Microscopic Extrathyroidal Extension Research Articles

Diagnostic Accuracy of Preoperative Radiologic Findings in Papillary Thyroid Microcarcinoma: Discrepancies with the Postoperative Pathologic Diagnosis and Implications for Clinical Outcomes.

The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups. In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed. The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery. Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.

Clinicopathological Characteristic of Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma at Dr. Hasan Sadikin Hospital 2016-2021

Background Initial therapy for differentiated thyroid carcinoma (DTC) is thyroidectomy with or without cervical lymph node dissection. Furthermore, radioactive iodine (RAI) is given to patients by considering risk stratification and other patient factors. Although most cases of DTC have a good prognosis after standard therapeutic approaches, the risks of local recurrence and distant metastases can be as high as 20% and 10%. Among these patients, two-thirds showed RAI-refractory. This is concerning because 10-year survival rate is less than 10%. This study aimed to analyze the clinicopathological characteristics of RAI-refractory DTC. Methods This is a case-control study. Data was collected from the Department of Nuclear Medicine and Molecular Theranostics and Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin Hospital, Bandung period 1 January 2016 - 31 December 2021. Results Clinicopathological factors associated with RAI-refractory DTC are age, sex, aggressive histologic subtype, LVI (lymphovascular invasion), m-ETE (microscopic extrathyroid extension), TNM (tumor, nodal, metastasis) stage, and ENE (extranodal extension), with p-value <0.05. Meanwhile, there was no significant difference in the histologic type between RAI-refractory and non-RAI-refractory groups. Conclusion In the pathology report, it is necessary to include prognostically relevant tumor histopathological characteristics. In addition to histologic type, histologic subtype, and tumor size, other features such as presence and extent of capsular invasion, LVI, microscopic and macroscopic ETE, ENE, and number and size of metastatic lymph nodes, have been shown to provide additional prognostic information and are required in standard pathology reports for DTC.

Novel prognostic nomogram for predicting recurrence-free survival in medullary thyroid carcinoma.

Recently, there have been attempts to improve prognostication and therefore better guide treatment for patients with medullary thyroid carcinoma (MTC). In 2022, the International MTC Grading System (IMTCGS) was developed and validated using a multi-institutional cohort of 327 patients. The aim of the current study was to build upon the findings of the IMTCGS to develop and validate a prognostic nomogram to predict recurrence-free survival (RFS) in MTC. Data from 300 patients with MTC from five centres across the USA, Europe, and Australia were used to develop a prognostic nomogram that included the following variables: age, sex, AJCC stage, tumour size, mitotic count, necrosis, Ki67 index, lymphovascular invasion, microscopic extrathyroidal extension, and margin status. A process of 10-fold cross-validation was used to optimize the model's performance. To assess discrimination and calibration, the area-under-the-curve (AUC) of a receiver operating characteristic (ROC) curve, concordance-index (C-index), and dissimilarity index (D-index) were calculated. Finally, the model was externally validated using a separate cohort of 87 MTC patients. The model demonstrated very strong performance, with an AUC of 0.94, a C-index of 0.876, and a D-index of 19.06. When applied to the external validation cohort, the model had an AUC of 0.9. Using well-established clinicopathological prognostic variables, we developed and externally validated a robust multivariate prediction model for RFS in patients with resected MTC. The model demonstrates excellent predictive capability and may help guide decisions on patient management. The nomogram is freely available online at https://nomograms.shinyapps.io/MTC_ML_DFS/.

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.

