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.

Central lymph nodes in frozen sections can effectively guide extended lymph node resection for papillary thyroid carcinoma.

OBJECTIVES: The scope of lateral neck lymph node dissection (LND) in papillary thyroid carcinoma (PTC) remains controversial. Our research aimed to explore the value of central lymph node metastasis (CLNM) in frozen sections for predicting neck lateral lymph node metastasis (NLLNM) and to guide clinical surgeons in performing surgical lymph node dissection. PATIENTS: A total of 275 patients with PTC with suspected 'Cervical lymph node metastasis (LNM, including CLNM and NLLNM)' underwent unilateral or bilateral thyroidectomy and an intraoperative frozen diagnosis of central lymph nodes (LNs), as well as central and neck lateral LND. Validity indices and consistency of central LNs in frozen sections were calculated. In total, 216 patients then met the inclusion criteria and were enrolled in the follow-up study. The clinical and pathological data of the patients were retrospectively analyzed. The relationship between the number, metastatic diameter, and the ratio of CLNM to NLLNM was investigated. RESULTS: CLNM in frozen and paraffin-embedded sections was associated with NLLNM. Univariate and multivariate analyses revealed the following risk factors for NLLNM metastasis: maximum diameter, total number, and ratio of metastatic LNs. A significant result was obtained when a cut-off value of 2.050 mm for the maximum metastatic diameter, 5.5 in the total number, and 0.5342 for the CLNM ratio level was used. Interaction term analyses showed that the association between the number of CLNM and NLLNM differed according to maximum diameter. CONCLUSION: Central LNs in frozen sections accurately predicted NLLNM. In patients with PTC with >5 CLNMs, ≥2 and ≤5 CLNMs and maximum metastatic diameter > 2 mm, neck lateral LND should be considered. Our findings will facilitate the identification of patients who are likely to benefit from extended lateral neck LND.

A prediction model for identifying high-risk lymph node metastasis in clinical low-risk papillary thyroid microcarcinoma.

BACKGROUND: The presence of high-volume lymph node metastasis (LNM) and extranodal extension (ENE) greatly increases the risk of recurrence in patients with low-risk papillary thyroid microcarcinoma (PTMC). The goal of this research was to analyze the factors that contribute to high-risk lymph node metastasis in patients with low-risk PTMC. METHODS: We analyzed the records of 7344 patients who were diagnosed with low-risk PTMC and treated at our center from January 2013 to June 2018.LNM with a high volume or ENE was classified as high-risk lymph node metastasis (hr-LNM). A logistic regression analysis was conducted to identify the risk factors associated with hr-LNM. A nomogram was created and verified using risk factors obtained from LASSO regression analysis, to predict the likelihood of hr-LNM. RESULTS: The rate of hr-LNM was 6.5%. LASSO regression revealed six variables that independently contribute to hr-LNM: sex, age, tumor size, tumor location, Hashimoto's thyroiditis (HT), and microscopic capsular invasion. A predictive nomogram was developed by integrating these risk factors, demonstrating its excellent performance. Upon analyzing the receiver operating characteristic (ROC) curve for predicting hr-LNM, it was observed that the area under the curve (AUC) had a value of 0.745 and 0.730 in the training and testing groups showed strong agreement, affirming great reliability. CONCLUSION: Sex, age, tumor size, tumor location, HT, and microscopic capsular invasion were determined to be key factors associated with hr-LNM in low-risk PTMC. Utilizing these factors, a nomogram was developed to evaluate the risk of hr-LNM in patients with low-risk PTMC.

A novel wavelet-transform-based convolution classification network for cervical lymph node metastasis of papillary thyroid carcinoma in ultrasound images.

Preoperative assessment of cervical lymph nodes metastasis (CLNM) for accurate qualitative and locating diagnosis is important for choosing the best treatment option for patients with papillary thyroid cancer. Non-destructive, non-invasive ultrasound is currently the imaging method of choice for lymph node metastatic assessment. For lymph node characteristics and ultrasound images, this paper proposes a multitasking network framework for diagnosing metastatic lymph nodes in ultrasound images, in which localization module not only provides information on the location of lymph nodes to focus on the peripheral and self regions of lymph nodes, but also provides structural features of lymph nodes for subsequent classification module. In the classification module, we design a novel wavelet-transform-based convolution network. Wavelet transform is introduced into the deep learning convolution module to analyze ultrasound images in both spatial and frequency domains, which effectively enriches the feature information and improves the classification performance of the model without increasing the model parameters. We collected 510 patient data (N = 1376) from Shanghai Sixth People's Hospital regarding ultrasound lymph nodes in the neck, as well as used three publicly available ultrasound datasets, including SCUI2020 (N = 2914), DDTI (N = 480), and BUSI (N = 780). Compared to the optimal two-stage model, our model has improved its accuracy and AUC indexes by 5.83% and 4%, which outperforms the two-stage architectures and also surpasses the latest classification networks.

