Gene mutations as predictors of central lymph mode metastasis in cN0 PTC: A meta-analysis.

Gene mutations could predict the tumor progression and prognosis, which are us to predict CLNM in patients with cN0 PTC, however, these results are not consistent. This meta-analysis tried to identify gene mutations which could predict CLNM in patients with cN0 PTC. A systematic search was performed for identifying relevant literature published prior to July 2023 in three search engines: PubMed, EMBASE and Web of Science. Studies that investigated the gene mutations for CLNM in patients with cN0 PTC were included in our meta-analysis. Sixteen studies, including 6095 cN0 PTC with BRAF mutations were include in our meta-analysis. The prevalence of CLNM in cN0 PTC ranged from 13.7% to 50.6%. The pooled analysis demonstrated that BRAFV600E mutation is significantly associated with CLNM (OR = 2.01, 95% CI: 1.55-2.60, p < 0.001) in PTC and PTMC (OR = 1.70, 95% CI: 0.51-1.81, p < 0.001). Whereas, cN0 PTC with TERT (OR = 1.94, 95% CI: 0.51-7.36, p = 0.33) and KRAS (OR = 0.57, 95% CI: 0.51-1.81, p = 0.34) mutations might not contribute to predict CLNM. Our analysis identified that BRAF mutation was a predictive factor for cN0 PTC, as well as for cN0 PTMC, which could be useful for clinician to accurately choose prophylactic CLND and better manage cN0 PTC.

[Calcitonin measurement in fine-needle washout fluids in detecting medullary thyroid cancer].

BACKGROUND: The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy wash-out fluid is a promising tool in the diagnosis of medullary thyroid cancer. AIMS: We assessed the potential usefulness and the diagnostic significance of Ct-FNAB alone in comparison with cytology in the diagnosis and localization of primary or metastatic MTC. MATERIALS AND METHODS: For this purpose, we retrospectively examined data from 67 patients with suspicious thyroid nodules and/or lymph nodes who ultimately underwent surgical treatment at the Endocrinology Research Centre in 2015-2020. The primary endpoint of the study was to evaluate the diagnostic accuracy of Ct-FNAB when compared to cytological examination. The secondary endpoint was to determine the optimal diagnostic level for use in clinical practice. RESULTS: The obtained results showed that high Ct-FNAB concentrations were present in all histologically proven MTC, either in thyroid gland (sensitivity 92.5%, specificity 100%) or neck masses (sensitivity 88.5%, specificity 100%). The optimal diagnostic threshold for Ct-FNAB values from thyroid nodes was > 122 pg/ml, from lymph nodes >35.8 pg/ml. CONCLUSIONS: Our findings suggest that Ct-FNAB is a highly reliable diagnostic procedure to identify primary and recurrent/metastatic MTC. The actual relevance of this technique in the management of MTC needs further longitudinal studies in a larger number of patients.

Clinical, cytological, and pathological characteristics of metastatic renal cell carcinoma to the thyroid: A study of 14 cases at a Japanese single institution.

A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.

Lesiones metastásicas a glándula tiroides. Una serie de casos / Metastatic lesions to the thyroid gland. Case series

Las lesiones metastásicas representan hasta un 3 % de los tumores malignos de la glándula tiroides. La mayoría de los casos se originan de tumores de células renales y de pulmón. El abordaje diagnóstico implica una alta sospecha clínica en pacientes con primarios conocidos, sin embargo, puede ser la manifestación inicial de una enfermedad maligna extensa no diagnosticada hasta en un 20 % a 40 % de los pacientes. La biopsia por aguja fina ha demostrado buen rendimiento para el diagnóstico de los nódulos metastásicos. El pronóstico y la opción del tratamiento quirúrgico dependen del control local del primario y del estado de la enfermedad sistémica asociada, por lo tanto, debe ser individualizado. Por lo general, hasta un 80 % de los pacientes con compromiso de la tiroides tienen enfermedad metastásica multiorgánica, y la intención del tratamiento quirúrgico es con fines paliativos para prevenir las complicaciones derivadas de la extensión local de la enfermedad a las estructuras del tracto aerodigestivo superior en el cuello. Se presenta a continuación, una serie de seis casos de pacientes con lesiones metastásicas a glándula tiroides con primarios en riñón, mama y de melanomas

