and differential markers of thyroid cancers is needed to improve preoperative diagnosis and reduce unnecessary treatments. Here, we assessed the expression of RASSF1A, DIRAS3, and AKAP9 genes, and the presence of BRAF V600E point mutation in benign and malignant thyroid lesions in a Polish cohort (120 patients). We have also performed a comparative analysis of gene expression using data obtained from the Gene Expression Omnibus (GEO) database (307 samples). The expression of RASSF1A and DIRAS3 was decreased, whereas AKAP9's was increased in pathologically changed thyroid compared with normal thyroid tissue, and significantly correlated with e.g., histopathological type of lesion papillary thyroid cancer (PTC) vs follicular thyroid cancer (FTC), patient's age, tumour stage, or its encapsulation. The receiver operating characteristic (ROC) analysis for the more aggressive FTC subtype differential marker suggests value in estimating RASSF1A and AKAP9 expression, with their area under curve (AUC), specificity, and sensitivity at 0.743 (95% CI: 0.548-0.938), 82.2%, and 66.7%; for RASSF1A, and 0.848 (95% CI: 0.698-0.998), 54.8%, and 100%, for AKAP9. Our research gives new insight into the basis of the aggressiveness and progression of thyroid cancers, and provides information on potential differential markers that may improve preoperative diagnosis.

3D virtual histopathology by phase-contrast X-ray micro-CT for follicular thyroid neoplasms.

Histological analysis is the core of follicular thyroid carcinoma (FTC) classification. The histopathological criteria of capsular and vascular invasion define malignancy and aggressiveness of FTC. Analysis of multiple sections is cumbersome and as only a minute tissue fraction is analyzed during histopathology, under-sampling remains a problem. Application of an efficient tool for complete tissue imaging in 3D would speed-up diagnosis and increase accuracy. We show that X-ray propagation-based imaging (XPBI) of paraffin-embedded tissue blocks is a valuable complementary method for follicular thyroid carcinoma diagnosis and assessment. It enables a fast, non-destructive and accurate 3D virtual histology of the FTC resection specimen. We demonstrate that XPBI virtual slices can reliably evaluate capsular invasions. Then we discuss the accessible morphological information from XPBI and their significance for vascular invasion diagnosis. We show 3D morphological information that allow to discern vascular invasions. The results are validated by comparing XPBI images with clinically accepted histology slides revised by and under supervision of two experienced endocrine pathologists.

Epidemiological and histopathological characteristics of thyroid carcinoma in a Tunisian health care center.

Thyroid carcinoma (TC) accounts for almost 0.5%-1% of total malignancies. Its incidence is increasing rapidly worldwide. Several studies have drawn up the epidemiological profile of TC and its clinical and pathological features. However, to date, no similar studies have been conducted in Tunisia. To establish an epidemiological profile of TC in a Tunisian health care institute and to analyze its clinical and histopathological characteristics in our institute. We present a retrospective study reviewing the cases of TC diagnosed in our institution in a 4-year period. We collected a sample of 192 cases of TC. It consisted of 31 males and 161 females (83.8%) with a sex-ratio M/F of 0.19. The mean age was 46.4 years. Papillary thyroid carcinoma was the most frequent histological subtype. The multifocality rate was 33.8%. The mean size of TC was 2.2 ± 1.9 cm. 60.9% of TC were staged pT1 and 20.3% had nodal involvement. Papillary thyroid microcarcinomas were noted in 37.5% of cases. Our results were consistent with those of the literature. A high proportion of pT1 and pN0 tumors were noted in our series, suggesting that TC's diagnosis and management was performed at an early stage of the disease in our institution. In addition, our study enabled us to notice the impact of the Coronavirus disease 19 crisis on the management of TC in our institution. Further studies are needed to establish the epidemiological profile of TC in Tunisia and to assess its clinical and pathological features.

Update on current diagnosis and management of anaplastic thyroid carcinoma.

