Malignant Thyroid Research Articles

Expression of TSPAN1 and its link to thyroid nodules: one step forward on the path to thyroid tumorigenesis biomarkers.

Thyroid cancer is ranked as the most common malignancy within the endocrine system and the seventh most prevalent cancer in women globally. Thyroid malignancies require evaluating biomarkers capable of distinguishing between them for accurate diagnosis. We examined both mRNA and protein levels of TSPAN1 in plasma and tissue samples from individuals with thyroid nodules to aid this endeavour. In this case-control study, TSPAN1 was assessed at both protein and mRNA levels in 90 subjects, including papillary thyroid cancer (PTC; N = 60), benign (N = 30), and healthy subjects (N = 26) using enzyme-linked immunosorbent assay (ELISA) and SYBR-Green Real-Time PCR, respectively. TSPAN1 plasma levels were decreased in PTC and benign compared to healthy subjects (P = 0.002). TSPAN1 mRNA levels were also decremented in the tumoral compared to the paired normal tissues (P = 0.012); this drop was also observed in PTC patients compared to benign patients (P = 0.001). Further, TSPAN1 had an appropriate diagnostic value for detecting PTC patients from healthy plasma samples with a sensitivity of 76.7% and specificity of 65.4% at the cutoff value < 2.7 (ng/ml). TSPAN1 levels are significantly reduced in patients with benign and PTC, demonstrating its potential value as a diagnostic biomarker. Additionally, the significant reduction in TSPAN1 mRNA expression within PTC tumor tissues may suggest its involvement in tumor progression and development. Further studies, including larger-scale validation studies and mechanistic investigations, are imperative to clarify the molecular mechanisms behind TSPAN1 and, ultimately, its clinical utility for treating thyroid disorders.

Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, characterized by a range of subtypes that differ in their cytologic features, clinical behavior, and prognosis. Accurate cytologic evaluation of PTC using fine-needle aspiration is essential but can be challenging due to the morphologic diversity among subtypes. This review focuses on the distinct cytologic characteristics of various PTC subtypes, including the classic type, follicular variant, tall cell, columnar cell, hobnail, diffuse sclerosing, Warthin-like, solid/trabecular, and oncocytic PTCs. Each subtype demonstrates unique nuclear features, architectural patterns, and background elements essential for diagnosis and differentiation from other thyroid lesions. Recognizing these distinct cytologic patterns is essential for identifying aggressive subtypes like tall cell, hobnail, and columnar cell PTCs, which have a higher risk of recurrence, metastasis, and poorer clinical outcomes. Additionally, rare subtypes such as diffuse sclerosing and Warthin-like PTCs present unique cytologic profiles that must be carefully interpreted to avoid diagnostic errors. The review also highlights the cytologic indicators of lymph node metastasis and high-grade features, such as differentiated high-grade thyroid carcinoma. The integration of molecular testing can further refine subtype diagnosis by identifying specific genetic mutations. A thorough understanding of these subtype-specific cytologic features and molecular profiles is vital for accurate diagnosis, risk stratification, and personalized management of PTC patients. Future improvements in diagnostic techniques and standardization are needed to enhance cytologic evaluation and clinical decision-making in thyroid cancer.

Artificial intelligence-enhanced infrared thermography as a diagnostic tool for thyroid malignancy detection

