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Objectives: To analyze the variant‐specific survival benefits and usage patterns of standardized treatment combinations of surgery (S), radioactive iodine ablation (RAI), and thyroid‐stimulating hormone suppression therapy (THST) for high‐risk differentiated thyroid cancer. Study Design: Retrospective cohort study. Setting: National Cancer Database. Methods: The 2004‐2017 National Cancer Database was queried for patients receiving definitive surgery for high‐risk papillary, follicular, or Hurthle cell thyroid cancer. Cox proportional hazards and Kaplan‐Meier analyses assessed for treatment‐associated survival. Results: Of 21,076 cases, 18,214 underwent survival analysis with a mean ± SD age of 50.6 ± 17.1 years (71.3% female). When compared with surgery alone, S + RAI was associated with reduced mortality in papillary (hazard ratio [HR], 0.574; P <.001) and follicular (HR, 0.489; P =.004) thyroid cancer. S + RAI + THST was associated with reduced mortality in papillary (HR, 0.514; P <.001), follicular (HR, 0.602; P =.016), and Hurthle cell (HR, 0.504; P =.021) thyroid cancer. In papillary thyroid cancer, S + RAI (91.3%), S + THST (89.2%), and S + RAI + THST (92.7%) were associated with higher 5‐year overall survival rates than surgery (85.4%, all P <.001). Papillary thyroid cancer treatments involving THST were associated with higher 5‐year overall survival rates than corresponding regimens without THST (all P <.001). In follicular thyroid cancer, S + RAI (73.9%) and S + RAI + THST (78.7%) were associated with higher 5‐year overall survival rates than surgery (65.6%, all P <.05). In Hurthle cell thyroid cancer, S + RAI (66.5%) and S + RAI + THST (73.4%) were associated with higher 5‐year overall survival rates than surgery (53.7%, all P <.05). On linear regression, THST usage increased by 77.5% (R2 = 0.944, P <.001), while RAI usage declined by 11.3% (R2 = 0.320, P =.035). Conclusions: High‐risk differentiated thyroid cancer exhibited varying susceptibilities to different treatment combinations depending on histology, with greatest responses to regimens that included RAI. Physician practices have trended toward decreased RAI and increased THST usage. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. However, real-world data of its effectiveness and safety in various clinical situations are lacking. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib with variable clinical situations. Selpercatinib showed good efficacy in all four patients without significant side effects. Despite facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy, although drug safety and durability through long-term use should be further validated. Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib. The first patient was a 63-year-old male with advanced medullary thyroid cancer (MTC) treated with vandetanib. Six months ago, he had an intracranial hemorrhage and swallowing difficulty. He started selpercatinib with percutaneous endoscopic gastrostomy (PEG). For 11 months, a partial response (PR) was observed stably with PEG administration without any more cardiovascular events. The second patient was a 67-year-old female with advanced MTC treated with vandetatib. After selpercatinib treatment, a PR was observed for most metastatic sites, including choroidal metastasis. The third patient was a 32-year-old female with advanced papillary thyroid cancer (PTC) without history of systematic treatment. For six months, a PR was observed at her metastatic site with manageable adverse events. The last patient was a 59-year-old female with advanced PTC treated with lenvatinib. She suffered from a panic disorder and pleural pain due to metastasis during lenvatinib treatment. After selpercatinib treatment, her pain and panic symptoms were improved. Facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy regardless of previous treatment or metastatic site. [ABSTRACT FROM AUTHOR]