Well-differentiated thyroid carcinoma has a favorable prognosis with a 5-year survival rate of over 95%. However, the undifferentiated or anaplastic type accounting for < 0.2%, usually in elderly individuals, exhibits a dismal prognosis with rapid growth and disappointing outcomes. It is the most aggressive form of thyroid carcinoma, with a median survival of 5 mo and poor quality of life (airway obstruction, dysphagia, hoarseness, persistent pain). Early diagnosis and staging are crucial. Diagnostic tools include biopsy (fine needle aspiration, core needle, open surgery), high-resolution ultrasound, computed tomography, magnetic resonance imaging, [(18)F]fluoro-D-glucose positron emission tomo-graphy/computed tomography, liquid biopsy and microRNAs. The BRAF gene (BRAF-V600E and BRAF wild type) is the most often found molecular factor. Others include the genes RET, KRAS, HRAS, and NRAS. Recent management policy is based on surgery, even debulking, chemotherapy (cisplatin or doxorubicin), radiotherapy (adjuvant or definitive), targeted biological agents and immunotherapy. The last two options constitute novel hopeful management modalities improving the overall survival in these otherwise condemned patients. Anti-programmed death-ligand 1 antibody immunotherapy, stem cell targeted therapies, nanotechnology achievements and artificial intelligence imple-mentation provide novel promising alternatives. Genetic mutations determine molecular pathways, thus indicating novel treatment strategies such as anti-BRAF, anti-vascular endothelial growth factor-A, and anti-epidermal growth factor receptor. Treatment with the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has been approved by the Food and Drug Administration in cases with BRAF-V600E gene mutations and is currently the standard care. This neoadjuvant treatment followed by surgery ensures a two-year overall survival of 80%. Prognostic factors for improved outcomes have been found to be younger age, earlier tumor stage and radiation therapy. A multidisciplinary approach is necessary, and the therapeutic plan should be individualized based on surveillance and epidemiology end results.

Case Series of Surgical Treatment in Pediatric Thyroid Carcinoma in a Single Institution.

The prevalence of thyroid carcinoma (TC) among pediatric and adolescent populations is infrequent, yet its global occurrence is escalating. Insufficient information pertaining to TC in the pediatric populace of Indonesia presents issues in the identification and management of patients with this condition. The objective of this study is to provide a detailed account of a collection of pediatric TC cases that were recorded at a tertiary care center throughout an extended interval of eight years. The present study conducted a retrospective data analysis of ten patients who received a diagnosis of TC during the period spanning from 2014 to 2022. The present study focused on analyzing the clinical manifestation, diagnostic measures, treatment modalities, and immediate postoperative consequences of TC. All patients diagnosed with thyroid cancer exhibited the presence of neck lump. Nine patients underwent total thyroidectomy, while one patient underwent isthmolobectomy. The histopathologic evaluation confirmed the diagnosis of thyroid cancer in every individual. There were a significant number of patients, up to 50%, who encountered complications after undergoing surgery. Two patients reported the hoarseness of voice, whereas two other patients experienced the signs of hypocalcemia. Only one patient exhibited both these symptoms simultaneously. The implementation of total thyroidectomy as a surgical intervention in pediatric patients poses a notable challenge. Postoperative monitoring for potential complications following surgery for total thyroidectomy is imperative. The current study provides evidence that the utilization of total thyroidectomy in combination with lymph node dissection as indicated in patients with lymph node metastases in pediatric patients with thyroid carcinoma leads to a significant reduction in the probability of recurrence of lymph node enlargement. During the performance of surgical procedures, meticulous observation plays a key role in mitigating the risk of postoperative complications, such as hypoparathyroidism, hypocalcemia, and injury to the recurrent laryngeal nerve. Thus, it is imperative to conduct follow-up procedures for post-surgical interventions among pediatric patients diagnosed with TC.

