Follicular Adenoma Research Articles

Diagnostic significance of ultrasound characteristics in discriminating follicular thyroid carcinoma from adenoma.

Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland and has a greater propensity for haematogenous metastasis. However, the preoperative differentiation of FTC from follicular thyroid adenoma (FTA) is not well established. Certain ultrasound characteristics are associated with an increased risk of thyroid malignancy, but mainly for papillary thyroid cancers and not for FTC. This retrospective study aimed to evaluate the ultrasound characteristics of FTC and the value of ultrasound characteristics in differentiating FTC from FTA. A total of 96 patients with pathologically confirmed FTC or FTA who underwent preoperative thyroid ultrasound were included in this study. The ultrasound and pathological characteristics were evaluated. Our data revealed that the incidences of lesions with tubercle-in-nodule, spiculated/microlobulated margins, mixed vascularization, egg-shell calcification, central stellate scarring, extension toward the capsule and chronic lymphocytic thyroiditis were significantly higher in the FTC group (all p < 0.05). After adjusting for confounding factors, lesions with mixed vascularization (odds ratio [OR]: 2.038, P = 0.019), central stellate scarring (OR: 87.992, P = 0.007), extension toward the capsule (OR: 22.587, P = 0.010), and chronic lymphocytic thyroiditis (OR: 9.195, P = 0.006) were independently associated with FTC. Furthermore, combined with chronic lymphocytic thyroiditis, mixed vascularization, central stellate scarring, and extension toward the capsule showed high discriminatory accuracy in predicting FTC (AUC: 0.914; sensitivity: 96.5%; specificity: 71.8%; p < 0.001). In combination with chronic lymphocytic thyroiditis, mixed vascularization, central stellate scarring, and extension toward the capsule have greater accuracy in differentiating FTCs from FTAs.

Mitochondrial Proteome Defined Molecular Pathological Characteristics of Oncocytic Thyroid Tumors.

Oncocytic thyroid tumors are characterized by an elevated mitochondrial density within the cells, distinguishing them from other thyroid tumors, exhibit distinct clinical behaviors, including increased invasiveness and iodine therapy resistance. However, the proteomic alterations in oncocytic thyroid tumors remain inadequately characterized. In this study, we analyzed 156 Asian patients with oncocytic thyroid adenomas (OA) and carcinomas (OCA) to explore their clinical, genetic, and proteomic features. Genetic testing of 73 samples revealed frequent mutations in TERT, NRAS, EIF1AX, EZH1, and HRAS, with TERT promoter mutations being exclusive to OCAs. Proteomic analysis identified 66 mitochondrial-specific proteins significantly highly expressed in oncocytic tumors than in non-oncocytic tumors. This led to the development of a thyroid oncocytic score (TOS) to quantify oncocytic characteristics. Among these proteins, isocitrate dehydrogenase 2 (IDH2) was substantially overexpressed in oncocytic tumors and further confirmed by immunohistochemistry in oncocytic tumor slides (n = 41) and non-oncocytic tumor slides (n = 40). Moreover, IDH2 is significantly overexpressed in OCA compared to OA highlighting its potential as a biomarker for differential diagnosis of oncocytic tumors and malignancy. These findings improve the understanding of oncocytic thyroid tumors molecular pathology and suggest IDH2 as a valuable marker for clinical management.

Coexisting parathyroid adenoma, thyroid carcinoma, and tuberculosis of thyroid: a case report

BackgroundCoexisting parathyroid adenoma, thyroid carcinoma, and tuberculosis of thyroid is a very rare phenomenon. Primary thyroid tuberculosis is itself very rare despite high global prevalence of tuberculosis in developing countries. Majority of thyroid tuberculosis identified in postoperative histopathology or cytopathology. The coexistence of thyroid cancer with tuberculosis or parathyroid adenoma has been reported in the literature but not a single case of the three pathologies coexisting together has been found in the literature published. We are presenting a rare case of a constellation of synchronous parathyroid adenoma, thyroid carcinoma, and thyroid tuberculosis. This case report will provoke researchers to work on understanding the association of hypercalcemia or chronic inflammation leading to development of malignancy or parathyroid adenoma in the presence of hypothyroidism will give future perspective in managing such patients.Case presentationA Islam lady aged 45 years old, diagnosed with hypothyroidism, was evaluated for pregnancy loss and rapid weight gain from 13 years back and started on tablets of levothyroxine 25 µg once daily. She was doing well until the past 2 years; there after she noticed insidious onset of a swelling over anterior aspect of right side of the neck and bone pain in back and lower limbs. Patient underwent routine investigations and was found to have raised serum calcium (11.4 mg/dl) and parathyroid hormone (253 pg/ml). Anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) level were normal. Ultrasounds showed multiple nodules in both lobe of thyroid and left inferior parathyroid adenoma. The patient underwent total thyroidectomy with left inferior parathyroidectomy, and final histopathology showed features of subacute granulomatous thyroiditis along with hurthle cell change in right lobe of thyroid. The left lobe additionally showed necrotizing epitheloid cell granulomas, which on Zeihl–Neelson staining revealed presence of acid-fast bacilli. Sections from the isthmus show a focus of papillary thyroid microcarcinoma. The left inferior parathyroid gland sent as a frozen sample was found to be parathyroid adenoma. On 6-month follow-up, the patient was feeling much relief in bone pain and tolerating antitubercular drugs uneventfully.ConclusionCoexistence of parathyroid adenoma, nonmedullary thyroid carcinoma, and thyroid tuberculosis is extremely rare. Surgery is curative for hyper parathyroidism and thyroid carcinoma. Thyroid tuberculosis responds well to current antitubercular drugs. Its etiology needs to be explored more; the probable hypothesis is chronic inflammation due to latent tuberculosis might leads to development of thyroid carcinoma and parathyroid adenoma. Further studies need to be done for better understanding of underlying mechanism and better management options for such patients. To the best of our knowledge, similar cases have not been reported.