Well-differentiated thyroid cancer (WDTC) is the most common thyroid malignancy, and the worldwide incidence is increasing. Early stage disease is curable with surgery. We hypothesized that patients who live at greater distances from health care institutions or have complicating socioeconomic barriers may present with more advanced diseases and have worse outcomes. The National Cancer Database (NCDB) was used to identify patients who were diagnosed with WDTC between 2004 and 2018. Race, ethnicity, insurance status, income status, and distance from residence to health care clinic of diagnosis (great circle distance [GCD]) were analyzed with respect to the severity of disease at presentation (stage) and outcomes. Binary logistic regression and Cox regression were used to determine associations between socioeconomic variables and tumor stage or survival. The Hispanic (OR: 1.49, CI: 1.45-1.54, P < 0.001) and Asian (OR: 1.49, CI: 1.43-1.55, P < 0.001) populations had higher odds of developing an advanced disease when compared to the White population separately. Patients without insurance displayed higher odds of developing an advanced disease at diagnosis compared to those with insurance (OR: 1.39, CI: 1.31-1.47, P < 0.001). Adjusted-Cox regression analysis of survival revealed that Black patients had detrimental survival outcomes when compared to White patients (HR: 1.24, P < 0.001), and patients with private insurance had improved survival outcomes when compared to those without insurance (HR: 0.58, P < 0.001). Hispanic and Asian patients were found to be more likely to present with an advanced disease but also displayed greater overall survival when compared to the White population. The Black population, patients without insurance, and patients with lower income status exhibited worse survival outcomes. [ABSTRACT FROM AUTHOR]

Lack of consensus exists on an algorithm to screen for synchronous distant metastases in patients presenting with papillary thyroid carcinoma (PTC). A 68-year-old male presented with a 3 cm supraclavicular neck mass. Computed tomography (CT) scan revealed a 1.3 cm left thyroid lobe nodule and 3 cm left level 3 and 4 lymphadenopathy. Ultrasound-guided fine needle aspiration was positive for PTC. Patient underwent total thyroidectomy and lymph node dissection with molecular testing confirming BRAF V600E+ PTC. Six weeks post-operatively, he developed left hip pain and numbness. Magnetic resonance imaging (MRI) revealed a large sacral mass and multiple bony lesions confirmed to be osseous metastases. Given the relatively rapid report of hip pain after surgery, metastases were likely synchronous at presentation and may have been detected with earlier suspicion. Further investigation is necessary to systematically stratify risk of synchronous distant metastases in patients with metastatic PTC. [ABSTRACT FROM AUTHOR]

BackgroundPapillary thyroid cancer (PTC) is the fastest increasing cancer in the United States; incidence increases with age. It generally has a favorable prognosis but may behave more aggressively in older patients. This study aims to describe national treatment patterns for low-risk PTC in older adults.Materials and methodsThe Surveillance, Epidemiology, and End Results-Medicare database was used to identify patients ≥66 y treated for clinical T1N0M0 PTC between 1996 and 2011. Multivariable logistic regression was used to identify factors associated with extent of surgery (total thyroidectomy versus lobectomy) and radioactive iodine (RAI) administration. Cox proportional hazards modeling was used to estimate the effect of treatment type on disease-specific survival (DSS).ResultsThree thousand two hundred and fourteen patients met inclusion criteria; 77.6% were women, median age was 72 y, and mean tumor size was 0.7 cm. 42.7% had preoperatively diagnosed PTC (versus incidental). 65.4% underwent total thyroidectomy, 29.0% lobectomy, and 5.6% lobectomy followed by completion thyroidectomy; 33.4% received postoperative RAI. Five- and 10-year DSS were 98.9% and 98.3%, respectively. After adjustment, larger tumor size (1.1-2 cm), multifocality, and a preoperative PTC diagnosis were associated with greater odds of undergoing more extensive surgery and receiving RAI (P  0.05).ConclusionsMost older adults with PTC underwent total thyroidectomy and a third received RAI; neither treatment improved DSS. In the growing elderly population, less extensive interventions for PTC may reduce morbidity and improve quality of life while preserving an excellent prognosis.

BackgroundTotal thyroidectomy is more common than lobectomy for low-risk papillary thyroid cancer, despite equipoise in survival. Because postoperative morbidity increases with age, we aimed to investigate how the extent of thyroidectomy affects short-term outcomes among older patients.MethodsUsing the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients aged ≥66 years who were treated between 1996 and 2011 for papillary thyroid cancer with tumors ≤2 cm in diameter. We used multivariable logistic regression to evaluate the effect of extent of surgery on complications, emergency-department visits, and unplanned readmissions.ResultsAmong 3,341 selected patients, 77.3% were female, mean age was 72.9 years, and tumors averaged 0.8 cm in diameter. A total of 67.6% of patients underwent total thyroidectomy, and 32.4% underwent lobectomy. Total thyroidectomy was associated with complications (odds ratio = 1.99) and readmissions (odds ratio = 1.59; both P < 0.01). Complications were higher in female patients (odds ratio = 1.34), black patients (versus white patients, odds ratio = 1.65), and those with ≥2 comorbidities (vs 0, odds ratio = 1.43; all P < 0.01). Black patients and those with ≥2 comorbidities had more emergency-department visits (odds ratio = 1.50 and 1.92, respectively) and readmissions (odds ratio = 2.19 and 2.29, respectively; all P < 0.01).ConclusionTotal thyroidectomy for older adults with low-risk papillary thyroid cancer may lead to potentially avoidable complications and readmissions, particularly for black and female patients. In many cases, lobectomy may be a safer and less costly alternative.

