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Langenbeck's Archives of Surgery Apr 2024Treating an infiltration of the recurrent laryngeal nerve (RLN) by thyroid carcinoma remains a subject of ongoing debate. Therefore, this study aims to provide a novel...
PURPOSE
Treating an infiltration of the recurrent laryngeal nerve (RLN) by thyroid carcinoma remains a subject of ongoing debate. Therefore, this study aims to provide a novel strategy for intraoperative phenosurgical management of RLN infiltrated by thyroid carcinoma.
METHODS
Forty-two patients with thyroid carcinoma infiltrating the RLN were recruited for this study and divided into three groups. Group A comprised six individuals with medullary thyroid cancer who underwent RLN resection and arytenoid adduction. Group B consisted of 29 differentiated thyroid cancer (DTC)patients who underwent RLN resection and ansa cervicalis (ACN)-to-RLN anastomosis. Group C included seven patients whose RLN was preserved.
RESULTS
The videostroboscopic analysis and voice assessment collectively indicated substantial improvements in voice quality for patients in Groups A and B one year post-surgery. Additionally, the shaving technique maintained a normal or near-normal voice in Group C one year post-surgery.
CONCLUSION
The new intraoperative phonosurgical strategy is as follows: Resection of the affected RLN and arytenoid adduction is required in cases of medullary or anaplastic carcinoma, regardless of preoperative RLN function. Suppose RLN is found infiltrated by well-differentiated thyroid cancer (WDTC) during surgery, and the RLN is preoperatively paralyzed, we recommend performing resection the involved RLN and ACN-to-RLN anastomosis immediately during surgery. If vocal folds exhibit normal mobility preoperatively, the MACIS scoring system is used to assess patient risk stratification. When the MACIS score > 6.99, resection of the involved RLN and immediate ACN-to-RLN anastomosis were performed. RLN preservation was limited to patients with MACIS scores ≤ 6.99.
Topics: Humans; Thyroid Neoplasms; Male; Female; Middle Aged; Adult; Recurrent Laryngeal Nerve; Thyroidectomy; Vocal Cord Paralysis; Aged; Voice Quality; Neoplasm Invasiveness; Treatment Outcome
PubMed: 38676783
DOI: 10.1007/s00423-024-03323-x -
Biomedicines Mar 2024In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th), was published. Large-scale genomic analyses such as... (Review)
Review
In 2022, the new WHO Classification of Endocrine and Neuroendocrine Tumors, Fifth Edition (beta version) (WHO 5th), was published. Large-scale genomic analyses such as The Cancer Genome Atlas (TCGA) have revealed the importance of understanding the molecular genetics of thyroid tumors. Consequently, the WHO 5th was fundamentally revised, resulting in a systematic classification based on the cell of origin of tumors and their clinical risk. This paper outlines the following critical points of the WHO 5th. 1. Genetic mutations in follicular cell-derived neoplasms (FDNs) highlight the role of mutations in the MAP kinase pathway, including , , and , as drivers of carcinogenesis. Differentiated thyroid cancers such as follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC) have specific genetic alterations that correlate with morphological classifications: -like tumors (RLTs) and p.V600E-like tumors (BLTs), respectively. 2. The framework for benign lesions has been revised. The WHO 5th introduces a new category: "developmental abnormalities". Benign FDNs comprise "thyroid follicular nodular disease", follicular thyroid adenoma (FTA), FTA with papillary architecture, and oncocytic adenoma (OA). "Hürthle cell adenoma/carcinoma" is renamed oncocytic adenoma/carcinoma of the thyroid (OA/OCA), which can be distinguished from FTA/FTC by its unique genetic background. 3. Low-risk tumors include NIFTP, TT-UMP, and HTT, and they have an extremely low malignant potential or an uncertain malignant potential. 4. PTC histological variants are reclassified as "subtypes" in the WHO 5th. 5. The concept of high-grade carcinomas is introduced, encompassing poorly differentiated thyroid carcinoma (PDTC), differentiated high-grade thyroid carcinoma (DHGTC), and high-grade medullary thyroid carcinoma (MTC). 6. Squamous cell carcinoma is included in anaplastic thyroid carcinoma (ATC) in the WHO 5th due to their shared genetic and prognostic features. 7. Other miscellaneous tumors are categorized as salivary-gland-type carcinomas of the thyroid, thyroid tumors of uncertain histogenesis, thymic tumors within the thyroid, and embryonal thyroid neoplasms. The WHO 5th thus emphasizes the importance of classifying tumors based on both genetic abnormalities and histomorphology. This approach aids in achieving accurate pathological diagnosis and facilitates the early selection of appropriate treatment options, including molecular targeted therapies.