On Vascular Lesions of the Thyroid Gland with Emphasis on Intrathyroidal Hemangioma: Clinicopathologic Characterization of Two Cases and Review of the Literature

Mesenchymal neoplasms of the thyroid gland are exceptionally rare accounting for less than 0.5% of all intrathyroidal tumors with hemangiomas comprising merely 6% of them. The clinicopathologic characteristics of two additional examples of thyroid hemangioma together with a thorough review of the pertinent literature are presented. A 62-year-old man and an 18-year-old woman presented with asymptomatic, soft-to-palpation, mobile nodules of the right thyroid lobe classified as TI-RADS 5 and TI-RADS 4, respectively, on ultrasound imaging. Microscopically, lesions featured a circumscribed, unencapsulated, lobular proliferation of variably-sized, congested, vascular channels lined by a single layer of flattened, cytologically bland endothelial cells, together with interspersed residual follicles. Vascular endothelial cells were strongly positive for CD31, CD34 and ERG, and negative for pancytokeratin AE1/AE3, TTF1, and PAX8. A diagnosis of cavernous hemangioma was rendered in the clinical setting of Hashimoto thyroiditis and follicular adenoma, respectively. Following inclusion of the current cases, a total of 53 intrathyroidal hemangiomas were identified in the literature with a patient mean age of 48.9 years (range = 0.17-84) and a slight female predilection (F:M = 1.4:1). A proclivity for the right thyroid lobe (59.6%) was noted with the striking majority of cases exhibiting features of cavernous hemangioma (95.2%). Prognosis is favorable and surgical resection is considered curative. The occasionally alarming clinical presentation in conjunction with absence of pathognomonic imaging features and limited diagnostic accuracy of FNA cytopathology for such lesions renders surgical intervention necessary for definitive diagnosis of intrathyroidal hemangiomas and exclusion of other epithelial and non-epithelial pathologic entities.

Outcomes of Radiofrequency Ablation for Autonomously Functioning Thyroid Adenomas-Mayo Clinic Experience.

Autonomously functioning thyroid nodules (AFTNs) constitute 5% to 7% of thyroid nodules and represent the second most common cause of hyperthyroidism following Graves' disease. Currently, radioactive iodine (RAI) and surgery are the standard treatment options, and both incur a risk of postprocedural hypothyroidism and other surgery and radiation-related complications. This work aimed at assessing the efficacy of radiofrequency ablation (RFA) as an alternative treatment option for resolving hyperthyroidism and the nodule volume rate reduction (VRR) and its associated adverse events. A total of 22 patients underwent RFA for a solitary AFTN. Seventy-two percent (n = 16) had subclinical hyperthyroidism, 9% (n = 2) had overt hyperthyroidism, and 18% (n = 4) were biochemically euthyroid on antithyroid medication. Average pretreatment TSH was 0.41 mIU/L (SD = 0.98) and free T4 1.29 ng/dL (SD = 0.33). Following a single RFA session, hyperthyroidism resolved in 90.9% (n = 20) and average VRR (61.13%) was achieved within 3 to 6 months following the ablation. Except for 1 nodule, none of the nodules grew during the follow-up period (16.5 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and 2 developed mild hypothyroidism requiring levothyroxine therapy. Two patients developed recurrent hyperthyroidism and elected to undergo lobectomy and repeat RFA respectively. No serious adverse effects were noted in this cohort. RAI and/or surgery represent the standard of care for toxic adenomas, but RFA shows excellent efficacy and safety profile. Therefore, at centers with RFA expertise, it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications.