The Value of Ki-67 Labeling Index in Central Lymph Node Metastasis and Survival of Papillary Thyroid Carcinoma: Evidence From the Clinical and Molecular Analyses.

BACKGROUND: Recent evidence suggests that the Ki-67 labeling index is associated with lymph node metastasis and the prognosis of papillary thyroid carcinoma (PTC). METHODS: We retrospectively evaluated the clinicopathological features of consecutive PTC patients between Jan 2019 and Oct 2020 in our medical center. The molecular analysis was also conducted by using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) program. The Chi-square test was performed for the comparison of variables between patients with central lymph node metastasis (CLNM) and not. Besides, univariate and stepwise multivariate logistic regression analyses were further used to determine the risk factors for CLNM in PTC. RESULTS: Our results showed that male gender (odd ratio (OR) = 3.02; 95% CI: 1.81-5.04), tumor size >1 cm (OR = 2.81; 95% CI: 1.84-4.29), multifocality (OR = 2.08; 95% CI: 1.31-3.30, and Ki-67 labeling index (>3% and ≤5%: OR = 1.20; 95% CI: .73-1.97; >5%: OR = 3.85; 95% CI: 1.62-9.14) were independent risk factors for CLNM. After excluding the patients with harvested central lymph nodes <3, increased Ki-67 labeling index was still associated with the number of CLNM and the lymph node ratio. Additionally, the expression level of Ki-67 was significantly correlated with a higher N stage and worse disease-free survival in TCGA and validated GSE60542 datasets. CONCLUSIONS: Higher Ki-67 labeling index (>5%) is significantly associated with the CLNM in PTC patients, like other indicators of the male gender, larger tumor size, and multifocality. Besides, the Ki-67 was also determined to be associated with CLNM and DFS in PTC patients, which may act as an important molecular marker in PTC.

Nomogram for predicting skip metastasis in cN0 papillary thyroid cancer patients at increased risk of lymph node metastasis.

BACKGROUND: Skip lymph node metastasis (SLNM) refers to lateral lymph node metastasis (LLNM) without involving central lymph node (CLN). Some microscopic nodal positivity may be difficult to detect before surgery due to atypical imaging characteristics. These patients are misdiagnosed as having clinically node-negative (cN0) papillary thyroid cancer (PTC) even after central lymph node dissection, leading to a high risk of developing LNM after surgery. Current prediction models have limited clinical utility, as they are only applicable to predict SLNM from clinically node-positive (cN+) PTC, not cN0 PTC, and this has little impact on treatment strategies. OBJECTIVES: This study aimed to establish a nomogram for preoperatively assessing the likelihood of SLNM in cN0 PTC patients with increased risk of LNM, thus optimizing their therapeutic options. MATERIAL AND METHODS: The records of 780 PTC patients undergoing thyroidectomy along with bilateral central lymph node dissection were retrospectively reviewed. The cN0 patients with postoperative LLNM (occult SLNM) and cN+ patients without central lymph node metastasis (CLNM) (typical SLNM) were included in the SLNM group (n = 82). The CLNM-negative cN0 patients without postoperative LLNM were assigned to the non-SLNM group (n = 698). The independent correlates of SLNM constituted the nomogram for determining the likelihood of SLNM in high-risk cN0 PTC patients. RESULTS: The independent correlates of SLNM were age (hazard ratio (HR) = 1.016), tumor location (HR = 1.801), tumor size (HR = 1.528), and capsular invasion (HR = 2.941). They served as components in the development of the nomogram. This model was verified to present acceptable discrimination. It showed good calibration and a decent net benefit when the predicted probability was <60%. CONCLUSIONS: We developed a nomogram incorporating preoperative clinical data to predict the probability of SLNM development in high-risk cN0 PTC patients, which contributed to their optimized treatment options.

