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Introduction: Thyroid oncocytic carcinoma, also known as Hürthle cell carcinoma (HCC), is a rare subtype of thyroid cancer with unique characteristics. Radioiodine therapy, while less effective for HCC due to poor radioiodine accumulation in tumor, has shown improved survival rates for tumors larger than 2 cm. Adjuvant radioiodine therapy is recommended in certain cases, particularly for older patients with a worse prognosis. Methods: This study reviewed data from 18 HCC cases compared to the overall patient population (OPP) at our center between 2019 and 2022. Results: The mean age at diagnosis was higher for HCC patients compared to OPP, with varying responses to therapy observed. Assessment of response to therapy after one year revealed 26.7%, 20%, 20%, and 33.3% of HCC patients with excellent, indeterminate, biochemical incomplete, and structural incomplete responses, which were 41.5%, 24.7%, 13%, and 20.7% in OPP, respectively. The Kaplan curve of patient survival showed an average of 100±13.5 months. Conclusion: Approximately 44% of HCC patients showed excellent survival outcomes after radioiodine therapy, highlighting its importance as a treatment option for HCC. Further research is needed to optimize treatment choices and improve patient outcomes in this less common subtype of thyroid cancer. [ABSTRACT FROM AUTHOR]

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC. [ABSTRACT FROM AUTHOR]

Background: Oncocytic carcinoma (OCA) was recently reclassified as a distinct differentiated thyroid carcinoma (DTC). Given its rarity, OCA studies are limited. This study describes the characteristics of OCA in a 20‐year cohort. Methods: Retrospective analysis of patients with OCA at a single tertiary care hospital from 2000 to 2021. Results: Fifty‐one OCA patients (22M:29F) were identified. The mean age at diagnosis was 60.3 years; 90% presented as palpable mass; 24% had a family history of thyroid cancer. None had vocal fold paresis. On ultrasound, most tumors were solid and hypoechoic. FNA (n = 14) showed Bethesda‐4 lesions in 93%. All were treated surgically. Histologically, 63% demonstrated angioinvasion, 35% had lymphovascular invasion, and 15% had extrathyroidal extension. Radioactive iodine was used as adjunct therapy in 77%. Conclusion: OCA has distinct features that distinguish it from other DTCs, and additional focused studies will help clarify the aggressive nature, treatment options, and prognosis of the disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Differential diagnosis by optical microscopy on biopsies of low-incidence tumors of the same organ can be difficult, hampering patient management, particularly in the many places around the world lacking advanced facilities for cancer diagnosis beyond a histopathology laboratory. Examples of these tumors are the Hurthle cell, anaplastic, and medullary carcinomas of the thyroid. Currently, there are no specific biomarkers detectable by optical microscopy for any of them. We study the Chaperone System of these tumors by immunohistochemistry to determine if its components show distinctive levels and distribution patterns. Here we report that the molecular chaperones Hsp27, Hsp60, and Hsp90, show quantitative levels and distribution patterns different for each tumor and different from those of a benign thyroid pathology, goiter. Therefore, the reported methodology offers a promising tool to diagnose these three malignancies, and for revealing clues about the role of the three chaperones in carcinogenesis of thyroid tissue. Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of cases, information, and histopathological images, especially in the many areas around the world in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore, cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological images with reliable biomarkers, which can help them to reach a differential diagnosis. We are investigating whether components of the chaperone system (CS), such as the molecular chaperones, can be considered dependable biomarkers, whose levels and distribution inside and outside cells in the tumor tissue could present a distinctive histopathological pattern for each tumor type. Here, we report data on the chaperones Hsp27, Hsp60, and Hsp90. They presented quantitative levels and distribution patterns that were different for each tumor and differed from those of a benign thyroid pathology, goiter (BG). Therefore, the reported methodology can be beneficial when the microscopist must differentiate between HC, AC, MC, and BG. [ABSTRACT FROM AUTHOR]

Context: It is unclear whether radioactive iodine (RAI) therapy could improve cancer-specific survival (CSS) in patients with Hürthle cell carcinoma (HCC) of the thyroid. Objective: To investigate the effect of RAI on CSS in HCC patients. Methods: HCC patients who underwent total thyroidectomy (TT) were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. The Kaplan-Meier method and the Cox proportional hazards regression model were used to evaluate CSS. Propensity score-matched (PSM) analyses were performed to control the influence of potential confounders. Results: A total of 2279 patients were identified. RAI treatment was not significantly associated with improved CSS in overall or PSM cohort. Subgroup analyses indicated similar results, even in patients with aggressive features such as age 55 years or older, tumor size greater than 40 mm, distant disease in SEER staging, extrathyroidal extension, and lymph node metastases (all P > .05). Conclusion: RAI has no statistically significant influence on the CSS in HCC patients. This information may aid in decision-making for RAI therapy in these patients. [ABSTRACT FROM AUTHOR]

Background: Hürthle cell carcinoma (HCC) of the thyroid is rare. There are contrasting data on its clinical behavior. The aim of this study was to describe clinic-pathological features and outcomes of HCC patients at our institution, in order to adapt our surgical management. Methods: We retrospectively studied 51 cases of HCC treated at the interdisciplinary endocrine center of the University Hospital of Cologne, Germany between 2005 and 2020. Results: Patients median age was 63 years (range 29-78) with 64.7% of cases being female. Primary treatment included surgery and postoperative radioiodine therapy with 3.7 GBq in all patients. Surgery consisted of total thyroidectomy in all cases and additional central lymphadenectomy in 90.2% of cases. The median number of harvested lymph nodes was 11 (range 2-31). Lymph node involvement was found in two (4.3%) pT4a tumors. In all other cases (95.7%), central lymphadenectomy was prophylactic and lymph nodes were free of metastasis in final histopathology. Twelve (23.5%) patients with incomplete biochemical response to primary treatment were diagnosed with structural relapse during the course of disease, for which seven (58.4%) underwent resection of isolated cervical metastasis. Histopathology revealed soft tissue implants in all cases and cervical surgery led to biochemical and radiologic cure in only two (28.5%) cases. Five (41.6%) patients developed metastatic disease, followed by systemic therapy in two patients. Vascular invasion of the primary tumor was significantly associated with relapse (p<0.01). Conclusions: Recurrence of HCC was common in this study. Given the low rate of lymph node metastases both in this study and in recent literature and the nature of relapse (soft tissue instead of nodal metastasis), the benefit of routine prophylactic central lymph node dissection for HCC remains unclear, especially in the absence of vascular invasion from the primary tumor. [ABSTRACT FROM AUTHOR]