Molecular Profiling and Surgical Outcomes in Indeterminate Thyroid Nodules: Experience from a Tertiary Care Center

Abstract Introduction/Objective This study examines molecular results(MR) and surgical follow-up(SFU) of cytologically- indeterminate thyroid nodules. Methods/Case Report Atypia-of-undetermined significance/suspicious-for-follicular-neoplasm cases that underwent Quest/ThyroSeq molecular testing between 2015-2022 were analyzed for MR, SFU and lymph node metastasis(LNM). Results (if a Case Study enter NA) 417 cases(Quest=192, ThyroSeq=225). 59% had SFU. 43% malignancy rate.SFU for Quest(49%): non-neoplastic(NNP)=20%, neoplastic(NP)=80%. MR in these cases:NRAS=48, HRAS=19, BRAF=15, KRAS=8, RET/PTC=3, PAX8=2. SFU: papillary thyroid carcinoma(PTC)=35, non-invasive-follicular-thyroid- papillary-neoplasm with papillary-like nuclear features(NIFTP)=20, thyroid nodular follicular disease(TFND)=18, follicular adenoma(FA)=10, follicular carcinoma(FC)=5, oncocytic carcinoma(OC)=1, lymphocytic thyroiditis(LT)=1. Surgical-molecular correlation(SMC): PTC in 3/3 RET/PTC-mutated, 14/15 BRAF-mutated cases. 1 TFND was BRAF- positive. RAS-mutated category: NIFTP=20,PTC=18,TFND=17,FA=9, OA=5, FC=5, LT=1. In RAS-mutated PTCs, NRAS was most common(n=13), followed by HRAS(n=4) and KRAS(n=1). 2 PAX8-mutated cases showed FA and OC. 9/41 malignant cases, all PTC, had LNM, MR:BRAF=6, HRAS=2, RET/PTC=1.SFU for ThyroSeq(68%): NN=10%, NNP=90%. MR:NRAS=34, copy number alterations(CNAs)=25, HRAS=14, BRAF=13, KRAS=11, gene expression alterations(GEA)=7, THADA+IGF2BP3=7, CNAs Hurthle cell type(HCT)=6, EIF1AX=6, DICER1=4, PAX8- PPARG fusion=4, CNAs+GEA=3, NTRK3=3, TERT=2, RAS+EIF1AX=2, TERT+CNAs=2, EIF1AX=1, EZH1=1, RET/PTC1 fusion=1, ALK=1, BRAF K601E=1,RAS+TERT=1, RAS+TERT+PTEN+EIF1AX=1, TERT+BRAF=1, TERT+EIF1AX=1,TP53+CNAs=1. SFU:PTC=39, NIFTP=31, OA=21, FA=20, papillary microcarcinoma(PMiC)=13, TFND=10, OC=7, LT=6, FC=5, poorly differentiated carcinoma(PdC)=1.10/13 BRAF-mutated cases were PTC, other 3 PMiC. SFU of RAS-mutated cases(n=59):TFND=6, LT=4, NIFTP=19, FA=8, OA=4, PTC=13, PMiC=2, FC=2. RAS mutations in PTC: KRAS=6, HRAS=4, NRAS=3. SFU of CNAs-HCT: OA=3, OC=2, TFND=1. Infrequently detected mutations with SFU of PTC:RET/PTC(1/1), ALK(1/1), RAS+TERT(1/1), TERT+BRAF(1/1), BRAF K601E(1/1), RAS+EIF1AX(1/2). SFU of RAS+TERT+PTEN+EIF1AX:PdC. 11/65 malignant cases, all PTC had LNM:BRAF=5, KRAS=3, CNAs=1, EIF1AX=1, TERT+BRAF=1. Conclusion Substantial proportion of cases with positive MR underwent surgical resection. BRAF-positive and CNAs- HCT correlated with PTC and oncocytic neoplasms, respectively. BRAF-positive PTCs had a higher incidence of LNM compared to wild-type cases(46% vs.18%).