Clinical Study on the Risk Factors for the Recurrence of Papillary Thyroid Carcinoma.

INTRODUCTION: Papillary thyroid carcinoma is the most common endocrine malignancy and the most common type of thyroid cancer, accounting for approximately 85% of all thyroid cancer cases. It usually has a favorable course, with the 10-year survival rate exceeding 90%. However, the literature reports a recurrence rate of 7-23% after initial surgical treatment. It is important to consider medical treatment policies for this recurrence. METHODS: In this study, we examined the risk factors for the recurrence of papillary thyroid carcinoma. We treated 274 patients with thyroid papillary carcinoma at our hospital between 2009 and 2018. RESULTS: Recurrence occurred in 20 cases (7.3%). Lympho-vascular invasion and lateral cervical lymph node metastasis made significant independent contributions. CONCLUSION: The selection of the surgical mode should be based on the recurrence and after comprehensive consideration of the clinical features.

[A Case of Surgery for Skin Metastasis of Papillary Thyroid Carcinoma in a Very Elderly Patient to Improve the Quality of Life].

The patient was a 100-year-old woman who underwent right lobe thyroidectomy for papillary thyroid cancer in another hospital around 1990. She developed local recurrence in 2010 and underwent anterior tracheal local recurrence resection in May 2017. Subsequently, metastases were confirmed in the lateral cervical lymph nodes, but the patient only received TSH suppression because of her advanced age. Multiple pulmonary metastases developed in November 2020 and supraclavicular lymph node metastases in July 2021, but the patient was under the care of a visiting physician on best supportive care. The patient was referred to our hospital in January 2022 due to the appearance of a cutaneous mass in the sternal incision area, which gradually increased in size. A well-mobile, well-defined, spherical mass was found in the sternotomy area. The maximum diameter was 19 mm. The cytological findings were consistent with cutaneous metastasis of papillary thyroid carcinoma. As the patient was elderly and had multiple pulmonary metastases, she was temporarily observed. However, by June 2022, the mass had increased from 19 mm to 33 mm with cutaneous discoloration. There was no tendency for multiple pulmonary metastases to grow during this period. The decision was made to operate in order to prevent a decline in quality of life due to self-destruction of the cutaneous metastasis. The tumor was removed under general anesthesia, including the cutaneous discoloration, and reconstructed with a rhomboid skin flap. Post-operatively, there was no local recurrence or significant increase in pulmonary metastases. It is suggested that resection of cutaneous metastasis of malignant tumors may be effective in preserving quality of life even in a 100-year-old elderly patient like the present case and should be considered as an indication.

Clinical features of multifocal papillary thyroid carcinoma and risk factors of cervical metastatic lymph nodes.

OBJECTIVE: To analyze the clinical features of multifocal papillary thyroid carcinoma (PTC) and the risk factors of cervical metastatic lymph nodes. METHODS: A total of 1524 patients with papillary thyroid carcinoma admitted in Gansu Provincial Cancer Hospital from January 2020 to August 2021 were enrolled, including 492 cases of multifocal PTC and 1032 cases of unifocal PTC. The clinicopathologic features of multifocal PTC and unifocal PTC were analyzed by comparing their differences in gender, ethnicity, age, body mass index, accompanying diabetes mellitus, accompanying hypertension, preoperative thyroid stimulating hormone and thyroglobulin levels, location of lesions, maximum diameter of lesions, sum of lesion diameters, central metastatic lymph nodes, lateral cervical metastatic lymph nodes, presence of Hashimoto's thyroiditis, and thyroid capsule invasion. Patients were also assessed according to the presence or absence of central metastatic lymph nodes and lateral cervical metastatic lymph nodes to understand clinicopathological parameter differences, and multivariate logistic regression analysis was used to explore the risk factors. RESULTS: Compared with unifocal PTC group, multifocal PTC group had significantly higher proportion of patients aged over 55 years, accompanying hypertension, central metastatic lymph nodes or cervical metastatic lymph nodes, Hashimoto's thyroiditis and capsule invasion (all P<0.05); 55.1% of patients with multifocal PTC had lesions distributed bilaterally, and the maximum diameter and diameter sum of the lesions were greater than those in unifocal PTC group (all P<0.01). Multivariate logistic regression analysis showed that male, maximum diameter of lesion more than 7 mm, capsular invasion were independent risk factors for central metastatic lymph nodes (all P<0.05); while male, maximum diameter of lesion more than 7 mm, preoperative thyroglobulin more than 55 ng/mL, and central metastatic lymph nodes were risk factors for lateral cervical metastatic lymph nodes in patients with multifocal PTC (all P<0.05). CONCLUSION: Patients with multifocal PTC have significantly higher central and lateral cervical metastatic lymph nodes, particularly for male patients with a maximum diameter of lesion more than 7 mm, invasion of capsule, and preoperative thyroglobulin more than 55 ng/mL.

