Hürthle Cell Research Articles

Retrospective evaluation of radioactive iodine ablation therapy in the Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) and Thyroid tumors with uncertain malignity potential

Background: Noninvasive Follicular Thyroid Neoplasm (NIFTP), Well differantiated thyroid tumor with uncertain malignity potential (WDT-UMP), follicular thyroid tumor with uncertain malignity potential (FT-UMP), and Hurtle cell neoplasia with uncertain malignity potential (HCN-UMP) have been included in the classification of thyroid tumors by WHO, with the incidence of thyroid cancer increasing every passing year. There is no consensus regarding the follow-up and treatment processes of these tumors. Our study aims to shed light on our clinical practice by evaluating the follow-up processes of the groups with and without radioactive iodine ablation in patients followed up with these diagnoses.
 Material and Methods: The 49 patients older than 18 years of age and followed for at least 12 months, who were performed subtotal and total thyroidectomy between 2015 and 2020 and were diagnosed with WDT- UMP, FT-UMP, HCN-UMP, and NIFTP according to histopathological examination were included to the study.
 Results: Tumor type rates did not differ between the groups that received and did not receive RAI treatment (p=0.361). The mean follow-up period did not differ between the groups that received and did not receive RAI treatment. Also the rates of RAI treatment according to tumor size did not differ (p=0.413). Tumor size was larger than 4 cm in 13 patients, and 1 patient from this group had received RAI treatment. Recurrence was not detected in the 49 patients included in our study who received or not receive RAI treatment. 
 Conclusions: Some studies recommend giving RAI to these borderline thyroid tumors larger than 4 cm. But in our study no recurrence was detected in patients who did not receive RAI. That supports the view that patients could be followed without RAI treatment even if they are large tumors.

Copy number variations identified in thyroid FNA specimens are associated with Hürthle cell cytomorphology.

The fine-needle aspiration (FNA) diagnosis of thyroid Hürthle cell neoplasms (HCNs) remains challenging. This study explored a possible association of copy number variations (CNVs) with Hürthle cell lesions of the thyroid. Thyroid FNA cases that were diagnosed as follicular lesion of undetermined significance (FLUS) or follicular neoplasm (FN)/HCN for which the ThyroSeq version 3 genomic classifier test was performed were retrieved. A total of 324 thyroid FNA cases (228 FLUS cases, 46 HCN cases, and 50 FN cases) were included in the study. FLUS cases were further classified as Hürthle cell type (follicular lesion of undetermined significance-Hürthle cell type [FLUS-HCT]; 20 cases) or non-Hürthle cell type (follicular lesion of undetermined significance-non-Hürthle cell type [FLUS-NHCT]; 208 cases). HCN and FLUS-HCT cases showed a higher prevalence of CNVs (23 of 66 [35%]) in comparison with those classified as FN or FLUS-NHCT (14 of 258 [5%]; P < .001). A total of 105 patients had histopathologic follow-up. Cases with CNVs were more likely to be neoplastic (18 of 26 [69%]) and associated with Hürthle cell changes (14 of 26 [54%]) in comparison with cases without any molecular alterations (neoplastic, 8 of 24 [33%]; Hürthle cell changes, 2 of 24 [8%]; P < .05). In HCN/FLUS-HCT cases with CNVs (n = 14), Hürthle cell changes (13 of 14 [93%]) and neoplasms (9 of 14 [64%]) were more likely to be seen on surgical follow-up in comparison with the 17 cases without CNVs (Hürthle cell changes, 6 of 17 [35%]; neoplastic, 3 of 17 [18%]; P < .05). CNVs identified in thyroid FNA cases are associated with Hürthle cell morphology and are suggestive of a neoplasm with Hürthle cell features in thyroid FNAs classified as FLUS-HCT/HCN. This finding may be helpful in triaging patients who would benefit from surgical management.