Background: Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) are rare and aggressive thyroid cancers with limited published data comparing their outcomes or regarding their subtypes. The aim of this study was to describe clinicopathological features and compare clinical outcomes of patients with FTC and HCC based on the 2017 World Health Organization definition and extent of vascular invasion (VI). Methods: We retrospectively studied 190 patients with HCC and FTC primarily treated with surgery at Memorial Sloan Kettering Cancer Center between 1986 and 2015. Patients were classified as minimally invasive (MI), encapsulated angioinvasive with focal VI (EA-FVI), encapsulated angioinvasive with extensive VI (EA-EVI), and as widely invasive (WI). To compare clinical outcomes, patients were grouped as follows: group 1 = FTC-MI and FTC EA-FVI, group 2 = FTC EA-EVI and FTC-WI, group 3 = HCC-MI and HCC EA-FVI, group 4 = HCC EA-EVI and HCC-WI. Outcomes of interest were overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and distant recurrence-free survival (DRFS). Outcomes were determined using the Kaplan–Meier method and compared with log-rank test. Results: Patients with HCC (n = 111) were more likely to be older than 55 years old (59% vs. 27%, p < 0.001) with a tendency to present with more extensive VI (33% vs. 19%, p = 0.07) compared with FTC (n = 79). Comparing groups 1, 2, 3, and 4, group 4 patients were more likely to recur (DFS 98%, 93%, 98% vs. 73%, respectively, p = 0.0069). There was no statistically significant difference in OS, DSS LRRFS, or DRFS. Stratified by extent of VI (no, focal, and extensive VI), patients with extensive VI were more likely to recur (RFS 100%, 95%, 77%, p = 0.0025) and had poorer distant control (DRFS: 100%, 95%, 80%, p = 0.022), compared with patients absent or focal VI. Conclusions: Accurate assessment of the extent of VI and tumor phenotype (follicular vs. Hurthle) are essential in identifying patients at higher risk of recurrence. [ABSTRACT FROM AUTHOR]

Background: Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis. Methods: This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009. Results: The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS). Conclusion: The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nationwide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging. [ABSTRACT FROM AUTHOR]

Introduction: Hürthle cell carcinoma (HCC) comprises about 5% of thyroid carcinoma cases. Partly because of its rarity there is much we still need to know about HCC as compared to other histological cancer subtypes. Methods: We conducted a systematic literature review following PRISMA guidelines and meta-analysis, from 2000 to 2020, to investigate the main characteristics of HCC and clarify information concerning tumor behavior and treatment. Results: Our review included data from 9638 patients reported in 27 articles over the past 20 years. This tumor occurred more frequently in women (67.5%). The mean age was 57.6 years, and the mean size of the neoplasm at diagnosis was 30 mm. Extrathyroidal extension was common (24%) but lymph node metastasis was not (9%). Total thyroidectomy was the most common surgical approach, with neck dissection usually performed in cases with clinically apparent positive neck nodes. Radioiodine therapy was frequently applied (54%), although there is no consensus about its benefits. The mean 5- and 10-year overall survival was 91% and 76%, respectively. Conclusion: This review serves to further elucidate the main characteristics of this malignancy. HCC of the thyroid is rare and most often presents with a relatively large nodule, whereas lymph node metastases are rare. Given the rarity of HCC, a consensus on their treatment is needed, as doubts remain concerning the role of specific tumor findings and their influence on management. [ABSTRACT FROM AUTHOR]

Background: Follicular thyroid carcinoma is the second most common malignancy of the thyroid gland. In 2016, the so-called Hurthle cell thyroid carcinoma, formerly known as the oxyphilic variant of the follicular thyroid carcinoma, was reclassified by the World Health Organization as a separate pathological entity, which accounts for approximately 3% of all thyroid cancers. Although Hurthle cell thyroid carcinomas are known for their more aggressive tumor biology, metastases are observed in a minority of cases, and long-term survival can be expected. However, disseminated disease is often associated with poor outcome.Case Presentation: In the presented case, a 63-year-old Caucasian female was incidentally diagnosed with Hurthle cell thyroid carcinoma after undergoing hemithyroidectomy for a nodular goiter. Following completion thyroidectomy, two courses of radioactive iodine therapy were administered. After 4 years of uneventful follow-up, the patient gradually developed metastases in five different organs, with the majority representing unusual sites, such as heart, kidney, and pancreas over a course of 14 years. The lesions were either treated with radioactive iodine therapy or removed surgically, depending on iodine avidity.Conclusion: Follicular and Hurthle cell thyroid carcinoma are known to potentially spread hematogenously to typical sites, such as lung or bones, however; unusual metastatic sites as presented in our case can also be observed. A search of the literature revealed only scattered reports on patients with multiple metastases in unusual locations. Furthermore, the observed long-term survival of our patient is contradictory to the existing data. As demonstrated, recurrent disease may appear years after the initial diagnosis, emphasizing the importance of consistent aftercare. Radioactive iodine therapy, extracorporeal radiation therapy, and surgical metastasectomy are central therapeutic components. In summary, our case exemplifies that thorough aftercare and aggressive treatment enables long-term survival even in recurrent Hurthle cell thyroid carcinoma displaying unusual multisite metastases. [ABSTRACT FROM AUTHOR]

Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the origin of the cell, and even which cells in particular may be designated as such still challenge pathologists and confound those treating patients with a diagnosis of "Hürthle cell" anything within the diagnosis, especially if that anything is a sizable mass lesion. The diagnosis of Hürthle cell adenoma (HCA) or Hürthle cell carcinoma (HCC) has typically relied on a judgement call by pathologists as to the presence or absence of capsular and/or vascular invasion of the adjacent thyroid parenchyma, easy to note in widely invasive disease and a somewhat subjective diagnosis for minimally invasive or borderline invasive disease. Diagnostic specificity, which has incorporated a sharp increase in molecular genetic studies of thyroid tumor subtypes and the integration of molecular testing into preoperative management protocols, continues to be challenged by Hürthle cell neoplasia. Here, we provide the improving yet still murky state of what is known about Hürthle cell tumor genetics, clinical management, and based upon what we are learning about the genetics of other thyroid tumors, how to manage expectations, by pathologists, clinicians, and patients, for more actionable, precise classifications of Hürthle cell tumors of the thyroid. [ABSTRACT FROM AUTHOR]