ATA risk stratification in papillary thyroid microcarcinoma has low positive predictive value when identifying recurrence

BackgroundRising incidence of papillary thyroid microcarcinomas (PTMC) has raised concerns for overdiagnosis. Utility of the American Thyroid Association Risk Stratification System (ATA-RSS) 2015 in predicting risk of disease recurrence in patients with PTMC was assessed. MethodsElectronic health records of patients who underwent total thyroidectomy were queried. ATA-RSS 2015 risk stratification was performed on those with PTMC, and validity for predicting disease recurrence was calculated. ResultsWith 10-year median follow up, recurrence was higher in PTMC patients with high/intermediate vs low ATA risk (33 % vs 4 %, p = 0.002). Sensitivity of ATA-RSS for detecting recurrence was 60 %, specificity 90 %, PPV 33.3 %, NPV 96.6 %, and accuracy 88 %. When microscopic extrathyroidal extension (ETE) was excluded as an intermediate risk criterion, PPV improved to 50 % and accuracy improved to 92.5 % ConclusionsATA-RSS 2015 predicts recurrence in PTMC with high NPV but low PPV. Exclusion of microscopic ETE improved PPV, which may help prevent overtreatment.

A multicenter prospective study of lateral neck lymph node mapping in papillary thyroid cancer.

Despite the high incidence of lateral neck lymph node (LN) metastasis in papillary thyroid cancer (PTC), the management of the lateral neck remains controversial. We aimed to map the draining LNs in the lateral neck using carbon nanoparticles and explore its potential in neck evaluation. We conducted a multicenter, prospective study in PTC patients who had non-palpable yet suspicious metastatic lateral LNs on ultrasound and/or computed tomography (CT) but could not be confirmed by fine needle aspiration. Carbon nanoparticle suspension was injected peritumorally into the thyroid and modified lateral neck dissection was subsequently performed. A total of 154 patients were enrolled for analysis. And 5,070 lateral LNs were removed, of which 1,079 (21.3%) were dyed. The median of dyed LNs was 6 per case (range, 1-33). The distribution of dyed LNs in neck compartments was IV > III > IIA > IIB/V, independent of tumor size, location, multifocality or microscopic extra-thyroidal extension (ETE). Compared with undyed LNs, the probabilities of metastasis in dyed LNs were significantly increased in compartment III, IV, V, and II-V (III: 29.3% vs. 15.4%, P<0.001; IV: 26.3% vs. 14.5%, P<0.001; V: 16.7% vs. 3.3%, P=0.005; II-V: 26.3% vs. 10.0%, P<0.001). The relative risks of metastasis in dyed LNs compared with undyed LNs were 1.90, 1.82, 5.04 and 2.62 in compartment III, IV, V, and II-V, respectively. It was the first prospective multicenter study to map the lateral neck LNs with carbon nanoparticles, which could help surgeons visualize the suspicious LNs during surgery. Instead of unguided LN biopsy, this method has a potential role in lateral neck assessment for indeterminate lateral LNs in PTC.

A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma

Diffuse sclerosing variant papillary thyroid carcinoma (DS-PTC) is characterized clinically by a predilection for children and young adults, bulky neck nodes, and pulmonary metastases. Previous studies have suggested infrequent BRAFV600E mutation but common RET gene rearrangements. Using strict criteria, we studied 43 DS-PTCs (1.9% of unselected PTCs in our unit). Seventy-nine percent harbored pathogenic gene rearrangements involving RET, NTRK3, NTRK1, ALK, or BRAF; with the remainder driven by BRAFV600E mutations. All 10 pediatric cases were all gene rearranged (P = .02). Compared with BRAFV600E-mutated tumors, gene rearrangement was characterized by psammoma bodies involving the entire lobe (P = .038), follicular predominant or mixed follicular architecture (P = .003), pulmonary metastases (24% vs none, P = .04), and absent classical, so-called “BRAF-like” atypia (P = .014). There was no correlation between the presence of gene rearrangement and recurrence-free survival. Features associated with persistent/recurrent disease included pediatric population (P = .030), gene-rearranged tumors (P = .020), microscopic extrathyroidal extension (P = .009), metastases at presentation (P = .007), and stage II disease (P = .015). We conclude that DS-PTC represents 1.9% of papillary thyroid carcinomas and that actionable gene rearrangements are extremely common in DS-PTC. DS-PTC can be divided into 2 distinct molecular subtypes and all BRAFV600E-negative tumors (1.5% of papillary thyroid carcinomas) are driven by potentially actionable oncogenic fusions.