PubMed: 38672067
DOI: 10.3390/biomedicines12040712 -
Annals of the Royal College of Surgeons... Apr 2024Medullary thyroid carcinoma (MTC) is a rare thyroid cancer arising from the calcitonin-secreting parafollicular cells. Previous studies suggested a preoperative...
INTRODUCTION
Medullary thyroid carcinoma (MTC) is a rare thyroid cancer arising from the calcitonin-secreting parafollicular cells. Previous studies suggested a preoperative calcitonin level >200ng/l is an indication for prophylactic lateral neck dissection (LND) to remove micrometastases and improve survival outcomes.
METHODS
This retrospective single-centre study assessed the efficacy of preoperative calcitonin levels as a marker for determining need for prophylactic LND in MTC. Data were obtained on demographics, preoperative calcitonin levels, size and laterality of index tumour, type of neck dissection (central neck dissection (CND), LND), nodes removed, levels with involved nodes, number of nodes histologically involved, mortality, adjuvant therapy and locoregional recurrence.
RESULTS
A total of 33 patients were identified from St George's University Hospitals NHS Foundation Trust between 1 January 2001 and 19 August 2021; 8 were excluded for data quality issues. Of the 18 classified with a high preoperative calcitonin level (>200ng/l), 10 (56%) had a LND and 8 (44%) had a CND. In the low-calcitonin group, three (43%) patients had a CND only and four (57%) had a LND. There was no difference in absolute or disease-free survival between the low and high groups (=0.960, =0.817), or between those who had a CND and LND in the high-calcitonin group (=0.607, hazard ratio (HR) 0.55; =0.129, HR 8.78).
CONCLUSION
There was no statistically significant difference in outcomes between high and low calcitonin groups. A selective approach to performing LND in MTC patients based on clinical and imaging findings suggesting disease presence in the lateral neck should be explored further.
PubMed: 38661438
DOI: 10.1308/rcsann.2024.0033 -
Journal of the Endocrine Society Apr 2024Next-generation sequencing (NGS) analysis of sporadic medullary thyroid carcinoma (sMTC) has led to increased detection of somatic mutations, including M918T, which has...
CONTEXT
Next-generation sequencing (NGS) analysis of sporadic medullary thyroid carcinoma (sMTC) has led to increased detection of somatic mutations, including M918T, which has been considered a negative prognostic indicator.
OBJECTIVE
This study aimed to determine the association between clinicopathologic behavior and somatic mutation identified on clinically motivated NGS.
METHODS
In this retrospective cohort study, patients with sMTC who underwent NGS to identify somatic mutations for treatment planning were identified. Clinicopathologic factors, time to distant metastatic disease (DMD), disease-specific survival (DSS), and overall survival (OS) were compared between somatic mutations.
RESULTS
Somatic mutations were identified in 191 sMTC tumors, including M918T (53.4%), other codons (10.5%), (18.3%), somatic indels (8.9%), and wild-type (WT) status (8.9%). The median age at diagnosis was 50 years (range, 11-83); 46.1% were female. When comparing patients with M918T, Other, and WT (which included and WT), there were no differences in sex, TNM category, systemic therapy use, time to DMD, DSS, or OS. On multivariate analysis, older age at diagnosis (HR 1.05, < .001; HR 1.06, .001) and M1 stage at diagnosis (HR 3.17, = .001; HR 2.98, = .001) were associated with decreased DSS and OS, respectively, but mutation cohort was not. When comparing M918T to indels there was no significant difference in time to DMD, DSS, or OS between the groups.
