PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma: A Multi-institutional Study.

Anti-PD immunotherapy is currently under investigation in anaplastic thyroid carcinoma (ATC). Tumor cell surface PD-L1 expression is considered predictive of therapeutic response. Although papillary thyroid carcinoma has been widely studied for PD-L1 expression, there are limited data on ATC. In this retrospective multi-institutional study involving 9 centers across Asia, 179 ATCs were assessed for PD-L1 expression using the SP263 (Ventana) clone. A tumor proportion score (TPS) ≥1% was required to consider a case PD-L1-positive. PD-L1 expression was compared with the histological patterns, the type of specimen (small or large), tumor molecular profile (BRAF V600E and TERT promoter mutation status), and patient outcome. PD-L1 expression in any co-existent differentiated thyroid carcinoma (DTC) was evaluated separately and compared with ATC. Most ATCs (73.2%) were PD-L1-positive. The median TPS among positive cases was 36% (IQR 11% to 75%; range 1% to 99%). A high expression (TPS ≥ 50%) was noted in 30.7%. PD-L1-negative cases were more likely to be small specimens (P=0.01). A negative result on small samples, hence, may not preclude expression elsewhere. ATCs having epithelioid and pleomorphic histological patterns were more likely to be PD-L1-positive with higher TPS than sarcomatoid (P<0.01). DTCs were more frequently negative and had lower TPS than ATC (P<0.01). Such PD-L1 conversion from DTC-negative to ATC-positive was documented in 71% of cases with co-existent DTC. BRAF V600E, but not TERT promoter mutations, correlated significantly with PD-L1-positivity rate (P=0.039), reinforcing the potential of combining anti-PD and anti-BRAF V600E drugs. PD-L1 expression, however, did not impact the patient outcome.

Seven years of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Rate of Acceptance and Variation of Diagnostic Approaches Across Different Continents.

CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

Modified surgical fusion: VATS and BABA approach for ectopic intrathoracic and cervical thyroidectomy.

Ectopic goitre, presenting as an isolated thoracic mass without connection to the main thyroid gland enlargement, is a rare occurrence. We describe a case where a patient reported persistent dry cough and back pain for 1 year, along with throat discomfort unresponsive to medication. A 2×1 cm swelling was noted over the right anterior aspect of the neck. Extensive evaluation, including chest X-rays and contrast-enhanced CT of the thorax, revealed a mediastinal mass suggestive of an ectopic thyroid.This case presents a distinctive scenario involving the simultaneous presence of ectopic mediastinal and cervical thyroid lesions. Both were effectively managed using a minimally invasive approach, combining video-assisted thoracic surgery for the excision of the mediastinal mass and a bilateral axillo-breast approach for the cervical lesion in a single procedure. This approach yielded minimal morbidity, aesthetically pleasing outcomes and rapid recovery. Remarkably, such a case has not been previously documented in the available literature.

Assessment of prognostic factors in pediatric adrenocortical tumors: the modified pediatric S-GRAS score in an international multicenter cohort-a work from the ENSAT-PACT working group.

OBJECTIVE: Pediatric adrenocortical carcinoma (pACC) is rare, and prognostic stratification remains challenging. We aimed to confirm the prognostic value of the previously published pediatric scoring system (pS-GRAS) in an international multicenter cohort. DESIGN: Analysis of pS-GRAS items of pACC from 6 countries in collaboration of ENSAT-PACT, GPOH-MET, and IC-PACT. METHODS: We received patient data of the pS-GRAS items including survival information from 9 centers. PS-GRAS score was calculated as a sum of tumor stage (1 = 0; 2-3 = 1; 4 = 2 points), grade (Ki67 index: 0%-9% = 0; 10%-19% = 1; ≥20% = 2 points), resection status (R0 = 0; RX/R1/R2 = 1 point), age (<4 years = 0; ≥4 years = 1 point), and hormone production (androgen production = 0; glucocorticoid-/mixed-/no-hormone production = 1 point) generating 8 scores and 4 groups (1: 0-2, 2: 3-4, 3: 5, 4: 6-7). Primary endpoint was overall survival (OS). RESULTS: We included 268 patients with median age of 4 years. The analysis of the pS-GRAS score showed a significantly favorable prognosis in patients with a lower scoring compared to higher scoring groups (5-year OS: Group 1 98%; group 2 87% [hazard ratio {HR} of death 3.6, 95% CI of HR 1.6-8.2]; group 3 43% [HR of death 2.8, 95% CI 1.9-4.4]; group 4: OS 18% [HR of death 2.1, 95% CI 1.7-2.7]). In the multivariable analysis, age (HR of death 3.5, 95% CI 1.8-7.0), resection status (HR of death 5.5, 95% CI 2.7-11.1), tumor stage (HR of death 1.9, 95% CI of HR 1.2-3.0), and Ki67 index (HR of death 1.7, 95% CI 1.2-2.4) remained strong independent outcome predictors. Especially infants < 4 years showed more often low-risk constellations with a better OS for all tumor stages. CONCLUSION: In an international multicenter study, we confirmed that the pS-GRAS score is strongly associated with overall survival among patients with pACC. Age, resection status, stage, and Ki67 index are important parameters for risk stratification.