Evaluation of the etiological factors of thyroid gland neoplasms: our clinical experience

Objective: Thyroid cancer (TC), the most common endocrine malignancy worldwide, has a 10-year survival rate of more than 90% and a better prognosis than other malignancies. However, there are still conflicting data on the stimulators of cancer development, and benign thyroid diseases, such as goiter, benign thyroid nodules, Graves’ disease, chronic thyroiditis, breast cancer and various factors including age, gender, consumption of vegetables, fiber food, hypercaloric diet, and tobacco and alcohol use are considered to be responsible. In this study, we aimed to evaluate patients with thyroid neoplasms who underwent surgical treatment in terms of etiological factors discussed in light of the literature.&#x0D; Material and Method: In our study, patients who underwent surgery with the diagnosis of thyroid gland neoplasms between 2010 and 2020 were evaluated. A total of 371 patients were included in the study. Statistical analyses were performed using IBM SPSS Statistics v. 22.&#x0D; Results: Of the 371 cases included in the study, 78.16% were female and 21.83% were male. The histopathological distribution of diagnoses was as follows: 76.28% papillary thyroid carcinoma (PTC), 4.31% follicular thyroid carcinoma (FTC), 14.29% follicular adenoma (FA), 0.54% Hurthle cell carcinoma (HCC), 3.77% Hurthle cell adenoma (HCA), and 8.08% medullary thyroid carcinoma (MTC). A total of 567 etiological factors were detected in 371 cases, and the highest factors ratio (1.94) being detected in the FTC group and the lowest (1.49) in the FA group. The most common of these factors was chronic lymphocytic thyroiditis (CLT) (35.31%). While the most common etiological factor in the PTC diagnosis group was thyroid and other non-breast cancers and the history of radiotherapy resulting from their treatment, it was a family history of thyroid cancer in the HCA group. Other systematic organ diseases, CLT, and breast cancer were the most common factors. The body mass index was the highest in the MTC group and the lowest in the PTC group.&#x0D; Conclusion: Increased human development index, technological developments, greater accessibility of ultrasonography, and better diagnostic sensitivity have led to an increase in the detection of TC. Knowledge of the underlying etiological factors is important for the development of preventive measures and achieving more successful results in terms of diagnosis and treatment.

Mitonuclear Genotype Remodels the Metabolic and Microenvironmental Landscape of Hurthle Cell Carcinoma

Mitonuclear Genotype Remodels the Metabolic and Microenvironmental Landscape of Hurthle Cell Carcinoma

Nomogram Using Host and Tumor Factors to Predict Survival in Individual Patients with Well Differentiated Thyroid Cancer

<h3>Purpose/Objective(s)</h3> Patients with well-differentiated thyroid cancer generally have an excellent outcome. Nonetheless, a subset of patients will do poorly. Traditionally, the TNM system is used to counsel patients on probability of survival. However, this system applies to a population rather than individual patients. In contrast, nomograms utilize several variables to determine outcome in individual patients. The objective of our study was to use tumor and host factors in patients with well differentiated thyroid cancer to develop a nomogram predictive of disease-specific survival (DSS). This would lead to a better guided and personalized assessment of patient's treatment and follow up and would allow us to better counsel patients moving forward. <h3>Materials/Methods</h3> From our departmental thyroid database of 6,259 patients treated with surgery from 1986 to 2015, we excluded patients with incomplete staging data (n=15). Our final cohort consisted in 6,244 patients. Tumor and host variables predictive of survival were identified and used to design a nomogram for DSS. The previously published pretreatment peripheral blood H-index (([Neutrophils x Monocytes]/[Lymphocytes x Hemoglobin X Albumin]) x 100) was used as the surrogate marker for the host status. Multiple imputation was implemented on missing data of the peripheral blood variables. Unadjusted and adjusted HRs were calculated using the Cox proportional hazard model for DSS. A p-value <0.05 was considered significant. Nomograms predictive of 5, 10, 15 and 20-year DSS were created from the model. Statistical analysis was performed using the R software package (http://www.r-project.org). <h3>Results</h3> Median age was 47.4 years (IQR 37.1-58.0), 72% were female. Most cases were Papillary Carcinomas (95.4%), and 2.4% Follicular Carcinomas and 2.2% Hurthle Cell Carcinomas. Following AJCC 8^th Edition, 88.0% were Tx/T1/T2, 68.9% were Nx/N0, and 98.7% M0. H-index values ranged from 0.04 to 18.38 (median 1.17, IQR 0.79-1.75). Increased age, non-papillary carcinoma pathologies, higher TNM, and higher H-index were significantly associated with worse DSS in the multivariable analysis. Based on this model, predictive nomograms were created. Age and distant metastasis were the variables that conferred a higher score in the nomogram and therefore the ones associated with poorer outcomes. H-index incorporated additional stratification of patient's risk by adding information about the host to the generally used tumor factors. <h3>Conclusion</h3> Using tumor and host factors, we have created a nomogram which predicts survival in individual patients with well differentiated thyroid cancer. By having a more precise prediction of each patient's outcomes we can better guide treatment, follow up and counseling.