CONCLUSION
Somatic mutations do not portend compromised DSS or OS in a cohort of sMTC patients who underwent clinically motivated NGS.
PubMed: 38660141
DOI: 10.1210/jendso/bvae048 -
Journal of the Endocrine Society Apr 2024Genetic analysis of sporadic medullary thyroid carcinoma (MTC) has revealed somatic variants in , , and occasionally other genes. However, around 20% of patients with...
CONTEXT
Genetic analysis of sporadic medullary thyroid carcinoma (MTC) has revealed somatic variants in , , and occasionally other genes. However, around 20% of patients with sporadic MTC lack a known genetic driver.
OBJECTIVE
To uncover potential new somatic or germline drivers, we analyze a distinct cohort of patients with sporadic, very early-onset, and aggressive MTC.
METHODS
Germline and somatic DNA exome sequencing was performed in 19 patients, previously tested negative for germline variants.
RESULTS
Exome sequencing of 19 germline samples confirmed the absence of and identified an pathogenic variant in 1 patient. Somatic sequencing was successful in 15 tumors revealing variants in 80%, predominantly p.Met918Thr, which was associated with disease aggressiveness. In -negative tumors, pathogenic variants were found in and . The germline and somatic variants were observed in a patient without a prior clinical diagnosis of neurofibromatosis type 1, demonstrating that the loss of heterozygosity of functions as a potential MTC driver. Somatic copy number alterations analysis revealed chromosomal alterations in 53.3% of tumors, predominantly in -positive cases, with losses in chromosomes 9 and 22 being the most prevalent.
CONCLUSION
This study reveals that within a cohort of early-onset nonhereditary MTC, remains the major driver gene. In -negative tumors, and are drivers of sporadic MTC. In addition, in young patients without a germline mutation, a careful clinical evaluation with a consideration of germline gene analysis is ideal to exclude Neurofibromatosis type 1 (NF1).
PubMed: 38655100
DOI: 10.1210/jendso/bvae059 -
Journal of the American College of... Jul 2024About 75% of medullary thyroid cancers (MTCs) are sporadic with 45% to 70% being driven by a RET mutation. Selpercatinib is an approved treatment for RET-mutated (mut...
BACKGROUND
About 75% of medullary thyroid cancers (MTCs) are sporadic with 45% to 70% being driven by a RET mutation. Selpercatinib is an approved treatment for RET-mutated (mut RET ) MTC; however, treatments are needed for wild-type RET MTC (wt RET ). Genomic alterations and transcriptomic signatures of wt RET MTC may reveal new therapeutic insights.
STUDY DESIGN
We did a retrospective analysis of MTC samples submitted for DNA/RNA sequencing and programmed cell death ligand 1 expression using immunohistochemistry at a Clinical Laboratory Improvement Amendments/College of American Pathologists-certified laboratory. Tumor microenvironment immune cell fractions were estimated using RNA deconvolution (quanTIseq). Transcriptomic signatures of inflammation and MAP kinase pathway activation scores were calculated. Mann-Whitney U, chi-square, and Fisher's exact tests were applied (p values adjusted for multiple comparisons).
RESULTS
The 160-patient cohort included 108 mut RET and 52 wt RET MTC samples. wt RET tumors frequently harbored mitogen-activated protein kinase (MAPK) pathway mutations, including HRAS (42.31%), KRAS (15.7%), NF1 (6.7%), and BRAF (2%), whereas only 1 MAPK pathway mutation ( NF1 ) was identified among mut RET MTC. Recurrent mutations seen in wt RET MTC included MGA , VHL, APC , STK11 , and NFE2L2 . Increased transcriptional activation of the MAPK pathway was observed in patients with wt RET harboring mutations in MAPK genes. Although the frequency of programmed cell death ligand 1 expression was similar in wt RET and mut RET (10.2% vs 7%, p = 0.531), wt RET tumors were more often tumor mutational burden high (7.7% vs 0%, p = 0.011), and wt RET MTC exhibited higher expression of immune checkpoint genes.