It has been widely described that cancer genomes have frequent alterations to the epigenome, including epigenetic silencing of various tumor suppressor genes with functions in almost all cancer-relevant signalling pathways, such as apoptosis, cell proliferation, cell migration and DNA repair. Epigenetic alterations comprise DNA methylation, histone modification, and microRNAs dysregulated expression and they play a significant role in the differentiation and proliferation properties of TC. In this review, our group assessed the published evidence on the tumorigenic role of epigenomics in Hurthle cell neoplasms (HCN), highlighting the yet limited, heteregeneous and non-validated data preventing its current use in clinical practice, despite the well developed assessment techniques available. The identified evidence gaps call for a joint endeavour by the medical community towards a deeper and more systematic study of HCN, aiming at defining epigenetic markers in early diagnose, allowing for accurate stratification of maligancy and disease risk and for effective systemic treatment. [ABSTRACT FROM AUTHOR]

Hürthle cell carcinoma (HCC) is a distinct type of thyroid canc er genetically characterized by DNA copy number alterations (CNA), typically of genome haploidization type (GH-type). However, whether CNA also occurs in benign Hürthle cell adenomas (HCA) or Hürthle cell hyperplastic nodules (HCHN), and have diagnostic impact in fine-needle aspiration (FNA) samples, remains unknown. To address these questions, we (1) analyzed 26 HCC, 24 HCA, and 8 HCHN tissues for CNA and other mutations using Th yroSeq v3 (TSv3) next-generation sequencing panel, and (2) determined cancer rate in 111 FNA samples with CNA and known surgical outcome. We identified CNA, more often of the GH-type, in 81% of HCC and in 38% HCA, but not in HCHN. Among four HCC with distant metastasis, all had CNA and three TERT mutations. Overall, positive TSv3 results were obtained in 24 (92%) HCC, including all with ATA high risk of recurrence or me tastasis. Among 111 FNA cases with CNA, 38 (34%) were malignant and 73 (66%) benign. A significant correlation between cancer rate and nodule size was observed, particularly among cases with GH-type CNA, where every additional centimeter of nodule size increased the malignancy odds by 1.9 (95% CI 1.3-2.7; P = 0.001). In summary, the results of this study demonstrate that CNA characteristic of HCC also occur in HCA, although with lower frequency, and probability of cancer in nodules with CNA increases with nodule size. Detection of CNA, in conjunction with other mutations and nodule size, is helpful in predicting malignancy in thyroid nodules. [ABSTRACT FROM AUTHOR]

Purpose: There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT). Methods: We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival. Results: Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0–19.8) vs. 20.1 years (95% CI 19.0–21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309–0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years). Conclusions: Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT. [ABSTRACT FROM AUTHOR]

Multiple primary malignancies are defined as two or more primary malignant tumors diagnosed in one individual; they are further classified to synchronous or metachronous based on the period between each cancer diagnosis and the other. The diagnosis of four synchronous cancers is exceedingly rare. We report a case of a 72-year-old man, diagnosed with synchronous quadruple cancers, Hurthle cell carcinoma and papillary carcinoma of the thyroid, as well as squamous cell carcinoma and carcinoid tumor of the lung. [ABSTRACT FROM AUTHOR]

Hurthle cell carcinoma is a rare subtype of follicular thyroid carcinoma. Its aggressive nature and poor prognosis require prompt diagnosis and treatment, which is often challenging. We herein report a case of a woman who complained of lumps on her left and right neck which move with swallowing motion for 15 years, and have gotten bigger in the previous 6 months. Follicular thyroid carcinoma was first suspected based on previous fine needle aspiration biopsy. Total thyroidectomy and selective neck dissection procedure were performed and histopathology examination post-surgery showed Hurthle cell carcinoma. The patient also received thyroid replacement hormone therapy. This case discusses the diagnosis and management of Hurthle cell carcinoma leading to better patient outcome. [ABSTRACT FROM AUTHOR]

Purpose: Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11 % of PTC cases. Its clinical course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC. Methods: A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients' demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox's multivariate regression model was used to identify independent prognostic factors for survival. Results: OPTC patients were significantly older (55.2 ± 12.3 years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (p value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8 cm for OPTC patients, 1.5 ± 1.2 cm for PTC patients, p value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (p value 0.046). However, this difference was not observed anymore after matching for risk factors (p value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097–1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant. Conclusion: At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching. [ABSTRACT FROM AUTHOR]

The most usual form of the endocrine carcinoma is thyroid cancer (TC). In addition to papillary thyroid carcinoma (PTC), recent studies revealed incidence of RET/PTC rearrangement in other tumors, like Hürthle cell carcinoma (HCC) and even in noncarcinomatous disorders like Hashimoto's thyroiditis. Here, we present a case with concurrence of papillary thyroid carcinoma and Hürthle cell carcinoma. A 60-year-old woman referred to our hospital with a mass in her neck. Physical examinations revealed painful swelling in the thyroid. Ultrasonographic examination showed two hypoechoic nodules in the right lobe. Hürthle cell variant papillary carcinoma was suggested in the cytology report of the fine needle aspiration. Permanent histopathological diagnosis was co-existence of papillary thyroid carcinoma and Hürthle cell carcinoma. The patient was asymptomatic in 14 months follow up. Concurrence of papillary carcinoma and Hürthle cell carcinoma is a rare form of thyroid malignancies, with doubtful cytogenetic findings and biological behaviors. The results showed that it is necessary for the surgeons and pathologists to be aware of lesions for the optimal diagnostic and therapeutic interventions. Also, it is vital to follow up patients with the Hashimot's thyroiditis who have multiple nodules to detect occult thyroid cancers and decide for better therapeutic programs. [ABSTRACT FROM AUTHOR]