Introduction Thyroid nodules are common, and investigation is crucial for excluding malignancy. Increased intranodular vascularity is frequently observed in malignant tumors, which can be detected through increased skin surface temperatures using noninvasive infrared thermography. We aimed to develop a diagnostic tool for thyroid cancer using infrared thermal images combined with an artificial intelligence (AI) algorithm. Methods We conducted a prospective cross-sectional study involving participants with thyroid nodules undergoing thyroid surgery. Infrared thermal images were collected using a thermal camera on the day prior to surgery. In combination with the final thyroid pathological reports, we utilized a machine learning model based on the pre-trained ResNet50V2 model, a convolutional neural network, to evaluate diagnostic accuracy for malignancy diagnosis. Results The study included 98 participants, 58 with malignant thyroid nodules and 40 with benign thyroid nodules, as determined by pathological results. The AI-enhanced infrared thermal image analyses demonstrated good performance in distinguishing between benign and malignant thyroid nodules, achieving an accuracy of 75% and a sensitivity of 78%. These parameters were slightly lower than those of the AI-model predictor that integrated current practice using preoperative thyroid ultrasound findings and cytological results, yielding an accuracy of 81% and a sensitivity of 84%. Conclusions The infrared thermal images, assisted by an AI model, exhibit good performance in distinguishing thyroid malignancy from benign nodules. This imaging modality has great potential to be used as a noninvasive screening tool for adjunct evaluation of thyroid nodules.

Cancer-Specific Integrin Imaging With 68Ga-Trivehexin: A Potential Imaging for Accurate Staging of Thyroid Malignancy.

68Ga-Trivehexin is a novel radiotracer binding to "cancer-specific integrin αvβ6." 68Ga-Trivehexin has high specificity for tumor cells and, thus, has the potential to replace 18F-FDG PET/CT due to its limited specificity in the head and neck cancer. Here, we present one case of papillary thyroid carcinoma, where 68Ga-Trivehexin PET CT demonstrated accurate staging compared with 18F-FDG PET/CT.

Diagnostic significance of ultrasound characteristics in discriminating follicular thyroid carcinoma from adenoma

BackgroundFollicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid gland and has a greater propensity for haematogenous metastasis. However, the preoperative differentiation of FTC from follicular thyroid adenoma (FTA) is not well established. Certain ultrasound characteristics are associated with an increased risk of thyroid malignancy, but mainly for papillary thyroid cancers and not for FTC.ObjectivesThis retrospective study aimed to evaluate the ultrasound characteristics of FTC and the value of ultrasound characteristics in differentiating FTC from FTA.MethodsA total of 96 patients with pathologically confirmed FTC or FTA who underwent preoperative thyroid ultrasound were included in this study. The ultrasound and pathological characteristics were evaluated.ResultsOur data revealed that the incidences of lesions with tubercle-in-nodule, spiculated/microlobulated margins, mixed vascularization, egg-shell calcification, central stellate scarring, extension toward the capsule and chronic lymphocytic thyroiditis were significantly higher in the FTC group (all p < 0.05). After adjusting for confounding factors, lesions with mixed vascularization (odds ratio [OR]: 2.038, P = 0.019), central stellate scarring (OR: 87.992, P = 0.007), extension toward the capsule (OR: 22.587, P = 0.010), and chronic lymphocytic thyroiditis (OR: 9.195, P = 0.006) were independently associated with FTC. Furthermore, combined with chronic lymphocytic thyroiditis, mixed vascularization, central stellate scarring, and extension toward the capsule showed high discriminatory accuracy in predicting FTC (AUC: 0.914; sensitivity: 96.5%; specificity: 71.8%; p < 0.001).ConclusionsIn combination with chronic lymphocytic thyroiditis, mixed vascularization, central stellate scarring, and extension toward the capsule have greater accuracy in differentiating FTCs from FTAs.

SATB2 is an Emergent Biomarker of Anaplastic Thyroid Carcinoma: A Series with Comprehensive Biomarker and Molecular Studies.