CONCLUSIONS
We identified molecular alterations and immune-related features that distinguish wt RET from mut RET MTC. Although RET mutation drives MTC in the absence of other alterations, we showed that wt RET MTC frequently harbors MAPK pathway mutations. These findings may indicate a potential basis for MAPK-targeted therapy, possibly in combination with immuno-oncology agents for selected patients with wt RET MTC.
Topics: Humans; Thyroid Neoplasms; Retrospective Studies; Proto-Oncogene Proteins c-ret; Female; Middle Aged; Male; Carcinoma, Neuroendocrine; Adult; Aged; Transcriptome; Mutation; Molecular Targeted Therapy; Mitogen-Activated Protein Kinases; Tumor Microenvironment; Aged, 80 and over; Genomics; Young Adult
PubMed: 38651727
DOI: 10.1097/XCS.0000000000001098 -
Cureus Mar 2024Thyroid cancer, though relatively uncommon among all cancer types, stands as the primary form of endocrine tumor. Over the last 20 years, there has been a significant...
BACKGROUND AND OBJECTIVE
Thyroid cancer, though relatively uncommon among all cancer types, stands as the primary form of endocrine tumor. Over the last 20 years, there has been a significant uptick in its occurrence. Papillary thyroid carcinoma (PTC), which is well-differentiated, emerges as the dominant subtype, in regions where iodine levels are deemed adequate. The study aimed to study the clinicopathological profile of patients diagnosed with thyroid malignancies at the Muslim Educational Society (MES) Medical College Perinthalmanna.
MATERIALS AND METHODS
This is a retrospective study undertaken at the MES Medical College by the Department of General Surgery and Endocrine Surgery. The study focuses on patients who have been diagnosed with thyroid cancer through a biopsy. Case sheets of all those patients diagnosed with thyroid malignancy were referred from the Medical Records Library to collect the relevant medical and sociodemographic data. This data was entered in the proforma, which was transferred to the Excel sheet and processed in IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, United States).
RESULTS
The study included predominantly middle-aged individuals (40-60 years), with 22 (55%) falling within this age range, followed by 14 (35%) aged between 20 and 40 years, and only four (10%) above 60 years. Female patients constituted 82.5% of the study group. Most cases presented with swelling lasting less than six months 23 (57.5%), while only four (10%) had swelling lasting more than five years. Compression symptoms were rare, with only three (7.5%) experiencing dysphagia or dyspnea. Pain was reported in two (5%) of the cases. Hypothyroidism, toxic manifestations, or hoarseness were observed in one (2.5%) of the patients. Regarding swelling characteristics, most were greater than 4 cm in size (29, 72%) and firm in consistency (25, 62.5%). Nodular surfaces were present in 19 (47.5%) of the cases, while 38 (95%) of the swellings were mobile. Palpable lymph nodes were noted in 13 (32.5%) of cases. Radiologically, hypoechoic lesions were observed in 26 (65%) of cases, with microcalcification in 29 (72.5%) and peripheral vascularity in 31 (77.5%). Papillary carcinoma was the most common histological type (34, 85%), with medullary and follicular carcinomas accounting for five (12.5%) and one (2.5%), respectively. An association was found between the duration of swelling and histological type (p = 0.05) and between the mobility of swelling and histological type (p < 0.05). However, no significant associations were observed between imaging findings and histological type (p > 0.05). The gender distribution did not show a statistically significant association with histological type.
CONCLUSION
The findings of the study revealed a statistically insignificant association between age, gender, clinical features, and the histological type of thyroid malignancy. Additionally, there was no statistically significant association between the histological type of thyroid malignancy and the size or type of surface or consistency of thyroid swelling or ultrasonographic findings of the swelling like echogenicity, microcalcification, increased peripheral vascularity, or loss of peripheral halo.