Metastatic lesions represent up to 3% of malignant tumors of the thyroid gland. Most cases originate from lung and renal cell tumors. The diagnostic approach implies a high clinical suspicion in patients with known primaries, however, it can be the initial manifestation of an extensive undiagnosed malignant disease in up to 20% to 40% of patients. Fine-needle biopsy has shown good performance for the diagnosis of metastatic nodules. The prognosis and the option of surgical treatment depend on the local control of the primary condition and the state of the associated systemic disease, therefore it must be individualized. In general, up to 80% of patients with thyroid involvement have multi-organ metastatic disease and surgical treatment is intended to be palliative to prevent complications resulting from local extension of the disease to structures of the upper aerodigestive tract in the neck. A case series of six patients with metastatic lesions to the thyroid gland with primaries in the kidney, breast and melanomas is presented below

Tyrosine kinase inhibitor treatment and long-term follow-up for metastatic malignant struma ovarii.

Metastatic malignant struma ovarii (MMSO) is a very rare disease (in the United States, less than one case in 10 million females annually). However, this incidence rate is due to a paucity of data regarding diagnosis, treatment, and follow-up. Herein, we describe the case of a 14-year-old female who presented with MMSO, which later metastasized and was followed up on for over 10 years. The patient underwent right oophorectomy surgery and was then treated with a combination of radioactive iodine followed by iodine scans to detect the absorption of radioiodine in the metastatic sites, and radiation therapy to treat skeletal lesions. She subsequently received treatment with the tyrosine kinase inhibitors (TKIs), sorafenib and then lenvatinib, as treatments for advanced disease, thereby achieving long-term disease stability. This case report, which adds to the limited data available on MMSO treatment, suggests that patients treated with a combination of radioactive iodine, radiation therapy, and TKIs can result in good responses and long-term overall survival.

Predictive molecular pathology in metastatic thyroid cancer: the role of RET fusions.

BACKGROUND: Rearranged during transfection (RET) gene fusions are detected in 10-20% of thyroid cancer patients. Recently, RET fusion-positive metastatic thyroid cancers have attracted much attention owing to the FDA approval of two highly selective anti-RET tyrosine kinase inhibitors, namely, selpercatinib, and pralsetinib. AREAS COVERED: This review summarizes the available evidence on the biological and predictive role of RET gene fusions in thyroid carcinoma patients and the latest screening assays currently used to detect these genomic alterations in histological and cytological specimens. EXPERT OPINION: Management of advanced thyroid carcinoma has significantly evolved over the last decade thanks to the approval of three multikinase inhibitors, i.e. sorafenib, lenvatinib, cabozantinib, and of two selective RET-tyrosine inhibitors, i.e. selpercatinib and pralsetinib. In this setting, the detection of RET-fusions in advanced thyroid cancer specimens through the use of next-generation sequencing has become a commonly used strategy in clinical practice to select the best treatment options.

Spinal metastases from thyroid cancer: Some prognostic factors.

BACKGROUND: Spinal metastases (SpMs) from thyroid cancers (TC) significantly reduce quality of life by causing pain, neurological deficits in addition to increasing mortality. Moreover, prognosis factors including surgery remain debated. METHODS: Data were stored in a prospective French national multicenter database of patients treated for SpM between January 2014 and 2017. Fifty-one consecutive patients affected by TC with 173 secondary SpM were included. RESULTS: Mean overall survival (OS) time for all patients from the diagnosis of a thyroid SpM event was 9.1 years (SD 8.7 months). The 1-year, 5-year and 10-year survival estimates were 94% (SD 3.3), 83.8.0% (SD 5.2), and 74.5% (SD 9.9). The median period of time between primary thyroid tumor diagnosis and the SpM event was 31.4 months (SD 71.6). In univariate analysis, good ECOG-PS (status 0 and 1) (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001) and no epidural involvement (p = 0.01), were associated with longer survival, whereas cancer subtype (p = 0.436) and spine surgery showed no association (p = 0.937). Cox multivariate proportional hazard model only identified good ECOG-PS: 0 [HR: 0.3, 95% CI 0.1-0.941; p < 0.0001], 1 [HR: 0.8, 95% CI 0.04-2.124; p = 0.001] and ambulatory neurological status: Frankel E [HR: 0.262, 95% CI 0.048-1.443; p = 0.02] to be independent predictors of better survival. CONCLUSION: For cases presenting SpM from TC, we highlighted that the only prognostic factors were the progression of the cancer (ECOG-PS) and the clinical neurological impact of the SpM (Frankel status). Surgery should be discussed mainly for stabilization and neurological decompression.