Quality of Life in Patients Undergoing Endoscopic Thyroidectomy Versus Conventional Open Thyroidectomy: Interim Results From Randomized Trial.

OBJECTIVE: We determined whether endoscopic thyroidectomy (ET) is associated with better health-related quality of life (QoL) compared with open thyroidectomy. METHODS: We randomly assigned 28 patients aged older than 18 years, Bethesda IV or less on cytology and gland volume of <40 mL to undergo hemithyroidectomy through either open or endoscopic (axillo-breast approach/bilateral axillo-breast approach) technique. The primary outcome was QoL scores on the Short Form-36 and Thyroid-Specific Questionnaire at 2, 6, and 12 weeks postsurgery. Secondary outcomes were postoperative complications, hospital stay, and pain scores. RESULTS: The generic QoL scores based on Short Form-36 were statistically nonsignificant between the two groups. QoL scores based on Thyroid-Specific Questionnaire were statistically significant (P < 0.05) favoring open thyroidectomy in the following domains: (1) numbness at 2, 6, and 12 weeks (P = 0.04, 0.004, and 0.005, respectively), (2) shoulder impairment at 2 weeks (P = 0.017), and (3) favoring ET in cosmesis at 6 and 12 weeks (P = 0.037 and 0.02, respectively). ET has longer operative time (104.6 ± 25.4 vs 123 ± 8.9 min; P = 0.03), longer hospital stays (2.8 ± 0.4 vs 2.4 ± 0.5; P = 0.056) and higher pain scores at 2 and 6 weeks (P = 0.007 and 0.012, respectively) but decreased intraoperative bleeding (33.5 ± 6.4 vs 29.1 ± 3.7 mL; P = 0.037). CONCLUSION: ET has higher cosmetic satisfaction, increased numbness, and shoulder movement impairment during short-term postsurgery follow-up. Both techniques are similar in impacting general physical, mental, and social health-related QoL. (Clinical Trials Registry of India, Reg. No. CTRI/2020/07/026374).

Identification of potential targetable genes in papillary, follicular, and anaplastic thyroid carcinoma using bioinformatics analysis.

PURPOSE: To perform an extensive exploratory analysis to build a deeper insight into clinically relevant molecular biomarkers in Papillary, Follicular, and Anaplastic thyroid carcinomas (PTC, FTC, ATC). METHODS: Thirteen Thyroid Cancer (THCA) datasets incorporating PTC, FTC, and ATC were derived from the Gene Expression Omnibus. Genes differentially expressed (DEGs) between THCA and normal were identified and subjected to GO and KEGG analyses. Multiple topological properties were harnessed and protein-protein interaction (PPI) networks were constructed to identify the hub genes followed by survival analysis and validation. RESULTS: There were 70, 87, and 377 DEGs, and 23, 27, and 53 hub genes for PTC, FTC, and ATC samples, respectively. Survival analysis detected 39 overall and 49 relapse-free survival-relevant hub genes. Six hub genes, BCL2, FN1, ITPR1, LYVE1, NTRK2, TBC1D4, were found common to more than one THCA type. The most significant hub genes found in the study were: BCL2, CD44, DCN, FN1, IRS1, ITPR1, MFAP4, MKI67, NTRK2, PCLO, TGFA. The most enriched and significant GO terms were Melanocyte differentiation for PTC, Extracellular region for FTC, and Extracellular exosome for ATC. Prostate cancer for PTC was the most significantly enriched KEGG pathway. The results were validated using TCGA data. CONCLUSIONS: The findings unravel potential biomarkers and therapeutic targets of thyroid carcinomas.