Fine Needle Aspiration and Core Biopsy of Liver Mass as First Time Diagnosis of Sarcomatoid Anaplastic Thyroid Carcinoma, A Rare Malignancy Presenting at an Unexpected Body Site

Abstract Introduction/Objective Anaplastic thyroid carcinoma (ATC) is a fatal malignancy. We report an unusual case of a patient with ATC whose chief complaint and clinical history were listed as “jaundice and liver mass” without mention of disease in the neck. Methods/Case Report A 66-year-old female presented to the emergency department with worsening “yellow-green skin discoloration” for a few weeks. She also reported worsening dyspnea and recent dysphagia with solid foods, fatigue, abdominal pain and recent hemoptysis. Physical examination revealed conjunctival icterus, jaundice, a tender neck mass, right upper chest wall tenderness and palpable lymphadenopathy in the lower neck. Assessment notes indicated inability to carry out self-care and being bedridden, even though she reported having been active, swimming and cycling, up to one month before her presentation. Computed tomography studies confirmed findings compatible with widespread malignancy with mass lesions in her liver, lungs, adrenals, kidneys, neck, pancreas, gallbladder, and brain. Mild anemia, hemoglobin 10.5g/dL, mild leukocytosis, leukocytes 17,000/mm3, were confirmed. Bilirubin was 15µmol/L, and hepatic enzymes were elevated. An ultrasound-guided liver biopsy was performed and evaluated for cytologic features, histologic features and pattern of immunoreactivity. The combined cytomorphologic and histologic features were those of a pleomorphic sarcomatoid high-grade malignancy with variably spindled to epithelioid morphology and associated necrosis. Immunohistochemical studies performed on sections from the accompanying core biopsy confirmed the malignant cells to be positive with CK-AE1/AE3, CK 7, TTF-1, GATA3, PAX8, SATB2, and BRAF V600E. The malignant cells were nonreactive with CK 20, thyroglobulin, calcitonin, napsin, CDX2, PCEA, and ER. The combined clinical setting, imaging findings, cytomorphology, histomorphology and ancillary testing results together allowed for a specific diagnosis of metastatic anaplastic thyroid carcinoma. The patient was referred for palliative care services and died within a few days of diagnosis. Results (if a Case Study enter NA) NA Conclusion Metastatic disease from a sarcomatoid ATC, as diagnosed in this case, is an important differential diagnosis to keep in mind when an elderly patient presents with multisite metastases from an undefined primary source. Clinical, radiological and laboratory correlations are of paramount importance in correlating with cytomorphology/histomorphology and in helping to determine the best panel of IHC studies to consider.

Measurement of calcitonin and cea in the needle washout fluid from thyroid nodule for the diagnosis of medullary thyroid carcinoma