Extrathyroidal extension or tumor size of primary lesion influences thyroid cancer outcomes.

Extrathyroidal extension (ETE) is a determined factor of T3 and T4 stage of differentiated thyroid cancer (DTC) in American Joint Committee on Cancer. We aimed to compare clinical outcomes between different extent of ETE according to tumor size. Patients diagnosed with DTC were collected from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. They were categorized into two groups by presence of lymph node metastases (LNM) or distant metastases (DM): group A: no presence of LNM and DM, and group B: presence of LNM or DM. Each group was further divided into four groups according to tumor size: <1 cm, 1-2 cm, 2-4 cm, >4 cm. ETE was divided into three groups by the extent: no ETE, microscopic ETE, and macroscopic ETE. Kaplan-Meier method and log-rank test were used to analyze cancer-specific survival (CSS). 91,975 patients were included. In groups A and B, for tumor size 1 cm, there was no significant difference in CSS between no ETE and microscopic ETE, while a significant difference was observed between no ETE and macroscopic ETE. For tumor size >1 cm, there were significant differences in CSS (both no ETE vs. micro ETE and no ETE vs. macro ETE). We suggests that when tumor size is more than 1 cm, micro ETE is significantly associated with poorer outcome. T3 and T4 stages may take account into tumor size rather than merely based on the presence and extent of ETE. It may be prudent to revisit the omission of micro ETE in TNM staging.

Does total tumour diameter, multifocality, number of tumour foci, or laterality predict lymph node metastasis or recurrence in differentiated thyroid cancer?

Data regarding laterality, focality, or total tumour diameter (TTD) in papillary thyroid cancer (PTC) are limited. We aimed to investigate the impact of focality, TTD, number of tumour foci, or laterality on aggressive features in PTC. Patients were categorized based on maximum tumour diameter (MTD) (≤ 10 vs. > 10 mm), focality, laterality, or the number of tumour foci (1/2/ ≥ 3). We also categorized the patients as follows: Group 1, unifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 2, multifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 3, multifocal microcarcinoma (MTD ≤ 10/TTD > 10 mm); Group 4, unifocal macrocarcinoma (MTD > 10/TTD > 10 mm); Group 5, multifocal macrocarcinoma (MTD > 10/TTD > 10 mm). The mean diagnosis age (n = 511) was 44.7 (± 12.7) years, the majority of the patients were < 55 years old (n = 310) and female (n = 416). An increasing number of tumour foci were associated with a higher MTD or TTD, a higher ratio of extrathyroidal extension (ETE), vascular or lymphatic invasion, lymph node metastasis (LNM) or distant metastasis, or the need for radioactive iodine (RAI). There was no difference in the parameters between Group 3 and Group 2, or Group 4. Vascular invasion, American Thyroid Association high risk, LNM at diagnosis, and RAI total dose were higher in Group 5 than in Group 3. Microscopic or macroscopic ETE, T1b, and T4a were positive predictors for recurrence. Male sex, multifocality, number of tumour foci (≥ 3), MTD (> 10 mm), TTD (> 10 mm), Group 5, microscopic or macroscopic ETE, lymphatic or vascular invasion, RAI need, T2, and T4b were positive predictors for LNM. MTD and TTD increase the risk of LNM but not the recurrence in PTC. TTD, multifocality, and bilaterality can be considered risk factors in PTC staging systems and risk calculators.