Thyroglobulin measurements in washouts of fine-needle aspiration biopsy in the monitoring of patients with differentiated thyroid carcinoma.

INTRODUCTION: Approximately 35% patients with papillary thyroid carcinoma (PTC) and 13% with follicular thyroid carcinoma (FTC) present with metastases of cervical lymph nodes (LNs) at the time of diagnosis. In addition, 15-20% of patients treated with total thyroidectomy develop, after an interval of five years, metastases to the neck LNs on ultrasound examination. Fine-needle aspiration biopsy (FNAB) represents the gold standard technique for the detection of cervical LNs metastases. The aim of the study was to evaluate the diagnostic performance of the technique of thyroglobulin (Tg) measurement of washout FNAB (FNAB-Tg) in diagnostics of LNs metastases in different groups of patients with differentiated thyroid carcinoma (DTC). MATERIAL AND METHODS: Two hundred FNAB-Tg samples from 200 patients [158 women; 42 men; mean age 51.37 ± 16.77 (53)] diagnosed with DTC were examined for the assessment of the diagnostic utility of FNAB-Tg from suspicious LNs. FNAB-Tg ranged from 1.96 to 5000 ng/mL in metastatic LNs [mean; 1510 ± 1486 ng/mL (958.5)] and from 0.04 to 635.9 ng/mL in nonmetastatic LNs [mean; 57.86 ± 319.19 ng/mL (1.96)], p < 0.001. RESULTS: The most accurate diagnostic performance was displayed for the concentration of 33.28 ng/mL in FNAB-Tg with AUC of 0.91 and high sensitivity and specificity (0.92 and 0.93). FNAB-Tg in conjunction with the cytopathological examination of suspicious LNs in differentiated thyroid carcinoma (DTC) patients increases the diagnostic accuracy of FNAB (sensitivity 0.99; specificity 0.99; AUC 1.00). CONCLUSIONS: FNAB-Tg may be particularly useful in detecting LN metastases in DTC patients, and in differential diagnosis of various LN metastasizing malignancies. The combination of FNAB and FNAB-Tg measurement has high specificity and sensitivity in the detection of LN metastases of DTC.

Primary Versus Secondary Anaplastic Thyroid Carcinoma: Perspectives from Multi-institutional and Population-Level Data.

Primary (or de novo) anaplastic thyroid carcinoma (ATC) is ATC without pre-existing history of differentiated thyroid carcinoma (DTC) and no co-existing DTC foci at the time of diagnosis. Secondary ATC is diagnosed if the patient had a history of DTC or co-existing DTC components at time of diagnosis. This study aimed to investigate the incidence, clinical presentations, outcomes, and genetic backgrounds of primary versus secondary ATCs. We searched for ATCs in our institutional databases and the Surveillance, Epidemiology, and End Result (SEER) database. We also performed a systematic review and meta-analysis to analyze the genetic alterations of primary and secondary ATCs. From our multi-institutional database, 22 primary and 23 secondary ATCs were retrieved. We also identified 620 and 24 primary and secondary ATCs in the SEER database, respectively. Compared to primary ATCs, secondary ATCs were not statistically different in terms of demographic, clinical manifestations, and patient survival. The only clinical discrepancy between the two groups was a significantly larger tumor diameter of the primary ATCs. The prevalence of TERT promoter, PIK3CA, and TP53 mutations was comparable between the two subtypes. In comparison to primary ATCs, however, BRAF mutations were more prevalent (OR = 4.70; 95% CI = 2.84-7.78) whereas RAS mutations were less frequent (OR = 0.43; 95% CI = 0.21-0.85) in secondary tumors. In summary, our results indicated that de novo and secondary ATCs might share many potential developmental steps, but there are other factors that suggest distinct developmental pathways.