8751 Radiofrequency Thermal Ablation in 32 Patients with Toxic Adenomas with Resolution of Hyperthyroidism in All Cases

Abstract Disclosure: L.G. Amato: None. E.M. Volpi: None. L.D. Volpi: None. P.M. Carani: None. A. Rahal: None. Introduction: In the general population, thyroid nodules are found in 3-7% of individuals on physical examination and in 20-76% on ultrasound. Around 8-10% of benign nodules may present autonomous behavior, being called hot nodules, causing symptoms of hyperthyroidism and being called toxic adenomas (TA). In TAs, autonomous hormone production can be caused by somatic activating mutations of genes regulating thyroid growth and hormone synthesis caused by somatic activating mutations of genes regulating thyroid growth and hormone synthesis. Classically, the proposed treatment for autonomous nodules was surgical resection or radioiodine ablation (RAI). In this context, the prevalence of hypothyroidism after the procedure varies from 2% to 3% following lobectomy, and lower after isthmusectomy in the unique circumstance in which the TA is confined to the thyroid isthmus. A study following 684 patients with TA treated with RAI reported a progressive increase in overt and sub-clinical hypothyroidism. Potential complications following near-total/total thyroidectomy include the risk of permanent hypoparathyroidism (&amp;lt; 2.0%) or recurrent laryngeal nerve injury (RLN) (&amp;lt; 2.0%). A small risk of permanent RLN injury exists with surgery for TA. Following RAI therapy, there have been reports of new-onset Graves Disease (up to 4% prevalence) as well as concern for thyroid malignancy and a very minimal increase in late non thyroid malignancy. Radiofrequency ablation (RFA) has been a precise and effective alternative for the treatment of many benign thyroid nodules over the past ten years, including hot nodules. RFA could preserves normal thyroid function compared to surgery or RAI. Clinical case: We evaluated the effectiveness of a single session of RFA in 32 patients with TA, through hormonal status, achieving normalization of thyroid and volumetric reduction of the nodule. Among the 32 patients included in this study, aged between 25 and 88 years, of these, 31 were women and 1 was a man, all of whom underwent a single RFA procedure (“moving shot” technique associated with hydrodissection). We had a single case of a reversible complication: a patient who had transient vocal cord paralysis, with total reversal. There was a reduction in the volume of all nodules as well as all patients progressed to a state of euthyroidism within 60 days of follow-up. Conclusion: A single session of RFA was effective in treating autonomous nodules, restoring euthyroidism in all patients. Presentation: 6/3/2024

8141 A Rare Case of Follicular Adenoma with Osseous Metaplasia and Mature Bone Formation- Is Surveillance Important?

Abstract Disclosure: K. Madani: None. Y. Al-Khazraji: None. D.H. Sacoto: None. G.K. Rai: None. R. Belokovskaya: None. A.A. Franco-Akel, MD: None. Osseous metaplasia and mature bone formation (MBF) are common in malignant thyroid and parathyroid tumors. It is very unusual to have MBF in a benign tumor-like follicular adenoma, as in the case we describe. We found only twelve such cases reported in the literature, and none addressed the cancer risk or need for surveillance for the development of potential malignancy. Thus, further studies are required to investigate the need for surveillance in patients not undergoing excision and in those with remnant thyroid tissue post-removal of the adenoma for recurrence. A 43-year-old female with history of hyperlipidemia and hypothyroidism had an incidental finding of midline neck mass during the evaluation of a left upper extremity lipoma. Ultrasound of the neck showed two nodules in the Left (L) thyroid lobe: a complex nodule measured 2.2 x 1.2 x 2.1 cm and a calcified nodule measuring 1.5 x 0.8 x 0.6 cm. MRI of the neck revealed a 1.9 cm heterogeneously enhancing nodule in the mid to lower pole of the L thyroid lobe. The patient had symptoms suggestive of compression, such as dysphagia, odynophagia, and hoarseness; thus, left hemothyroidectomy was performed. Tissue biopsy was notable for follicular adenoma with osseous metaplasia and mature bone formation. The patient remained clinically and biochemically euthyroid, with only mildly elevated thyrotropin level, and treatment with levothyroxine 25 mcg once daily was initiated. On post-surgical follow-up, there was a lack of data to support close monitoring modality and strategy for the remnant thyroid lobe and neck nodal compartments. We concluded with the patient to follow up in a clinical visit for a physical exam of the neck and to obtain a follow-up sonogram at an interval of six months, in addition to monitoring TSH levels to guide hypothyroidism therapy. Osseous metaplasia has not been established as a premalignant condition, but in certain tissues like the esophagus, metaplasia is a risk factor for malignant conversion, for instance, in Barrett’s esophagus leading to esophageal adenocarcinoma. Moreover, MBF in thyroid tissue has been attributed to the activity of basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2), which are linked with mitogenesis and tumorigenesis. Thus, the question arises if post-excision surveillance is required in patients with a history of osseous metaplasia in remnant thyroid tissue post-lobectomy or partial thyroidectomy. At this point, more epidemiological data on similar cases may help us understand the true risk of this clinical scenario, in order to develop a reasonable approach for surveillance. Presentation: 6/3/2024

