Classic Papillary Thyroid Carcinoma Research Articles

Predicting tall-cell subtype of papillary thyroid carcinomas independently with preoperative multimodal ultrasound.

This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. 46 TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, color Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesion were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. Univariate and multivariate analysis identified that extrathyroidal extension (OR, 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥ 14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: p = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm)+2.957 × (if aspect ratio≥0.91)+2.819 × (if extra-thyroidal extension)]. The prediction model had a good discrimination performance for TCPTC: the AUC, sensitivity and specificity were 0.928, 0.848 and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923 and 0.926. Ultrasound has potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extrathyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful to predict TCPTC. Multimodal ultrasound prediction of TCPTC were supplements to preoperative cytological diagnosis and molecular diagnosis on PTC subtypes.

Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases.

Anaplastic lymphoma kinase (ALK) gene fusions are rare in papillary thyroid carcinoma (PTC) but may serve as a therapeutic target. This study aims to evaluate the preoperative cytologic findings and clinicopathologic features of a series of eight ALK-rearranged PTCs from our pathology archives and consultations. All cases were confirmed by ALK D5F3 immunohistochemistry and six with additional targeted RNA-based next-generation sequencing (NGS). The original fine-needle aspiration (FNA) cytology diagnosis included the Bethesda System (TBS) category II in three (37.5%), TBS III in two (25%), TBS V in two (25%), and TBS VI in one (12.5%). Six cases had available FNA cytology and were reviewed. The cytologic features showed microfollicular architecture as well aslimited or reducednuclear elongation and chromatin alterations in all six. Nuclear grooves and pseudoinclusions were absent in two cases, rarely or focally noted in three, and frequently found in one. Two cases initially diagnosed asTBS II, showing microfollicular architecture without well-developed nuclear features, were revised to TBS III (with architectural atypia only). For histologic correlations, four were infiltrative follicular variant PTCs, three as classic subtype PTC with predominant follicular growth, and one as solid/trabecular subtype PTC. All eight cases demonstrated reducedPTC nuclear features with respect to nuclear elongation and chromatin alterations compared to thosetypically identified in "BRAF-like" PTCs. The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the "RAS-like" nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.

Abstract 6277: Tall cell variant papillary thyroid carcinoma from Middle Eastern patients have worse outcome than classical papillary thyroid carcinoma using propensity score matching

Abstract The tall cell variant of Papillary Thyroid Carcinoma (TCV-PTC) is the most common aggressive variant of PTC. The impact of TCV-PTC on patients’ prognosis still remains controversial. Moreover, the clinico-pathological and prognostic effect of TCV-PTC from Middle Eastern ethnicity remains unexplored. We aimed to study TCV-PTC in comparison to classical PTC in Middle Eastern patients and their impact on prognosis. We performed a retrospective cohort study of tall cell variant (TCV-PTC) and classic variant of papillary thyroid carcinoma (CV-PTC) after post-surgical radioactive iodine therapy. We used the propensity score matching (1:3 matching ratio) to account for differences between recipients of TCV-PTC vs CV-PTC. Univariate and multivariate analysis were performed to assess the independent factors for persistent/recurrent disease. Kaplan-Meier curve analyses were used to compare disease-free survival (DFS). In total, 174 (16.3%) patients with TCV-PTC and 891 (83.7%) patients with CV-PTC were included. After propensity score matching, 174 pairs of patients were selected (TCV-PTC, n = 174; CV-PTC, n = 522). In the matched analysis, higher proportions of TCV-PTC experienced persistent/recurrent disease compared with CV-PTC (25.7% vs 31.4%; p = 0.0119). In multivariate analyses of clinical and tumor characteristics, histological type of TCV-PTC (odds ratio, 2.09; 95% confidence interval, 1.28-3.40; p = 0.0031) was associated with increased risk of persistent/recurrent disease. The five-year DFS rates for the TCV-PTC and CV-PTC groups were 48.5% and 73.1%, respectively. The Kaplan- Meier analysis indicated that the TCV-PTC group (p < 0.0001) had shorter DFS. In conclusion, when other clinico-pathological factors were similar, this propensity score matched analysis showed that histological subtype TCV-PTC is by itself an independent predictive marker of persistent/recurrent disease in Middle Eastern patients. Therefore, individualized therapeutic approaches might be needed for this aggressive PTC subtype. Citation Format: Khawla S. Al-Kuraya, Sandeep K. Parvathareddy, Abdul K. Siraj, Saeeda O. Ahmed, Nabil Siraj, Manal Manakhan, Hassan Aldossari. Tall cell variant papillary thyroid carcinoma from Middle Eastern patients have worse outcome than classical papillary thyroid carcinoma using propensity score matching [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6277.