Background. medullary thyroid carcinoma (mtc) produces serum markers including calcitonin (ct) and carcinoembryonic antigen (cea). The measurement of ct in fine-needle aspirate washout fluid (FNA-CT) improves the cytological diagnosis of mtc. However, no data are available about cut-off values for FNA-CT using currently immunoassay. The measurement of cea in the needle washout fluid (FNa-cea) in mtc has not been studied.Objective: to assess the diagnostic value and propose cut-off values for FNA-CT and FNacea in the thyroid nodule to diagnose mtc.Material and Methods. We conducted a retrospective analysis of 164 samples of fine-needle aspirate washout fluid collected from 92 patients with thyroid nodules, who underwent FNa followed by cytological examination and measurement of FNA-CT. seventeen cases with mtc and 41 with non-mtc nodules were histologically verified. one hundred and six nodules identified as non-mtc by cytology were not operated on. FNa-cea was additionally studied in 29 samples. The cut-off value was determined by Roc analysis.Results. The FNA-CT level was &gt;2000 pg/ml in all mtc nodules, except for one, in which the FNA-CT level was 638 pg/ml. In non-mtc nodules, the FNA-CT levels were &lt;10 pg/ml and &lt;100 pg/ml in 81 % and 90 %, respectively, however, it was &gt;500 pg/ml in 5 %, and &gt;1000 pg/ml in 2 %. At a cut-off value of 590 pg/ml, the sensitivity and specificity of FNA-CT were 100 % and 96 %, and at a cut-off of 1721 pg/ml, the corresponding values were 94 % and 99 %. The false positive FNA-CT values were 3.7 % and 1.2 % at the cut-off values of 590 pg/ml and 1721 pg/ml, respectively. The median levels of FNa-cea in mtc and non-mtc nodules were 59.3 ng/ml and 1.5 ng/ml, respectively. At a cut-off value of 7.5 ng/ml, the sensitivity of FNa-cea was 86 % and specificity was 100 %. Additional measurement of FNa-cea prevented all false-positive results of FNA-CT, but did not detect 2 mtcs with low FNa-cea levels (false-negative rate of 6.9 %). Among samples with FNA-CT value of &gt;590 pg/ml and negative cytology (n=9), FNa-cea differentiated mtc with 100 % sensitivity and specificity.Conclusion. The maximum sensitivity of FNA-CT in the thyroid nodule was at a cut-off value of 590 pg/ml (100 %), the maximum specificity was at a cut-off value of 1721 pg/ml (99 %). Risk of false positive result is the major challenge of FNA-CT. to reduce false-positive results, we recommend to measure FNa-cea in the nodules with negative cytology and high level of FNA-CT. At a cut-off value of 7.5 ng/ml, FNa-cea allows the false-positive FNA-CT to be excluded.

SAT509 The Clinical Significance of Cribriform Morular Thyroid Carcinoma

Abstract Disclosure: G. Soh: None. K. Sek: None. S. Yang: None. M. Nga: None. S. Mok: None. We present two young (aged below 30) female patients who were diagnosed with the rare cribriform morular thyroid carcinoma. Both patients presented with neck swellings and underwent total thyroidectomy for the thyroid malignancies. The histological diagnosis prompted subsequent genetic evaluation. Both patients demonstrated genotypic and phenotypic evidence of familial adenomatosis polyposis (FAP) syndrome. One of the patients had a mutation which resulted in a premature translational stop signal in the adenomatous polyposis coli (APC) gene. She was eventually diagnosed with adenocarcinoma in 2 colonic polyps and underwent a curative pan-proctocolectomy. The other patient was diagnosed clinically with FAP as she had multiple (30-40) colonic polyps which were tubular adenomas. She had a variant of unknown significance in the APC gene. She declined surgery and remained on colonoscopic surveillance. Both patients’ thyroid cancers are in clinical remission. While uncommon, diagnosing cribriform-morular thyroid carcinoma is significant as 25 to 30% of patients harbour genetic mutations in the APC gene on chromosome 5q21. This is associated with FAP syndrome, an autosomal dominant genetic syndrome characterized by young-onset colonic polyposis, usually of malignant potential. Additionally, these patients may exhibit features of Gardner’s syndrome, a subset of FAP syndrome in which patients can develop extra-colonic manifestations such as osteomas of the mandible and supernumerary teeth. Histologically, cribriform morular thyroid carcinoma are well circumscribed and show a variable combination of follicular, cribriform, papillary, trabecular, solid and morular patterns. There is nuclear and cytoplasmic staining for beta catenin, as the inactivating APC mutation causes a loss of beta catenin destruction complex, impeding beta catenin degradation and increasing its nuclear translocation. This is a key event in thyroid tumorigenesis. The diagnosis of cribriform morular thyroid carcinoma should alert the clinician about the possibility of FAP with consideration for further clinical and genetic evaluation to confirm the diagnosis. References1)Cameselle-Teijeiro, J. M., Peteiro-González, D., Caneiro-Gómez, J., Sánchez-Ares, M., Abdulkader, I., Eloy, C., Melo, M., Amendoeira, I., Soares, P., &amp; Sobrinho-Simões, M. (2018). Cribriform-morular variant of thyroid carcinoma: A neoplasm with distinctive phenotype associated with the activation of the Wnt/β-catenin pathway. Modern Pathology, 31(8), 1168–1179. https://doi.org/10.1038/s41379-018-0070-2 2)Peiling Yang, S., &amp; Ngeow, J. (2016). Familial non-medullary thyroid cancer: Unraveling the Genetic Maze. Endocrine-Related Cancer, 23(12). https://doi.org/10.1530/erc-16-0067 Presentation Date: Saturday, June 17, 2023

