Hürthle Cell Carcinoma Research Articles

Morphological Spectrum of Lesions Seen in Thyroidectomy Specimens At A Tertiary Care Institute

Objective: To determine the morphological spectrum of thyroid lesions encountered in thyroidectomy specimens at a tertiary care institute. Methods: It was a retrospective study conducted in Pathology Department, Allama Iqbal Medical College, Lahore. A retrospective manual collection of data was done from record registers, for the years 2012 & 2013. Results: A total of 307 cases were retrieved with age range of 16-70 years. Amongst them, 47 were males and 260 were females. Non neoplastic conditions outnumbered the neoplastic lesions as 229(75%) cases were of colloid goiter. Hashimoto thyroiditis was present in 12(3.9%) specimens and associated hyperplastic changes were seen in 15(4.9%) cases. There were 19(6.2%) cases of papillary carcinoma, 3(0.9%) cases of follicular carcinoma, 3(0.9%) cases of medullary carcinoma, 1(0.3 %) case of insular carcinoma and 2(0.6%) anaplastic carcinoma. Papillary microcarcinoma was seen in 4(1.3 %) cases and medullary microcarcinoma in 1(0.3%) case. Follicular adenoma comprised 29(9.4%) cases and Hurthle cell adenoma 3(0.9%) cases. Study data also showed 1(0.3%) rare case of hyalinizing trabecular tumor. Conclusion: Non neoplastic thyroid diseases are more common as compared to neoplastic lesions. Papillary carcinoma is most common thyroid malignancy encountered in our setting. Key Words: Thyroidectomy, Colloid goiter, papillary carcinoma

Molecular profile of Hürthle cell carcinomas: recurrent mutations in the Wnt/β-catenin pathway.

Genomic alterations in Hürthle cell carcinomas (HCC) include chromosomal losses, mitochondrial DNA mutations, and changes in the expression profile of the PI3K-AKT-mTOR and Wnt/β-catenin pathways. This study aimed at characterizing the mutational profile of HCC. Next-generation sequencing (NGS) of 40 HCC using a 102-gene panel including, among others, the MAPK, PI3K-AKT-mTOR, Wnt/β-catenin, and Notch pathways. HCC was widely invasive in 57.5%, and lymph node and distant metastases were diagnosed in 5% and 7.5% of cases. During follow-up, 10% of patients presented with persistent/recurrent disease, but there were no cancer-related deaths. Genetic alterations were identified in 47.5% of HCC and comprised 190 single-nucleotide variants and 5 insertions/deletions. The Wnt/β-catenin pathway was most frequently affected (30%), followed by MAPK (27.5%) and PI3K-AKT-mTOR (25%). FAT1 and APC were the most frequently mutated genes and present in 17.5%. RAS mutations were present in 12.5% but no BRAF mutation was found. There was no association between the mutational profile and clinicopathological features. This series of HCC presents a wide range of mutations in the Wnt/β-catenin, MAPK and PI3K-AKT-mTOR pathways. The recurrent involvement of Wnt/β-catenin pathway, particularly mutations in APC and FAT1, are of particular interest. The data suggest that mutated FAT1 may represent a potential novel driver in HCC tumorigenesis and that the Wnt/β-catenin pathway plays a critical role in this distinct thyroid malignancy.

Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses.

Cytologic diagnosis of thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma (FACHAC) is challenging due to cytomorphologic features that overlap with other follicular-patterned lesions. This study was designed to analyze diagnostic categories (DCs) of preoperative fine needle aspiration cytology (FNAC) of histologically proven thyroid FACHACs to evaluate under- or misdiagnoses in FNAC and elucidate potential causes for such phenomena. A total of 104 thyroid nodules with preoperative FNAC which were diagnosed as FACHAC in resection specimens were included in this study. Of these, 66 cases had also undergone thyroid core needle biopsy (CNB); FNAC and CNB DCs were compared in these cases. Various cytologic and histologic parameters were compared between the nodules with different FNAC DCs. After a review of FNAC slides, DCs were re-assigned in 20 (19.2%) out of the 104 cases. Of the 66 cases with CNB diagnoses which were mostly classified as lower DCs in FNAC, 31 (47.0%) were diagnosed as suspicious for a follicular neoplasm in CNB. Cases which were underdiagnosed in FNACs were associated with lower cellularity, predominant macrofollicular pattern, absence of microfollicles arranged in trabecular pattern, and absence of transgressing vessels in cytology smears. High cellularity, microfollicles arranged in trabecular pattern, nucleolar prominence, and large cell dysplasia were more frequently found in malignancy than in benign neoplasm. In conclusion, thyroid FACHACs seem to be under- and misdiagnosed in preoperative FNAC. Innate characteristics of the nodules were associated with under-diagnosis as well as the quality of the FNAC specimens. Certain cytomorphologic features can be helpful in differentiating malignancy among FACHACs.