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive thyroid malignancy typically comprised of undifferentiated tumor cells with various histologic morphologies, which makes the diagnosis challenging. These tumors commonly show loss of thyroglobulin and TTF1 with preservation of cytokeratin (67%) and Paired Box Gene 8 (PAX8) (55%) expression. Identification of a sensitive immunohistochemical stain to aid in the diagnosis of ATC would be beneficial. Immunohistochemistry (IHC) against special AT-rich sequence-binding protein 2 (SATB2) protein is a sensitive and specific marker expressed in colorectal adenocarcinoma and bone or soft tissue tumors with osteoblastic differentiation. However, SATB2 is also expressed in other sarcomatous/undifferentiated neoplasms lacking osteoblastic differentiation. Using quantitative reverse transcription PCR (RT-qPCR) we showed that there is variable expression of SATB2 mRNA expression in ATCs. To evaluate the role of SATB2 protein expression in ATC, we performed PAX8, SATB2, pancytokeratin (AE1/AE3 & CAM5.2), claudin-4 and TTF1 immunostaining on 23 cases. ATCs showed retained expression of PAX8 in 65% (15/23); SATB2 was detected in 74% (17/23); pancytokeratin was expressed in 65% (15/23); claudin-4 was expressed in 35% (8/23) and TTF1 showed expression in 13% (3/23) of cases. Furthermore, 83% (5/6) of ATCs which lacked SATB2 expression, retained PAX8 expression, while 88% (7/8) of the tumors without PAX8 expression were positive for SATB2. Differentiated follicular cell-derived thyroid cancers (n = 30), differentiated high grade thyroid carcinoma (n = 3), and poorly differentiated thyroid carcinoma (n = 8) were negative for SATB2 immunoreactivity. Next-generation selected cases detected the commonly identified oncogenic variants including those in BRAF, RAS, TP53, and TERT promoter. Overall, we hereby demonstrate that SATB2 IHC may be used to support the diagnosis of ATC.

Thyroid Malignancies With Thymic Differentiation: Outcomes of Rare SETTLE and CASTLE Tumors.

Spindle epithelial tumors with thymus-like differentiation (SETTLE) and carcinomas showing thymus-like differentiation (CASTLE) are rare intrathyroid tumors. This retrospective cohort study included patients diagnosed with SETTLE, CASTLE, and papillary thyroid carcinoma (PTC) from 2004 to 2020 within the National Cancer Database (NCDB). Demographic, tumor, and treatment characteristics were compared. Overall survival (OS) was analyzed using the Kaplan-Meier method and Cox regression models. This study identified 19 patients with CASTLE, 11 with SETTLE, and 483 474 with PTC. CASTLE and SETTLE patients had larger tumors, lymphovascular invasion, and positive surgical margins. They were rarely treated with radioactive iodine treatment but frequently received external beam radiation and chemotherapy. Five-year OS was significantly lower for CASTLE and SETTLE compared to PTC. SETTLE was associated with an increased risk of death. SETTLE and CASTLE are rare intrathyroid tumors with worse survival compared to PTC, often managed with radiation, chemotherapy, and surgery.

085. Survival Time of Anaplastic Thyroid Cancer with Various of Therapeutic Modalities

Background: Anaplastic carcinoma of the thyroid (ATC) is the most aggressive thyroid gland malignancy. Therapies modalities were controversial due to its poor survival prognosis. The survival data after various therapeutic modalities for ATC is still limited. Methods: This study is a retrospective cohort study by taking data from the Cancer Registry in Bali, Denpasar, Indonesia. All patients with anaplastic thyroid cancer who visited Sanglah Hospital in the range 2018 to 2020 were included in this study. Data regarding duration of survival, received treatment modalities, tumor size from radiological data, and laboratories were analyzed with SPSS 25.0. Results: This study included 10 subjects with ATC, mostly male with a mean age of 60.7 years old. The mean survival was 74.8 days with a median survival of 74.5 days. Of the ten patients, 2 patients died without getting any therapy, both surgical and medical therapy. In this study, there was a significant difference in duration of survival between therapeutic modalities. There was no influence of tumor volume factors, gap from initial presentation to therapeutic modality, nodes involved, blood gas analysis at the initial presentation, NLR, PLR, TSH, and FT4 for the survival time of anaplastic thyroid cancer. Conclusion: There is a significant difference in duration of survival between therapeutic modalities for anaplastic ca thyroid. Even so, isthmectomy, tracheostomy, and chemotherapy therapy, only provide an extension of survival time for an average of 40 days.