Diagnostic and prognostic utility of TROP-2, SLP-2, and CXCL12 expression in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most frequent thyroid malignancy. Histopathological examination is widely accepted as the gold standard test for the diagnosis of PTC. However, the histopathological examination sometimes can't differentiate PTC from other thyroid diseases. Differentiating PTC from other thyroid diseases is essential for a therapeutic approach and prognosis. The current study was performed to investigate the utility of TROP-2, SPL-2, and CXCL12 mRNA and protein expression in discriminating PTC from other thyroid diseases that mimic PTC. The current study was performed on 75 cases of surgically resected thyroid glands. The cases were distributed in two groups: the PTC group and the non-PTC group. The PTC group consisted of 35 cases (25 patients of the classic PTC variant and 10 patients of the PTC follicular variant). The non-PTC group consisted of 40 cases (10 cases were multinodular goiter, 5 cases were Graves' disease, 5 cases were Hashimoto thyroiditis, 15 patients were follicular adenoma (FA) and 5 cases were follicular carcinoma). TROP-2, SPL-2, and CXCL12 mRNA expression were estimated by qRT-PCR, and protein expression was estimated by immunohistochemistry. There were upregulated TROP-2, SPL-2, and CXCL12 mRNA and protein expressions in PTC compared to non-PTC (P< 0.001, for each). There was a statistically significant upregulation in the mRNA expression of the three genes among PTC cases with larger tumor sizes (P< 0.001, for each), those with tumor stages III and IV (P= 0.008, 0.002 and < 0.001 respectively), and those with LN metastasis (P< 0.001, for each). Moreover, there was a statistically significant upregulation in CXCL-12 gene expression among PTC cases with extra-thyroid extension (P< 0.001). mRNA expression of TROP-2, SPL-2, and CXCL12 among PTC cases increased in larger tumor size, tumor stages III and IV, and LN metastasis. Moreover, there was an increase in CXCL-12 gene expression among PTC cases with extra-thyroid extension. Thus, TROP-2, SPL-2, and CXCL12 expressions could be possible diagnostic and prognostic markers in PTC.

Correlation between genetic alterations and clinicopathological features of papillary thyroid carcinomas.

To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (<45 years). Among the 22 genes tested, the BRAF mutation rates showed a significant difference between the PTC and benign groups. In the subgroup analysis, younger age (odds ratio = 12.512, 95% confidence interval: 3.126-50.087) was an independent risk factor for LNM. In further analyses, BRAF mutation was significantly associated with LNM in the older subgroup (age ≥ 45 years), suggesting that the BRAF mutation test has greater value for determining PTC prognosis in the older age group. Our findings will provide a more comprehensive understanding of the relationship between gene mutations and PTC and may contribute to improved PTC management.

Are there specific cytologic features that can predict BRAFV600E mutational status of papillary thyroid carcinoma in fine-needle aspiration specimens?