Impact of microscopic extrathyroidal extension on differentiated thyroid cancer post-surgical risk of recurrence: a retrospective analysis

PurposeIn the last edition of the American Joint Committee on Cancer (AJCC) staging system, differentiated thyroid cancers (DTC) showing microscopic extrathyroidal extension (mETE) are considered comparable to intrathyroidal cancers for their clinical behavior and prognosis. The aim of the study is to evaluate the impact of this updated assessment of T, when applied to the postoperative recurrence risk stratification, according to the American Thyroid Association Guidelines (ATA-RR).MethodsOne-hundred DTC patients who underwent total thyroidectomy were retrospectively evaluated. The downstaging of mETE was introduced in the definition of T, and the updated classification defined as modified ATA-RR (ATAm-RR). For each patient, post-surgical basal and stimulated thyroglobulin (Tg) levels, neck ultrasound (US) and post-ablative 131-I whole body scan (WBS) reports were considered. The predictive performance (PP) of disease recurrence was calculated both for each single parameter, as well as for all of them.ResultsAccording to ATAm-RR classification, 19/100 patients (19%) were downstaged. ATA-RR proved a significant PP for disease recurrence (DR) (sensitivity 75.0%, specificity 63.0%, p = 0.023). However, ATAm-RR performed slightly better due to an increased specificity (sensitivity 75.0%, specificity 83.7%, p < 0.001). For both classifications, the PP was optimal when all the above-mentioned predictive parameters were considered.ConclusionOur results suggest that the new assessment of T considering mETE resulted in a downgrading of ATA-RR class in a significant number of patients. This provides a better PP for disease recurrence, and the best PP was obtained when considering the whole predictive variables together.

Perineural Invasion in Papillary Thyroid Cancer: A Rare Indicator of Aggressive Disease.

Perineural invasion (PNI) is associated with aggressive tumor behavior, increased locoregional recurrence, and decreased survival in many carcinomas. However, the significance of PNI in papillary thyroid cancer (PTC) is incompletely characterized. Patients diagnosed with PTC and PNI from 2010-2020 at a single, academic center were identified and matched using a 1:2 scheme to patients without PNI based on gross extrathyroidal extension (ETE), nodal metastasis, positive margins, and tumor size (±4 cm). Mixed and fixed effects models were used to analyze the association of PNI with extranodal extension (ENE)-a surrogate marker of poor prognosis. In total, 78 patients were included (26 with PNI, 52 without PNI). Both groups had similar demographics and ultrasound characteristics preoperatively. Central compartment lymph node dissection was performed in most patients (71%, n = 55), and 31% (n = 24) underwent a lateral neck dissection. Patients with PNI had higher rates of lymphovascular invasion (50.0% vs. 25.0%, p = 0.027), microscopic ETE (80.8% vs. 44.0%, p = 0.002), and a larger burden [median 5 (interquartile range [IQR] 2-13) vs. 2 (1-5), p = 0.010] and size [median 1.2 cm (IQR 0.6-2.6) vs. 0.4 (0.2-1.4), p = 0.008] of nodal metastasis. Among patients with nodal metastasis, those with PNI had an almost fivefold increase in ENE [odds ratio [OR] 4.9 (95% confidence interval [CI] 1.5-16.5), p = 0.008] compared with those without PNI. More than a quarter (26%) of all patients had either persistent or recurrent disease over follow-up (IQR 16-54 months). PNI is a rare, pathologic finding that is associated with ENE in a matched cohort. Additional investigation into PNI as a prognostic feature in PTC is warranted.