Afirma Testing in Thyroid Nodules with Indeterminate Cytology: A single Medical Institute Experience

Abstract Introduction/Objective About 10 to 30% of thyroid fine needle aspiration (FNA) nodules have indeterminate cytology, including Bethesda III, IV, and V. Afirma Gene Expression Classifier (GEC) measuring the expression of 167 mRNA was designed to classify the indeterminate thyroid nodules into benign and suspicious categories. This study aimed to evaluate the clinical performance of the Afirma GEC testing in these indeterminate thyroid lesions. Methods Medical records of patients with indeterminate thyroid FNA results and corresponding Afirma GEC results from November 2012 to December 2019 were retrieved. Subsequent surgical follow-up results were obtained. GEC results were compared to the histologic diagnoses. Results 1. There were 77 cases with indeterminate thyroid FNA results. Cytology diagnosis included 67 Bethesda III and 10 Bethesda IV. Afirma GEC results were benign for 41 cases (53%), suspicious for 32 cases (42%), and non- diagnostic for 4 cases (5%). Twenty seven of 32 cases (84%) with suspicious GEC results had surgical follow-up which revealed 12 malignant and 15 benign histologic diagnoses. Only 11 of 41 cases (27%) with benign GEC results had surgery which showed 8 benign and 3 malignant diagnoses. Based on the data, the sensitivity of this test is 80% and specificity is 65%. Positive predictive value (PPV) is 44% and negative predictive value (NPV) is 73%. The false positive cases include 5 Hurthle cell adenoma, 4 nodular hyperplasia, 3 follicular adenoma, 2 Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFPT), and 1 lymphocytic thyroiditis. The false negative cases include 2 minimally invasive follicular carcinoma (from same patient) and 1 papillary thyroid carcinoma. Conclusion 1. We demonstrated in this study that a little more than half of the cases with indeterminate thyroid cytology had negative Afirma GEC results. 2.Afirma test has relatively low specificity (65%) and PPV (44%). The sensitivity (80%) and NPV (73%) is relatively higher but is lower than the values in most literature. This could be due to the fact that majority of the Afirma GEC negative cases in this study did not have surgical follow-up and the sample size is small. 3.Afirma GEC test is a relatively good “rule-out” molecular test for indeterminate thyroid nodules but is not a reliable “rule-in” test due to the low specificity and PPV.

Hürthle cell neoplasms of the thyroid: Pathologic outcomes and ultrasonographic analysis.

BackgroundFine‐needle aspiration (FNA) of thyroid nodules suspicious for Hürthle cell neoplasms (HCN) have uncertain rate of malignancy. We aim to characterize rate and predictors of malignancy at our institution and compare these findings with established literature to help guide management.MethodsSingle tertiary‐referral center, retrospective study of 166 adults who underwent hemithyroidectomy or total thyroidectomy following FNA suspicious for HCN from 1998‐2018. Demographic information and surgical histopathologic results were collected. Preoperative ultrasonography was independently scored on the American College of Radiology Thyroid Imaging Reporting and Data System (TI‐RADS) by a board‐certified head and neck radiologist.ResultsThere were 39 males and 127 females. Overall, 25 (15.1%) patients had carcinoma, with 15 (9%) being Hürthle cell carcinoma (HCC). Men had higher incidence of carcinoma (25.6% v. 11.8%, P = .035), and especially older males. Contralateral carcinoma was seen in 3 of 13 (23.1%) patients that underwent completion thyroidectomy. Patients with carcinoma had larger nodules (average diameter 3.3 cm versus 2.5 cm, respectively, P = .01), but no association with TI‐RADS.ConclusionAdults with nodules suspicious for HCN have significant risk of malignancy consistent with prior studies. Older males and larger nodule diameter are associated with malignancy in this cohort, but TI‐RADS grade is not. These findings provide a framework for management and counseling for lesions suspicious for HCN.