BRAFV600E mutation is the most common molecular alteration found in papillary thyroid carcinoma (PTC) and has been linked to recurrent disease or possibly more aggressive behavior. Some studies have reported sickle-shaped nuclei (SSN) and plump pink cells (PPC) to be predictive markers of BRAF mutation in FNA cytology. We aimed to evaluate the reproducibility of the aforementioned cytologic features. A computerized search for diagnosed PTC surgical pathology cases tested for BRAFV600E mutation by Sanger DNA sequencing was performed. Blinded to BRAF results, the corresponding cytology was reviewed for presence of SSN and PPC. Classic nuclear PTC (CNPTC) features, cystic change, and psammoma bodies were also evaluated. The results were correlated with BRAFV600E mutational status and histologic subtypes. Study cohort consisted of 113 cases (74 BRAFV600E mutated, 39 BRAFV600E wild type). SSN and combined CNPTC /SSN had positive predictive value of 74% and 75%, respectively. CNPTC showed 92% sensitivity and 20% specificity. Psammoma bodies had 92% specificity and 5% sensitivity. The presence of combined PPC/SSN showed 80% specificity, 27% sensitivity, and diagnostic accuracy of 45%. CNPTC was seen in 60/61 (98%) SSN and 45/45 (100%) PPC. There was no significant statistical association between SSN, PPC, and CNPTC with specific histologic subtypes and BRAF mutational status. CNPTC is sensitive but not specific for BRAF mutational status. SSN, PPC, and CNPTC are not predictive markers for the presence of BRAF mutation or histologic subtypes. Additional studies may be needed to further corroborate these findings.

Molecular Genetics Augment Cytopathologic Evaluation and Surgical Planning of Pediatric Thyroid Nodules

PurposeMolecular genetic testing in conjunction with cytopathology may improve prediction of malignancy in thyroid nodules, particularly those with indeterminate cytology (Bethesda III/IV). Though now commonplace in adults, pediatric data are limited. This study examines molecular genetics of pediatric nodules with correlation to cytologic and histologic classification at time of surgery and the distribution of mutations. MethodsRetrospective chart review of 164 patients <22 years who underwent surgical resection of a thyroid nodule between 2002 and 2020 with molecular testing on fine-needle aspiration biopsy (FNA) or final histopathology. Results85 (52 %) of 164 patients undergoing thyroid resection had available molecular genetic testing. BRAF V600E testing was performed on the FNA samples of 73 (86 %) patients and on 15 (18 %) surgical specimens; 31 (37 %) were positive. Of the remaining 54 patients, 21 had additional mutation/fusion testing. In 17 (81 %) cases, an alternate mutation/fusion was identified including 8 gene fusions, 3 DICER1 mutations, 4 NRAS mutations, one BRAF variant, and one unknown variant. BRAF, DICER1 mutations, and gene fusions predicted malignancy. Greater than 95 % of BRAF mutations were in Bethesda V/VI lesions and associated with classic variant PTC whereas fusions and DICER1 mutations clustered in Bethesda IV nodules. Bethesda III nodules harbored BRAF and NRAS mutations. In Bethesda IV nodules, a gene fusion or DICER mutation altered the surgical decision-making (upfront thyroidectomy rather than lobectomy) in 70 % of nodules submitted for genetic testing. ConclusionExpanded molecular genetic testing on FNA of pediatric thyroid nodules, particularly Bethesda III/IV, may improve prediction of malignancy and augment surgical decision-making. Level of EvidenceIII.

Significance of P63 Expression in Papillary and Follicular Thyroid Carcinoma

Background: Papillary thyroid carcinoma (PTC) is the most frequent histologic type of all thyroid malignancies followed by follicular thyroid carcinoma (FC). Follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common variant of PTC. A diagnostic dilemma may arise, when histologically the distinctive nuclear features are either not well developed or present focally within an encapsulated thyroid lesion. A panel of immunomarkers has been tested to overcome the limitation of histopathology. P63 is commonly used immunomarkers among them. Objectives: The aim of the present study was to see the expression of P63 in PTC including FVPTC and FC in order to evaluate their possible roles in the differential diagnosis between these two mimics. Patients and methods: This cross-sectional descriptive study was conducted over 44 cases with histologically confirmed papillary and follicular thyroid carcinoma. Immunohistochemistry was done for P63. Results: Out of the 44 cases, 39 were histologically diagnosed as papillary thyroid carcinoma (27 were classical PTC &amp; 12 were FVPTC) and the rest 5 were follicular thyroid carcinoma. In the present study, P63 showed 74.4% positivity with varying intensity and extent of staining in papillary thyroid carcinoma. Positive immunoreactivity of P63 was highly significant in distinguishing papillary from follicular thyroid carcinoma (P=0.003). Conclusion: This study suggested that the use of P63 may be helpful in the diagnosis of papillary and follicular thyroid carcinoma along with histopathological examination. TAJ 2023; 36: No-2: 121-128

Prevalence of Differentiated High-Grade Thyroid Carcinoma Among Well-Differentiated Tumors: A Systematic Review and Meta-Analysis.