Cerebellar Metastasis From Thyroid Carcinoma With Prominent 123 I Uptake But Less Impressive MRI Findings in a Pediatric Patient.

ABSTRACT: Papillary thyroid carcinoma in childhood frequently presents with locoregional lymph node metastases. The distant metastases often involve lungs and the bone, whereas brain metastasis is rare. We report a case of classic variant-papillary thyroid carcinoma with right cerebellar metastasis in a 7-year-old girl on a 123 I SPECT/CT study. A brain MRI on the same day shows a tiny millimetric enhancing nodule in the right cerebellum with no perceivable perilesional edema, confirming the 123 I scan findings.

Management dilemma in metastatic papillary thyroid carcinoma.

Papillary thyroid cancer is the most common type of well-differentiated thyroid cancer. It is associated with a survival rate greater than 95% with appropriate treatment, particularly in younger patients. We present the unique case of a 25-year-old male with severe Autistic spectrum disorder (ASD) with a right level V neck mass of several months. Due to his severe ASD, his first assessment was conducted in the hospital foyer, and every subsequent clinical assessment and blood test required a general anaesthetic (GA). He was subsequently diagnosed with T2 N1b M0 (Stage I) papillary thyroid cancer. He required extensive multidisciplinary team (MDT) input to determine the goal for his treatment whilst taking into consideration perioperative care, wound management, compliance with exam and blood tests, radioactive iodine administration and lifelong medication requirements if total thyroidectomy was considered. Following multiple MDT and family meetings, the decision was made to proceed with right hemi-thyroidectomy, right level I-V and central neck dissection. He required one-week stay in the intensive care unit under sedation post-operatively, and was discharged from hospital a further six days later with no complications. He is currently being followed-up every six months which presents its own challenges. This case highlights the extraordinary challenges and considerations that need to be made when dealing with surgical pathology in a patient with severe intellectual disability, even in the setting of a relatively common surgical pathology.

Management of lateral neck nodes in common and aggressive variants of thyroid cancer.

PURPOSE OF REVIEW: Although nodal metastasis in thyroid cancer does not have a major impact on outcome, it does have some prognostic implication in adverse metastasis and aggressive histology. The purpose of this review is to discuss evaluation and management of lateral neck nodes in thyroid cancer. RECENT FINDINGS: There is a high incidence of central and lateral neck node metastasis in thyroid cancer. Appropriate preoperative evaluation is key prior to first surgical procedure. The distribution of nodal metastasis is well recognized and so generally a modified neck dissection is recommended from levels II through V. The risk of nodal metastasis at level IIb is rare. The complications of lateral neck dissection, though rare, are of significant importance to the quality of life. SUMMARY: Appropriate preoperative evaluation, including good ultrasound and CT scan with contrast, is recommended. Preoperative FNA of the lateral neck node will be helpful, along with thyroglobulin management if indicated. The neck dissection should include significant levels of neck, avoiding neural injury. Nonsurgical therapies may be recommended in selected patients.

Long-Term Efficacy of Ethanol Ablation as Treatment of Metastatic Lymph Nodes From Papillary Thyroid Carcinoma.