The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile

Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated with even more adverse outcome than classical PDTC cases, but its specific molecular features are largely unknown. Our aim was to explore the immune-related gene expression profile of oncocytic and classical PDTC, in correlation with clinical and pathological characteristics (including programmed death ligand 1 [PD-L1] expression) and outcome, and in comparison with a control group of well-differentiated follicular carcinomas (WDFCs), including conventional follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). A retrospective series of 48 PDTCs and 24 WDFCs was analyzed by means of NanoString technology employing the nCounter PanCancer Immune Profiling panel. Gene expression data were validated using quantitative real-time polymerase chain reaction. Oncocytic PDTCs showed a specific immune-related gene expression profile, with higher expression of LAIR2, CD274, DEFB1, IRAK1, CAMP, LCN2, LY96, and APOE, and lower expression of NOD1, as compared to conventional PDTCs. This molecular signature was associated with increased intratumoral lymphocytic infiltration, PD-L1 expression, and adverse outcome. Three of these genes, CD274, DEFB1, and IRAK1, as well as PD-L1 expression, were also the hallmarks of HCCs as compared to FTCs. By contrast, the panel of genes differentially regulated in PDTCs as compared to WDFCs was unrelated to the oncocytic phenotype. Our results revealed a distinctive immune-related gene expression profile of oncocytic PDTC and confirmed a more aggressive outcome in this cancer subtype. These findings may provide guidance when exploring novel immunotherapeutic options for oncocytic PDTC patients.

Proton Beam Therapy for Differentiated Thyroid Cancer: Initial Report of the Mayo Clinic Experience

External beam radiation therapy (EBRT) is utilized in a subset of high-risk patients with differentiated thyroid cancer (DTC). Proton beam therapy is an attractive modality given the potential enhanced biological dose with improved sparing of normal structures. We review our multi-site, single-institution experience of intensity-modulated proton therapy (IMPT) for DTC. Eight patients with DTC who underwent IMPT from 2016 to 2018 were reviewed at our institution. Patient, tumor, and treatment characteristics were recorded. Overall survival (OS), freedom-from distant metastasis (FFDM), and freedom-from local-regional recurrence (FFLR) were recorded. Survival rates were calculated using Kaplan-Meier estimates. Acute and chronic toxicities were recorded based on CTCAE v4.03. Median follow-up is 15.7 (range, 5.4-27.5) months for all patients. Median age at treatment with IMPT is 62.6 (range, 50.1-75.9) years and the majority are female (63%). Histologies included Hurthle cell (37.5%) and papillary carcinoma (62.5%); 1 patient had tall cell variant. The median adjuvant (50%) or definitive (50%) IMPT dose is 70 (range, 30-70) Gy. One patient received 30 Gy in 5 fractions. Concurrent chemotherapy was not administered for any patient in this cohort. At 2 years, all patients are alive, FFDM is 85.7% (95% CI, 45-99%), and FFLR is 71.4% (95% CI, 33-94%). One patient underwent tracheostomy for acute grade 4 laryngeal edema. There were no other grade≥3 acute or chronic treatment-related toxicities. IMPT is feasible and provides promising local control for recurrent DTC. Larger studies are needed to determine the role of IMPT for DTC.

Epidemiology and Surgical Characteristics of Thyroid Cancer in United Arab Emirates: Review of 100 Consecutive Patients

Background and Objectives: Thyroid cancer incidence is increasing globally. There is limited data regarding the epidemiology of thyroid cancer in the Middle East and North Africa region. This region has also experienced socioeconomic changes recently that have influenced the histopathological and epidemiological pattern of thyroid cancer. The aim of this study is to evaluate the histological, epidemiologic, and surgical factors of thyroid cancer patients who underwent thyroidectomy at Cleveland Clinic Abu Dhabi. Materials and Methods: A retrospective review of patients who underwent thyroidectomy and found to have thyroid cancer over a 2-year period from July 2015 - July 2017. The histopathological data were reviewed based on the College of American Pathologists Protocol for Carcinomas of Thyroid Gland (American Joint Committee on Cancer, 7th edition, 2010). Results: One hundred patients underwent surgery for thyroid carcinoma in our patient population. In these cancer patients, the female to male ratio was 5.25:1 and 71 patients (71%) were below 45 years of age. The most common surgery performed was total thyroidectomy at 75.7%. Papillary thyroid carcinoma (PTC) was the most common pathology in 89%, followed by follicular thyroid carcinoma (FTC) in 9%, one case of mixed papillary follicular carcinoma, and one case of Hurthle cell carcinoma. Hypocalcemia was the most common postoperative complication (20.6%). Conclusion: PTC, traditionally seen in iodine sufficient regions, is the most common histologic subtype of thyroid cancer and its rates are increasing in the United Arab Emirates (UAE). Female gender and age <45 were associated with thyroid carcinoma in our UAE patient cohort.