Background: The current edition of the World Health Organization (WHO) classification of endocrine tumors introduced grading for follicular cell-derived thyroid cancer. Tumors with necrosis and/or high mitotic count but not fulfilling the Turin criteria for poorly differentiated carcinoma will be reclassified as differentiated high-grade thyroid carcinoma (DHGTC). However, the impact of this reclassification has not been evaluated. In this study, we performed a systematic review and meta-analysis to estimate the prevalence of this new entry across thyroid tumor subtypes. Methods: In this systematic review and meta-analysis, studies reporting data on necrosis and/or mitoses in well-differentiated thyroid carcinoma (WDTC) were used to estimate the prevalence of DHGTC. Heterogeneity and potential publication bias were also evaluated. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and quality assessment was performed using a modification of the Newcastle-Ottawa scale. The study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022378716). Results: In clinically unselected patients, the prevalence of DHGTC in WDTC was 0.072 [95% confidence interval, CI, = 0.045-0.113]. The proportion of high-grade tumors greatly varied across growth patterns and subtypes. Overall, the prevalence of DHGTC was higher in follicular thyroid carcinoma (FTC; 0.146 [CI = 0.101-0.205]) than in papillary thyroid carcinoma (PTC; 0.059 [CI = 0.036-0.097]). Diffuse sclerosing, follicular, and classic subtype PTC had the lowest rates of high-grade features (i.e., 0.018 [CI = 0.004-0.084]; 0.036 [CI = 0.010-0.124]; and 0.042 [CI = 0.027-0.066], respectively), while a greater proportion of solid trabecular and histologically aggressive PTC could be reclassified as DHGTC (i.e., 0.154 [CI = 0.067-0.314] and 0.168 [CI = 0.108-0.252], respectively). Similar proportions were obtained for minimally and widely invasive FTC (i.e., 0.136 [CI = 0.058-0.287] and 0.152 [CI = 0.086-0.254], respectively). Finally, in a cohort of patients with poor prognosis (i.e., fatal cases, metastatic and radioiodine resistant tumors, cases with biochemical recurrence), the proportion of DHGTC was 0.287 [CI = 0.155-0.469]. Conclusions: Following the current WHO indications, some tumors will be reclassified as DHGTC. The proportion of tumors with high-grade features is relevant in FTC, solid trabecular, and histologically aggressive PTC subtypes. A remarkable enrichment in DHGTC among patients with poor prognosis confirms the negative impact of high-grade features on outcome.

Clinicopathological profile of Papillary thyroid carcinoma in a tertiary cancer hospital in Nepal

Background: Differentiated thyroid cancers (DTC), including papillary thyroid carcinoma (PTC), are on the rise. This study provides a detailed examination of PTC cases in a tertiary care cancer hospital in Nepal, aiming to understand its clinical characteristics and treatment patterns. We conducted a retrospective analysis of PTC, including demographics, features of tumor, and treatment modalities. Methods: A retrospective cross-sectional study assessed cases of PTC from January 2022 to December 2022. Patient data were collected and analyzed, focusing on demographics, tumor attributes, and treatment approaches. Results: Among 105 patients, females were predominant (female-to-male ratio 5.2:1), and ethnic diversity was observed. Most patients were from Lumbini Pradesh. The mean age was 40.78 years. Fine-needle aspiration cytology (FNAC) showed Bethesda VI as the most common classification. Primary treatment involved total thyroidectomy (76.25%). Classical PTC was the major histopathological variant (78.1%). Tumors were frequently located in the right lobe (55.25%). Unifocal tumors were prevalent (74.28%), with an average size of 2.74 cm. Lymph node metastasis occurred in 49.5% of patients. Intermediate-risk patients constituted the majority (53.5%). Conclusion: This study offers crucial insights into PTC's clinical spectrum in Nepal, aiding in tailored patient care strategies. The findings contribute to informed decision-making for enhanced treatment outcomes.