Subcutaneous panniculitis-like T-cell lymphoma: fever and facial swelling with hemophagocytic syndrome.

We report a case of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a young man presenting with fever and facial swelling. He had pancytopenia and hemophagocytic syndrome (HPS) on evaluation. The histopathological examination of skin punch biopsy from the face and chest wall showed SPTCL. Given the associated HPS, he was started on steroid and multidrug chemotherapy following which he had symptomatic improvement.

Deciphering pancreatic neuroendocrine tumors: Unveiling through circulating small extracellular vesicles.

The survival rate over a five-year period for rare pancreatic neuroendocrine tumors (PanNET) is notably lower compared to other neuroendocrine tumors due to late-stage detection, which is a consequence of the absence of suitable diagnostic markers; therefore, there exists a critical need for an early-stage biomarker-specific to PanNETs. This study introduces a novel approach, investigating the impact of small extracellular vesicles (sEV) in PanNET growth and metastasis. As proof of concept, this study shows a correlation between sEV concentration in controls and PanNET. Notably, higher sEV concentrations were observed in PanNETs than in controls (p < 0.0001) with a sensitivity of 100%. Further, apparent differences were observed in the sEV concentrations between controls and grades 1 PanNET (p = 0.005). The expression of sEV markers was confirmed using CD63, TSG101, CD9, Flotillin-1, and GAD65 antibodies. Additionally, the expression of cancer marker BIRC2/cIAP1 (p = 0.002) and autophagy marker Beclin-1 (p = 0.02) were observed in plasma-derived sEVs and PanNET tissue. This study represents the first to indicate the increased secretion of sEV in PanNET patients' blood plasma, proposing potential function of sEV as a new biomarker for early-stage PanNET detection.

Head-to-Head Comparison of SSTR Antagonist [68Ga]Ga-DATA5m-LM4 with SSTR Agonist [68Ga]Ga-DOTANOC PET/CT in Patients with Well Differentiated Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Imaging Study.

Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [68Ga]Ga-DOTANOC and [68Ga]Ga-DATA5m-LM4 in the detection of primary and metastatic lesions in patients with well differentiated gastroenteropancreatic (GEP) NETs. Histologically proven GEP-NET patients underwent [68Ga]Ga-DOTANOC & [68Ga]Ga-DATA5m-LM4 PET/CT scans, which were analyzed. The qualitative analysis involved the visual judgment of radiotracer uptake validated by the morphological findings using CT, which was considered as the reference standard. Quantitative comparisons were presented as the standardized uptake value (SUV) corrected for lean body mass: SULpeak, SULavg, and tumor-to-background ratios (TBR). In total, 490 lesions were confirmed via diagnostic CT. The lesion-based sensitivity of [68Ga]Ga-DATA5m-LM4 PET/CT was 94.28% (462/490) and 83.46% (409/490) for [68Ga]Ga-DOTANOC PET/CT (p < 0.0001). [68Ga]Ga-DATA5m-LM4 had statistical significance over [68Ga]Ga-DOTANOC in liver metastases [100% vs. 89.4%; p < 0.0001 (292 vs. 253 {283 lesions on CT})] and bone metastases [100% vs. 82.9%; p = 0.005 (45 vs. 34 {41 lesions on CT})]. Statistical significance was also noted for the TBR SULpeak of the primary and liver lesions. [68Ga]Ga-DATA5m-LM4 showed better sensitivity and a higher target-to-background ratio than [68Ga]Ga-DOTANOC PET/CT. [68Ga]Ga-DATA5m-LM4 PET/CT can be used to quantify the extent of skeletal and liver metastases for better planning of SSTR agonist- or antagonist-based therapy.

Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study.