8049 Beyond Metastasis: Parasitic Thyroid Tissue Mimicking Thyroid Cancer

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. N.A. Mungo: None. This case study details a complex clinical scenario involving a patient with diaphoresis and a familial history of thyroid cancer. Initial suspicions of functionally active metastatic thyroid cancer led to a thyroidectomy and cervical lymph node dissection, only to reveal unexpected parasitic thyroid tissue. This case highlights the importance of meticulous evaluation and follow up similar presentations, shedding light on the rarity of this phenomenon.The patient, experiencing a year of diaphoresis unresponsive to estradiol therapy, underwent imaging revealing multiple thyroid nodules. A left superior nodule (TI-RADS 4) and a more concerning right mid-posterior nodule (TI-RADS 5) prompted fine needle aspiration (FNA). FNA of the right thyroid nodule exhibited Bethesda category III atypia, no molecular samples were taken at that time, while cervical lymph node FNA yielded nondiagnostic results.Subsequent ultrasound showed no interval change in the right thyroid nodule but raised concerns about increased solid components and decreased echogenicity in other nodules. Due to patient concerns of positive family history of thyroid cancer, the lymph node was biopsied. The result yielded a low cellular sample, but follicular thyroid tissue was present. The patient elected to undergo thyroidectomy as she did not want to continue monitoring. Pathology revealed parasitic thyroid tissue in the lymph node and nodular follicular thyroid disease, with no evidence of papillary thyroid carcinoma in the gland. Notably, the patient had no history of thyroid surgeries, ruling out traumatic rupture or implantation from a follicular adenoma. However, the possibility of follow-up metastatic follicular carcinoma cannot be entirely excluded on histologic grounds.Follow-up tests were recommended, encompassing mutational analysis, whole-body scans, and thyroglobulin (Tg) monitoring. Molecular analysis did not favor cancer. Tg levels remained at (18 ng/ml, n&amp;lt; 35ng/ml) of initial evaluation six weeks post surgery and repeat testing is pending. Ablative radioactive iodine therapy may be appropriate as resection of all parasitic thyroid tissue can prove difficult.This case emphasizes the diagnostic challenges posed by the rare occurrence of parasitic thyroid tissue, often mistaken for metastatic thyroid cancer. The findings contribute to our understanding of uncommon thyroid pathologies. The clinical implications of this case extend to the importance of heightened clinical suspicion in intricate endocrine cases. Presentation: 6/3/2024

8373 High suspicion for thyroid cancer in patient with thyroid Hemiagenesis

Abstract Disclosure: L. Aoun: None. S. Almardini: None. M. Anise: None. F. Haddadin: None. F. Saliba: None. J. Zaidan: None. Background: Thyroid Hemiagenesis (THA) is a rare condition characterized by congenital absence of one lobe of the thyroid gland. Notably, THA is more prevalent in females and the left lobe is more likely to be absent with or without the isthmus. Most patients are euthyroid, and diagnosis is usually incidental, so the true prevalence of THA is uncertain as there are certainly undiagnosed cases. Studies have shown a link between THA, thyroid cancer, and hyperparathyroidism. We present a case of THA and high suspicion for thyroid cancer. Case Presentation: 54-year-old female with history of Rheumatoid arthritis who presented for evaluation of incidental thyroid nodules, occasional palpitations, tremors, and mild change in her voice. She denied abnormal weight loss or diarrhea. No history of radiation to the neck and no family history of thyroid disease or thyroid cancer. The thyroid exam showed an enlarged left palpable nodule. Labs significant for TSH 1.6 mIU/L (normal: 0.4-4 mIU/L), FT4 0.8 ng/dl (normal 0.7-1.9 ng/dL) and T3 77ng/dL (normal: 60-180 ng/dL). Thyroid U/S showed left hemiagenesis and right sided nodules biggest is 1.1 cm solid, hypoechoic with coarse calcifications, FNA was recommended and showed follicular lesion of undetermined significance, molecular testing was done and Thyroseq came back intermediate to high risk RAS and EIF1AX positive reflecting a 70 % probability of cancer. Based on these results, surgery was recommended, and the patient underwent right thyroidectomy. Surgery was uncomplicated and despite reported higher risk of hyperparathyroidism patient’s calcium and PTH were normal, and no parathyroid adenomas were identified intraoperatively. The pathology from the thyroidectomy showed follicular adenoma of 1 cm and no malignancy. She was started on Synthroid 100mcg daily post op. Discussion: This case demonstrates a case of a benign thyroid nodule and preserved parathyroid levels in the setting of thyroid hemiagenesis. Usually in THA, the contralateral lobe is at an increased risk for pathology of compensatory hypertrophy or hyperplasia. According to available studies, cancer association with THA was more common in left hemiagenesis and parathyroid adenomas more common ipsilateral to hemiagenesis . Despite Our patient’s FNA revealed atypical findings, molecular testing revealed RAS and EIF1AX positive, marking intermediate to high cancer risk. However, the thyroidectomy pathology report unveiled no evidence of malignancy, contraindicating the anticipated high cancer risk in those with left THA. This case highlights the rarity of THA and different possible presentations and cancer risks. Presentation: 6/2/2024

Tight Junctions and Cancer: Targeting Claudin-1 and Claudin-4 in Thyroid Pathologies.