Long-term impact of prophylactic central neck dissection in non-invasive classic papillary thyroid carcinoma

BackgroundThe utilization of prophylactic central neck dissection (pCND) in cases of non-invasive clinical node-negative (cN0) papillary thyroid carcinoma (PTC) remains a topic of debate, with a dearth of long-term evidence. Materials and methodsWe retrospectively reviewed 1181 cN0 PTC patients from 1997 to 2011. Of these, 641 underwent pCND (pCND + group) and 540 did not (pCND-group). Propensity score matching (PSM) was used to identify similar patients. Event-free survival and long-term complications including permanent hyperparathyroidism and permanent recurrent laryngeal nerve (RLN) paralysis were analyzed after PSM. ResultsThe pCND + group had more aggressive characteristics. In the matched cohort after PSM, the 5-year, 10-year, and 15-year EFS rates were 98.9 %, 98.2 %, and 97.1 % for the pCND + group, and 97.7 %, 97.1 %, and 97.1 % for the pCND-group, respectively. There was no statistically significant difference in EFS rates between the two groups (Log Rank P = 0.38). There was no statistically significant difference in the incidence of permanent hyperparathyroidism (3.3 % vs. 1.5 %, P = 0.08) and permanent RLN paralysis (1.7 % vs. 0.9 %, P = 0.13) between the pCND+ and pCND– groups. ConclusionOur study, with a median follow-up duration of 107 months, indicates that pCND does not lead to a significant reduction in nodal recurrence among non-invasive cN0 PTC patients.

Prediction of classical versus non classical papillary thyroid carcinoma subtypes from cytology of nodules classified according to TIRADS

PurposeOur purposes were: 1) to estimate the prediction performance (PP) of cytology in identifying papillary thyroid carcinoma (PTC) subtypes; 2) to explore how the PTC subtypes distribute among the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories.MethodsNodules were included if both the histology with the PTC subtype report and the cytology report with the possible PTC subtype were available. The PP was calculated by making the proportion of True positives/False positives+false negatives.Results309 cytologically “suspicious for malignancy” and “malignant” thyroid nodules with PTC histology were evaluated. ACR TI-RADS categorization for classical PTC was significantly different from non-classical PTC (p-value 0.02). For the whole cohort the PP of cytologically classical cases was 0.74, while that of cytologically non classical cases was 0.41. ACR TI-RADS categorization was not significantly different for aggressive vs non-aggressive PTC subtypes (p-value 0.1). When considering only aggressive or non-aggressive PTC subtypes, the PP of cytologically classical cases was respectively 0.86 and 0.87, while that of cytologically non classical cases was respectively 0.27 and 0.22. The PP of cytologically classical cases was 0.73 and 0.79, respectively for macroPTCs and microPTCs, while that of cytologically non classical cases was 0.55 and 0.33, respectively for macroPTCs and microPTCs.ConclusionCytology examination reliably performed in predicting classical PTC versus non classical PTC subtypes. ACR TI-RADS categorization was significantly different among classical PTC versus non classical PTC subtypes.