Incidental Node Metastasis as an Independent Factor of Worse Disease-Free Survival in Patients with Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) have high node metastasis rates. Occasionally after thyroidectomy, the pathological report reveals node metastasis unintentionally resected. The present study aimed to evaluate the prognosis of these patients. A retrospective cohort of patients submitted to thyroidectomy with or without central compartment neck dissection (CCND) due to PTC with a minimum follow-up of five years. A total of 698 patients were included: 320 Nx, 264 pN0-incidental, 37 pN1a-incidental, 32 pN0-CCND and 45 pN1a-CCND. Patients with node metastasis were younger, had larger tumors, higher rates of microscopic extra-thyroidal extension, and angiolymphatic invasion and most received radioiodine therapy. Treatment failure was higher in patients pN1a-incidental and pN1a-CCND (32% and 16%, respectively; p < 0.001-Chi-square test). Disease-free survival (DFS) was lower in patients pN1a-incidental compared to patients Nx and pN0-incidental (p < 0.001 vs. Nx and pN0-incidental and p = 0.005 vs. pN0-CCND) but similar when compared to patients pN1a-CCND (p = 0.091)-Log-Rank test. Multivariate analysis demonstrated as independent risk factors: pT4a (HR = 5.524; 95%CI: 1.380-22.113; p = 0.016), pN1a-incidental (HR = 3.691; 95%CI: 1.556-8.755; p = 0.003), microscopic extra-thyroidal extension (HR = 2.560; 95%CI: 1.303-5.030; p = 0.006) and angiolymphatic invasion (HR = 2.240; 95%CI: 1.077-4.510; p = 0.030). Patients that were pN1a-incidental were independently associated with lower DFS.

Thyroid Collision Tumors: The Presence of the Medullary Thyroid Carcinoma Component Negatively Influences the Prognosis.

The retrospective study included 69 cases diagnosed with TCTs (with simultaneous MTC and PTC components), MTC and PTC. All tumors were comparatively assessed for the classical histopathological prognostic features, including a new grading system for MTC. The main component of TCTs had more frequent microscopic extrathyroidal extension (mETE) (p = 0.000), lymphovascular invasion (LVI) (p = 0.000), perineural invasion (PNI) (p = 0.044), and lymph node metastasis (p = 0.042). Additionally, the TCTs' MTC component presented with more frequent LVI (p = 0.010). Comparing TCTs' MTC and PTC components with MTC-only tumors and PTC-only tumors revealed that only the TCTs' MTC components had statistically significant more frequent mETE (p = 0.010) than MTC-only tumors. When applied to the MTC component of TCTs, the pathological parameters of the new grading system of MTC showed no correlations with other microscopic or clinical aspects. Using classical pathological prognostic features, the comparative analysis revealed that the main TCTs' component was more aggressive than the minor one. Contrary to PTCs, in TCTs, the medullary component was more aggressive than the papillary one, but also more aggressive than MTC-only tumors.

Is multifocality a risk factor in low-risk papillary thyroid cancer?

Multifocality in papillary thyroid cancer (PTC) is a common event, ranging from 18% to 87%. Additional multiple foci are frequently very small and generally detected in pathology specimens. The mechanisms of intrathyroidal spread, and its correlation with age, gender, tumour size, and lymph node metastases remain unclear. Moreover, studies assessing the prognostic impact of PTC multifocality have yielded non-univocal results. We aimed to evaluate the following: a) the histopathological and clinical characteristics associated with multifocal PTC; and b) the impact of multifocality on the long-term outcome. We analysed a consecutive series of 2814 PTC patients without evidence of microscopic extrathyroidal extension (T1a, T1b, and T2), all of whom had undergone total thyroidectomy and were followed-up (median 4.7 years) in our thyroid clinic. Females comprised 81.3% and males 18.7% (F/M = 4.4/1), with a median age at diagnosis of 45.0 years. Patients were subdivided into 2 groups: 72.7% unifocal tumour and 27.3% multifocal tumour. Post-surgical radioiodine ablation (RAI) (30-100 mCi of 131-I) was performed in 1425 (50.6%) patients. All patients were periodically followed with thyroglobulin and anti-thyroglobulin antibodies measurements and with neck ultrasonography under L-thyroxine therapy and subjected to additional radioiodine administration or another therapeutic measure if not cured. Patients in the multifocal group were older (median age 46.4 vs. 44.5 years, respectively, p < 0.05) and presented a lower F/M ratio (F/M = 3.7/1 and 4.7/1; p = 0.01). T1a and T1b tumours showed no significant difference in multifocality rate whereas T2 tumours were less frequently multifocal (14.2% vs. 10.9%, p < 0.05). Multifocal tumours were more frequent in N1b (11.3% vs. 7.8%, p < 0.01) and less frequent in Nx (50.5% vs. 56.8%, p < 0.01), with no difference between the N0 and N1a groups. The clinical outcome was similar in the 2 group of patients (88.2 % in the unifocal group vs. 90.2% in the multifocal group). Multifocality is more frequent in older and male patients, in smaller tumours, and in N1b. However, multifocality "per se" was not associated, in our study, with worse clinical outcome in PTC patients.