Hurthle cell carcinoma – A case report

Hurthle cell carcinoma – A case report

Is thyroid cancer prognosis affected by solid organ transplantation?

BackgroundThyroid nodules discovered incidentally during transplant may prolong time to transplantation. Although data suggest that incidence of thyroid cancer increases after solid organ transplantation, the impact on prognosis in differentiated thyroid cancer is not well characterized. MethodsWe performed a retrospective review of patients with history of thyroid cancer and solid organ transplantation at our institution. ResultsA total of 13,037 patients underwent solid organ transplantation of which there were 94 patients with differentiated thyroid cancer (0.7%). Of these, 50 patients (53%) had cancer pre–solid organ transplantation, whereas 44 patients (47%) developed cancer post–solid organ transplantation. Papillary histology was most common (88%), followed by follicular (3%), Hurthle cell (3%), and medullary (2%) carcinomas. One patient in the post-transplant cohort died from metastatic thyroid cancer 11.8 years after transplantation. There were 5 patients in the pre-transplant group and 4 patients in the post-transplant group who had recurrent thyroid disease. There were no patients treated for differentiated thyroid cancer pre–solid organ transplantation that experienced disease recurrence after transplantation. Disease-free survival at 5 and 10 years was 95.8% and 92.1% (confidence interval 84.9–99.2%, 80.0–97.4%) in the pre–solid organ transplantation group vs 89.7% and 84.4% in the post (confidence interval: 80.0–96.3% and 79.0–93.1%, P = .363), respectively. ConclusionSurvival outcomes and recurrence rates in patients with thyroid cancer are not significantly affected by solid organ transplantation. A history of thyroid cancer or discovery of thyroid nodules during transplant screening should not be a contraindication for transplant listing.

Histological features of BRAF V600E-mutant anaplastic thyroid carcinoma.

Treatment with a BRAF inhibitor, alone or in combination with a MEK inhibitor, may be considered for BRAF-mutant anaplastic thyroid carcinoma (ATC). The purpose of this study was to characterise the histology of BRAF V600E-mutant ATC. We identified 28 ATC that were consecutively resected between 2003 and 2019. All tumour slides for each case were evaluated for the presence of a precursor tumour and for ATC morphology (sarcomatoid, pleomorphic giant cell, epithelioid or squamous). BRAF V600E mutation status was determined by BRAF V600E IHC or molecular analysis (OncoPanel NGS). Eighteen (64%) ATC had an associated well-differentiated precursor, including 10 (36%) with associated papillary thyroid carcinoma (PTC) and eight (29%) with associated follicular thyroid carcinoma (FTC) or Hürthle cell carcinoma (HCC). Most ATC (19 cases, 68%) demonstrated a mixed anaplastic morphology. Squamous morphology was present in four cases. Ten (36%) ATC had a BRAF V600E mutation. All ATC that had a PTC precursor had a BRAF V600E mutation (and all ATC with a BRAF V600E mutation had a PTC precursor), whereas no ATC with an FTC or HCC precursor had a BRAF V600E mutation. All four cases of ATC with a squamous morphology had a PTC precursor and a BRAF V600E mutation. In our cohort, the presence of a PTC precursor predicted the presence of the BRAF V600E mutation, whereas ATC with an FTC or HCC precursor lacked a BRAF V600E mutation. A squamous morphology was associated with the presence of a PTC precursor and a BRAF V600E mutation.

Diagnostic Value of Six Thyroid Imaging Reporting and Data Systems (TIRADS) in Cytologically Equivocal Thyroid Nodules.