Partial Thyroidectomy With Incidental Metastatic Lymph Nodes

The need for completion thyroidectomy in patients with incidental metastatic lymph nodes after partial thyroidectomy is unclear. To investigate the outcomes of patients with incidental metastatic lymph nodes following partial thyroidectomy. A retrospective review of a prospectively maintained thyroid cancer database from 1985 to 2015 was carried out at a head and neck surgery practice at a tertiary referral cancer center. A total of 74 patients who underwent thyroid lobectomy or thyroid isthmusectomy between 1985 and 2015 and were found to have incidental metastatic lymph nodes on final pathologic analysis and were selected to be observed without immediate completion thyroidectomy were included. A separate group of additional 11 patients who underwent immediate completion thyroidectomy was also identified and reviewed. Analysis took place from February to May 2022. Recurrence-free survival outcomes of patients found to have incidental metastatic lymph nodes on final pathologic analysis following partial thyroidectomy with no immediate completion thyroidectomy. A total of 74 patients were observed, with a median (IQR) age of 39 (28-49) years; 44 (59%) were women. Sixty-four patients underwent thyroid lobectomy and 10 patients had isthmusectomy. Classic papillary thyroid carcinoma was the most common histologic type (34 [46%]). Vascular invasion and microscopic extrathyroidal extension were present in 11 patients (16%) and 22 patients (30%), respectively. Positive margins were identified in 5 patients (7.8%). Size of metastatic lymph nodes ranged between 0.07 cm and 1.2 cm. No extranodal extension was reported. A total of 52 patients (70%) were classified as intermediate risk for recurrence based on the American Thyroid Association risk stratification system. The median (IQR) follow up was 48.15 (15.4-86.1) months, during which only 1 patient had a regional recurrence. Another patient underwent delayed completion thyroidectomy for a contralateral lobe malignant abnormality. Recurrence-free survival, disease-specific survival, and overall survival were 97.4%, 100%, and 96.2%, respectively. A separate group of 11 patients who underwent immediate completion thyroidectomy were reviewed. These patients were more likely to have tall-cell papillary thyroid carcinoma (6 [55%] vs 13 [18%]), multifocality (9 [82%] vs 28 [41%]), microscopic extrathyroidal extension (8 [73%] vs 22 [30%]), and positive margins (3 [30%] vs 5 [7.8%]) compared with patients who were under observation only. Completion thyroidectomy may not be necessary in appropriately selected patients who are found to have incidental metastatic lymph nodes (N1a) after partial thyroidectomy for localized well-differentiated thyroid cancer.

Radioactive iodine administration is not associated with improved disease-specific survival in classic papillary thyroid carcinoma greater than 4 cm confined to the thyroid

BackgroundWe aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid Association guidelines regarding their management. MethodsThe Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival. ResultsThere were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval [0.39–1.58], P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval [1.69–7.26], P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval [1.02–1.06], P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm. ConclusionAdjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine.

Comparison of Treatment and Prognosis Between Follicular Variant Papillary Thyroid Carcinoma and Classical Papillary Thyroid Carcinoma.

This cohort study evaluated the associations of different treatments with the prognosis of follicular variant papillary thyroid carcinoma (FVPTC) and classical papillary thyroid carcinoma (CPTC) patients. The data of 69034 PTC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The 5-year mortality of CPTC and FVPTC patients receiving surgery, radiation and combination therapy were compared. The univariable and multivariable cox proportional risk models explored the associations between different treatments and the 5-year mortality in CPTC and FVPTC patients. The 5-year mortality of CPTC patients was 2.81% and FVPTC patients was 2.47%. Compared with CPTC receiving lobectomy and/or isthmectomy, those not receiving surgery were associated with increased risk of 5-year mortality [Hazards ratio (HR)=3.27, 95% confidence interval (CI): 2.55-4.20] while total thyroidectomy was correlated with reduced risk of 5-year mortality (HR=0.67, 95%CI: 0.55-0.80). Radioactive iodine (RAI) was linked with decreased risk of 5-year mortality in CPTC patients (HR=0.57, 95%CI: 0.50-0.65). CPTC patients undergoing both surgery and radiation were related to decreased risk of 5-year mortality compared with those receiving surgery only (HR=0.55, 95%CI: 0.48-0.63). CPTC patients receiving neither surgery nor radiation (HR=4.53, 95%CI: 3.72-5.51) or those receiving radiation (HR=1.98, 95%CI: 1.13-3.48) were correlated with elevated risk of 5-year mortality. The elevated risk of 5-year mortality in FVPTC patients was reduced in those undergoing RAI (HR=0.63, 95%CI: 0.51-0.76). In conclusion, combination therapy was associated with decreased risk of 5-year mortality in CPTC and FVPTC patients, which might provide a reference for the management of these patients.

THU224 Is Chronic Lymphocytic Thyroiditis Associated With Aggressive Differentiated Thyroid Cancer In A Predominantly Hispanic Pediatric Population?