SAT552 Thyroid Mass With Both Anaplastic, Papillary Carcinoma Treated With Surgery, Radiation Therapy, Paclitaxel Chemotherapy

Abstract Disclosure: T.H. Hoang: None. D. Whiteman: None. P. Luceri: None. V. Del Signore: None. Introduction: Anaplastic thyroid carcinoma, while rare, is extremely aggressive and overall survival is poor. Median survival is a mere 4 months from time of diagnosis and mortality approaches 100%. We present a case of anaplastic thyroid carcinoma in the setting of differentiated thyroid carcinoma that has shown response to total thyroidectomy, radiation, and chemotherapy over the course of several months. Case Presentation: A 58 year old female who originally presented with the sensation of a lump in her throat in 2012. Thyroid ultrasound at that time revealed a thyroid mass (3 x 2 x 2 cm, mixed echogenicity) of the right thyroid lobe. Two thirds of the mass was solid with increased vascularity; the remaining was cystic. Originally, cytology revealed benign follicular cells, colloid, Hurthle cells and macrophages, and was negative for malignancy. She was diagnosed with a nodular goiter and she was lost to follow up. She again complained of a 15 pound weight loss associated with a lump in her neck in 2021. A repeated thyroid ultrasound revealed a 7cm right sided thyroid nodule with mass effect on the trachea. Repeated cytology showed atypia of undetermined significance. Molecular analysis was positive for EIF1AX, NRAS, &amp; TERT mutations. ENT recommended a total thyroidectomy due to the molecular mutations and the patient’s compressive symptoms. Surgical pathology was consistent with a right-sided, anaplastic thyroid carcinoma arising from an encapsulated, well-differentiated thyroid carcinoma confined to the thyroid and measuring 5.5 cm (Stage IV CT3a, cN0, cM0). Interestingly, the anaplastic component of the tumor was only 15% of the overall mass with the other portion being well-differentiated papillary thyroid carcinoma. She received 6000cGy of external beam radiation with concurrent paclitaxel (60mg/m2) for 6 weekly cycles. A PET/CT four months later showed no evidence of local or distant metastatic disease. CT Chest, Abdomen, Pelvis with contrast did not reveal metastatic disease either. Later, CT soft tissue of her neck showed no residual or recurrent tumor. MRI Brain was negative for acute findings, including metastatic disease. At the current time, she is 18 months from her original diagnosis of anaplastic thyroid carcinoma. She continues to follow with medical oncology and endocrinology and there has been no evidence of recurrent disease. Discussion: When present, it is common for anaplastic thyroid carcinoma to be associated with both papillary and follicular thyroid carcinoma. Regardless of association, anaplastic thyroid carcinoma remains aggressive and median survival is measured in months. Treatment includes surgery, radiation and chemotherapy which can contribute to an increase in 2 year survival to 42% from 18% without treatment. Advancements in the treatment of anaplastic thyroid carcinoma are needed as the recurrence of aggressive disease is unfortunately expected. Presentation Date: Saturday, June 17, 2023

Possibilities of immunocytochemical staining for HBME-1 expression in the «diagnostic search» of differentiated thyroid cancer. Own investigation