Risk staging with prophylactic unilateral central neck dissection in low-risk papillary thyroid carcinoma

ObjectiveCurrent guidelines favor thyroid lobectomy for intrathyroidal cT1bT2cN0 papillary thyroid carcinoma. Prophylactic neck dissection (PND) is not recommended for these low-risk tumors due to the lack of high-level evidence on improvement in outcomes, but the information from PND may be used for staging. The aim of this study was to evaluate the rate of upstaging with ipsilateral PND. Materials and methodsRetrospective study of patients with intrathyroidal unifocal cT1bT2cN0 papillary thyroid carcinoma from 2008 to 2021. All patients underwent total thyroidectomy and PND. Tumors were classified as low or intermediate risk based on the information from pathological analysis of the primary tumor and then from adding the analysis of the lymph nodes. The difference between the tumor-only and the PND-added risk staging was evaluated. ResultsThree hundred three patients (241 women, median age 45, median tumor size 17 mm) were included. Microscopic extrathyroidal extension was found in 23.4%, aggressive histology in 6.6%, vascular invasion in 29.3%, and lymph node metastases in 37.3%. One hundred ten patients (36.3%) were intermediate-risk based on the primary tumor. An additional 26 (8.6%) were upstaged to intermediate-risk based on the ipsilateral PND and 2% based on the contralateral PND. Kaplan-Meier 10-year event-free survival in tumors upstaged with ipsilateral PND was not statistically different from intermediate-risk tumors based on the primary tumor characteristics (92% versus 90.9%, Log Rank p = 0.943). ConclusionsIpsilateral PND upstaged low-risk cT1bT2cN0 patients to intermediate risk in only 8.6% of cases, and contralateral PND in an additional 2%. Routinely performing PND may not be warranted.

Association of comprehensive thyroid cancer molecular profiling with tumor phenotype and cancer-specific outcomes

BackgroundMolecular testing improves the diagnostic accuracy of thyroid cancer. Whether specific molecular testing results are associated with tumor phenotype or provide prognostic information needs further delineation. MethodsConsecutive thyroid cancer patients after index thyroidectomy with ThyroSeq version 3 (Rye Brook, NY) molecular testing obtained on preoperative fine-needle aspiration or thyroidectomy specimens from patients with thyroid cancer were categorized into 3 molecular risk groups based on detected mutations, fusions, copy number alterations, and/or gene expression alterations and correlated with histopathology and recurrence, defined as biochemical or structural. ResultsOf 578 patients, 49.9%, 37.5%, and 12.6% had molecular risk group–low, molecular risk group–intermediate, and molecular risk group–high cancers, respectively. With a median 19-month follow-up, 9.1% patients recurred. Compared with molecular risk group–low, molecular risk group–intermediate cancers were diagnosed in younger patients and more often had microscopic extrathyroidal extension, involved margins, and nodal disease. Compared with molecular risk group–intermediate, molecular risk group–high cancers were diagnosed in older patients and more often had gross extrathyroidal extension and vascular invasion. In multivariable analysis, recurrence was more likely in molecular risk group–high cancers than in molecular risk group–intermediate (hazard ratio = 4.0; 95% confidence interval, 1.9–8.6; P < .001) and more likely in molecular risk group–intermediate than in molecular risk group–low (hazard ratio = 5.0; 95% confidence interval, 2.0–12.5; P < .001). ConclusionUsing modern comprehensive genotyping, the genetic profile of thyroid cancers can be categorized into 3 novel molecular risk groups that were associated with histopathologic phenotype and recurrence in short-term follow-up.