Purpose. Radioactive iodine (RAI) is widely used for adjuvant therapy after thyroidectomy, while its value for thyroid cancer has been controversial recently. The primary objectives of this study were to clarify the influence of Radioactive iodine (RAI) on the survival in rare oxyphilic subtype of thyroid cancer (Hürthle cell carcinoma, HCC). Methods. Patients diagnosed with oxyphilic thyroid carcinoma from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results Program database. The Kaplan-Meier method was used to compare overall survival (OS) and cancerspecific survival (CSS) among patients who had adjuvant RAI use or not. Univariate and multivariate Cox proportional hazard models were performed for survival analysis, and subsequently visualized by nomogram. Results. In all, 2,799 patients were identified, of which 1529 patients had adjuvant RAI use while 1,270 patients had not. Based on multivariate Cox analysis, the RAI therapy confers an improved OS for HCC patients (HRD0.57, 95% CI [0.44-0.72], P <0:001), whereas it has no significant benefit in the survival analysis regarding CSS (HR D 0.79, 95% CI [[0.47-1.34], P D0:382). In a subgroup analysis, the same survival benefit of RAI treatment on OS, but not CSS was observed among patients stratified by AJCC stage and tumor extension. Nevertheless, patients with regional lymph node metastasis benefited from RAI therapy both in OS and CSS (P <0:001, respectively). Furthermore, nomograms used for predicting long term survival of HCC patients exhibited a better prediction power for OS compared with traditional tumor, nodal and metastatic (TNM) stage made by American Joint Committee on Cancer (AJCC) (C-index D 0.833 of the nomogram model vs. 0.696 of the AJCC system). Conclusions. This study suggests that RAI therapy is significantly associated with improved OS in patients with Hürthle cell carcinoma. However, there was no association between treatment with radioiodine and CSS, possibly due to small number of deaths that were related to HCC. [ABSTRACT FROM AUTHOR]

Although differentiated thyroid carcinomas typically pursue an indolent clinical course, it is important to identify the subset of tumors that are most likely to behave aggressively so that patients with these tumors are counseled and treated appropriately. Extent of disease is fundamental to the prognostication for differentiated thyroid carcinoma; however, there are additional histologic features of the tumor separate from extent of disease that have been shown to affect clinical course. This review will start with a discussion of aggressive variants of papillary thyroid carcinoma, move to the prognostic significance of vascular invasion in follicular thyroid carcinoma, and finish with a discussion of Hürthle cell carcinoma, with an emphasis on why it is not considered a subtype of follicular thyroid carcinoma in the 2017 WHO Classification of Tumors of Endocrine Organs. [ABSTRACT FROM AUTHOR]

Objective: To present a case of lingual thyroid Hürthle cell carcinoma (HCC).Clinical Presentation and Intervention: A 37-year-old female presented with dysphagia and recurrent haemorrhage. Histopathology was suggestive of HCC; the tumour was excised by the trans-glossal approach which provided adequate exposure and helped avert external scarring or mandibular osteotomy. Histopathology showed a tumour-positive right lateral resection margin. This prompted referral to nuclear medicine for radio-iodine ablation.Conclusion: Lingual thyroid cases should be followed up closely and fine-needle aspiration biopsy should be considered when in doubt. [ABSTRACT FROM AUTHOR]

We illustrate a case of synchronous malignant solitary fibrous tumor of the thoracic cavity, and widely invasive thyroid Hurthle cell carcinoma. The Hurthle cell carcinoma was found to harbor distinct areas of malignant solitary fibrous tumor. This is a unique case of tumor-to-tumor metastasis that, to the best of our knowledge, has not been previously reported. [ABSTRACT FROM AUTHOR]

Renal metastasis from thyroid cancer is uncommon, and computed tomography and magnetic resonance imaging findings cannot clearly differentiate renal metastases from renal cell carcinoma. However, I-131 total body scans almost always reveal radioiodine avidity in metastatic renal lesions from thyroid cancer but not in renal cell carcinoma. Hence, I-131 total body scans can be used for diagnosis and treatment planning in this rare patient population. These findings were reported mostly from the follicular variant of papillary thyroid cancer and follicular thyroid cancer. This report presents a case of renal metastasis from Hurthle cell follicular carcinoma with a literature review. The previous report on treatment options in well-differentiated renal thyroid cancer metastases included nephrectomy and radioiodine treatment. Patients with renal metastases typically also had other distant metastases and thus had poor prognoses and treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Hurthle cell carcinoma makes up 3 to 5% of all thyroid cancers and is considered to be a true rarity. The aim of our study was to analyze clinical characteristics and survival rates of patients with Hurthle cell carcinoma.Methods: Clinical data regarding basic demographic characteristics, tumor grade, type of surgical treatment and vital status were collected. Methods of descriptive statistics and Kaplan-Meier survival curves were used for statistical analysis. Cox proportional hazards regression was used to identify independent predictors.Results: During the period from 1995 to 2014, 239 patients with Hurthle cell carcinoma were treated at our Institution. The average age of the patients was 54.3, with female to male ratio of 3.6:1 and average tumor size was 41.8 mm. The overall recurrence rate was 12.1%, with average time for relapse of 90.74 months and average time without any signs of the disease of 222.4 months. Overall 5-year, 10-year and 20-year survival rates were 89.4%, 77.2%, 61.9% respectively. The 5-year, 10-year and 20-year cancer specific survival rates were 94.6%, 92.5%, 87.4%, respectively. When disease free interval was observed, 5-year, 10-year and 20-year rates were 91.1%, 86.2%, 68.5%, respectively. The affection of both thyroid lobes and the need for reoperation due to local relapse were unfavorable independent prognostic factors, while total thyroidectomy as primary procedure was favorable predictive factor for cancer specific survival.Conclusion: Hurthle cell carcinoma is a rare tumor with an encouraging prognosis and after adequate surgical treatment recurrences are rare. [ABSTRACT FROM AUTHOR]

Background: Distant metastases (DM) are a rare occurrence in well-differentiated thyroid carcinoma. The aim of this study was to analyze the clinical, pathologic, and molecular features of primary thyroid carcinoma with low-risk histology that develop DM. Methods: A detailed clinicopathologic review and targeted next-generation sequencing were performed on a cohort of well-differentiated thyroid carcinoma lacking gross extrathyroidal extension, extensive vascular invasion, or significant lymph node metastases but exhibiting DM. Results: Primary well-differentiated thyroid carcinoma with low-risk histologic features and DM was a rare occurrence, accounting for only 3% of metastatic non-anaplastic thyroid carcinoma. All 15 cases meeting the inclusion criteria harbored DM at presentation. The majority (11/15) of these tumors were follicular variant of papillary thyroid carcinoma (PTC), especially the encapsulated form ( n = 8). The remaining patients harbored encapsulated Hürthle cell carcinoma ( n = 2), encapsulated follicular carcinoma ( n = 1), and an encapsulated papillary carcinoma classical variant ( n = 1). Of the 12 encapsulated carcinomas, 10 had capsular invasion only and no vascular invasion. Ninety-two percent of the tumors exhibited extensive intra-tumoral fibrosis. Among the eight tumors that were subjected to next-generation sequencing analysis, a RAS mutation was the main driver (5/8), and TERT promoter mutation was highly prevalent (6/8). In four cases, TERT promoter mutations were associated with RAS or BRAF mutations. BRAF-mutated classical variant of papillary carcinoma also presented with DM but was less common (1/8). In 11/15 cases, the clinician was able to diagnose distant disease based on the clinical presentation. In 3/4 incidental cases that were genotyped, TERT promoter mutations were found. Conclusions: When DM occur in primary thyroid carcinoma with low-risk histology, they are almost always found at presentation. The majority are encapsulated follicular variant of PTC with capsular invasion only. TERT promoter mutations occur at a higher rate than that seen in PTC in general and may help explain the aggressive behavior of these histologically deceptive primary carcinomas. [ABSTRACT FROM AUTHOR]