Purpose: Claudins are tight junction proteins partaking in epithelial-mesenchymal transition and cancer progression. In this study, we investigated the expression patterns of claudin-1 and claudin-4 in thyroid pathologies, discussed their links with the pathogenesis of thyroid cancers, and reviewed the therapeutic potential of targeting claudins in cancers. Methods: The research group 162 cores of thyroid samples from patients (70 female and 11 male) diagnosed with thyroid adenoma, goiter, papillary, medullary, and anaplastic thyroid cancers. All samples were stained for the expression of claudin-1 and claudin-4, and the analysis of IHC was performed. Results: Goiter samples showed negative claudin-1 and mostly positive expression of claudin-4. Papillary thyroid cancer and thyroid adenoma showed positive expression of claudin-1, while claudin-4 was positive in papillary thyroid cancers, goiters, and adenomas. In The Cancer Genome Atlas cohort, claudin-1 and claudin-4 were overexpressed in papillary thyroid cancer compared to normal thyroid tissues. Patients with high claudin-1 expression had significantly lower 5-year overall survival than patients with low claudin-1 levels (86.75% vs. 98.65, respectively). In multivariate analysis, high claudin-1 expression (HR 7.91, CI 95% 1.79-35, p = 0.006) and advanced clinical stage remained statistically significant prognostic factors of poor prognosis in papillary thyroid cancer. Conclusions: The pattern of claudin-1 staining was pathology-specific and changed between cancers of different histology. This phenomenon may be associated with the different pathogenesis of thyroid cancers and early metastasis. The loss of claudin-1 and claudin-4 characterized more aggressive cancers. Several studies have shown the benefits of targeting claudins in cancers, but their implementation into clinical practice requires further trials.

Psammoma bodies in thyroid: are they always indicative of malignancy? A multi-institutional study.

Traditionally, psammoma bodies (PB) have been considered as tale-tell evidence of papillary thyroid carcinoma (PTC) and are frequently encountered in classic and other subtypes of PTCs. However, the presence of PBs in the thyroid gland does not always indicate malignancy. The leading hypothesis on their origin suggests that PB are remnants of papillary structures that have undergone thrombosis, necrosis, and subsequent calcification. From January 2010 to May 2024, 26 patients with psammoma bodies associated with benign thyroid lesions, mainly thyroid follicular nodular disease (TFND), Hashimoto thyroiditis (HT), Graves' disease, and follicular adenomas, were found. The case cohort included 16 females and 10 males with a median age of 49.3years. The series included 12 TFND, two HT, and 12 follicular adenomas (11 out of 12 were oncocytic adenomas). Twenty-four out of 26 underwent total thyroidectomy. In 24 out of 26 cases, the entire lobes and parenchyma were included and serial cuts at multiple levels were performed in cases with PB but without any evidence of malignancy. Even though the detection of PB is associated with a malignant thyroid lesion, especially PTC and its subtypes, our multi-institutional series showed that in a minority PB can be found in a variety of benign thyroid lesions. Evaluation of the entire thyroid parenchyma at multiple levels is mandatory to exclude sub-centimeter papillary thyroid carcinoma.

Questions about a risk of malignancy of toxic adenomas and the problems of their preoperative diagnosis

Questions about a risk of malignancy of toxic adenomas and the problems of their preoperative diagnosis

Management of follicular thyroid carcinoma.

Follicular thyroid carcinoma (FTC) is the second most common histological type of thyroid carcinoma. This review aims to summarize the available evidence and guidelines and provide an updated consensus regarding the management of FTC. The cytoarchitectural features of FTC are similar to those of follicular adenoma (FA), and it is difficult to preoperatively distinguish between FA and FTC. For nodules with Bethesda class III-V cytology, molecular test results (if available) should be considered before the operation. However, it should be noted that molecular tests are not available in all countries. The goals of initial surgical therapy for patients with FTC are to improve overall and disease-specific survival, reduce the risk of persistent/recurrent disease and associated morbidity, and permit accurate disease staging and risk stratification while minimizing treatment-related morbidity and unnecessary therapy. Previous studies have reported some prognostic factors such as distant metastasis, age, tumor size, vascular invasion, TERT promoter mutation, and histological subtype. In particular, the degree of vascular invasion is becoming increasingly important. Evaluating these prognostic factors is essential for prognostic prediction and precise management of patients with FTC. Recurrence and distant metastasis of FTC are treated with radioactive iodine (RAI). However, some FTCs become refractory to RAI. Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin-angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