Eggshell Calcifications at Thyroid Ultrasound: A Sample-focused Analysis of Cytological Findings and Post-thyroidectomy Pathological Correlates

Eggshell calcifications at thyroid ultrasound are connected to the challenging field of thyroid nodules and/or malignancy from a multidisciplinary perspective. Calcifications may be found in malignant and benign tumors; typically, micro-calcifications are identified in the papillary type of cancer, being equivalent to psammoma bodies in the pathological report. The risk of macro-calcifications, however, is more nuanced; recent data suggest a potential connection with a differentiated malignancy as well. Eggshell calcifications, a distinct type of macro-calcification, are generally considered benign findings, especially uninterrupted forms. Yet, the real incidence is not clear, which is why the topic remains open. In this narrative review, we analyzed eggshell calcifications in relationship with cytological diagnosis upon fine needle aspiration and post-thyroidectomy histological report. A PubMed-based search of the English-language papers using several keywords identified 171 articles. We only included original studies (no timeline restriction). After removing duplicates and applying the inclusion and exclusion criteria, 14 original studies were analyzed. The number of subjects per study varied (N=61 to 2678) so did the number of analyzed nodules per study (a maximum of 2902). Some studies found connections with benign features; others revealed a higher risk of malignancy at fine needle aspiration. Data remain heterogeneous, and oftentimes, studies investigated it only as a secondary endpoint. A high TI-RADS score is important in malignancy prediction, while eggshell calcification might add to the positive predictive value, yet, this trait is difficult to classify as a standalone element. Nevertheless, an interrupted pattern does not exclude thyroid cancer.

Blue light-driven cell cycle arrest in thyroid cancer via Retinal-OPN3 complex

BackgroundPapillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy, with a rising incidence. Traditional treatments, such as thyroidectomy and radiotherapy, often lead to significant side effects, including impaired thyroid function. Therefore, there is an urgent need for non-invasive therapeutic approaches. This study aims to explore the potential of photobiomodulation therapy (PBMT), a non-invasive treatment using specific wavelengths of light, in the management of PTC.MethodsWe investigated the effects of blue light PBMT on PTC cells, focusing on the Retinal-OPSIN 3 (OPN3) complex’s role in mediating cellular responses. Blue light exposure was applied to PTC cells, and subsequent changes in cellular proliferation, cell cycle progression, and protein expression were analyzed. Statistical tests, including one-way ANOVA and t-tests, were used to evaluate the significance of the findings.ResultsBlue light exposure led to the dissociation of 11-cis-retinal from OPN3, resulting in the accumulation of all-trans retinal. This accumulation disrupted cellular proliferation pathways and induced G0/G1 cell cycle arrest in PTC cells. The Retinal-OPN3 complex was found to be a key mediator in these processes, demonstrating that thyroid cells can respond to specific light wavelengths and utilize their photoreceptive potential for therapeutic purposes.ConclusionsOur findings suggest that PBMT, through the modulation of the Retinal-OPN3 complex, offers a promising non-invasive approach for treating PTC. This study highlights the therapeutic potential of light signal transduction in non-ocular tissues and opens new avenues for non-invasive cancer therapies.

Malignancy Risk Associated with Radioactive Iodine Therapy for Graves’ Disease

BackgroundRadioactive iodine therapy (RAI) is a frequently chosen therapy for Graves’ disease. The aim of this study was to determine whether RAI for Graves’ disease increases the risk of thyroid malignancy. MethodsA retrospective analysis was performed of all Graves’ disease patients who underwent thyroidectomy at a single institution between 2013-2022. Comparative analyses were performed with cohorts based on RAI therapy as the primary grouping variable. Results413 patients were identified, of which 38 received RAI prior to surgery. RAI treated patients were more likely to undergo surgery for known malignancy or indeterminate nodules. RAI patients were also more likely to have malignancies larger than 1cm. Among RAI treated patients, those who developed malignancy were older at the time of Graves’ diagnosis and received early RAI therapy. ConclusionsUse of RAI for treatment of Graves’ disease increases the progression of thyroid carcinoma, but not the prevalence. Older age and early RAI therapy may be risk factors for malignancy in RAI treated patients.

