Metastases Of Differentiated Thyroid Carcinoma Research Articles

Biomarker Identification and Risk Prediction Model Development for Differentiated Thyroid Carcinoma Lung Metastasis Based on Primary Lesion Proteomics.

The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. Through proteomic analysis of large samples of primary lesion and dual validation employing parallel reaction monitoring and IHC, we identified eight hub proteins as potential biomarkers. By expanding the sample size and conducting statistical analysis on clinical features and hub protein expression, we constructed three risk prediction models. This study identified eight hub proteins-SUCLG1/2, DLAT, IDH3B, ACSF2, ACO2, CYCS, and VDAC2-as potential biomarkers for predicting LMDTC risk. We developed and internally validated three risk prediction models incorporating both clinical characteristics and hub protein expression. Our findings demonstrated that the combined prediction model exhibited optimal predictive performance, with the highest discrimination (AUC: 0.986) and calibration (Brier score: 0.043). Application of the combined prediction model within a specific risk threshold (0-0.97) yielded maximal clinical benefit. Finally, we constructed a nomogram based on the combined prediction model. As a large sample size study in LMDTC research, the identification of biomarkers through primary lesion proteomics and the development of risk prediction models integrating clinical features and hub protein biomarkers offer valuable insights for predicting LMDTC and establishing personalized treatment strategies.

Thyroglobulin Antibody (TgAb) Positive is an Independent Risk Factor for Lymph Node Metastasis in Patients with Differentiated Thyroid Carcinoma.

To investigate the relationship between lymph node metastasis and the clinicopathologic features of differentiated thyroid carcinoma (DTC) patients with thyroglobulin antibody (TgAb) positive and negative. A total of 443 patients with DTC were included in this study. Clinicopathological data of the patients were collected, including tumor size, clinical stage, calcification, Hashimoto's thyroiditis, extra-membrane infiltration, BRAF V600E mutation status, and thyroid-related hormone and antibody levels. The relationship between of lymph node metastasis and clinicopathologic features was analyzed. There were 227(51.2%) TgAb negative and 216(48.8%) TgAb positive DTC patients. Compared with patients without lymph node metastasis, DTC patients with lymph node metastasis had a higher proportion of patients with <55 years of age, maximum tumor diameter >1cm, calcification, BRAF V600E mutation, and TgAb positive. Multivariate regression logistic analysis showed that <55 years old (odds ratio (OR): 2.744, 95% CI: 1.665-4.522, P<0.001), maximum tumor diameter >1cm (OR: 2.163, 95% CI: 1.431-3.271, P<0.001), BRAF V600E mutation (OR: 2.489, 95% CI: 1.397-4.434, P=0.002), and TgAb positive (OR: 1.540, 95% CI: 1.020-2.326, P=0.040) were risk factors for lymph node metastasis. Maximum tumor diameter >1cm and BRAF V600E increased the risk by more than one fold for lymph node metastasis in TgAb-negative and TgAb-positive DTC patients. Younger age (<55 years old), maximum tumor diameter >1cm, BRAF V600E mutation, and TgAb positive were independent risk factors for lymph node metastasis in DTC. And maximum tumor diameter >1cm and BRAF V600E mutation were risk factors for lymph node metastasis both in TgAb positive and negative DTC patients.

Diagnostic Efficacy of FNA-Tg in DTC Cervical LN Metastasis and its Impact Factors: A Large Retrospective Study.