Differentiating BRAF V600E- and RAS-altered encapsulated follicular-patterned thyroid tumors based on morphology remains challenging. This study aimed to validate an 8-score scale nuclear scoring system and investigate the importance of nuclear pseudoinclusions (NPIs) in aiding this differentiation. A cohort of 44 encapsulated follicular-patterned tumors with varying degrees of nuclear atypia and confirmed BRAF V600E or RAS alterations was studied. Nuclear parameters (area, diameter, and optical density) were analyzed using a deep learning model. Twelve pathologists from eight Asian countries visually assessed 22 cases after excluding the cases with any papillae. Eight nuclear features were applied, yielding a semi-quantitative score from 0 to 24. A threshold score of 14 was used to distinguish between RAS- and BRAF V600E-altered tumors. BRAF V600E-altered tumors typically demonstrated higher nuclear scores and notable morphometric alterations. Specifically, the nuclear area and diameter were significantly larger, and nuclear optical density was much lower compared to RAS-altered tumors. Observer accuracy varied, with two pathologists correctly identifying genotype of all cases. Observers were categorized into proficiency groups, with the highest group maintaining consistent accuracy across both evaluation methods. The lower group showed a significant improvement in accuracy upon utilizing the 8-score scale nuclear scoring system, with notably increased sensitivity and negative predictive value in BRAF V600E tumor detection. BRAF V600E-altered tumors had higher median total nuclear scores. Detailed reevaluation revealed NPIs in all BRAF V600E-altered cases, but in only 2 of 14 RAS-altered cases. These results could significantly assist pathologists, particularly those not specializing in thyroid pathology, in making a more accurate diagnosis.

Multiple palisaded encapsulated neuromas presenting as cobblestoned plaques over palms and oral cavity.

Palisaded encapsulated neuroma (PEN) is a benign circumscribed nerve sheath tumor usually seen as a solitary painless papule on the face in middle-aged adults. We report a 22-year-old male with multiple adolescent-onset PENs distributed extensively, including the oral cavity and palms, contrary to the typical presentations. The lesions formed cobblestoned plaques and were confirmed through a skin biopsy, showing characteristic nodules of wavy spindle cells forming interlacing fascicles with interspersed clefts, and positive staining for specific markers, including markers for axons and perineurium. Notably, this case deviates from the usual presentation, shedding light on atypical manifestations of PEN in a young individual without any features suggestive of a neurocutaneous syndrome or multiple endocrine neoplasia syndrome.

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Role of 18Fluorocholine Positron Emission Tomography/Computed Tomography in the Localization of Culprit Lesions in Patients of Persistent/Recurrent Primary Hyperparathyroidism: A Prospective Study in COVID Times.

Introduction: Recurrent/persistent primary hyperparathyroidism in patients who have undergone previous parathyroidectomy is a challenging condition. Imaging is important for localizing the parathyroid adenoma for re-exploration and 18F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) seems ideal for this purpose. Aim: This prospective study attempted to ascertain the utility of 18F-FCH PET/CT as an investigation in preoperative localization of abnormal parathyroid tissue in recurrent/persistent primary hyperparathyroidism while comparing it with 99mTc-Sestamibi dual-phase scintigraphy with early single-photon emission CT (SPECT)/CT and neck ultrasonography (USG). Methods: Twenty patients with biochemical features of recurrent/persistent primary hyperparathyroidism were enrolled into this study. They underwent neck USG, 99mTc-Sestamibi dual-phase scintigraphy with early SPECT/CT and 18F-FCH PET/CT for localization of parathyroid lesions. Six patients underwent surgical resection of the detected lesions, 3 were awaiting surgery, and 11 were managed conservatively. One patient died due to COVID. Results: The calculated positive predictive values on a per-lesion basis of neck USG, 99mTc-sestamibi scintigraphy and early SPECT/CT and 18F-FCH PET/CT in the cohort of the 5 operated patients were 75% (3/4), 71.4% (5/7), and 71.4% (5/7), respectively. On a per-patient basis, the lesion detection rate was 100% for 99mTc-sestamibi scan and FCH PET (5/5) and 80% on neck USG (4/5). Conclusion: 18F-FCH PET/CT is a highly accurate imaging modality for the detection of parathyroid lesions in patients with recurrent/persistent primary hyperparathyroidism.

Comparison of Neck Ultrasonography, Dual Phase 99mTc-Sestamibi with early SPECT-CT & 18F-Fluorocholine PET-CT as First Line Imaging in Patients with Primary Hyperparathyroidism.