The aim was to compare the usefulness of selected thyroid sonographic risk-stratification systems in the diagnostics of nodules with indeterminate/suspicious cytology or unequivocal cytology in a population with a history of iodine deficiency. The diagnostic efficacy of ACR-TIRADS (the American College of Radiology Thyroid Imaging Reporting and Data Systems), EU-TIRADS (European Thyroid Association TIRADS), Korean-TIRADS, Kwak-TIRADS, AACE/ACE-AME-guidelines (American Association of Clinical Endocrinologists/ American College of Endocrinology-Associazione Medici Endocrinologi guidelines) and ATA-guidelines (American Thyroid Association guidelines) was evaluated in 1000 nodules with determined histopathological diagnosis: 329 FLUS/AUS (10.6% cancers), 167 SFN/SHT (11.6% cancers), 44 SM (77.3% cancers), 298 BL (benign lesions), 162 MN (malignant neoplasms). The percentage of PTC (papillary thyroid carcinoma) among cancers was higher in Bethesda MN (86.4%) and SM (suspicion of malignancy) nodules (91.2%) than in FLUS/AUS (57.1%, p < 0.005) and SFN/SHT (suspicion of follicular neoplasm/ suspicion of Hürthle cell tumor) nodules (36.8%, p < 0.001). TIRADS efficacy was higher for MN (AUC: 0.827–0.874) and SM nodules (AUC: 0.775–0.851) than for FLUS/AUS (AUC: 0.655–0.701) or SFN/SHT nodules (AUC: 0.593–0.621). FLUS/AUS (follicular lesion of undetermined significance/ atypia of undetermined significance) nodules assigned to a high risk TIRADS category had malignancy risk of 25%. In the SFN/SHT subgroup none TIRADS category changed nodule’s malignancy risk. EU-TIRADS and AACE/ACE-AME-guidelines would allow diagnosing the highest number of PTC, FTC (follicular thyroid carcinoma), HTC (Hürthle cell carcinoma), MTC (medullary thyroid carcinoma). The highest OR value was for Kwak-TIRADS (12.6) and Korean-TIRADS (12.0). Conclusions: TIRADS efficacy depends on the incidence of PTC among cancers. All evaluated TIRADS facilitate the selection of FLUS/AUS nodules for the surgical treatment but these systems are not efficient in the management of SFN/SHT nodules.

Loss of Function SETD2 Mutations in Poorly Differentiated Metastases from Two Hürthle Cell Carcinomas of the Thyroid.

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.

Hurthle cell carcinoma in childhood: A retrospective analysis of five cases and review of pediatric literature.

the available studies on Hurthle cell carcinoma (HCC) in pediatric age are scarce and based on isolated case reports. Aims of the present study were to review the available pediatric literature on HCC (2000-2019), to describe the cohort of children with this cancer histotype, and to estimate its relative prevalence in pediatric age. We retrospectively reconstructed an HCC course in five patients<19 years who were identified in our departments during the period 2000-2019, and we reviewed the available pediatric studies on this differentiated thyroid cancer (DTC) variant. HCC occurred with a relative prevalence of 5.8% at a median chronological age of 12.5 years. None of HCC patients exhibited, at diagnosis, thyroid dysfunction, extensive lateral neck disease, or distant metastases, and all showed a persistent remission over time. Three patients showed, at diagnosis, antecedents of other diseases (Hashimoto's thyroiditis, neurofibromatosis type 1, and osteosarcoma). (1) In childhood, the relative prevalence of HCC among different thyroid cancer histotypes is 5.8%, that is close to the one previously reported both in the general population and in other less numerous children's cohorts; (2) HCC may develop even early, at the age of 7; (3) in childhood, HCC does not seem to have a more aggressive behavior when compared with other DTC histotypes; (4) antecedents of other diseases are not infrequent in the history of children with HCC.