Thyroglobulin in needle washout fluid (FNA-Tg) has the advantage of compensating for the low sensitivity of cytological analysis (FNAC) in differentiated thyroid carcinoma (DTC) lymph node (LN) metastasis. However, studies of large data sets to support this view and identify the best cutoff of FNA-Tg are lacking. Our study aimed to determine the best cutoff of FNA-Tg and explore the impact factors of FNA-Tg. A total of 1106 suspicious LNs from patients treated at West China Hospital from October 2019 to August 2021 were included. Parameters were compared between metastatic and benign LNs, and the best cutoff value of FNA-Tg was identified by ROC curves. The impact factors of FNA-Tg were analyzed. In the nonsurgery group, after correcting for the effect of age and short diameter of LN, FNA-Tg was the independent risk factor for cervical LN metastasis of DTC (odds ratio [OR]: 1.048; 95% CI, 1.032-1.065). In the surgery group, after correcting for the effects of serum thyrotropin, serum Tg, long diameter of LN, and short diameter of LN, FNA-Tg was the independent risk factor for cervical LN metastasis of DTC (OR: 1.019; 95% CI, 1.006-1.033). The best cutoff value of FNA-Tg was 25.17 μg/L, and the area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 0.944, 0.847, 0.978, 0.982, 0.819, and 0.902, respectively. FNA-Tg highly correlated with FNA-TgAb (P < .01; Spearman correlation coefficient = 0.559), but FNA-TgAb positivity did not undermine the diagnostic efficacy of FNA-Tg for DTC LN metastasis. The best cutoff value of FNA-Tg was 25.17 μg/L in diagnosing DTC cervical LN metastasis. FNA-Tg highly correlated with FNA-TgAb, but FNA-TgAb had no influence on the diagnostic efficacy of FNA-Tg.

Nomogram-Based Prediction of Risk of Cervical Lymph Node Metastasis in Differentiated Thyroid Carcinoma

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

Epidemiological aspects of differentiated thyroid carcinoma metastases

Epidemiological aspects of differentiated thyroid carcinoma metastases

Beta-elemene inhibits differentiated thyroid carcinoma metastasis by reducing cellular proliferation, metabolism and invasion ability.

BackgroundAccelerated glycolysis is a characteristic of carcinoma. The herb-derived compound, beta (β)-elemene, has shown promising anticancer effects against various tumors by inhibiting aerobic glycolysis. However, its activity against thyroid carcinoma and the mechanism is still unknown.MethodsDifferentiated thyroid carcinoma (DTC) cell lines, including papillary thyroid carcinoma (PTC) cell lines (IHH-4, TPC-1, K1), and follicular thyroid carcinoma (FTC) cell line (FTC133) were treated with different concentration of β-elemene. The viability of DTC cells was analyzed using the CCK8 method. Cell cycle and apoptosis analysis were performed by flow cytometry and western blotting. The cell invasion ability was evaluated in Transwell assays. Energy metabolism in living cells was measured using a Seahorse XF analyzer. The antitumor effects of β-elemene were analyzed in vivo in a nude mouse xenograft tumors model.ResultsCCK8 assays showed β-elemene significantly inhibited DTC cell proliferation in a dose- and time-dependent manner. β-elemene promoted cell apoptosis, with increased expression of cleaved caspase-9 and decreased BCL-2 expression. Transwell assays showed that β-elemene significantly inhibited the invasion ability of DTC cells. β-elemene also reduced angiogenesis by decreasing VEGF expression in DTC cells. β-elemene reduces the basal oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and maximal glycolytic capacity as well as maximal respiration and ATP production. Moreover, β-elemene inhibited tumor growth in a mouse xenograft model in vivo.ConclusionsIn this study, we have provided the first evidence of the antitumor effects of β-elemene, which was shown to inhibit cell proliferation, promote apoptosis, induce cell cycle arrest, inhibit cell invasion ability and reduce angiogenesis. Furthermore, we showed that β-elemene significantly inhibits the respiratory and glycolytic ability of human DTC cells. Thus, our findings show the potential of β-elemene as a novel treatment for DTC.