Subcutaneous implantation of oncocytic thyroid cell aggregates nine years later from thyroidectomy. A case report.

Introduction and importanceSubcutaneous implantation of thyroid tissue is a rare clinical condition that involves the head and neck region and occurs after surgery, diagnostic procedures or cervical trauma.Case presentationA 90-year old woman with two skin nodules on her thyroidectomy scar was hospitalized and treated by two surgical excisions. Histologically, these lesions were two aggregates of cutaneous oncocytic thyroid cells. In the patient's clinical history there was a total thyroidectomy for multinodular goiter, performed 9 years previously and at which a well-encapsulated subcapsular oncocytic adenoma of the left lobe was also incidentally discovered. At 12 months of follow-up, the patient is showed well and her wounds healed.Clinical discussionSubcutaneous colonization or seeding of thyroid tissue is a rare occurrence reported in the literature for both benign and malignant pathologies; among the malignant ones, the implantation of follicular carcinoma cells is the most frequent. Only in one previous case, to our knowledge, subcutaneous colonization originating from oncocytic thyroid (or Hurthle) cell neoplasms has been described.ConclusionWe report an unusual case of double subcutaneous implantation of oncocytic thyroid cells on the cervical scar of an elderly woman, nine years after total thyroidectomy.

Immune characterization of thyroid neoplasm's and its variants using immunohistochemical markers: CK-19, Galectin-3 and Hector Battifora mesothelial-1

BackgroundNodular lesions of the thyroid are amongst the common palpable lesions that are encountered by the pathologists in the fine needle aspiration clinics and not only aspiration smears, but even biopsy sections pose significant challenges in their characterization and further classification. Neoplastic lesions of the thyroid have shown a steady rise worldwide and are diagnosed at age younger than most other cancers. Histopathology remains the gold standard in diagnosis and classification of thyroid neoplasms, with variable sensitivity and specificity of immunohistochemical markers, also attributed to variation in the inclusion criteria. We classified the thyroid neoplasms based on WHO Classification (2017) and aimed to study the diagnostic utility of immunohistochemical markers - CK-19, Galectin-3 and Hector Battifora mesothelial-1 performed on manual tissue microarray sections to differentiate various variants of papillary carcinoma from its mimickers, specifically follicular patterned papillary neoplasms from other follicular patterned lesions. MethodProspective study of neoplastic lesions of thyroid from July 2018 to August 2020. Authors describe the clinico-radiological, cytological, histo-morphological and immunohistochemical features of neoplastic nodular lesions of the thyroid. ResultsProspective analysis of nodular thyroid lesions yielded 76 cases, of which 38 were neoplastic. Cytology showed discordance in 10/24 cases, amongst the discordant cases, 70% were confirmed as papillary carcinoma. CK-19 showed high expression in all variants of papillary carcinomas (24/24), low expression in well differentiated tumor of uncertain malignant potential (WD-TUMP) and medullary carcinoma. It was negative in follicular and Hurthle cell neoplasms. Galectin-3 showed 100% specificity and HBME-1 showed 100% sensitivity in diagnosis of papillary carcinoma and its variants. Adenomatoid nodules did not express Gal-3 which helped in their differentiation from FVPTC. ConclusionsGal-3 in combination either with CK-19 or HBME-1 improves the sensitivity and specificity of detection of papillary carcinoma, its variants and its differentiation from follicular patterned lesions to 100% with a significant p value.