Objective — to investigate HBME-1 expression variants on cytological material classified as doubtful (III, IV, V), according to the Bethesda categories, to evaluate the value of the HBME-1 expression test on the corresponding histological material of nodular goiter, follicular tumor with an uncertain potential for malignancy for the differential diagnosis of thyroid carcinoma (ThC). Materials and methods. The analysis was performed on the data of 14 patients with thyroid nodular lesions and cytological Bethesda categories III, IV, and V (“gray zone“). The HBME-1 expression was determined by the results of immunocytochemical (ICC) and immunohistochemical (IHC) staining with the use of mouse monoclonal antibodies against human HBME-1 (1 : 500; cat № BSB 3459; «Bio SB» «Bioscince for the World» Santa Barbara USA). The HBME-1 expression grade was calculated as the sum of the score for staining intensity and cytoplasmic positive cells square, present in the IHC sample. HBME-1 positive result was considered with an IHC score &gt;6 point. Results. From 14 investigated patients, five were defined as HBME-1 positive. According to the postoperative histological conclusion for the group of HBME-1 positive patients, thyroid carcinoma was diagnosed in four subjects, including three cases of papillary ThC and one follicular ThC; in one patient follicular tumor of uncertain malignant potential (FT-UMP) was reported. Importantly, immunocytochemical and immunohistochemical HBME-1 reactions in the specimens of these patients were of the same intensity. Among 9 HBME-1 preoperative negative patients, none had malignancy according to the final histological study. Nodular goiter was diagnosed in six patients, and tumor of uncertain malignant potential (FT-UMP) was reported for three subjects. Histological specimens of all 9 patients were HBME-1 negative as well. The obtained results demonstrated an increase in cancer detection rates with increasing Bethesda category. Application of statistical software for biomedical research МedCalc revealed that positive predictive value (PPV) of the HBME-1 expression test was 80% (95% confidence interval CI 38.4—96.3%), and diagnostic efficiency was 92.9% (CI 66.1—99.8%). These results suggest the great potential of the test, however, due to the limited observations, the confidence intervals are too wide. Conclusions. HBME-1 can be used as an immuno­cytochemical marker for the differentiation of benign and malignant thyroid nodules, its use will help to reduce the number of unnecessary surgical removals of benign tumors, which will improve the quality of life of patients and reduce the burden on medical services.

Exploring the application value of pro-gastrin-releasing peptide in the clinical diagnosis and surgical treatment of medullary thyroid carcinoma.

To investigate the relationship between pro-gastrin-releasing peptide (ProGRP) and the clinical characteristics of patients with medullary thyroid carcinoma (MTC) and the value of ProGRP in surgical treatment monitoring. A total of 347 patients with MTC and non-MTC malignant and benign thyroid diseases were enrolled. The concentrations of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), calcitonin (CT), and ProGRP were determined by Elecsys® assays. The NSE, CEA, CT, and ProGRP levels in different thyroid disease groups were compared, and ProGRP levels in different clinicopathological feature groups pre and postoperatively were further compared. The CT, CEA, NSE, and ProGRP levels were upregulated in the MTC group compared to those in the non-MTC malignant and benign thyroid disease groups. The area under the receiver operating characteristic curve (AUC) of ProGRP for the diagnosis of MTC was 0.832(0.787-0.871), similar to that of CT and CEA. The sensitivity and specificity were 71.4% and 92.7%, respectively, and the optimal cut-off value was 61.8 pg/mL. The AUC of ProGRP combined with CT or CEA for the diagnosis of MTC was 0.933 (0.900-0.958) and 0.922 (0.886-0.949), respectively, which were higher than those of a single index. ProGRP levels were higher in patients with lymph nodes and distant metastases than in patients without metastases. The postoperative level of ProGRP was lower than that before treatment. ProGRP is comparable to CEA and CT as an MTC biomarker with broad prospects. It has potential application value in the progression of MTC assessment and the evaluation of surgical intervention effects.

Molecular imaging and related therapeutic options for medullary thyroid carcinoma: state of the art and future opportunities.