Role of [99mTc]Tc-Galacto-RGD2 SPECT/CT in identifying metastatic differentiated thyroid carcinoma after thyroidectomy and radioactive iodine therapy

PurposeIntegrin αvβ3, a member of the arginine-glycine-aspartate (RGD)-binding subfamily, is associated with tumor angiogenesis and metastasis. The aim of study is to investigate the clinical role of [99mTc]Tc-Galacto-RGD2 SPECT/CT in high-risk differentiated thyroid carcinoma (DTC) after thyroidectomy and radioactive iodine (RAI) therapy. MethodsThirty-six patients with high-risk DTC (20 males, 16 females; mean age: 59.9 ± 16.6 y) who underwent thyroidectomy and RAI therapy were consecutively enrolled in this study. All patients underwent [99mTc]Tc-Galacto-RGD2 SPECT/CT and diagnostic 131I whole-body scan 6 months after the last RAI treatment. A region of interest (ROI) was drawn and the ratio of tumor/non-target (T/NT) was calculated. Per-patient and per-lesion analysis was performed to evaluate the diagnostic efficacy. The final diagnosis was confirmed by histopathology and follow-up. Integrin αvβ3, CD31, and Ki-67 expression in the tumor were also analyzed for evaluation of angiogenesis and proliferation. ResultsOut of 36 patients, twenty-two had metastatic disease. By per-patient analysis, the area under the curve of [99mTc]Tc-Galacto-RGD2 SPECT/CT was marginally significantly higher than that of 131I whole-body scan and morphological imaging (P = 0.0034 and 0.0006). For per-lesion analysis, [99mTc]Tc-Galacto-RGD2 SPECT/CT identified 67 metastatic lymph nodes in 14 patients, 12 lung metastases in four patients, and 12 bone metastases in six patients; its sensitivity was significantly higher than that of 131I whole-body scan in detection of lymphatic (90.54% vs. 55.41%, P = 0.0124) and bone metastasis (92.31% vs. 30.77%, P = 0.046). The ratio of T/NT in metastatic lesions increased with the DTC upstaging. Conclusions[99mTc]Tc-Galacto-RGD2 SPECT/CT has high sensitivity in the detection of metastasis in high-risk DTC and further contributes to evaluation of tumor angiogenesis and radio‑iodine refractory status.

Clinical Status and Treatment of Liver Metastasis of Differentiated Thyroid Cancer Using Tyrosine Kinase Inhibitors.

Treatment of patients with liver metastasis of differentiated thyroid carcinoma (DTC) has not been sufficiently defined, because liver metastasis of DTC has been described mostly as case reports. Additionally, such patients are considered end-of-treatment responders. A relatively new approach using tyrosine kinase inhibitors (TKIs) may provide opportunities to manage systemic metastasis. This study aims to define the clinical features of DTC patients with liver metastasis and evaluate the benefits of TKIs. We retrospectively analyzed clinical features of 29 patients (mean age 67.8years) diagnosed with liver metastasis of DTC at our institution between January 1981 and May 2017. All patients had distant metastasis at other organ sites upon diagnosis of liver metastasis; 41% of them developed new metastasis afterward. Management after diagnosis of liver metastasis comprised palliative care (48%), radioactive iodine therapy (28%), and TKI therapy (24%). The median survival after diagnosis of liver metastasis was only 4.8months. Survival rates were significantly better in patients with performance statuses between 0 and 2 on the Eastern Cooperative Oncology Group scale at diagnosis of liver metastasis (n = 22, 76%) treated with TKI compared to those who were not (P = 0.017; log-rank test; hazard ratio 0.19). One-year survival rates were 71.4 and 26.7% for patients treated with or without TKI, respectively. Patients with liver metastasis had poor clinical prognosis. When other distant metastases existed at diagnosis of liver metastasis, TKI therapy was considered an effective therapeutic option for patients with liver metastasis of DTC.

Skull base metastasis from differentiated thyroid carcinoma: 3 cases report and review of literature