Using molecular testing to improve the management of thyroid nodules with indeterminate cytology: an institutional experience with review of molecular alterations.

Molecular testing has helped clinicians and cytopathologists to further categorize indeterminate thyroid fine needle aspiration (FNA) specimens. The purpose of the present study was to evaluate the accuracy of commercially available molecular tests, review their effects on patient treatment, and correlate the molecular alterations with the histologic findings. A pathology laboratory information system search identified thyroid FNAs performed at our institution between January 1, 2015 and June 30, 2020. The results of surgical follow-up and ancillary molecular testing were collected. We evaluated the accuracy of these tests and whether they could reduce the number of surgeries performed. Our laboratory information system search identified 510 cases reported as atypia of undetermined significance, 94 as suspicious for follicular neoplasm, and 44 as suspicious for follicular neoplasm, Hurthle cell type. Of the specimens, 343 had no ancillary molecular testing, 146 were sent for ThyGenX/ThyraMIR, and 136 were sent for ThyroSeq. Of the patients without molecular testing, 50.4% had undergone follow-up surgery compared with 30.8% after ThyGenX/ThyraMIR and 38.2% after ThyroSeq testing, resulting in 38.9% and 24.2% fewer surgeries and an odds ratio of 0.04 (95% confidence interval, 0.00-0.33) and 0.14 (95% confidence interval, 0.01-0.95), respectively. For ThyGenX/ThyraMIR testing, the risk of malignancy for high and moderate to high risk alterations was 80%, 28.6% for moderate and low to moderate risk alterations, and 23.1% for low risk alterations. For ThyroSeq, the risk of malignancy was 87.5% for high risk alterations, 36.8% for intermediate to high risk alterations, 27.3% for intermediate risk alterations, and 0% for low risk alterations. The areas under the curve for ThyGenX/ThyraMIR and ThyroSeq testing were 0.65 and 0.85, respectively. These findings suggest that, at our institution, both ThygenX/ThyraMIR and ThyroSeq can be used to effectively stratify cytology specimens based on the risk of malignancy and reduce the number of surgeries performed at our institution.

Neoadjuvant tyrosine kinase inhibitor therapy in locally advanced differentiated thyroid cancer: a series

IntroductionLocally advanced differentiated thyroid cancer (LADTC) management depends on a complex interplay of patient and tumour factors. When primary resection cannot be achieved, neoadjuvant tyrosine kinase inhibitor (TKI) therapy can be considered, but little evidence is available on its success and outcomes. Our aim was to describe a small series of LADTC managed with neoadjuvant TKI therapy.MethodsSuitable patients were prospectively identified in NHS Lothian February 2016 – March 2020.ResultsFour patients were eligible for inclusion, 3 females; 1 male, aged 39–79 years. All were T4a at presentation; three papillary and one Hurthle cell carcinoma. One had pulmonary metastases. Two refused laryngectomy, one was deemed unresectable with extensive tracheal involvement, and one commenced TKI due to COVID-19 related surgical delay. TKI treatment length varied from 1–18 months. There was a marked reduction in tumour volume and local extent in three cases, such that surgical resection without laryngectomy could be achieved. The fourth patient was intolerant of TKI. All ceased TKIs 2 weeks prior to total thyroidectomy, with neck dissection in three, and tracheal resection and re-anastomosis in two. All then had 3700MBq RAI and all patients are currently alive with 14–58 months follow-up. Two patients have no evidence of residual or recurrent disease. The M1 patient has stable low-volume local and distant disease, and one patient has stable low volume indeterminate pulmonary nodules.ConclusionNeoadjuvant TKI therapy in LADTC can be effective in reducing primary tumour extent to potentially facilitate limited surgical resection in a highly selected patient group.

Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Antitumor Activity.

Hurthle cell carcinomas (HCCs) are refractory to radioactive iodine and unresponsive to chemotherapeutic agents, with a fatality rate that is the highest among all types of thyroid cancer after anaplastic thyroid cancer. Our previous study on the genomic landscape of HCCs identified a high incidence of disruptions of mTOR pathway effectors. Here, we report a detailed analysis of mTOR signaling in cell line and patient-derived xenograft mouse models of HCCs. We show that mTOR signaling is upregulated and that targeting mTOR signaling using mTOR inhibitors suppresses tumor growth in primary tumors and distant metastasis. Mechanistically, ablation of mTOR signaling impaired the expression of p-S6 and cyclin A2, resulting in the decrease of the S phase and blocking of cancer cell proliferation. Strikingly, mTOR inhibitor treatment significantly reduced lung metastatic lesions, with the decreased expression of Snail in xenograft tumors. Our data demonstrate that mTOR pathway blockade represents a novel treatment strategy for HCC.

Follicular and Hurthle Cell Carcinoma: Comparison of Clinicopathological Features and Clinical Outcomes.

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.

Fine needle aspiration cytology of thyroid lesions and thyroid profile – a correlative study

Introduction The Fine Needle Aspiration Cytology (FNAC) is a simple, safe, cost-effective minimally invasive procedure for diagnosing thyroid nodules/swelling. Clinicians usually evaluate thyroid function by estimating T3, T4 and TSH level for therapeutic planning. In this study the importance of FNAC in the diagnosis of thyroid diseases was evaluated and FNAC findings were correlated with clinical features and thyroid profile. Materials and Methods The study was designed as prospective cross-sectional hospital based (laboratory investigation) study for 2 months duration (from 17th July, 2017 to 16th September, 2017). Fifty cases of thyroid swelling attending Pathology Department for FNAC were included in the study. For Each case thyroid profile was done. Result Total 50 patients of thyroid swelling were included in the study, out of which 46 were female (92%) and 4 were male (8%). Male to female ratio was 1:12.5. Mean age was 45.44 ±16.02 years. Out of 50 patients 35 (70%) had diffuse thyroid swelling, 9 (18%) had left lobe and 6 (12%) had right lobe involvement. All the 50 patients with thyroid lesion had a common complaint of neck swelling. Some had associated dysphagia (12 cases, 24%) and/ or dyspnoea (6 cases, 12%), and only 2 had hoarseness of voice. Among 38 cases of non-neoplastic lesions colloid goitre was the commonest comprising 20 cases (52.63%), followed by 11 cases ( 28.95%) lymphocytic thyroiditis, 4 cases (10.53%) of granulomatous thyroiditis and 3 cases (7.89%) of follicular hyperplasia. Among 12 cases of neoplastic lesions papillary carcinoma was the commonest consisting of 7 cases (58.33%), followed by follicular neoplasm (4 cases, 33.33%) and 1 case of Hurthle cell neoplasm. Most of the colloid goitre cases were euthyroid (60%), lymphocytic thyroiditis was commonly associated with hypothyroidism (45.5% cases), and most cases of granulomatous thyroiditis were euthyroid (50%). All the patients with follicular hyperplasia had hyperthyroidism. Most of the cases with papillary carcinoma were in euthyroid (3 of 7, 42.86%) and followed by subclinical hypothyroid state (2cases, 28.57%) and one case of each hypothyroidism and subclinical hyperthyroidism. Follicular neoplasm was commonly associated with euthyroid state (75% cases). One case of Hurthle cell neoplasm had hyperthyroidism. Conclusion Thyroid gland being superficial, it is easy to perform fine needle aspiration. Similar thyroid disease shows variable hormone profile in different patient and different stages of the disease. Hence, FNAC of thyroid lesions in conjunction thyroid hormonal analysis helps in proper assessment and management of patients with thyroid lesion.