Introduction: Successful surgical treatment for primary hyperparathyroidism requires accurate localization of abnormal parathyroid tissue in terms of location and number. Imaging is important for localizing the parathyroid adenoma, and there has been significant interest in 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) for this purpose. Aim: This study attempted to ascertain the utility of 18F-FCH PET/CT as a first-line investigation in preoperative localization of abnormal parathyroid tissue in primary hyperparathyroidism, in comparison with 99mTc-sestamibi dual-phase scintigraphy with early single-photon emission computed tomography (SPECT)/CT and neck ultrasonography. Materials and Methods: Fifty-five patients with biochemical features of primary hyperparathyroidism were enrolled in this study. They underwent neck ultrasonography, 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT, and 18F-FCH PET/CT for localization of parathyroid lesions. Thirty-three patients underwent surgical resection of the detected lesions. For two patients, clinical and biochemical follow-up was used as a gold standard. Results: A total of 40 lesions were resected in the 33 patients who underwent surgery. A further two lesions were localized in two patients with clinical and biochemical follow-up as the gold standard. Of these 42 lesions, 41 were detected in preoperative imaging and 1 lesion was noted intraoperatively and resected. 41/42 lesions were detected by 18F-FCH PET/CT (detection rate: 97.6%), 33/42 by 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT (detection rate: 78.5%), and 30/42 by neck ultrasonography (detection rate: 71.4%). Conclusion: Detection rates on 18F-FCH PET/CT were superior to both 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT and neck ultrasonography in preoperative localization of parathyroid lesions in patients with primary hyperparathyroidism.

Macrofollicular Architecture in Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Pitfall in Thyroid Practice.

BACKGROUND: Predominantly macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC-MF) is rare and often a cause of misinterpretation during pre-operative work-up and histopathology evaluation. We comprehensively evaluated the radiological, cytological, gross, microscopic, molecular and follow-up characteristics of four such cases, intending to increase its recognition and add our experience to the limited literature available. METHODS: All such histopathologically-proven cases of IEFVPTC-MF were retrieved from the departmental archives. The clinical details, thyroid ultrasound, cytology and thyroid scan findings were reviewed. Allele-specific PCR for BRAF p.V600E, KRAS, NRAS, and HRAS mutations, and FISH assays for ETV6::NTRK3 fusion and RET fusions were performed. RESULTS: There were four cases of IEFVPTC-MF diagnosed between 2021 and 2022, involving two males and two females. The median age at presentation was 27 years, and the duration of the disease was 1-10 years. Thyroid ultrasound was TR1 (benign; n = 1), TR2 (not suspicious; n = 2), or TR4 (moderately suspicious; n = 1). Cytology was categorized as nondiagnostic (n = 1), benign (n = 1), and atypia of undetermined significance (n = 1). The three nodules with available cytology smears showed abundant colloid. Cells were arranged as sheets/microfollicles/clusters. Nuclei were predominantly round with minimal/focal elongation, membrane irregularity, and cellular crowding. On gross examination, cut surfaces of the tumors showed variable amounts of colloid. The tumors were solid-cystic. Histopathology revealed partially encapsulated multinodular tumors. There were prominent pseudopapillae projecting into the lumina of macrofollicles. Nuclei were predominantly round with variable nuclear atypia, including chromatin clearing and multifocal presence of nuclear grooves. Pseudoinclusions were identified in two. Molecular analysis revealed NRAS codon 61 mutation and ETV6::NTRK3 fusion in one case each. Two patients had cervical lymph node and hematogenous metastases. Post-radio-active iodine, the response was structurally incomplete (n = 2), indeterminate (n = 1) and excellent (n = 1). CONCLUSIONS: Macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma is a major pitfall in thyroid oncology practice. Long-standing disease, and ultrasonographic and cytological features that overlap with benign disease, often lead to underdiagnosis during pre-operative evaluation. As patients may consequently develop distant metastases and have inadequate treatment response, there is a need for more vigilant understanding of the spectrum of macrofollicular thyroid disease for accurate diagnosis. ETV6::NTRK3 or other fusions, when found, present opportunities for targeted therapy.

Re-operative surgery for differentiated thyroid cancer: A single institutional experience of 182 cases.