A Recurrent Hurthle Cell Carcinoma: Decision Making of Diagnosis and Therapeutic Strategy

A Recurrent Hurthle Cell Carcinoma: Decision Making of Diagnosis and Therapeutic Strategy

Clinical characteristics and prognostic factors of Hurthle cell carcinoma: a population based study

BackgroundThyroid Hurthle cell carcinoma (HCC) is a rare disease with high risk of invasion and metastasis and poor prognosis. The clinical characteristics, prognosis and treatment of HCC are still controversial, and clinical data are still limited to some case reports. Therefore, understanding the characteristics and survival factors of HCC is clinically necessary.MethodsThis study collected data from HCC patients diagnosed pathologically from 2004 to 2015, including basic population characteristics, tumor characteristics, and epidemiological and survival data. The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to conduct a population cohort study.ResultsA total of 2101 HCC patients with an average age of 55.42 ± 15.27 years were enrolled in this study. Of them, 1740 (82.82%) patients had local disease, 245 (11.66%) had regional disease, and 89 (4.24%) had distant disease. Total thyroidectomy was performed in 1669 (79.44%) patients, partial thyroidectomy was performed in 382 (18.18%) patients, and radioactive iodine (RAI) was used in 1155 (54.97%) patients. The 5-year and 10-year cancer-specific survival rate was 95.4 and 92.6%, respectively. The distant disease group had significantly more male patients, multifocal tumors, and extensive tumors compared to the local disease group. Multivariate survival analysis showed that age (P < 0.05), SEER stage (P < 0.001), and T-stage (P = 0.001) had significant effects on survival. There was no significant difference in survival between total and partial thyroidectomy (P = 0.078), or between RAI and non-RAI (P = 0.733).ConclusionMale gender, multifocal tumors, and extended tumors are associated with increased risk of late stage HCC. Age over 45 years, distant SEER stage, and late T-stage are independent risk factors for mortality in HCC.

OR21-02 Impact of Nodule Size on the Probability of Hurthle Cell Carcinoma and Other Cancers in Thyroid Nodules with Multiple Chromosomal Copy Number Alterations

Fine-needle aspiration (FNA) of thyroid nodules yields indeterminate cytological diagnosis in ~20% of cases, confounding patient management. This includes Hurthle cell nodules, which typically yield Bethesda IV and III cytology. Chromosomal copy number alterations (CNA) are known to occur in thyroid tumors, particularly in Hurthle cell carcinomas (HCC) as well as in other typically follicular-patterned tumors including papillary thyroid carcinomas (PTC) and poorly differentiated thyroid carcinomas (PDTC). The aim of this study was to evaluate thyroid nodules tested positive for CNA but negative for all other genomic alterations using ThyroSeq v3 NGS assay in order to establish the probability of cancer in these nodules and find whether it is influenced by the pattern of CNA and nodule size. We evaluated 111 nodules with multiple CNA detected by ThyroSeq in FNA samples and available surgical pathology outcome. Of those, 69 (62%) nodules showed CNA changes consistent with genome near-haploidization (GNH) whereas 42 (38%) nodules had multiple chromosomal losses and gains (CLG). Nodule size ranged from 0.5-10.2 cm; cytology was Bethesda III in 54%, Bethesda IV in 43%, and Bethesda V-VI in 3% of cases, with Hurthle cells mentioned in the cytology report in 64% of cases. On surgical pathology, 38 (34%) of these nodules were malignant (including 24 HCC, 8 PTC, and 5 oncocytic PDTC) and 73 (66%) were benign (including 43 Hurthle cell and 18 follicular adenomas). No significant difference was observed in probability of malignancy between the two patterns of CNA (p=0.41). However, a significant correlation between the nodule size and probability of cancer was found (p=0.006). In specific CNA groups, correlation between cancer and nodule size remained significant for nodules with GNH pattern (P=0.0002), but not with CLG pattern (p=0.449). Specifically, cancer probability in nodules with GNH pattern and <2 cm in size was 14% (all cancers minimally-invasive), 2.0-2.9 cm was 33%, 3.0-3.9 cm was 50%, 4-4.9 cm was 67%, and ≥5 cm was 80%. Among high-risk cancers (widely-invasive or angioinvasive HCC, PDTC), all 10 tumors had the GNH pattern (p=0.01) and average nodule size of 4.9 cm (range, 2.1-8.5 cm). These findings suggest that CNA of both types are frequently found in Hurthle cell tumors, and probability of cancer in nodules with CNA and no other mutations increases with larger nodule size. This may help to refine the pre-operative assessment of cancer probability and risk of more aggressive disease and offer more tailored management to these patients.