Rate and Clinical Predictors of Malignancy in Thyroid Nodules with Indeterminate Cytology

Background: Fine needle aspiration cytology (FNAC) cannot differentiate between benign and malignant conditions in cytologically indeterminate thyroid lesions. Therefore, a minimum of diagnostic lobectomy is required for definitive diagnosis. The objective of this study is to identify the rate of malignancy and clinical features that may possibly predict malignancy in patients with these lesions, in Ethiopian hospitals. Methods: This was a retrospective review of the medical records of patients who underwent surgery for cytologically indeterminate thyroid lesions in three referral hospitals between September 2015 and September 2020. Results: Of 85 patients with indeterminate cytology findings, 56 (63.5%) were follicular, and 29 (34.1%) were reported to be hurthle cell neoplasms. Follicular lesions of undetermined significance (FLUS) and suspicious for follicular neoplasm were each reported in single cases (1.7%). Malignant disease was diagnosed in 19 (22.4%) of patients. A follicular variant of papillary cancer was detected in 7 (11.5%) patients. Hard nodule consistency was reported in 9 of 11 malignant lesions and 5 of 66 benign lesions. In multivariate binary logistic regression, hard nodule consistency was found to be associated with malignancy (P = 0.012, AOR = 7.28 (1.5, 34.54) 95% CI ). The ill-defined surface of a nodule was found to be associated with malignancy though the association was not statistically significant (P = 0.088, AOR = 0.162 (0.020, 1.313) 95% CI. Ultrasound evaluation of thyroid nodule was performed only in 41 (47.7%) of patients. Conclusion: The rate of malignancy in thyroid nodules with indeterminate cytology was 22.4%. The risk of malignancy was higher in patients with hard thyroid nodule consistency and ill-defined surface. Despite the established benefits of ultrasound for the evaluation of thyroid nodules, the current practice of its use in our setup is suboptimal. Keywords: Follicular; hurthle cell; indeterminate cytology; predictors of malignancy

Comparative Analysis About Clinical Manifestation and Prognostic Factors of Thyroid Follicular and Hurthle Cell Carcinoma

Background and Objectives Follicular thyroid carcinoma (FTC) is the second common thyroid cancer which comprises about 10% of differentiated thyroid carcinoma. Hurthle cell carcinoma (HCC) is a relatively rare disease that has been classified as a subtype of FTC. However, there have been insufficient reports about these two similar thyroid cancers in South Korea due to low incidences. This study aims to present clinical features and evaluate prognostic factors of FTC and HCC.Subjects and Method We reviewed data of 189 FTC and 12 HCC patients who underwent surgery in our center from January 2000 to December 2020. Variables such as clinical characteristics, surgical method, pathologic result, post-operative treatment, survival rate and prognostic factors were included in our study.Results As for age, 67.2% of patients in FTC group and 33.3% of patients in HCC group were older than 55 years-old (&lt;i&gt;p&lt;/i&gt;=0.017). The average tumor sizes of FTC and HCC were 2.98 and 3.1 cm, respectively. The 10-year overall survival rates of FTC and HCC were 96.5% and 100%, respectively. The 10-year disease free survival rates of FTC and HCC were 89.1% and 91.7%, respectively. Subclassification (widely invasive: &lt;i&gt;p&lt;/i&gt;=0.036) and initial distant metastasis (&lt;i&gt;p&lt;/i&gt;&lt;0.001) were significant prognostic factors in FTC.Conclusion This study will be helpful for diagnosis and treatment of FTC and HCC, which are relatively rare.

What&amp;apos;s New in Molecular Targeted Therapies for Thyroid Cancer?

Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.