Primary Thyroid Malignancies in Children and Adolescents - A Retrospective Analysis from a Tertiary Cancer Centre in South India

Primary Thyroid Malignancies in Children and Adolescents - A Retrospective Analysis from a Tertiary Cancer Centre in South India

Radiation Implication in Pediatric Second Primary Thyroid Malignancy (SPTM) Cumulative Incidence and Mortality in the United States: Large Cohort Evidence.

To assess racial and sex variances in second primary thyroid malignancy (SPTM) cumulative incidence and temporal trends and the radiation exposure effect in pediatric SPTM. A retrospective cohort study, a non-experimental epidemiologic design, was used to assess the cumulative incidence (CmI) and temporal trends as well as the exposure effect of radiation in SPTM among children, 0-19 years, in the Surveillance, Epidemiology, and End Results (SEER) registry, National Cancer Institute (NCI), USA. Percent change (PC) and annual percent change (APC) were used to examine CmI rates and temporal trends, while chi-square statistics and binomial regression models were used to examine variable distribution by race and to determine the exposure effect of radiation on SPTM as well as mortality, respectively. The frequency of pediatric thyroid cancer was (n = 3457) between 1973 and 2013/14, while the PC was 151.2 for all races but 99.8 among whites. Of all pediatric thyroid cancers diagnosed during this period, SPTM accounted for 3% (n = 99). Compared to whites, blacks/AA were 60% less likely to present with SPTM, adjusted risk ratio, aRR = 0.40, 99% CI 0.06-2.47, while other races were 18% more likely to develop SPTM, aRR = 1.18, 99% CI 0.48-2.87. Additionally, females relative to males were 63% less likely to be diagnosed with SPTM, aRR = 0.37, 99% CI 0.22-0.61. With respect to urbanicity, compared to children in rural areas, those in urban areas were 21% less likely to develop SPTM, aRR = 0.79, 99% CI, 0.12-5.35, while children in metropolitan areas were 40% less likely to develop SPTM, aRR = 0.60, 99% CI, 0.10-3.59. Although imprecise, there was a 5% increased risk of SPTM, with radiation as an exposure effect, aRR = 1.05, 99% CI 1.01-1.75. There are increasing temporal trends in pediatric SPTM with blacks relative to whites having observed lower incidence, despite an increasing percent change among blacks/AA, indicative of the disproportionate burden of this malignant neoplasm. SPTM risk was higher among males and in rural areas, while radiation as a risk for SPTM was clinically and biologically meaningful, albeit an observed statistically insignificant inference due to sampling variability, requiring intervention mapping in radiation exposure margination among children.

Endocrine Perspective of Cutaneous Lichen Amyloidosis: RET-C634 Pathogenic Variant in Multiple Endocrine Neoplasia Type 2

Background: Medullary thyroid carcinoma (MTC), the third most frequent histological type of thyroid malignancy, may be found isolated or as part of multiple endocrine neoplasia type 2 (MEN2). One particular subtype of this autosomal dominant-transmitted syndrome includes an association with cutaneous lichen amyloidosis, although, generally, a tide genotype–phenotype correlation is described in patients who carry RET proto-oncogene pathogenic variants. Methods: Our objective was to provide an endocrine perspective of a case series diagnosed with RET-positive familial MTC associated with cutaneous primary lichen amyloidosis amid the confirmation of MEN2. Six members of the same family had cutaneous lesion with different features (from hyperpigmented, velvety to red/pink appearance) and four of them harbored a RET pathogenic variant at 634 codon (exon 11): c.1900T&gt;G, p.634G (TGC634CGC). Results: All six patients were females with the lesion at the interscapular region. Except for two women, four of these subjects were investigated and had MTC (three of them with postoperatory confirmation). The youngest affected individual was 6 years old. The three adult females were confirmed with RET pathogenic variant during their 30s, while the girl underwent the familial screening as a newborn. None of them had primary hyperparathyroidism until the present time, except for one subject, and two out of the three adults also had bilateral pheochromocytoma. Notably, all patients were rather asymptomatic from the endocrine perspective at the moment when endocrine tumor/cancer was confirmed, and the skin was progressively affected a few years before the actual MEN2 confirmation. Conclusions: This case series highlights the following key message: awareness of the dermatologic findings in MTC/MEN2 patients is essential since lesions such as cutaneous lichen amyloidosis might represent the skin signature of the endocrine condition even before the actual endocrine manifestations. These data add to the limited published reports with respect to this particular presentation, noting the fact that RET-C634 is the most frequent pathogenic variant in MEN2-associated lichen amyloidosis; females are more often affected; the interscapular region is the preferred site; the age of diagnosis might be within the third decade of life, while we reported one of the youngest patients with the lesion. The same RET pathogenic variant is not associated with the same dermatologic features as shown in the vignette. The same RET mutation does not mean that all family members will present the same skin anomaly.