Abstract Disclosure: N. Solano: None. D. Baboun: None. A. Martinez-Sanchez: None. A. Diaz: None. A. Carrillo-Iregui: None. F. Alkhoury: None. Background: The risk of developing papillary thyroid carcinoma (PTC) appears to be increased among patients with chronic lymphocytic thyroiditis (CLT). Studies in adults have shown that the presence of CLT is associated with less aggressive PTC; however, this correlation is unclear in pediatric patients. Objective: The purpose of this study is to determine a possible correlation between CLT and markers of aggression severity using histopathological findings, tumor size, and lymph node involvement among patients with differentiated thyroid carcinoma (DTC) in a free-standing children’s hospital with a predominantly Hispanic population. Methods: Upon Institutional Review Board approval, we performed a retrospective chart review from 2012-2022 of 55 patients with a final diagnosis of DTC. We analyzed the correlation between CLT and histopathological findings. Statistical analysis was performed by using t-tests and chi-squared tests. Results: The patients reviewed were between 8-20 years of age. Forty-nine (89.1%) patients identified as Hispanic, and 41 (74.6%) were females. Twenty-five (45.5%) patients had a diagnosis of CLT; 19 (76.0%) of these patients had classic PTC, 3 (12.0%) had the follicular variant of PTC, and 3 (12.00%) had another variant of PTC. Of the 30 (54.5%) patients who did not have CLT, 13 (43.3%) had the classic variant of PTC, 10 (33.3%) had the follicular variant of PTC, and 7 (23.3%) had another variant of PTC. The distribution of the histopathological findings was significant (p=.048). Patients with CLT had significantly smaller tumor sizes (1.8 vs. 2.5 cm, respectively [p=.048]). Of the 36 patients with lymph node involvement, 20 (55.6%) had CLT. Of the 19 patients without lymph node involvement, 5 (26.3%) had CLT. The association between the presence of CLT and lymph node involvement was significant (p=.038). Conclusions: In our population, patients with CLT had a significantly higher presence of the classic variant of PTC. Studies in adults have shown a tendency of these lesions to have a higher risk of disease than those with the follicular variant. Patients with CLT had a smaller tumor size, likely as a result of earlier detection of thyroid nodules due to frequent clinical evaluations and thyroid ultrasounds. However, patients with CLT tended to have a higher frequency of lymph node involvement. More studies with pediatric populations are needed to clarify the possible association between CLT and DTC. Presentation: Thursday, June 15, 2023

SAT542 TDC or Not TDC: Isolated Ectopic Papillary Carcinoma in the Midline Neck with a Benign Native Thyroid

Abstract Disclosure: M. Fasen: None. L. Kosmiski: None. Background: Thyroglossal duct carcinoma is a rare entity, occurring in about 1% of all thyroglossal duct cysts (TDC). Several cases have reported PTC within a thyroglossal duct cyst. Initially thought to be a TDC, we present an unusual case of a midline ectopic papillary thyroid carcinoma with absence of features characteristic of a TDC in the context of benign native thyroid tissue. Clinical Case: A 19 year old female presents to the clinic with a progressively growing midline neck mass over the past five years associated with mild dysphagia. Physical exam was notable for 2 x 2 cm mobile nontender midline mass. Neck ultrasound demonstrated a complex cystic lesion measuring 3.8 x 3.4 x 2.5 cm with partial calcification and mildly vascular. The thyroid itself had no nodules. She underwent a Sistrunk procedure with follow-up pathology revealing 1.6 cm classical PTC that extended into surrounding soft tissue and focal invasion into skeletal muscle without a definitive remnant thyroglossal duct lining despite cystic architecture. The differential included PTC completely replacing the thyroglossal duct cyst, PTC arising from ectopic thyroid tissue or metastatic PTC. Due to the unclear origin of the PTC, decision was made to perform total thyroidectomy. Pathology of the thyroid and four lymph nodes were negative for malignancy confirming a PTC origin from an extra-thyroidal remnant. The patient’s course was complicated by post-operative hypocalcemia resolved with calcitriol and calcium carbonate. She is pending discussion with endocrinology regarding adjuvant radioactive iodine. Conclusion: Thyroglossal duct carcinoma, most commonly papillary carcinoma, is a rare condition that should be considered in patients presenting with cystic midline neck masses. Sistrunk surgery should be performed in all cases for tumor removal. Thyroidectomy in individuals with normal thyroid can be considered due to the probability of concomitant intraglandular thyroid cancer and enables management with adjuvant radio-iodine if needed. In this particular case, PTC was found without evidence of a TDC and suggests PTC arose from ectopic thyroid tissue. Ectopic thyroid tissue can undergo malignant transformation along with the native thyroid gland. There are only a few other reports of isolated ectopic thyroid tissue malignancy with a benign thyroid gland. Presentation Date: Saturday, June 17, 2023

Subcentimetric papillary thyroid carcinoma with extensive lymph node and brain metastasis: case report and review of literature.