CLINICOPATHOLOGICAL CHARACTERISTICS AND TREATMENT OUTCOME OF PATIENTS WITH METASTATIC DIFFERENTIATED THYROID CANCER

OBJECTIVE: To assess the clinicopathological characteristics and treatment outcomes of metastatic differentiated thyroid cancer (DTC) in our population. METHODS: In this retrospective, real world, single centered study was carried out at Aga Khan University Hospital, Karachi, Pakistan. Data from December 2020 to January 2000 was retrieved about 117 patients with metastatic DTC regarding age at diagnosis, gender, tumor size, extent &amp; spread of tumor and its histological characteristic. The treatment they received and the outcome in terms of status at last follow up was also recorded. RESULTS: Mean age at diagnosis was 46.6±17.2 years with equal male to female ratio (1:1). Most common site of metastasis was lung (n=15; 12.8%) followed by bone (n=11; 9.4%). Papillary carcinoma was the most common subtype (n=105; 89.7%) followed by follicular carcinoma occurring (n=9; 7.7%), hurthle cell carcinoma (n=2; 1.7%) and diffuse sclerosing variant carcinoma (n=1; 0.9%). Tumor size was &lt;4 cm in 54 (46.2%) patients and ≥4 cm in 63 (53.8%) patients. Cervical metastasis was found in 85 (72.6%) patients while extra thyroidal extensions outside the thyroid bed into the surrounding structures was present in 64 (54.7%) patients. The overall survival was 5.6±2.6 years. Ninety-six percent had complete surgical resection followed by radioactive iodine in 107 (91.5%) patients with 65 being given a dose of 150 mCi, 38 given a dose of 100 mCi and 4 given a dose of 50 mCi. CONCLUSION: Most significant factors in predicting outcome in metastatic DTC are age, extra thyroidal extension of primary tumor and distant metastasis.

Large thyroid nodules: should size alone matter?

The management of thyroid nodules ≥ 4cm is controversial due to conflicting evidence on the prevalence of malignancy and diagnostic accuracy of fine-needle aspiration cytology (FNAC). Some literature recommends routine excision of large thyroid nodules due to high cytology false negative rates (FNR). We aim to investigate the diagnostic accuracy of FNAC, prevalence of malignancy in large (≥ 4cm) thyroid nodules compared to nodules < 4cm, and the clinical and ultrasound characteristics of those large nodules with false negative cytology. This was a retrospective case-log review in a tertiary referral hospital. All thyroid nodules subjected to Ultrasound (US)-guided FNAC by the Interventional Radiology department between December 2011 and November 2017 were included. Data on patient demographics, thyroid US features, cytology findings, and surgical histology were collected and analyzed. Sensitivity, specificity, and FNR were calculated based on FNAC results and final post-operative histology. Factors associated with a false negative result were analyzed using univariate and multivariate analyses. A total of 4982 nodules were studied, including 4419 < 4cm and 563 ≥ 4cm. Malignancy rates were similar in both groups. For nodules ≥ 4cm, FNAC sensitivity was 40%, specificity 100%, and FNR 6.6% compared to 4.2% in nodules < 4cm. Within malignant nodules, there was a significantly higher proportion of follicular and Hurthle cell carcinomas in nodules ≥ 4cm. Amongst nodules ≥ 4cm, multivariate analysis revealed male gender to be an independent predictor of FNR (OR 3.32; 95% CI 1.29-8.59). Larger nodules ≥ 4cm have a similar malignancy rate as nodules < 4cm, and FNAC FNR is low at 6.6%. Management of large thyroid nodules should be individualized based on their clinical, sonographic and cytological features rather than routine surgery.

Pure Mucinous Breast Carcinoma with Micropapillary Pattern in a 32-Year-Old Female

Background: Mucinous carcinoma (MC) is a rare breast malignancy with a large extracellular mucin secretion. It has a good prognosis in comparison to other breast malignancies. Case presentation: We report a 32 years old female with multiple hard palpable masses in the left breast with rapid growth in 6 months. She was mentally retarded with lower limb varicose veins associated with mucocutaneous lesions on the face. She underwent ultrasound examination of the breast, thyroid and lower extremity veins. Core needle biopsy and fine needle aspiration from left breast lesions and right thyroid nodules showed MC and follicular lesion with hurtle cell change, respectively. Suspected metastasis in the left rib and calvarium in the subsequent bone scan survey and brain magnetic resonance imaging was reported. She underwent radical mastectomy and right hemi-thyroidectomy. Conclusion: Pure mucinous carcinoma with micropapillary pattern (MUMPC) is a new histology variant of Pure Mucinous Carcinoma (PMC) that shows favorable prognosis with less aggression and occurs in older patients. However, PMC in our patient occurred at a young age with greater aggression.