INTRODUCTION: Re-operative thyroid surgery (RTS) is performed in patients of differentiated thyroid cancer (DTC) with residual or recurrent disease. However, there is a paucity of literature discussing experience and technique of RTS. This study aims to address this gap by providing a comprehensive review of RTS for DTC, utilizing experiences from a dedicated complex thyroid surgical oncology program at the apex hospital in a developing country. METHODS: A retrospective analysis was conducted using data from the Department of Surgical Oncology's thyroid cancer database. The study period spanned from 2006 to 2022. Clinical presentation, prior surgical history, operative details of RTS, and post-operative outcomes were assessed. Descriptive analysis was performed. RESULTS: During the study period, a total of 182 patients underwent re-operative thyroid surgery (RTS). The primary surgeries performed prior to RTS included near-total or total thyroidectomy in most cases (69.2%), and approximately half of the patients (48.4%) had prior neck node interventions. The RTS procedures consisted of completion total thyroidectomy in 30.8% of cases and surgery for thyroid bed recurrence in 9.9% of cases, while central node dissection was performed in 46.2% of patients and unilateral or bilateral template neck dissection was performed in 41.8% of cases. Extended resections were required in 9.3% of patients. Post-operative complications included permanent hypoparathyroidism (2.7%) and unilateral recurrent laryngeal nerve palsy (1.6%). CONCLUSIONS: RTS is a complex procedure with high rates of post-operative morbidity reported in literature. Optimal outcomes require a multidisciplinary approach, thorough assessment, and skilled surgeons.

Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers.

PURPOSE: In the context of radioiodine-resistant follicular-cell derived thyroid cancers (RAI-R-FCTC), [18F]F-FDG PET/CT serves as a widely used and valuable diagnostic imaging method. However, there is growing interest in utilizing molecular imaging probes that target cancer-associated fibroblasts (CAFs) as an alternative approach. This study sought to compare the diagnostic capabilities of [68Ga]Ga-DOTA.SA.FAPi and [18F]F-FDG PET/CT in patients with RAI-R-FCTC. METHODS: In this retrospective study, a total of 117 patients with RAI-R-FCTC were included. The study population consisted of 68 females and 49 males, with a mean age of 53.2 ± 11.7 years. The aim of the study was to perform a comprehensive qualitative and quantitative assessment of [68Ga]Ga-DOTA.SA.FAPi and [18F]F-FDG PET/CT scans in RAI-R-FCTC patients. The qualitative assessment involved comparing patient-based and lesion-based visual interpretations of both scans, while the quantitative assessment included analyzing standardized uptake values corrected for lean body mass (SULpeak and SULavg). The findings obtained from the scans were validated by correlating them with morphological findings from diagnostic computed tomography and/or histopathological examination. RESULTS: Among the 117 RAI-R-FCTC patients, 60 had unilateral local disease, and 9 had bilateral lesions with complete concordance in the detection rate on both PET scans. [68Ga]Ga-DOTA.SA.FAPi had a higher detection rate for lymph nodes (95.4% vs 86.6%, p<0.0001), liver metastases (100% vs. 81.3%, p<0.0001), and brain metastases (100% vs. 39%, p<0.0001) compared to [18F]F-FDG. The detection rates for pleural and bone metastases were similar between the two radiotracers. For lung metastases, [68Ga]Ga-DOTA.SA.FAPi showed a detection rate of 81.7%, whereas [18F]F-FDG had a detection rate of 64.6%. Remarkably, [68Ga]Ga-DOTA.SA.FAPi was able to detect a bowel metastasis that was missed on [18F]F-FDG scan. The median standardized uptake values (SUL) were generally comparable between the two radiotracers, except for brain metastases (SULpeak [68Ga]Ga-DOTA.SA.FAPi vs. [18F]F-FDG: 13.9 vs. 6.7, p-0.0001) and muscle metastases (SULpeak [68Ga]Ga-DOTA.SA.FAPi vs. [18F]F-FDG: 9.56 vs. 5.62, p-0.0085), where [68Ga]Ga-DOTA.SA.FAPi exhibited higher uptake. CONCLUSION: The study results demonstrate the superior performance of [68Ga]Ga-DOTA.SA.FAPi compared to [18F]F-FDG PET/CT in detecting lymph nodal, liver, bowel, and brain metastases in patients with RAI-R-FCTC. These findings highlight the potential of [68Ga]Ga-DOTA.SA.FAPi as a theranostic tool that can complement the benefits of [18F]F-FDG PET/CT in the imaging of RAI-R-FCTC.