MON-LB88 Positive Predictive Value of TP53 Variants in Bethesda III/IV Thyroid Fine-Needle Aspirates

Introduction: Somatic DNA variants in the tumor suppressor gene TP53 have been reported in papillary thyroid carcinoma (PTC), Hürthle cell carcinoma (HCC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid carcinoma. However, TP53 variants are uncommon among cytologically indeterminate thyroid nodules, so their positive predictive value (PPV) for malignancy, when identified, is unknown. The original Afirma Xpression Atlas reported genomic variants from the mRNA of 511 genes, including TP53. Here we report the PPV of TP53 alterations among Afirma Genomic Sequencing Classifier (GSC) Suspicious Bethesda III/IV nodules in real-world clinical practice. Methods: A consecutive cohort of Afirma GSC Suspicious Bethesda III/IV nodules submitted to Veracyte for molecular analysis and positive for only TP53 alterations by the Xpression Atlas was identified. Local surgical pathology diagnoses were sought with IRB approval. One nodule per patient was included. Results: Thirty-eight TP53 variants were present among >13,000 Bethesda III/IV Afirma GSC Suspicious samples. Among the 22 with only a TP53 alteration, the first 16 consecutive nodules were included (7 nodules were Bethesda III and 9 nodules were Bethesda IV). Local surgical pathology diagnoses were available for 11 of these nodules. Seven nodules (64%) were malignant on surgical pathology: 3 cases of HCC, 1 PDTC, 1 follicular thyroid carcinoma (FTC), 1 follicular variant PTC, and 1 classical PTC. The mean size of malignant nodules was 3.6 cm (range 1-7.7 cm). The remaining four nodules (36%) were benign on surgical pathology, with a mean size of 2.6 cm (range 1.5-4.2 cm). Benign cases included 2 follicular adenomas (FA), 1 Hürthle cell adenoma (HCA), and 1 adenomatoid nodule (AN). Seven different TP53 variants were identified, and only one was observed at least 3 times (TP53: p.R248Q in 2 cases of HCC and 1 adenomatoid nodule). Given the small numbers, meaningful estimates of the variants’ individual PPVs could not be calculated. Conclusions: TP53 variants among Afirma GSC Suspicious Bethesda III/IV nodules are very rare and associated with malignancy in 64% of nodules based on local pathology review. A broad range of both benign and malignant neoplasms, including HCC, PDTC, FTC, PTC, FA, HCA, and AN, were reported among nodules with TP53 alterations. The prognostic value of finding an isolated TP53 variant in Afirma Suspicious nodules remains unknown.

A Report of a Rare Case of Hurthle Cell Carcinoma of Thyroid with Metachronous Renal Metastasis

AbstractRenal metastasis from Hurthle cell thyroid carcinoma is an extremely rare phenomenon which when present usually indicates widely disseminated disease. Herein, we present a case of Hurthle cell carcinoma of thyroid in a 58-year-old gentle lady, with metachronous renal metastasis which happens to be the fourth reported case in English literature.

Thyroid Aspiration Overview in the Diagnosis of Suspicious Malignancy (Thyroid Papillary Carcinoma)

BackgroundThyroid carcinoma is the most common malignancy in the endocrine system. Fine Needle Aspiration Biopsy (FNAB) is a preliminaryexamination to detect thyroid neoplasms. One of FNAB diagnostic category according to Bethesda is Suspicious for Malignancy(SFM). This study was conducted to assess the cytology feature of SFM category and its concordance with histopathologic result.MethodsThis retrospective study is a descriptive categoric study with cross sectional design of 40 samples. Secondary datas were arsip inlaboratory of Anatomical Pathology of FKUI/RSCM collected on 2015 diagnosa as suspect for malignancy of tiroid based onhistopathologic result.ResultsThe histopathological results of SFM were: PTC 20 cases (50%), Hurthle cell carcinoma 2 cases (5%), adenomatous goitre withPTC focus 11 cases (27%), adenomatous goitre with atypical cell 1 case (2%), adenomatous goitre 4 cases (10%), follicularadenoma 1 case (3%), Hashimoto's thyroiditis with atypical cell 1 case (3%). Positive predictive value was 82.5% with 94% ofmalignancies were papillary type. Cytology feature of SFM specimen: cellularity moderate (57.5%), macrofollicular (67.5%), nuclearchange powdery chromatin (85%). Giant cell were 18 cases (45%, cytoplasmic were 20 cases (50%), bubble gum colloid were, 9cases (22.5%).ConclusionMost of SFM specimen have malignant histopathologic result, especially papillary type. The positive predictive value of the SFMcategory is quite high, but there is still disconcordance on histopathologic results.