Background: Hürthle cell (HC) neoplasms are rare among pediatric thyroid cancers. HC adenomas (HCA) are typically benign and localized unilaterally without recurrence, and they are thus treated by hemithyroidectomy. HC carcinomas (HCC) can be bilateral and are more aggressive, necessitating total thyroidectomy. Diagnosis relies upon surgical histopathology demonstrating invasion for classification as HCC or lack of invasion in HCA, since fine needle aspiration fails to differentiate between the two. Methods: We report a case of a 14-year-old adolescent female with bilateral HCA. She had an initial left hemithyroidectomy for a large nodule measuring 2 x 1.5 x 1.2 cm 3 in the left lobe, while smaller subcentimeter nodules remained under surveillance in the right. One year later, a nodule in the right lobe doubled in size, necessitating a right hemithyroidectomy which also revealed HCA. Conclusion: To our knowledge, this is the first reported case of bilateral HCA in pediatrics. It highlights the importance of close surveillance of persistent small nodules, even in patients with previously documented benign lesions such as HCA, which are typically thought to be unilateral and localized. Both HCA and HCC remain unpredictable in behavior, and treatment of HCA should be individualized. [ABSTRACT FROM AUTHOR]

A 75-year-old male patient with non-avid radioiodine Hurthle cell carcinoma was evaluated by 99mTc- octreotide scintigraphy, in order to find possible metastatic lesions. A bony metastatic lesion was detected by this procedure which was confirmed by histopathology.99mTc-octreotide scintigraphy is a precise and cost-effective imaging modality for detection of non-iodine avid lesions in metastatic differentiated thyroid carcinomas. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, the impact of specific cytologic patterns in thyroid fine-needle aspiration (FNA) for follicular and Hurthle cell carcinoma is not known.Methods: The results of all thyroid FNAs performed from 1997 through 2015 with corresponding resections of follicular and Hurthle cell carcinomas were reviewed.Results: A total of 24 follicular carcinomas and 35 Hurthle cell carcinomas were identified. All FNA specimens from follicular carcinomas had a microfollicular component (3 of which were noted only in 3-dimensional groups), but only 18 cases (75%) had cytologic atypia, which most commonly consisted of enlarged nuclei with slightly pale chromatin. Diagnosing cases without cytologic atypia as benign would significantly decrease the sensitivity of the test (P = .02). Five Hurthle cell FNA specimens consisted of only scant Hurthle cells. The remaining Hurthle cell FNA specimens could be divided into those with large cell dysplasia (15 cases), those with small cell dysplasia (10 cases), cases with anisonucleosis insufficient for a diagnosis of large cell dysplasia (4 cases), and cases with Hurthle cells in flat sheets without atypia (1 case). Diagnosing cases with flat sheets without atypia as benign did not appear to affect the sensitivity of the test (P = 1.00).Conclusions: Diagnosing FNA specimens with microfollicles without atypia as benign appears to significantly reduce the sensitivity for follicular carcinoma to 75%; in contrast, diagnosing FNA specimens with Hurthle cells in flat sheets without anisonucleosis as benign does not. Cancer Cytopathol 2016;124:729-36. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Despite the increase in the incidence of thyroid carcinomas, the occurrence of collision tumors in the thyroid remains a rare event. We present the case of a 69-year-old female who presented to the emergency department with a chief complaint of painful neck swelling. Imaging revealed a large right hemithyroid mass and a left hemithyroid nodule. Fine needle aspiration of the lesions and subsequent total thyroidectomy revealed a Hürthle cell carcinoma in the right lobe and bilateral multicentric papillary carcinoma foci, including 2 foci with a classical pattern and 1 encapsulated follicular variant in the isthmus. BRAF gene mutation analysis revealed V600E gene mutation in the classical variants of papillary carcinoma and in the Hürthle cell carcinoma. The focus of follicular variant of papillary carcinoma in the isthmus and a sample from normal thyroid tissue did not harbor BRAF mutations. This case is remarkable in being an unusual report of a follicular Hürthle cell carcinoma harboring the BRAF V600E mutation and occurring in collision with multifocal papillary carcinoma. Documentation of such cases is important as it helps better understand the pathogenesis, clinical behavior, and radiologic findings of such rare lesions and to determine the optimal treatment modalities. [ABSTRACT FROM AUTHOR]

The EIF1AX gene is a novel cancer gene that has been reported in the tumorigenesis of papillary thyroid carcinoma, follicular variant papillary thyroid carcinoma, and anaplastic thyroid carcinoma. A 71-year-old woman presented with a right thyroid mass, which was follicular neoplasm on cytology. The fine needle aspirate of the nodule was examined by next-generation sequencing and found to harbor EIF1AX and TP53 mutations. Right thyroid lobectomy was performed with final pathology showing Hürthle cell carcinoma with capsular and vascular invasion. We report an EIF1AX mutation in a patient found to have Hürthle cell carcinoma. [ABSTRACT FROM AUTHOR]

Oncocytic follicular carcinoma (OFC)/Hürthle cell carcinoma represents 3-4 % thyroid carcinomas and can be associated with more aggressive behavior and compromised survival compared to non-oncocytic thyroid carcinoma. In this study, we utilized targeted next-generation sequencing to investigate the molecular alterations in a heterogeneous group of clinically aggressive OFC. A total of 12 cases of OFC were included in this study. Targeted next-generation sequencing was performed using panels of 47 or 20 genes, which are frequently mutated in solid tumors. The case cohort comprised eight cases of angioinvasive OFC, two cases of poorly differentiated OFC, one case of OFC with anaplastic change, and one case of OFC with capsular invasion only. Five out of 12 cases (42 %) harbored TP53 mutation. PTEN mutations were also seen in three cases with TP53 mutation (25 %). Based on this study, TP53 and PTEN are possibly involved in the pathogenesis of OFC. Further studies on a larger case cohort are needed to further elucidate this mechanism and its effect on clinical behavior of these intriguing tumors. [ABSTRACT FROM AUTHOR]