Solitary fibrous tumor in athyroid follicular adenoma

A28-year-old female patient developed a5.5 cm progressive thyroid nodule that was surgically removed due to local symptoms. Histologically, asolitary fibrous tumor (SFT) in athyroid adenoma was diagnosed. The tumor had aspecific NAB2-STAT6 fusion.Solitary fibrous tumors rarely occur in the thyroid gland and are described as both primary and secondary manifestations. The diagnosis, prognosis assessment and treatment decision are carried out analogously to SFT of other localizations.

Uncovering a Causal Connection between Gut Microbiota and Six Thyroid Diseases: A Two-Sample Mendelian Randomization Study.

Recent studies have established associations between the gut microbiota (GM) and thyroid diseases (TDs). However, their causal relationships remain elusive. To investigate this causality, we conducted a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data from MiBioGen and FinnGen, with GM as the exposure and six TDs as outcomes. We identified 32 microbial taxa linked to the risk of six TDs. The Clostridium innocuum group, Ruminiclostridium5, and Lachnoclostridium exhibited protective effects against nontoxic diffuse goiter (NDG). Conversely, an increased risk of NDG was associated with Ruminococcaceae UCG002, Alistipes, Methanobrevibacter, Marvinbryantia, and Ruminococcaceae UCG014. Bifidobacterium and Sutterella were protective against nontoxic multinodular goiter (NMG), while the Ruminococcus gauvreauii group and Rikenellaceae RC9 gut group heightened NMG risk. Protective effects against nontoxic single thyroid nodule (NSTN) were observed with Defluviitaleaceae UCG011, Ruminococcus1, and Ruminococcaceae UCG010, whereas increased risk was linked to Alistipes, the Ruminococcus gauvreauii group, and Lachnospiraceae UCG010. Ruminiclostridium9, Victivallis, and Butyricimonas offered protection against thyrotoxicosis with Graves' Disease (GD), while the Eubacterium rectale group, Desulfovibrio, Bifidobacterium, Collinsella, Oscillospira, and Catenibacterium were risk factors. For thyrotoxicosis with Plummer Disease (PD), protective taxa included Butyricimonas and Lachnospira, whereas Dorea, Eggerthella, Odoribacter, Lactobacillus, Intestinimonas, and Phascolarctobacterium increased risk. Lastly, Parasutterella was protective against thyrotoxicosis with toxic single thyroid nodule (TSTN), while increased risk was associated with Sutterella, Oscillibacter, and Clostridium sensu stricto1. Our findings support a causal relationship between specific GM and TDs at the genetic level, laying the foundation for future research into potential mechanisms and the identification of novel therapeutic targets.

Effect of Presence of Uni- or Bilateral Thyroid Adenoma on Recovery of Pituitary-Thyroid Axis and Creatinine Concentration in Radioiodine-Treated Cats.

Radioiodine therapy (RAIT) is the gold standard for treatment of hyperthyroidism in cats. The aim of this study was to evaluate the effect of the presence of uni- or bilateral thyroid adenoma on changes in total thyroxine (TT4), thyroid-stimulating hormone (TSH), and creatinine concentration over a period of 6 to 12 months following RAIT. Fifty-one hyperthyroid cats presented for RAIT between April 2021 and April 2022 were prospectively enrolled. Cats with an increased creatinine concentration (creatinine ≥ 140 µmol/L), renal morphology abnormalities, and suspected thyroid carcinoma were excluded. TT4, TSH, and creatinine were determined before and one week and one, three, six, and twelve months following RAIT. The effects of the re-examination timepoint following RAIT and the presence of uni- or bilateral thyroid adenoma based on technetium-99m scintigraphy on TT4, TSH, and creatinine were analysed by mixed effects modelling. Cats with bilateral adenoma had significantly higher TSH concentrations after RAIT compared to those with unilateral adenoma. TT4 concentration significantly decreased one week (p < 0.001) and again one month following RAIT (p < 0.001). TSH and creatinine concentration significantly increased one month post RAIT (both p < 0.001). As indicated by an increase in TSH concentration, the pituitary-thyroid axis needs a minimum of one month post RAIT to recover from hyperthyroidism-induced suppression, but hypothyroidism necessitating levothyroxine supplementation might not be diagnosed before 6 or even 12 months post RAIT. Although creatinine did not increase significantly after one month post RAIT in this cohort, an increased creatinine concentration was detected at later timepoints in individual cats.