Skull base metastasis from differentiated thyroid carcinoma (DTC), including papillary and follicular thyroid carcinoma, is a rare manifestation and easily misdiagnosed. In this study, we reported three cases whose initial clinical presentation was skull base metastasis complaints with the presence of silent primary sites. Based on the thyroid ultrasound and histopathology (identifying skull base and primary thyroid tumor), the final diagnoses of DTC metastasis to skull base were confirmed. Two patients underwent removal of metastasizing tumors in the skull base and primary thyroid cancer, and have respectively survived 58 months and 4 months since then. Another patient underwent tumor removal of the metastasizing skull base carcinoma leaving the primary lesion intact. However, the patient died of recurrent carcinoma after 18 months. We compared the diagnosis and treatment processes of three patients with DTC metastasis to skull base, and referenced the reported cases in the literature. In conclusion, DTC metastasis to skull base is a rare occurrence and hence easy to be misdiagnosed as primary skull base carcinoma. Clinical records, imaging tests, histopathology and immunohistochemistry are mandatory for differential diagnosis and final diagnosis. Surgical resection of both the primary and metastatic lesions is the recommended treatment. In cases where tumors are removed completely via surgery, no further treatment is necessary postoperatively when meticulously following up is in place. However, in cases where tumors are postoperative residual, radiation therapy after surgery is a feasible option.

Highly Concordant Key Genetic Alterations in Primary Tumors and Matched Distant Metastases in Differentiated Thyroid Cancer.

Distant metastases uncommonly occur in differentiated thyroid carcinoma (DTC), but they are a frequent cause of thyroid cancer-related death. Genomic alterations in metastatic tumors, and the relationship with their corresponding primary tumors in DTC, are poorly understood. The objective of this study was to investigate whether genetic alterations in primary tumors are concordant with distant metastases in DTC patients. Surgical samples from primary and matched distant metastatic tumor pairs from 17 DTC patients, and three additional unpaired metastatic tumors from two patients, were analyzed using targeted next-generation sequencing (Ion Torrent Ampliseq cancer panel) with a focus on known recurrent somatic mutations in thyroid cancer. Additionally, TERT promoter mutations were assessed by direct sequencing. BRAF mutations were found in 8/10 patients with papillary thyroid carcinoma (PTC). A NRAS mutation was detected in one patient with follicular variant PTC. TERT promoter mutations were detected in 8/10 patients with PTC, and most were coexistent with a BRAF mutation (7/8 BRAF-positive PTC patients, and one BRAF-negative PTC patient). In follicular thyroid carcinoma, NRAS was the most frequently observed mutation (4/9 patients), followed by HRAS (two patients) and KRAS (one patient). TERT promoter mutations were found in 6/7 RAS-positive follicular thyroid carcinoma patients. Key somatic alterations such as BRAF and RAS mutations were highly concordant between primary and matched metastatic tumors without discrepancies. The BRAF or RAS mutant allelic frequency was higher in matched metastatic tumors than in the corresponding primary tumors (35% vs. 25% for BRAF mutation, p = 0.04; and 40% vs. 34% for RAS mutation, p = 0.002). TERT promoter mutations were also mostly concordant in matched tumors (concordance rate 93%). BRAF, RAS, and TERT mutations are highly prevalent in metastatic DTC, and are concordant between primary and metastatic DTC. This high concordance suggests that primary tumors may reflect the key somatic alterations in matched metastatic DTC. Frequent coexistent TERT promoter and BRAF or RAS mutations in metastatic DTC also suggests its important role in the progression of DTC.

Predictive value of antithyroglobulin antibody on recurrence or metastasis following ablation in differentiated thyroid carcinoma

Objective To investigate the value of serum thyroglobulin (Tg) and antithyroglobulin antibody (TgAb) in differentiated thyroid carcinoma complicated with Hashimoto's thyroiditis after thyroid ablation.Methods Serum Tg and TgAb levels and the status of illness in 154 differentiated thyroid carcinoma patients with coexistent Hashimoto's thyroiditis and confirmed pathology after surgery followed by remnant ablation were performed during three years follow up.Tg and TgAb levels were assessed by chemiluminescent immunoassay assay.The cases were divided into three groups (according to the level of Tg):Tg ≤ 1 μg/L group,1 μg/L＜Tg ≤ 10 μg/L group and 10 μg/L＜Tg≤ 100 μg/L group.TgAb＞40 kIU/L was considered as positive,Cox's proportional hazard model was used to analyse prognostic value in different levels of Tg and TgAb for disease-free survival and recurrence.Results Compared with 1 μg/L＜Tg≤ 10 μg/L group and 10 μg/L＜Tg≤ 100 μg/L group,the relative risk in reflecting cancer recurrence (TgAb＞40 kIU/L) in Tg ≤ 1 μg/L group was 27.000 (95 ％ CI 6.727-108.374).The value of TgAb＞40 kIU/L in Tg≤ 1 μg/L group was greatly increased and highly correlated with metastasis.However,In the condition of Tg＞ 1 μg/L,the disease will be based on the level of TgAb.Conclusion The value of TgAb＞40 kIU/L in Tg ≤ 1 μg/L group seems to be the optimal cutoff value correlated with recurrence and metastasis of differentiated thyroid carcinoma. Key words: Thyroid carcinoma ; Hashimoto's thyroiditis ; Thyroglobulin ; Antithyroglobulin antibody