Predictive value of ultrasonic features and microscopic extrathyroidal extension in the recurrence of PTC

PurposeTo determine the clinical value of ultrasonic features, especially extrathyroidal extension (ETE), in the prediction of PTC recurrence. MethodA total of 863 patients with PTC confirmed by pathological examinations from January 2012 to August 2018 were selected in this study, including 59 cases of recurrence. The Cox-proportional hazards regression analysis and Kaplan-Meier method were adopted to determine the relationship between the variables and recurrence free survival (RFS). ResultsThe recurrence rate of PTC is 6.8 %. Tumor maximum diameter, margin, multifocality, microcalcifications, ETE and preoperative lymph node metastasis were valuable predictive factors in univariate survival analysis. Tumor larger than 20 mm, multifocality and lateral cervical lymph node metastasis were independent risk factors for PTC recurrence, and lymph node metastasis has the highest hazard ratio (HR). Preoperative lateral cervical lymph node metastasis was more often found in the gross and extensive ETE groups. Microscopic ETE has little value in predicting PTC recurrence and has no correlation with preoperative cervical lymph node metastasis. ConclusionsTumor maximum diameter >20 mm, multifocality and lateral cervical lymph node metastasis were independent risk factors for PTC recurrence. Preoperative lateral cervical lymph nodes should be carefully examined when gross ETE and extensive ETE were detected. Microscopic ETE has no impact on preoperative cervical lymph node metastasis or tumor recurrence.

Radioactive Iodine Ablation Can Reduce the Structural Recurrence Rate of Intermediate-Risk Papillary Thyroid Microcarcinoma: A Meta-Analysis.

Background The incidence of papillary thyroid microcarcinoma (PTMC) has significantly increased in recent years, and the decision to use radioactive iodine (RAI) ablation in low-risk (LR) and intermediate-risk (IR) patients is controversial. The aim of this study was to evaluate whether RAI ablation can reduce the recurrence rate in LR-IR PTMC patients. Methods A comprehensive literature search of the PubMed, Embase, Cochrane Library, and Web of Science was conducted according to the PRISMA statement. Results There were 8 studies in English that fit our search strategy, and a total of 2847 patients were evaluated. The results of the meta-analysis showed RAI ablation in LR-IR PTMC patients did not reduce cancer recurrence (risk radio (RR) 0.56, 95% CI 0.19-1.70, P = 0.31). Nevertheless, we further performed data analysis and found that IR PTMC patients without RAI ablation had a higher rate of cancer recurrence than those who underwent RAI ablation (RR 0.23, 95% CI 0.11-0.49, P = 0.0001). Furthermore, patients with risk factors for lymph node metastasis (RR 0.16, 95% CI 0.06-0.42, P = 0.0002), microscopic extrathyroidal extension (RR 0.19, 95% CI 0.06-0.60, P = 0.005), and multifocality (RR 0.13, 95% CI 0.04-0.45, P = 0.001) in the absence of RAI ablation were more likely to have recurrence. Conclusions Based on our current evidence, RAI ablation can reduce the cancer recurrence rate over 5 years in IR PTMC patients, especially when patients have some risk factors, such as lymph node metastasis, microscopic extrathyroidal extension, and multifocality.

Prognostic Impact of Microscopic Extra-Thyroidal Extension (mETE) on Disease Free Survival in Patients with Papillary Thyroid Carcinoma (PTC).