Encapsulated carcinomas of follicular cell origin are subject to considerable controversies. This group includes an encapsulated/well-circumscribed (E/WC) follicular variant of papillary carcinoma (FVPTC) and encapsulated follicular and Hurthle cell carcinoma (EFC, EHC respectively). FVPTC usually presents as an E/WC tumor and less commonly as an infiltrative neoplasm. E/WC FVPTC rarely metastasizes to lymph nodes, whereas infiltrative tumors often present with cervical nodal metastases. Many studies revealed FVPTC in general to be genetically close to the follicular adenomas (FA)/EFC group of tumors. This is particularly true for the E/WC FVPTC which has a high rate of RAS and lack BRAFV600E mutations. Infiltrative FVPTC has an opposite molecular profile closer to classical papillary carcinoma than to FA/EFC ( BRAFV600E > RAS mutations). Noninvasive E/WC FVPTCs are extremely indolent even if treated with lobectomy alone. While EFC and EHC with capsular invasion only have an excellent outcome, those with extensive (≥4 foci) lymphovascular invasion (LVI) have a significant rate of distant recurrence. The prognosis of those with focal LVI seems good, but more studies are needed to confirm their behavior. In EHC, those with extensive/significant LVI have a different RNA expression profile than those with less LVI. EHC appear to recur earlier, are less RAI avid, and have a different mutation profile than EFC. Noninvasive E/WC FVPTC should be treated conservatively. There is therefore a need to reclassify the E/WC FVPTC in order to prevent overtreatment. In view of their molecular and behavioral differences, EHC should not be considered a subset of EFC. [ABSTRACT FROM AUTHOR]

Hürthle cell carcinoma (HCC) is a variant of a follicular carcinoma with a tendency to higher frequency of metastases and a lower survival rate. However, intracavitary cardiac metastases from thyroid HCC are extremely rare. We describe the case of a 57-year-old female with thyroid HCC, 5 years after total thyroidectomy, who presented with dyspnea associated with hypoxia and hypotension. The computed tomography angiogram showed extensive pulmonary embolism and a 6-cm right atrial mass while the lower-extremity deep vein thrombosis studies were negative. This patient received a cardiac thrombectomy using cardiopulmonary bypass support. However, intraoperatively, we found out that the mass was from the mediastinum, directly extending into the heart and clearly unresectable since it effaced at least 1/3 of the right atrial wall. The core biopsy of the mass confirmed that it was metastatic poorly differentiated HCC of thyroidal origin. The patient eventually died of respiratory failure due to a massive pulmonary embolism. For cancer patients with unexplained dyspnea, cardiac metastases should be considered regardless of anticoagulation prophylaxis, especially when there is no deep vein thrombosis in the lower limbs. Early recognition of intracavitary cardiac metastases may help in providing prompt treatment and improving the prognosis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hürthle cell lesions are difficult to classify by cytology alone. Molecular companion testing has added some insight, but has not resolved these diagnostic challenges. [ABSTRACT FROM AUTHOR]

Aims Oncocytic follicular carcinoma/Hürthle cell carcinoma ( OFCA/ HCCA) is a rare tumour of the thyroid gland that can be associated with an aggressive clinical course. Most OFCA/ HCCAs are large; however, tumours ≤20 mm can occur. The aim of this study was to report our experience with OFCA/ HCCA diagnosed at our institution. Methods and results One hundred and nineteen cases of OFCA/ HCCA were included in this study. Data points included age, sex, size of tumour, method of diagnosis, lymph node ( LN) status, and clinical follow-up. The cohort included 37 males and 82 females (average age: 55 years). Preoperative fine-needle aspiration ( FNA) was performed in 73 (61%) cases. Twenty-five (21%) tumours measured ≤20 mm and 94 (79%) measured >20 mm. Angioinvasion ( AI) was present in 48 (40%) cases, and LN metastases ( LNMs) in seven (6%) cases; of these, eight (17%) with AI and 1 (2%) with LNMs measured ≤20 mm. Clinical follow-up was available in 74 (62%) cases (range 12-144 months); 13 (17.5%) developed LNMs and six (8%) regional recurrence. Distant metastases ( DMs) were seen in 12 (16%) cases. Two cases with DMs and two with LN recurrence measured ≤20 mm. Conclusions Oncocytic follicular carcinoma/Hürthle cell carcinoma ( OFCA/ HCCA) can present as small (≤20 mm) tumours, and can be associated with AI, LNM, and DM. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to find out whether the presence or absence of certain cytological features can exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration (FNA) to minimize unnecessary surgery. Methods: Over a 17-year period, 127 hypercellular, oncocyte-exclusive, lymphocyte-absent aspirates obtained via ultrasound-guided FNA with on-site assessment had histology slides for review. The presence or absence of six cytological features (microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia, transgressing blood vessels and colloid) and one histological feature (macrofollicular component) were determined for each case independently by two cytopathologists. Results: Histology showed 12 (9.4%) cases of Hashimoto thyroiditis, 23 (18.1%) oncocytic adenomatoid nodules in nodular goitre, 66 (52.0%) oncocytic adenomas and 26 (20.5%) oncocytic carcinomas (13 minimally invasive without angioinvasion, six minimally invasive with angioinvasion, seven widely invasive). Histologically, a macrofollicular component was present in seven of 26 (26.9%) oncocytic carcinomas, including one case with abundant thin colloid. A microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia and transgressing vessels were present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. Conclusions: A macrofollicular component is frequently present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. None of the cytological features studied, including abundant colloid, can exclude oncocytic carcinoma. Oncocytic carcinoma can only be excluded by thorough histological examination of thyroidectomy specimens. A molecular marker is needed to triage oncocytic lesions in thyroid FNA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hurthle cell carcinoma (HCC) is an uncommon and more aggressive thyroid cancer. To date, there is a paucity of data at a population level. In this study, demographic, clinical, and pathologic characteristics of HCC were investigated and compared with other types of differentiated thyroid cancers (ODTCs). The authors also evaluated disease-specific survival and compliance with American Thyroid Association (ATA) management guidelines from 2009. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2009 was used to obtain data on patients with thyroid cancer. Data analyses were performed using chi-square tests, analysis of variance, Kaplan-Meier analysis, binary logistic regression, and Cox proportional hazards regression. RESULTS: In total, 3311 patients with HCC and 59,585 patients with ODTC were identified. Compared with ODTC, HCC was more common among men (31.1% vs 23.0% for ODTC; P < .001) and among older patients (mean age, 57.6 years vs 48.9 years for ODTC; P < .001). Patients with HCC presented with higher SEER disease stage ( P < .001), and their tumors were larger (36.1 mm vs 20.2 mm for ODTC; P < .001). Fewer patients underwent total thyroidectomy ( P = .028). Both overall and disease-specific survival were lower for patients with HCC ( P < .001), and neither improved over the last 2 decades ( P = .689). After adjustment, age ≥45 years, not undergoing surgery, and metastatic disease were strongly associated with a worse prognosis (hazard ratio >3.0). Compliance with recommended surgical treatment according to ATA guidelines was lower among patients with HCC aged ≥65 years (odds ratio [OR], 1.43; P = .002) and among unmarried patients (OR, 1.29; P = .004). Predictors of noncompliance with ATA guidelines for treatment with radioactive implants or radioisotopes were age ≥65 years (OR, 1.31; P = .017), diagnosis between 1988 and 1997, no surgery, and partial thyroidectomy (OR, 1.81, 19.48, and 4.02, respectively; P < .001). CONCLUSIONS: HCC has more aggressive behavior and compromised survival compared with ODTC. The current results indicated that it may be important to consider a different staging system or separate practice guidelines. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Hürthle cells (HCs) and HC change, along with the frequently employed synonyms "oncocytes/oncocytic change" or "oxyphils/oxyphilic change," are not infrequently described on fine-needle aspiration biopsy (FNAB) reports of thyroid lesions. The description of HCs on FNAB reports may cause significant concern to the clinician; however, placing the finding in the appropriate clinical context may alleviate some anxiety. Not all oxyphilic cells are true HCs and not every aspirate containing HCs is or should be considered equivalent to an HC neoplasm (HCN). There are many benign thyroid lesions associated with HCs or HC change. For clinicians, it may be difficult to discern the significance of these findings and to determine an appropriate course of action. A skilled and experienced cytopathologist is invaluable in discriminating the subtle features that distinguish these lesions from those warranting a more aggressive approach. The diagnosis of HC carcinoma relies on histopathologic scrutiny and evidence of capsular and/or vascular invasion or metastasis to lymph nodes or distant organs. Many investigators have sought clinical, radiographic, cytological, genetic, and other factors to attempt to discriminate pre-operatively between benign and malignant HCNs. To date, none have been definitively proven to be reliable. For now, because of the inability to determine the benign or malignant nature of such neoplasms based on cytology alone, a surgical approach is warranted. [ABSTRACT FROM AUTHOR]