Comparative serum proteomic analysis identified afamin as a downregulated protein in papillary thyroid carcinoma patients with non-131I-avid lung metastases

BackgroundThe loss of 131I uptake ability in metastases from differentiated thyroid carcinoma (DTC) is becoming a major obstacle in radioiodine treatment. However, there is no effective way to screen for 131I uptake ability in metastases. The identification of differentially expressed proteins by serum proteomics may contribute to our understanding of the mechanisms underlying the dedifferentiation of DTC.Materials and methodsSerum samples were obtained from papillary thyroid carcinoma patients with non-131I-avid lung metastases and 131I-avid lung metastases. Differential protein analysis was performed using two-dimensional gel electrophoresis. Candidate protein spots showing differences in expression between the two groups were identified by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and were validated by western blotting.ResultsWe found that afamin is downregulated in the serum of papillary thyroid carcinoma patients with non-131I-avid lung metastases.ConclusionAfamin may be a potential serum biomarker for early screening of 131I uptake ability in DTC metastases and could therefore be of value in guiding radioiodine treatment decisions.

Uncommon metastases from differentiated thyroid carcinoma.

Differentiated thyroid carcinoma (DTC) usually behaves in an indolent manner with low metastatic potential. The major sites of distant metastases are the lung and bone. Metastases to the brain, eye, breast, liver, kidney, muscle and skin are rare or relatively rare. These metastases have almost always appeared in patients with advanced disease and are often associated with poor prognosis but overlooked in clinical practice. Recognizing them has a significant impact on clinical decision-making and prognosis of the patients. Treatment in these patients should be individualized and an alternative therapeutic approach should be considered. Care should be taken to determine whether a (131)I uptake focus found at an unexpected site of (131)I- whole body scan (WBS) is a DTC metastasis or a false-positive (131)I uptake. Imaging with (131)I-SPET/CT is of incremental value in the finding of rare metastases from DTC. In conclusion, DTC can have unusual metastatic presentations and patterns. Post-therapy (131)I-WBS and (131)I-SPET/CT play an important role in the management of patients with DTC.

Localization and identification of parapharyngeal metastases from differentiated thyroid carcinoma by 131I‐SPECT/CT

Parapharyngeal metastasis is a rare event in differentiated thyroid carcinoma (DTC). The (131) I-single photon emission CT (SPECT)/CT allows better localization and definition for metastases in DTC. The aim of this study was to assess the value of (131) I-SPECT/CT for the diagnosis of parapharyngeal metastasis in patients with DTC. Consecutive patients with DTC (n = 561) treated with (131) I for the ablation of remnant or treatment of metastases were enrolled. A (131) I-SPECT/CT was performed when there were abnormal findings indicative of parapharyngeal metastasis on (131) I-whole-body scan (WBS). A total of 15 lesions were found to be parapharyngeal metastasis in 14 of 561 patients with DTC after the use of (131) I-SPECT/CT. The incidence rate of parapharyngeal metastasis was about 2.5% in DTC. Of the 15 lesions, only 5 lesions were CT-positive. The remaining 10 lesions were either ignored or indeterminate by the CT alone. The (131) I-SPECT/CT can identify parapharyngeal metastasis at an early stage. Parapharyngeal metastasis in DTC is relatively frequent after the use of (131) I-SPECT/CT.