Simple SummaryMicroscopic extra-thyroidal extension (mETE) in papillary thyroid carcinoma (PTC) has shown no effect on survival but controversy remains regarding its impact on disease recurrence. As it was removed from the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) classification in 2017, PTC tumors previously classified as pT3 are now downstaged to pT1 and pT2 tumors. This might imply that such tumors now need less aggressive treatments, especially complementary radioactive iodine treatment. We ought to assess if mETE remains a poor prognosis risk factor that still needs to be taken into account in the post-operative treatment strategy.Background: This study assessed the risk of reduced disease-free survival (DFS) and poor clinical outcome in patients with papillary thyroid carcinomas (PTC) with microscopic extra-thyroidal extension (mETE), as compared to PTC patients without mETE. Methods: Retrospective analysis of a prospective database of patients treated by total thyroidectomy and radioactive iodine (RAI) with a five-year follow-up and tumors < 40 mm. In total, 303 patients were analyzed: 30.7% presented tumors with mETE, and 69.3% without. mETE was defined as extra-thyroidal invasion without skeletal muscle involvement. The primary outcome, DFS, was defined as the interval between initial treatment and any subsequent PTC-related treatment. The second outcome was the clinical status at five years. Results: In univariate analyses, the five-year DFS was significantly lower for tumors with mETE (62.4% versus 88.1%, p < 0.001). In multivariate analysis, mETE and massive lymph node involvement (LNI) were independent prognostic factors, associated respectively with a hazard ratio of 2.55 (95% CI 1.48–4.40) and 8.94 (95% CI 4.92–16.26). mETE was significantly associated with a pejorative clinical outcome at five years, i.e., biochemical/indeterminate response and structural persistence (Respectively OR 1.83 (95% CI 0.83; 4.06) and OR 4.92 (95% CI 1.87; 12.97)). Conclusion: Our results suggest that mETE is an independent poor prognosis factor of reduced DFS and predictive of poor clinical outcome.

Tall Cell Histology – Comparison of T1 Tall Cell Variant and Classical Papillary Thyroid Carcinoma

<h3>Purpose/Objective(s)</h3> Tall cell histology in papillary thyroid carcinoma (PTC) is considered intermediate risk on ATA guidelines. However, it is unclear if patients with T1 tumors with tall cell histology require aggressive treatment. The objective of our study was to compare pathology and outcomes of patients with tall cell histology with that of classical PTC in T1 disease. <h3>Materials/Methods</h3> The study cohort was selected from our departmental database of differentiated thyroid cancers treated surgically between 1985 and 2015 (n=6,259). PTC cases demonstrating ≥30% tall cells were considered as tall cell variant (TCV). All T1 classical PTC and TCV were identified. Patient and tumor characteristics were compared between groups by Fisher exact test, chi-squared test or two sample t test. Survival and recurrence outcomes were compared using the log-rank test and Kaplan-Meier method. <h3>Results</h3> There were 712 TCV and 2,354 classical PTC patients with T1 tumors. Total thyroidectomy and lobectomy were done in 622 and 90 TCV patients compared to 1883 and 471 classical PTC patients. Central neck dissection was done in 140 TCV and 420 classical PTC patients. Lateral neck dissection was done in 89 TCV and 323 PTC patients. 208 and 87 TCV patients were N1a and N1b compared to 385 and 306 classical PTC patients. There was no significant difference between TCV and classical PTC in gender, age >55 years and vascular invasion. Compared to classical PTC, TCV cases were significantly more likely to demonstrate microscopic extrathyroidal extension (p<0.01), multifocality (p<0.01), larger size (mean 1.30cm in tall cell and 1.15cm in classical PTC) (p=0.02), less encapsulation (p<0.01) and treatment with radioactive iodine (p<0.01). Rates of central nodal disease were significantly higher in TCV cases (p<0.01), but there was no significant difference in rates of lateral nodal disease (p=0.61). There was no significant difference in overall survival (p=0.73), disease-specific survival (p=0.69) or locoregional recurrence (p=0.08). Of those that underwent lobectomy only, there was no significant difference in locoregional recurrence between classical PTC and TCV cases (p=0.79). For TCV cases only, there was no significant difference in locoregional recurrence between those that underwent lobectomy compared to those that had total thyroidecomy (p=0.08). <h3>Conclusion</h3> Despite having a higher rate of microscopic extrathyroidal extension and regional metastases, patients with T1 tall cell tumors have similar oncologic outcomes to patients with classical PTC.