We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case. Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival. PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome. Brain metastasis although rare indicate aggressive phenotypic features. Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.

BRAF V600E mutation co-existing with oncogenic mutations is associated with aggressive clinicopathologic features and poor prognosis in papillary thyroid carcinoma

BackgroundThe aim of this study was to evaluate the correlation among mutations in cancer-related genes, clinicopathologic features, and clinical outcome in classical papillary thyroid carcinoma (PTC). Patients and methodsA total of 130 patients with classical PTC who underwent curative surgery between April 2012 and June 2023 at Hokuto Hospital were included. Mutations in targeted regions of 160 cancer-related genes were detected by next-generation sequencing (NGS)-based cancer panel testing. ResultsThe BRAF V600E mutation was detected in 108 (83.1%) of 130 PTC patients. Among the 108 patients with the BRAF V600E mutation, other co-existing oncogenic mutations were found in 12 (9.2%) patients. When we divided into 3 groups of no mutations, BRAF V600E mutation alone, and BRAF V600E and other oncogenic mutations, significant differences were observed in terms of tracheal invasion (P = 0.0024), and bilateral neck lymph node metastasis (P = 0.0047). Kaplan–Meier analysis of overall survival (OS) revealed patients with BRAF V600E and other oncogenic mutations had significantly poorer survival than those with BRAF V600E mutation alone (P = 0.0026). Multivariate cox proportional hazard analysis revealed BRAF V600E and other oncogenic mutations was an independent prognostic factor for OS (HR: 10.559; 95%CI: 1.007-110.656, P = 0.0493). ConclusionsThe BRAF V600E mutation co-existing with other oncogenic mutations but not the BRAF V600E mutation alone was associated with aggressive clinicopathologic features, resulting in poor prognosis in patients with classical PTC. Detection of oncogenic mutations using NGS-based cancer panel testing could enhance understanding of the clinical features of classical PTC.

Detailed fine needle aspiration cytopathology findings of noninvasive follicular thyroid neoplasm with papillary-like nuclear features with nuclear grading correlated to that of biopsy and Bethesda category and systematic review.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses diagnostic challenge in fine needle aspiration cytopathology (FNAC). We aimed first to document our FNAC Bethesda categories (BCs) for all of our NIFTPs and compare our findings with those in the literature with series containing at least 14 cases each. Cases with final histopathological diagnoses of NIFTP and their preoperative FNAC were retrieved from 2006 to 2022 and our cytopathological BCs were documented. Then the slides were re-reviewed in a blinded manner for detailed classification and the results of both the BCs and blinded reclassification were compared with series in the literature for both BCs and detailed cytopathological review of the cases. Thyroid FNACs of 43 out of 86 patients with final NIFTP diagnoses were obtained. Females composed 72.1% (F/M: 31/12); mean age and mean tumor diameter was 47.6 (19-72 years) and 23.4 mm (7-60 mm), respectively. Totally 81.4% (35/43) were classified in the "indeterminate" diagnostic categories; namely 44.2% (19/43) were reported as atypia of undetermined significance (AUS; BC III), 20.9% (9/43) were follicular neoplasm (FN; BC IV), and 16.3% (7/43) were suspicious for malignancy (SM; BC V). No patient was diagnosed as positive for malignancy (BC VI), preoperatively. Detailed cytomorphologic reevaluation revealed heterogeneous cytopathologic findings and nuclear grade (especially nuclear enlargement, membrane irregularity and elongation) significantly increased with respect to BCs. Systematic review confirmed extremely heterogeneous cytomorphologic nature of NIFTP. NIFTPs were categorized most frequently as AUS, followed by FN and SM on FNAC. Our re-review were not able to specify features solely unique to NIFTP alone but may distinguish these cases from classic papillary thyroid carcinoma.