A study of association between serum thyroid stimulating hormone concentration and thyroid cancer and also to assess whether serum thyroid stimulating hormone levels are of value in predicting malignancy in patients with thyroid swelling

Background: Thyroid neoplasm includes both benign and malignant tumors arising in the thyroid gland. Although thyroid cancer accounts for less than 1% of all cancers, the challenge to clinicians is to identify the minority of thyroid nodules that harbor malignancy. There are a number of well-established predictors of malignancy in thyroid nodules. More recently a few studies have suggested that higher concentration of thyroid stimulating hormone (TSH), even within the normal range are associated with subsequent diagnosis of thyroid cancer in patients with thyroid nodules and even higher serum TSH levels have been found associated with advanced stages of thyroid cancer. Methods: A prospective study was conducted on 220 cases without overt thyroid dysfunction attending Department of general surgery, Pushpagiri institute of medical science, Thiruvalla. Results: In our study incidence of malignancy of thyroid carcinoma was highest in patients with serum TSH concentrations, in range of 3.5 mIU/l-5.25 mIU/l, 55 patients out of 220 patients. Individually, incidence of papillary carcinoma (PC) (36/55 patients), follicular carcinoma (FC) (17/55 patients) and Hurthle cell carcinoma (HCC) (2/55 patients) were more in patients with higher TSH. So, from the study it can be clearly state that elevated TSH can be used as an independent predictor of thyroid malignancy. Higher TSH values are associated with papillary thyroid carcinoma.Conclusions: An elevated TSH can be used as an independent predictor of thyroid malignancy, especially for anticipating a probability of papillary carcinoma of thyroid.

ONCOCYTIC INTRATHYROID PARATHYROID ADENOMA MASQUERADING AS HURTHLE CELL NEOPLASM: FINE NEEDLE ASPIRATION CYTOLOGY OF TWO CASES

Ectopic parathyroid adenomas in thyroid tissue are uncommon (0.7 - 6%), and their oncocytic variants are exceedingly rare. We report two cases of intrathyroid parathyroid adenoma which were diagnosed as Hurthle cell adenoma on cytology. Case 1 is a 49-year-old female with a 2.4 cm hypoechoic nodule in the left lateral neck. Electrochemiluminescent immunoassay of the aspirate revealed PTH level of 422 pg/ml, conrming the presence of hyperfunctional parathyroid tissue. Subsequent resection of the left thyroid lobe revealed an enlarged intrathyroidal parathyroid. Case 2 is a 58-year-old female with a 2.1 cm hypoechoic nodule in the posterior-mid left thyroid lobe. Strong overexpression of parathyroid hormone and Chromogranin A genes and low expression of thyrocyte-related genes suggested parathyroid origin of the cells sampled. MEN1 mutation and multiple copy number alterations indicated the neoplastic nature of the nodule. Parathyroid oxyphil cells and oncocytic thyrocytes share cytomorphological ndings and distinguishing them by cytology alone is challenging, especially when the targeted lesion is intrathyroidal. Distinguishing intrathyroid oncocytic parathyroid adenoma from oncocytic thyroid follicular lesions has signicant clinical implications as Bethesda-IV category lesions have 20%–30% risk of malignancy. While stippled chromatin or intracytoplasmic fat vacuoles may be suggestive of parathyroid origin, these are not specic. Classifying the origin of a nodule as parathyroid vs thyroid rests upon the detection of PTH in aspirate material by ECL, immunocytochemistry or next-generation sequencing. In parathyroid aspirates, PTH level 100 pg/mL is suggestive of the presence of PTH-secre ≥ ting tissue at the site biopsied or along the needle track.