PubMed: 38650763
DOI: 10.7759/cureus.56775 -
Surgical Case Reports Apr 2024Mixed medullary and follicular cell-derived thyroid carcinoma (MMFCC) is characterized by the coexistence of follicular and C cell-derived tumour cell populations within...
BACKGROUND
Mixed medullary and follicular cell-derived thyroid carcinoma (MMFCC) is characterized by the coexistence of follicular and C cell-derived tumour cell populations within the same lesion. Due to its rarity, its etiology and clinical course remain unclear, and treatment for advanced or recurrent cases has not been established.
CASE PRESENTATION
We report a case of MMFCC treated with selpercatinib. The patient was a 69-year-old male presenting with tumors in the right thyroid lobe and in the upper mediastinum. Fine-needle aspiration (FNA) cytology of the right thyroid lobe tumor revealed a medullary carcinoma; germline RET mutations were not detected. After resection of the right thyroid lobe with central node dissection, rapid intraoperative diagnosis of the mediastinal mass confirmed malignancy, leading to total thyroidectomy with excision of the upper mediastinal tumor. Histologically, the tumor in the right thyroid lobe and the pretracheal lymph node revealed a mixture of medullary and follicular carcinoma components, diagnosed as MMFCC. The mediastinal lymph node exhibited only medullary carcinoma components. At 11 months postoperatively, computed tomography scans showed enlargement of the right supraclavicular and upper mediastinal lymph nodes. FNA cytology of the right supraclavicular lymph node suggested the recurrence of medullary thyroid carcinoma. The gene panel testing (The Oncomine Dx Target Test Multi-CDx system®, Thermo Fisher SCIENTIFIC) of metastatic lymph node revealed RET somatic mutation (M918T). Treatment with selpercatinib was initiated, and both the cervical and mediastinal lymph nodes showed a reduction in size.
CONCLUSIONS
We report a rare case of selpercatinib use for MMFCC. Since RET mutations may occur frequently in MMFCC, selpercatinib could be effective in treating MMFCC.
PubMed: 38647958
DOI: 10.1186/s40792-024-01898-7 -
Cancer Management and Research 2024Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of... (Review)
Review
INTRODUCTION
Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC.
METHODS
A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers.
RESULTS
The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management.
CONCLUSION
Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.
PubMed: 38617188
DOI: 10.2147/CMAR.S440477 -
Archives of Endocrinology and Metabolism Apr 2024Although F-sodium fluoride (F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, itcan also occur in...
OBJECTIVE
Although F-sodium fluoride (F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, itcan also occur in metastatic sites without visible calcium deposition, leading to the hypothesis that visually undetectable calcium accumulation may be responsible for this uptake. The aim of this study was to indirectly support this hypothesis by analyzing the correlation between the degree of F-NaF uptake and radiodensity in extraosseous MTC metastases, since calcium deposition can increase attenuation even when not visually detectable.
SUBJECTS AND METHODS
Extraosseous metastatic lesions of 15 patients with MTC were evaluated using F-NaF positron-emission tomography (PET)/computed tomography (CT)and segmented by levels of standardized uptake value (SUV). The correlation between mean SUV and mean Hounsfield unit (HU) values was assessed for the entire group of segments and for two subgroups with different mean HU values.
RESULTS
Very high correlations were observed between mean SUV and mean HU values for both the entire group of segments and the subgroup with a mean HU value greater than 130 (p = 0.92 and p = 0.95, respectively; p < 0.01). High correlation (p = 0.71) was also observed in the subgroup with mean HU values ranging from 20 to 130 (p < 0.01).
CONCLUSION
The findings of the present study suggest that there is an association between F-NaF uptake and calcium deposition in extraosseous metastasesof MTC, supporting the hypothesis that visually undetectable calcium accumulation may be responsible for F-NaF uptake in regions without visible calcium deposition.
Topics: Humans; Calcium; Sodium Fluoride; Carcinoma, Neuroendocrine; Thyroid Neoplasms
PubMed: 38602746
DOI: 10.20945/2359-4292-2023-0152