Lesion dose in differentiated thyroid carcinoma metastases after rhTSH or thyroid hormone withdrawal: 124I PET/CT dosimetric comparisons

Renal radioiodine excretion is ~50% faster during euthyroidism versus hypothyroidism. We therefore sought to assess lesion dose/GBq of administered 131I activity (LDpA) in iodine-avid metastases (IAM) of differentiated thyroid carcinoma (DTC) in athyreotic patients after recombinant human thyroid-stimulating hormone (rhTSH) versus after thyroid hormone withdrawal (THW). We retrospectively compared mean LDpA between groups of consecutive patients (N=63) receiving 124I positron emission tomography/computed tomography (124I PET/CT) aided by rhTSH (n=27) or THW (n=36); we prospectively compared LDpA after these stimulation methods within another individual. Data derived from serial PET scans and one CT scan performed 2-96 h post-124I ingestion. A mixed model analysis of covariance (ANCOVA) calculated the treatment groups' mean LDpAs adjusting for statistically significant baseline intergroup differences: non-IAM were more prevalent, median IAM count/patient lower in cervical lymph nodes and higher in distant sites, median stimulated thyroglobulin higher, mean cumulative radioiodine activity greater and prior diagnostic scintigraphy more frequent in the rhTSH patients. Mean LDpAs were: rhTSH group (n=71 IAM), 30.6 Gy/GBq; THW group (n=66 IAM), 51.8 Gy/GBq. The difference in group means (rhTSH less THW), -21.2 Gy/GBq, was statistically non-significant (p=0.1667). However, the 95% confidence interval of that difference (-51.4 to +9 Gy/GBq) suggested a trend favouring THW. The within-patient comparison found 2.9- to 10-fold higher LDpAs under THW. We found some suggestions, but no statistically significant evidence, that rhTSH administration results in a lower radiation dose to DTC metastases than does THW. A large, well-controlled, prospective within-patient study should resolve this issue.

Effect of 131I therapy On differentiated thyroid carcinoma metastases

Objective To investigate the effect of iodine-131(131Ⅰ) therapy on patients with differentiated thyroid carcinoma concurrent metastases.Methods 50 cases with differentiated thyroid carcinoma after operation ac-cording to metastaticsites were given one of fractionated treatment,a total removal of dose(370～740)×107Bq,inter-val of 4 months.Results 35 of 50 patients(70.O%) had successful ablation of residual thyroid tissue after the first administration of radioiodine.Metastatic carcinoma in 18 cases,6 cases(33.3%) were cured,effective treatment was shown in 8 cases(44.4%)and treatment failure in 4 cases(22.2%);Thyroid metastasis before treatment were signifi-cantly higher than non-HTG thyroid metastasis(t=2.715,P<0.01),decreased significantly after treatment(t=2.844,all P<0.01);The contents of CD4+、CD8+、CD4+/CD8++ in treatment group after treatment[(26.5±4.7)%、(39.4±5.7)%、(0.6±0.4)%] were lower than before treatment[(38.3±5.6)%、(29.8±6.9)%、(1.4±0.5)%](t=2.345,t=2.244,t=2.451,all P<0.05).Conclusion Treatment with multiple hlsh doses of 131Ⅰ was safe and effective with little adverse side-effect. Key words: Thyroid neoplasms; Neoplasm metastasis; Isotopes,therapy

Cisto hepático benigno simulando metástase de carcinoma diferenciado de tireoide

The follow-up of differentiated thyroid carcinoma (DTC) for detecting persistent or recurrent disease is based on iodine whole body scan (WBS), the evaluation of the tumor marker thyroglobulin (Tg), the anti-thyroglobulin antibody (anti-Tg) and neck ultrasonography (US). Well known false-positive causes of WBS include inflammatory processes, some non-thyroid tumors, kidney or even sebaceous cysts . We reported a case of false-positive WBS, after therapeutic dose of (131I) NaI. We enphasize the importance of recognizing benign liver cysts mimicking DTC metastasis. False-positive and negative results may occur with WBS and must be recognized to avoid mismanagement.