The alternative value of thyroid stimulating hormone instead of thyroglobulin in differentiation of follicular thyroid neoplasm in Hashimoto's thyroiditis.

To provide novel aspects for the preoperative diagnosis and appropriate differentiation strategies for follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA). Among 25,765 cases, a total of 326 patients with follicular thyroid neoplasms between 2013 and 2019 were enrolled. Patient demographics, perioperative parameters, surgical profiles and oncologic outcomes were collected and analyzed. There were no significant differences in preoperative ultrasound findings between FTA and FTC patients. The true positive rate (sensitivity) and true negative rate (specificity) of fine needle aspiration (FNA) for FTA patients were 0.6956 and 0.5000, respectively, and those for FTC patients were 0.0714 and 0.9348, respectively. Patients with FTC presented significantly higher serum thyroglobulin (TG) levels than patients with FTA. Preoperative TG level was positively related to tumor invasiveness and recurrence or distant metastases in FTC patients. There were 55 patients with Hashimoto's thyroiditis (HT), accounting for 16.87% of enrolled patients. HT patients had significantly lower serum TG concentrations than antibody-negative patients. Among HT patients, no significant differences were observed in TG levels between the FTA and FTC groups. Instead, FTA patients had significantly higher serum thyroid stimulating hormone (TSH) levels and lower serum T3 (Triiodothyronine) levels compared to FTC patients. Serum TSH level >1.736U/L was associated with benign follicular neoplasms in HT patients according to the receiver operating characteristic (ROC) curve. Distinguishing FTC from FTA remains a challenge for ultrasonography and FNA. Serum TG should be measured as a risk factor of FTC. However, in HT patients, serum TSH levels can serve as a more reliable indicator for differentiating FTC from FTA preoperatively.

Ectopic thyroid adenoma diagnosed in a Senegal seabream (Diplodus bellottii, Steindachner 1882): Towards an accurate diagnosis.

Thyroid tissue in teleosts is located mainly in the pharyngeal region, usually reaching other adjacent anatomical locations. Herein, a nodular lesion located in the left operculum of a Senegal seabream (Diplodus bellottii) was surgically excised and sent for microscopical evaluation. Microscopically, the lesion presented irregular borders and consisted in columnar epithelial cells arranged in a tubulopapillary pattern, surrounding a central lumen filled with acellular, acidophilic and homogeneous, material ('colloid'). To determine the lesion's histogenesis, immunohistochemistry was performed employing antibodies for AE1/AE3, CK7, thyroglobulin and vimentin. The neoplastic cells presented low mitotic index and positive immunolabelling for CK7 and thyroglobulin. Therefore, a diagnosis of ectopic thyroid adenoma was made. Herein, the successful employment of antibodies classically used in mammals for accurate diagnosis of thyroid disorders is described. Proliferation of thyroid tissue in fish may reflect environmental and physiological imbalances, making the study and correct diagnosis of these tumours in this species important.

EIF1AX mutation in thyroid nodules: a histopathologic analysis of 56 cases in the context of institutional practices.

EIF1AX mutation has been identified as a driver mutation for papillary thyroid carcinoma (PTC) by The Cancer Genome Atlas (TCGA) study. Subsequent studies confirmed this mutation in PTC and Anaplastic Thyroid Carcinoma (ATC) but also reported EIF1AX mutation in Follicular nodular disease (FND) and benign thyroid nodules. In this study, we review thyroid nodules with EIF1AX mutation from two institutions: a tertiary care hospital (YNHH, n = 22) and a major cancer referral center (MSKCC, n = 34) and report the varying histomorphology in the context of additional genetic abnormalities and institutional practices. Pathology diagnoses were reviewed according to the WHO 5th edition and correlated with the type of EIF1AX mutation and additional concurrent molecular alterations, if any. Most cases were splice site type mutations. Cases consisted of 9 FND, 7 follicular (FA) or oncocytic adenomas (OA), 2 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 38 follicular-cell derived thyroid carcinomas. Of 8 cases with isolated EIF1AX mutation, 7 were FND, FA or OA (88%) and one was an oncocytic carcinoma (12%). Of 12 cases with EIF1AX and one additional molecular alteration, 9 (75%) were FND, FA or OA, 2 (17%) were NIFTPs and one (8%) was a poorly differentiated thyroid carcinoma. All 36 cases with EIF1AX mutation and molecular alterations were malignant (100%) and included TP53 and TERT promoter mutations associated with ATC (n = 8) and high-grade follicular cell-derived non-anaplastic carcinoma (HGC, n = 2). Isolated EIF1AX mutation was noted only in thyroid nodules seen at YNHH and were predominantly encountered in benign thyroid nodules including FND. Accumulation of additional genetic abnormalities appears to be progressively associated with malignant tumors.