Hürthle cell neoplasms (HCNs) are rare tumors of the thyroid gland. The definitive treatment for Hürthle cell carcinoma (HCC) is total thyroidectomy, while thyroid lobectomy is adequate for Hürthle cell adenoma (HCA). However, differentiating HCC from HCA either before or during surgery is a challenge. The purpose of this study was to identify factors that predict malignancy in patients with HCN. Between May 1994 and January 2007, 1,199 patients underwent thyroid surgery at an academic medical center. Medical records of 55 consecutive patients who underwent thyroid resections for the preoperative diagnosis of HCN were reviewed. Of the 55 patients with HCN, 46 (84%) had adenomas and 9 (16%) had carcinomas. Patients with HCC were significantly older than those with HCA (66 ± 6 years versus 53 ± 2 years, P = 0.01). Patients with carcinoma also had significantly larger thyroid nodules (4.5 ± 0.7 cm versus 2.5 ± 0.2 cm, P < 0.001). All HCNs less than 2 cm in diameter were benign. The malignancy rate increased with nodule size: 18% of nodules measuring 2–4 cm, and 44% of those larger than 4 cm were HCC. One patient with HCC had recurrence of the disease, but there were no disease-related deaths. Advanced patient age and larger nodule size are two important factors that predict malignancy in patients with HCN. In patients with these and other known risk factors for HCC, total thyroidectomy should be considered. [ABSTRACT FROM AUTHOR]

Background: To determine the incidence of cystic change of thyroid cancer detected by ultrasonography and to compare the diagnostic accuracy of fine-needle aspiration cytology (FNAC) postultrasonography in solid and cystic thyroid nodules. Methods: This retrospective study collected data for 6219 patients with thyroid nodules. Mean patient age was 49.7 ± 13.6 years. Of these 6219 patients, 1983 had cystic changes of thyroid nodules and 4236 had solid masses as detected by ultrasonography. Following FNAC, 506 of the patients with solid masses (11.9%) underwent surgical treatment, compared with 143 of those with cystic change of thyroid masses (7.2%). Results: Of the 649 nodules treated surgically in the solid and cystic change groups, 29.8% (151/506) and 9.1% (13/143) were malignant, respectively. Overall, after surgical treatment, 0.65% of cystic changes to thyroid lesions were diagnosed as thyroid cancer. Diagnostic accuracy of FNAC in cystic changes of the thyroid masses after ultrasonographic examination resembled that in solid thyroid nodules. Conclusions: Cystic changes of thyroid masses are common. Positive predictive value in diagnosing papillary carcinoma of thyroid masses with cystic changes is high. Notably, preoperative accurate diagnosis is difficult. [ABSTRACT FROM AUTHOR]

Hürthle cell carcinomas behave as the most aggressive variant of differentiated thyroid carcinoma of follicular origin, with frequent recurrences and higher morbidity. Its differential diagnosis with Hürthle cell adenoma remains a problem for the clinician and for the pathologist. The vertebrate lectins, galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation in thyroid neoplasms. Galectin-3, a β-galactoside binding protein, has been recently found to be highly expressed in papillary and follicular carcinomas. The current study was undertaken to investigate immunohistochemical reactivity for galectin-3 of thyroid specimen tissues with Hürthle cell adenomas ( n=14) and carcinomas ( n=17), follicular ( n=14) and papillary ( n=11) carcinomas, colloid goiter ( n=30), Hashimoto’s thyroiditis ( n=11), follicular adenoma ( n=9), and normal thyroid tissues ( n=18). Follicular (78.5%) and papillary (82.0%) carcinomas were frequently reactive for galectin-3, more often when some Hürthle cells were present. There was no galectin-3 immunostaining in any of the specimens from Hashimoto’s thyroiditis, colloid goiters or normal thyroid samples, whereas only one case of follicular adenoma was found positive (11.1%). By contrast, galectin-3 immunostaining in Hürthle cell carcinomas was significantly higher (59%) than in Hürthle cell adenomas (7.1%, p<0.05). These results suggest that galectin-3 may potentially serve as a marker in difficult differential diagnosis cases involving Hürthle cell adenomas and Hürthle cell carcinomas. [ABSTRACT FROM AUTHOR]