Primary tumour diameter as a risk factor for advanced disease features of differentiated thyroid carcinoma

To study the relationship between primary tumour size and the risk of advanced disease features (multifocal or locally invasive disease, lymph-node or distant metastases) in differentiated thyroid carcinoma (DTC). A retrospective chart review study. The study sample comprised 935 papillary (PTC) and 291 follicular thyroid carcinoma (FTC) patients treated in our hospital from 1978 to 2007. Kaplan-Meier analyses and log-rank tests were performed to calculate tumour size-adjusted cumulative risk of advanced disease features. Accounting for primary tumour diameter, there were no significant differences in cumulative risks of multifocal carcinoma (P = 0.12) or distant metastases (P = 0.49) between PTC and FTC. PTC showed higher cumulative risks of local invasion (P < 0.0001) or lymph-node metastases (P < 0.0001). The cumulative risk of tumour multifocality increased 5%/cm of primary tumour diameter. The cumulative risk of local invasion or lymph-node metastases in PTC and of distant metastases in DTC increased exponentially at a threshold tumour diameter of 10 mm. In FTC, lymph-node metastases are associated almost exclusively with primary tumours showing extrathyroidal growth. Starting with a 1 cm primary tumour diameter, increasing tumour size is associated with an exponentially increasing risk of local invasion or lymph-node or distant metastases of DTC. The current classification of carcinomas < 2 cm as T1 is therefore questionable.

False-negative thyroglobulin measurement in recurrent/metastatic thyroid carcinomas

Dear Sir, Park and colleagues recently compared thyroglobulin (Tg) measurement before radioiodine ablation (preablative Tg) to posttreatment whole-body scan (PT-WBS) in 824 patients with differentiated thyroid carcinoma (DTC). They reported that 52 patients (6.3%) had negative Tg (and Tg antibodies) but metastasis on PT-WBS, and recommended the complementary use of PT-WBS, regardless of the serum Tg results [1]. The preablative Tg measurement is of prognostic value as reported by many authors. However, independently of the Tg result, the PT-WBS allows us to evaluate the thyroid remnant (dictating the need for further diagnostic WBS even in low-risk patients) and to localize functioning DTC metastases. Globally, the PT-WBS is a powerful predictor of DTC patient outcome and is recommended, and to our knowledge no-one has suggested that it should be ruled out based on the preablative Tg measurement [2]. However, some questions concerning the Tg measurement as performed by Park et al. need to be further addressed:

Radioiodine therapy after pretreatment with bexarotene for metastases of differentiated thyroid carcinoma

To evaluate the effects of pretreatment with the retinoid X receptor (RXR) agonist bexarotene on the efficacy of radioiodine therapy for metastases of differentiated thyroid carcinoma (DTC) with limited uptake of radioiodine (I-131). An open prospective intervention study. Eight patients with metastases of DTC, with insufficient uptake of I-131 who showed increased uptake of radioiodine after previous treatment with bexarotene were treated with radioiodine (7400 MBq), preceded by 6 weeks of treatment with bexarotene 300 mg/day. Outcome parameters were serum thyroglobulin (Tg) levels and dimensions of metastases at computed tomography (CT), measured before and 6 months after therapy. Tissues of primary tumours were stained with antibodies against retinoic acid receptor (RAR) and RXR subtypes. Bexarotene pretreatment induced radioiodine uptake in metastases in all eight patients, although uptake was only discernable at single photon emission computed tomography (SPECT) and had incomplete matching with the metastases visualized by CT scanning. Six months after radioiodine therapy, six patients had progressive disease (defined as a > 10% increase in serum Tg and/or a > 25% increase in tumour dimensions), whereas two patients had stable disease. No relationship was observed between retinoid receptor staining pattern at immunohistochemistry and the outcome of therapy. Bexarotene therapy did not result in restoration of susceptibility to radioiodine therapy.