Due to its rarity and non-specific clinical presentation, accurate diagnosis, and optimal therapeutic strategy of medullary thyroid carcinoma (MTC) remain challenging. Molecular imaging provides valuable tools for early disease detection, monitoring treatment response, and guiding personalized therapies. By enabling the visualization of molecular and cellular processes, these techniques contribute to a deeper understanding of disease mechanisms and the development of more effective clinical interventions. Different nuclear imaging techniques have been studied for assessing MTC, and among them, PET/CT utilizing multiple radiotracers has emerged as the most effective imaging method in clinical practice. This review aims to provide a comprehensive summary of the current use of advanced molecular imaging modalities, with a particular focus on PET/CT, for the management of patients with MTC. It aims to guide physicians towards a rationale for the use of molecular imaging also including theranostic approaches and novel therapeutical opportunities. Overall, we emphasize the evolving role of nuclear medicine in MTC. The integration of diagnostics and therapeutics by in vivo molecular imaging represents a major opportunity to personalize treatment for individual patients, with targeted radionuclide therapy being one representative example.

The clinical and pathological significance of increased expression of the cannabinoid receptors CB-1R and CB-2R in patients with papillary thyroid carcinomas compared to benign thyroid lesions.

Papillary thyroid carcinoma is the most common malignancy of the endocrine system. Most papillary thyroid carcinoma patients enjoy excellent outcomes. However, in patients with biologically aggressive features, additional prognostic and predictive data may aid disease management. Dysregulation of the endocannabinoid system including the cannabinoid receptors 1 and 2 (CB-1R and CB-2R) during carcinogenesis has been extensively studied over the last few decades. The aim of this study was to evaluate immunohistochemically the expression levels of both receptors in patients with papillary thyroid carcinoma and benign diseases, and to compare these rates and the histopathologically and clinically prognostic features. The pathological materials and clinical data of 100 patients with papillary thyroid carcinoma and 40 with benign diseases were retrospectively re-evaluated. All tissues were immunohistochemically stained for CB-1R and CB-2R. The expression levels of CB-1R and CB-2R in papillary thyroid carcinomas, and benign lesions were recorded and compared with the pathological and clinical features. The expression levels of both receptors were significantly higher in papillary thyroid carcinoma patients than in those with benign conditions (P = 0.001). CB-1R expression correlated with both extrathyroidal extension (P = 0.022) and capsular invasion (P = 0.001). CB-2R expression was associated with the risk group of the American Thyroid Association stratification system (P = 0.004). Our study suggests that increased cannabinoid receptor expression contributes to thyroid carcinogenesis. The CB-2R expression level could provide additional information aiding risk management. Furthermore, the CB-1R and CB-2R antibodies might increase the accuracy of papillary thyroid carcinoma diagnosis when combined with the papillary thyroid carcinoma biomarkers assayed after fine-needle aspiration of neoplastic cells.

Expression data of FOS and JUN genes and FTIR spectra provide diagnosis of thyroid carcinoma

We explore the feasibility of using FOS and JUN gene expression and ATR-FTIR for diagnosis of thyroid cancer. For the study, 38 samples (6 non-neoplastic (NN), 10 papillary thyroid carcinoma (PTC), 7 follicular thyroid carcinoma (FTC), and 15 benign tumors (BT) were subjected to RNA extraction followed by quantitative real time PCR (qRT-PCR) and 30 samples (5 NN, 9 PTC, 5 FTC, and 11 BT) were used for Attenuated Total Reflectance – Fourier Transform Infrared (ATR-FTIR) followed by multivariate analysis. Of the above, 20 samples were used for both gene expression and ATR-FTIR studies. We found FOS and JUN expression in malignant tumor samples to be significantly lower than NN and benign. ATR-FIR after multivariate analysis could identify the difficult to diagnose FTC with 93 % efficiency. Overall, results suggest the diagnostic potential of molecular biology techniques combined with ATR-FTIR spectroscopy in differentiated thyroid carcinomas (PTC and FTC) and BT.