Metastatic Medullary Thyroid Cancer: The Role of 68Gallium-DOTA-Somatostatin Analogue PET/CT and Peptide Receptor Radionuclide Therapy.

CONTEXT: Metastatic medullary thyroid cancer (MTC) is a rare malignancy with minimal treatment options. Many, but not all, MTCs express somatostatin receptors. OBJECTIVE: Our aim was to explore the role of 68Ga-DOTA-somatostatin analogue (SSA) positron emission tomography (PET)/computed tomography (CT) in patients with metastatic MTC and to determine their eligibility for peptide receptor radionuclide therapy (PRRT). METHODS: We retrospectively identified patients with metastatic MTC who had 68Ga-DOTA-SSA PET/CT at 5 centers. We collected characteristics on contrast-enhanced CT, 68Ga-DOTA-SSA and 18F-FDG PET/CT. The efficacy of PRRT was explored in a subgroup of patients. Kaplan-Meier analysis was used to estimate time to treatment failure (TTF) and overall survival (OS). RESULTS: Seventy-one patients were included (10 local recurrence, 61 distant disease). Of the patients with distant disease, 16 (26%) had ≥50% of disease sites with tracer avidity greater than background liver, including 10 (10/61, 16%) with >90%. In 19 patients with contemporaneous contrast-enhanced CT, no disease regions were independently identified on 68Ga-DOTA-SSA PET/CT. Thirty-five patients had an 18F-FDG PET/CT, with 18F-FDG positive/68Ga-DOTA-SSA negative metastases identified in 15 (43%). Twenty-one patients had PRRT with a median TTF of 14 months (95% CI 8-25) and a median OS of 63 months (95% CI 21-not reached). Of the entire cohort, the median OS was 323 months (95% CI 152-not reached). Predictors of poorer OS included a short calcitonin doubling-time (≤24 months), strong 18F-FDG avidity, and age ≥60 years. CONCLUSIONS: The prevalence of high tumor avidity on 68Ga-DOTA-SSA PET/CT is low in the setting of metastatic MTC; nevertheless, PRRT may still be a viable treatment option in select patients.

Margin Positivity and Survival in Papillary Thyroid Microcarcinoma: A National Cancer Database Analysis.

BACKGROUND: The rising incidence of thyroid cancer has been attributed to increased detection of papillary thyroid microcarcinoma (PTMC). Although some PTMCs are thought to harbor aggressive pathologic features, the clinical significance of these features remains unclear. This study examines factors associated with survival in this patient population. STUDY DESIGN: Adults with PTMC, defined as papillary thyroid carcinoma ≤ 1.0 cm, who underwent thyroidectomy between 2004 and 2016, were identified in the National Cancer Database. Demographic and clinical variables were analyzed. The primary aim was to identify factors associated with survival. The secondary aim was to assess the association of microscopic margins on survival and to identify factors associated with margin positivity. Overall survival was estimated using Kaplan-Meier methods and compared using log rank tests. Cox proportional hazards and binary logistic regression models identified factors associated with survival and margin positivity, respectively. RESULTS: Of 77,817 patients with PTMC, 13,507 met inclusion criteria; 2,649 (20%) of these patients presented with advanced features: extrathyroidal extension (n = 916, 7%), lymphovascular invasion (n = 398, 3%), lymph node involvement (n = 2,003, 15%), and distant metastasis (n = 39, <1%). Microscopic margin positivity was present in 906 patients and associated with increased risk of death (hazard ratio 1.58, 95% CI 1.04-2.41). Academic facilities (odds ratio [OR] 0.75, 95% CI 0.59-0.95) and operative volume (OR 0.98, 95% CI 0.97-0.98) were associated with decreased margin positivity. CONCLUSIONS: Positive margin status was significantly associated with increased risk of death for PTMC. Higher operative volume and treatment at academic centers were associated with lower rates of margin positivity and may help improve survival outcomes in PTMC patients with aggressive features.

Graves disease and metastatic hormonal-active Hürthle cell thyroid cancer: A case report.

RATIONALE: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. PATIENT CONCERNS: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. DIAGNOSIS: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. INTERVENTIONS: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. OUTCOMES: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. LESSONS: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.

Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review.

BACKGROUND: It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC. METHODS: For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews. RESULTS: Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported. CONCLUSION: Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42019125245 .