CONTEXT: Ethanol ablation (EA) is considered an alternative to surgery for metastatic lymph nodes from papillary thyroid carcinoma (PTC) in selected patients. OBJECTIVE: The aim of this study was to evaluate the long-term efficacy and safety of this treatment. DESIGN AND SETTING: Adult patients with PTC who had received EA in lymph node metastasis at a tertiary referral center, and were included in a published study from 2011, were invited to participate in this follow-up study. METHODS: Radiologic and medical history were reviewed. Ultrasound examination of the neck was performed by radiologists, and clinical examination was performed by an endocrine surgeon. Response was reported according to predefined criteria for satisfactory EA treatment. Adverse events associated with EA were evaluated. Cause of death was reported for deceased patients. RESULTS: From the 2011 study, 51 of 63 patients were included. Forty-four patients were reexamined (67/109 lesions) and 7 patients were deceased. Median follow-up time from primary surgery was 14.5 years. Median follow-up from the latest performed EA in the 2011 study was 11.3 years. Local control was permanently achieved in most patients (80%). Recurrence within an ablated node was registered in 13 metastases in 10 patients. Seven of these patients also had recurrent disease elsewhere in the neck. No major side effects were reported. CONCLUSION: EA is a minimally invasive procedure with a low risk of complications. Our data suggest that EA is a safe and efficient treatment, providing excellent results for a large group of patients in the long term.

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.

Analysis of risk factors and prognosis in differentiated thyroid cancer with focus on minimal extrathyroidal extension.

AIMS: In contrast to all prior AJCC/TNM classifications for differentiated thyroid cancer (DTC) the 8th edition does not take minimal extrathyroidal extension (M-ETE) into consideration for local tumor staging. We therefore aimed to retrospectively assess the specific impact of M-ETE on the outcome of M-ETE patients treated in our clinic. METHODS: DTC patients with M-ETE and a follow-up time of ≥ 5 years were included and matched with an identical number of patients without M-ETE, but with equal histopathological tumor subtype and size. The frequency of initially metastatic disease among groups was compared using Fisher's exact test, the recurrence rate by virtue of log-rank test. Fisher's exact test and multivariate analysis were used to account for the presence of confounding risk factors. RESULTS: One hundred sixty patients (80 matching pairs) were eligible. With other confounding risk factors being equal, the prevalence of N1-/M1-disease at initial diagnosis was comparable among groups (M-ETE: 42.5 %; no M-ETE: 32.5 %; p = 0.25). No differences with regard to the recurrence rate were shown. However, M-ETE patients were treated with external beam radiation therapy more often (16.3 % vs. 1.3 %; p = 0.004) and received higher median cumulative activities of 131I (10.0 vs. 8.0 GBq; p < 0.001). DISCUSSION: Although having played a pivotal role for local tumor staging of DTC for decades M-ETE did not increase the risk for metastases at initial diagnosis and the recurrence rate in our cohort. Patients with M-ETE had undergone intensified treatment, which entails a possible confounding factor that warrants further investigation in randomized controlled trials.

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.

Urothelial carcinoma of the graft kidney with molecular analyses: a rare case report.

BACKGROUND: Malignancy after transplantation is a leading cause of death among kidney transplant recipients. However, donor-derived malignancies are rare. We report a case of a high grade papillary urothelial carcinoma arising in a transplanted kidney. CASE PRESENTATION: A 62-year-old female who received a kidney transplantation more than 30 years ago presented with urinary tract infection, acute renal failure, and hydronephrosis of the transplant kidney. Anterograde nephrostogram showed a large filling defect in the lower pole of the transplant kidney and in the proximal 3-4 cm of the ureter. A biopsy from the renal pelvic mass showed a high grade urothelial carcinoma. She underwent an anterior exenteration, resection of both transplant and native kidneys and bilateral pelvic lymph node dissection. Pathologic examination showed a high grade papillary urothelial carcinoma which appeared to arise in the pelvis of the graft kidney, involve the graft ureter and native urinary bladder. The tumor had metastasized to one left obturator lymph node but spared the two native kidneys and ureters. Short tandem repeat (STR) analysis confirmed the tumor to be of donor origin. Next-generation sequencing identified amplification of TERT and loss of CDKN2A/CDKN2B in the primary tumor. CONCLUSION: While it is known that transplant recipients have an increased risk of urothelial carcinoma compared to the general population, the lack of the well-documented risk factors, such as older age at transplantation, BK polyomavirus infection, and prolonged post-transplantation history and dissemination of the tumor in this case shed light on the de novo tumorigenesis of the graft kidney within the host microenvironment. Amplification of Telomerase reverse transcriptase (TERT) and loss of cyclin dependent kinase inhibitor 2A/2B (CDKN2A/CDKN2B) detected in the tumor by next gene sequencing suggests that they may play an important role in this case.

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study.

Background: Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. Methods: From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). Results: We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm3 (range: 0.003-38.18 cm3), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452, p = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904; p = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945; p = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. Conclusion: The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.