Ectopic thyroid tissue in adrenal gland – A case report and review of literature

Ectopic thyroid tissue along the line of descent of thyroid from foramen caecum along thyroglossal duct to the normal anatomic location in neck has been reported. Ectopic thyroid tissue in adrenal gland (ETTAG) is rarely encountered and very few cases have been reported in literature. The most common differential diagnosis to be considered when thyroid follicles are noted in adrenal gland are metastasis from a thyroid malignancy or a teratoma or an ectopic thyroid tissue in adrenal gland. We present a case of an adrenal incidentaloma in a young pregnant female which was diagnosed to be ectopic thyroid tissue in adrenal gland. The review of literature of similar cases of this rare embryological aberrance is discussed. To our knowledge, only 16 such cases have been documented in literature and our case is the first one from Indian subcontinent and the largest documented with respect to size.

Primary Squamous Cell Carcinoma of the Thyroid Gland Treated with Surgery and Concurrent Chemoradiotherapy, A Case Report

Introduction: Primary squamous cell carcinoma (PSCC) of the thyroid gland is one of the rarest types of all reported thyroid malignancies worldwide. It is very aggressive in nature and carries a poor prognosis. The surgical resection with adjuvant radiotherapy and chemotherapy is the most recommended treatment despite its poor reported outcome. Case presentation: A 56-year-old Asian man presented with non-tender swelling of the neck, Patient underwent total thyroidectomy and histopathology revealed carcinoma thyroid, squamous cell carcinoma, and all other primary squamous cell carcinoma were excluded by imaging and immunohistochemistry. The patient completed radiotherapy concurrent with chemotherapy but after one year of completion of treatment died due to local recurrence. Conclusion: PSCC of the thyroid gland is difficult to diagnose and is a great challenge for the managing team to plan for the best treatment option, due to its unfavorable rate of survival and lack of consensus management guidelines. EWMCJ Vol. 12, No. 1&amp;2, January-July 2024: 107-110

Bitter Taste Receptor Agonists Induce Apoptosis in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with a 20% recurrence rate. Bitter taste receptors (T2Rs) and their genes ( TAS2Rs ) may regulate survival in solid tumors. This study examined T2R expression and function in PTC cells. Three PTC cell lines (MDA-T32, MDA-T68, MDA-T85) were analyzed for expression using RT-qPCR and immunofluorescence. Live cell imaging measured calcium responses to six bitter agonists. Viability and apoptosis effects were assessed using crystal violet and caspase 3/7 activation assays. Genome analysis of survival was conducted. TAS2R14 was consistently highly expressed in all cell lines. Five bitter agonists produced significant calcium responses across all cell lines. All bitter agonists significantly decreased viability and induced apoptosis. Higher TAS2R14 expression correlated with better progression-free survival in patients (p<0.05). T2R activation by bitter agonists induces apoptosis and higher TAS2R expression is associated with survival, suggesting potential therapeutic relevance in thyroid cancer management.