Thirty-seven patients with Hürthle cell carcinoma of the thyroid gland underwent total thyroidectomy and then technetium-99m sestamibi (2-methoxyisobutylisonitrile), iodine-131 and thallium-201 wholebody scans. Twenty-two of them had elevated human serum thyroglobulin (HTg) levels. Among these 22 patients, abnormal uptake of I was seen in four (18.1%), abnormal uptake of Tl chloride in 15 (68.1%), and abnormal Tc-sestamibi accumulation in 18 (81.8%). No patients with normal levels had a positive whole-body scan. In comparison with the 1311 and 201T1 chloride images, the Tc-sestamibi images were of superior quality and detected significantly more ( P < 0.05) metastatic lesions of Hurthle cell carcinoma of the thyroid gland in patients with elevated HTg after total thyroidectomy. A mechanism is proposed that may explain these findings. [ABSTRACT FROM AUTHOR]

The use of the term "Hürthle cell neoplasm" as the gold standard should be discouraged as it makes evaluating these lesions more confusing. Recently, a number of studies have been conducted to define criteria that are more specific for Hürthle cell carcinoma (HCC). We herein report two cases of HCC of thyroid which were accurately diagnosed preoperatively using various cytological features described in the recent studies. A review of the literature is also presented. [ABSTRACT FROM AUTHOR]

Simple Summary: Hürthle cell carcinoma (HCC) represents 3–4% of thyroid carcinoma cases. It is characterized by its large, granular and eosinophilic cytoplasm, due to an excessive number of mitochondria. Hürthle cells can be identified only after fine needle aspiration cytology biopsy or by histological diagnosis after the surgical operation. Published studies on HCC indicate its putative high aggressiveness. In this article, current knowledge of HCC focusing on clinical features, cytopathological features, genetic changes, as well as pitfalls in diagnosis are reviewed in order to improve clinical management. Hürthle cell carcinoma (HCC) represents 3–4% of thyroid carcinoma cases. It is considered to be more aggressive than non-oncocytic thyroid carcinomas. However, due to its rarity, the pathological characteristics and biological behavior of HCC remain to be elucidated. The Hürthle cell is characterized cytologically as a large cell with abundant eosinophilic, granular cytoplasm, and a large hyperchromatic nucleus with a prominent nucleolus. Cytoplasmic granularity is due to the presence of numerous mitochondria. These mitochondria display packed stacking cristae and are arranged in the center. HCC is more often observed in females in their 50–60s. Preoperative diagnosis is challenging, but indicators of malignancy are male, older age, tumor size > 4 cm, a solid nodule with an irregular border, or the presence of psammoma calcifications according to ultrasound. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas, or clinically detectable cervical nodal metastases, but total thyroidectomy is recommended for tumors larger than 4 cm. The effectiveness of radioactive iodine is still debated. Molecular changes involve cellular signaling pathways and mitochondria-related DNA. Current knowledge of Hürthle cell carcinoma, including clinical, pathological, and molecular features, with the aim of improving clinical management, is reviewed. [ABSTRACT FROM AUTHOR]

Hürthle cell carcinomas (HCC) are rare differentiated thyroid cancers that display low avidity for radioactive iodine and respond poorly to kinase inhibitors. Here, using next-generation sequencing, we analyzed the mutational status of primary tissue and poorly differentiated metastatic tissue from two HCC patients. In both cases, metastatic tissues harbored a mutation of SETD2, each resulting in loss of the SRI and WW domains of SETD2, a methyltransferase that trimethylates H3K36 (H3K36me3) and also interacts with p53 to promote its stability. Functional studies of the novel p.D1890fs6* mutation (case 1) revealed significantly reduced H3K36me3 levels in SETD2-mutated tissue and primary cell cultures and decreased levels of the active form of p53. Restoration of SETD2-wildtype expression in the SETD2-mutant cells significantly reduced the expression of four well-known stemness markers (OCT-4, SOX2, IPF1, Goosecoid). These findings suggest potential roles for SETD2 loss-of-function mutations in HCC progression, possibly involving p53 destabilization and promotion of stemness. Their prevalence and potential treatment implications in thyroid cancer, especially HCC, require further study. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and treatment rationale of Hürthle cell carcinoma (HCC) following a patient with progressive and metastatic HCC. HCC was recently shown to harbor a distinct genetic make-up and the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kiase (PI3K)/AKT signaling pathways are potential targets for anti-cancer agents in the management of recurrent HCC. The presence or absence of gene variants can give a rationale for targeted therapies that could be made available in the context of drug repurposing trials. Methods: Treatment included everolimus, sorafenib, nintedanib, lenvatinib, and panitumumab. Whole genome sequencing (WGS) of metastatic tumor material obtained before administration of the last drug, was performed. We subsequently evaluated the rationale and efficacy of panitumumab in thyroid cancer and control cell lines after epidermal growth factor (EGF) stimulation and treatment with panitumumab using immunofluorescent Western blot analysis. EGF receptor (EGFR) quantification was performed using flow cytometry. Results: WGS revealed a near-homozygous genome (NHG) and a somatic homozygous TSC1 variant, that was absent in the primary tumor. In the absence of RAS variants, panitumumab showed no real-life efficacy. This might be explained by high constitutive AKT signaling in the two thyroid cancer cell lines with NHG, with panitumumab only being a potent inhibitor of pEGFR in all cancer cell lines tested. Conclusions: In progressive HCC, several treatment options outside or inside clinical trials are available. WGS of metastatic tumors might direct the timing of therapy. Unlike other cancers, the absence of RAS variants seems to provide insufficient justification of single-agent panitumumab administration in HCC cases harboring a near-homozygous genome. [ABSTRACT FROM AUTHOR]

The article presents a case report related to the differential diagnosis of unilateral proptosis which includes Graves' disease and retroorbital tumour. A 61-year-old man, with a history of double vision and painful swelling in the right eye, was examined. The examination showed bilateral periorbital oedema, reduced visual acuity in the right eye, blurring of the right optic disc and a diffuse goitre.