RAI therapy in low-risk papillary thyroid cancer: recurrence reduction and long-term outcomes in the Turkish population

PurposePapillary thyroid cancer (PTC) is the most common thyroid malignancy, characterized by its slow progression and favorable prognosis. This study re-evaluates the efficacy of radioactive iodine (RAI) therapy versus no RAI in low-risk PTC patients following total thyroidectomy.MethodsA retrospective analysis was conducted on 588 patients treated between 2010 and 2016 at a major tertiary center in Turkey. Patients were divided into two cohorts: those receiving total thyroidectomy (TT) with high-dose RAI (100 mCi) and those receiving TT alone. A matched cohort of 138 patients per group was analyzed to minimize bias.ResultsFollow-up data indicated that at 24 months, the RAI group demonstrated a higher percentage of excellent treatment responses (86%) compared to the non-RAI group (74%). Long-term follow-up showed that 99.3% of the RAI group achieved no evidence of disease (NED), versus 90.6% in the non-RAI group. Recurrence rates were significantly lower in the RAI group (1%) compared to the non-RAI group (5.8% with a > 2.0 ng/ml cut-off for biological events).ConclusionIn summary, the findings from this study underscore the efficacy of RAI therapy in reducing recurrence rates and enhancing long-term disease control in low-risk papillary thyroid cancer patients. While total thyroidectomy alone is effective, the addition of RAI therapy provides a marked improvement in treatment responses and reduces the risk of disease recurrence. This indicates that personalized treatment plans incorporating RAI may offer significant advantages in managing low-risk PTC.

Holomics and Artificial Intelligence-Driven Precision Oncology for Medullary Thyroid Carcinoma: Addressing Challenges of a Rare and Aggressive Disease.

Background/Objective: Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer comprising a disproportionate share of thyroid cancer-related mortalities, despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, which are designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for patients with MTC. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, which is an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. Methods: This article reviews how AI-driven precision oncology can enhance the diagnostic workup, staging, risk stratification, management, and follow-up care of patients with MTC by processing vast amounts of complex data quickly and accurately. Articles published in English language and indexed in Pubmed were searched. Results: AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in the management of MTC enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. Conclusions: The integration of holomics and AI in the management of patients with MTC represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of treatment and care of patients with MTC. By leveraging AI and holomics, we can strive toward making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being at all ages.

Clinical and Histopathological Features of Thyroid Cancer with TERT Promoter Molecular Alterations in Isolation Versus with Concurrent Molecular Alterations: A Multicenter Retrospective Study

Background/Objectives: Molecular testing of thyroid nodules enables the detection of genetic alterations, which can help assess the risk of malignancy and tumor behavior. While telomerase reverse transcriptase (TERTp) mutations are known to be associated with aggressive disease, their exact prognostic significance when occurring alone or with other molecular alterations remains underreported. Methods: This study examined patients with thyroid cancer treated at two tertiary care hospitals from 2017 to 2024. We compared tumor behavior in patients with TERTp molecular alterations occurring alone and with concurrent molecular alterations. Aggressive histologic subtypes were defined as tall-cell, hobnail, and columnar variants of papillary carcinoma, as well as poorly differentiated and anaplastic carcinoma. High-risk disease was defined according to the 2015 ATA guidelines as gross extrathyroidal extension, lymph node metastasis &gt;3 cm, postoperative elevated serum thyroglobulin, distant metastases, and/or positive resection margins. Statistical analysis was performed to assess differences between groups. Results: 30 patients with TERTp-positive thyroid malignancies were included. TERTp/BRAF V600E was the most prevalent mutation combination (n = 13, 43.3%), followed by TERTp alone (n = 8, 26.7%) and TERTp/RAS (n = 7, 23.4%). TERTp/EIF1AX/GNAS and TERTp/EIF1AX/PIK3CA were the least common combinations (n = 1, 3.3% each). Nodules with TERTp and concurrent mutations were significantly more likely to be classified as high-risk (p = 0.006) and were more frequently associated with aggressive histologic subtypes (p = 0.003) compared to those with TERTp mutations alone, which tended to exhibit more benign behavior. Conclusions: Thyroid carcinomas harboring both TERTp and concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast, TERTp mutations occurring alone do not confer an elevated risk.