BackgroundThe AJCC/UICC classification is widely used for predicting survival in papillary thyroid cancer (PTC), but has not been evaluated as a predictor of recurrence. The hypothesis of this study was that the eighth edition of the AJCC system can be used in this novel way.MethodsAll patients in the study underwent surgery for PTC at a high-volume endocrine surgery centre in France between 1985 and 2015. The seventh and eighth editions of the AJCC/UICC staging system for PTC were employed to predict recurrence and disease-specific survival using the Kaplan-Meier and log rank tests.ResultsAmong 4124 patients (79·7 per cent female), median age was 50 (i.q.r. 38-60) years; 3906 patients (94·7 per cent) underwent total thyroidectomy, with lymph node dissection in 2495 (60·5 per cent). The eighth edition of the AJCC/UICC staging system placed 91·8, 7·1, 0·4 and 0·7 per cent of patients in stages I-IV respectively. After reclassifying patients from the seventh to the eighth AJCC/UICC edition, the disease was downstaged in 23·8 per cent. Over a median follow-up of 7 years, 260 patients (6·4 per cent) developed recurrent disease, including 5·2 per cent of patients with stage I, 19·6 per cent with stage II, 59 per cent with stage III and 50 per cent with stage IV disease, according to the eighth edition. The eighth edition was a better predictor of recurrence than the seventh edition.ConclusionThe eighth edition of the AJCC/UICC staging system appears to be a novel tool for predicting PTC recurrence, which is a meaningful outcome for this indolent disease. The eighth edition can be used to risk-stratify patients, keeping in mind that other molecular and pathological predictive factors must be integrated into the assessment of recurrence risk.

Papillary thyroid carcinoma (PTC) is a type of cancer with one of the fastest increasing incidences worldwide. However, the therapeutic choices for PTC patients are limited and it is critical to further understand the molecular pathology underlying this disease. Squamous cell carcinoma antigens (SCCAs) are overexpressed in many tumors and participate in tumorigenesis. However, their roles in PTC are incompletely understood. Therefore, this study investigated the role of SCCA in PTC, evaluating its expression, its clinical implications and prognostic significance in PTC patient samples, as well as its function in vitro and in vivo, using a thyroid cancer cell line in which SCCA levels have been knocked down or overexpressed. In this study, SCCA expression levels were measured by immunohistochemistry (IHC) in non‑cancerous and tumor tissues. Kaplan‑Meier analyses assessed the survival in PTC patients. MTT assay, western blot analysis, invasion assay and xenograft tumor assay were used to calculate cell proliferation, migration, invasion and tumor growth. Our results showed that SCCA was overexpressed in PTC tissues and was correlated with the clinical stage of PTC. Patients with high SCCA expression had lower overall survival (OS), disease‑free survival (DFS), lymph node recurrence‑free survival (LNRFS), and distant recurrence‑free survival (DRFS), compared to patients expressing low level of the SCCA protein. SCCA knockdown suppressed thyroid cancer cell proliferation, invasion and reduced xenograft tumor growth, whereas SCCA overexpression increased cell proliferation, invasion and xenograft tumor growth. Mechanistically, the activation of Ras increased SCCA expression, and SCCA expression was positively correlated with Ras levels in the PTC tissues. In conclusion, SCCA protein is overexpressed in PTC and may represent a predictive prognostic factor for PTC patients. Furthermore, activation of the Ras/SCCA pathway plays an important role in promoting tumor growth, invasion and metastasis in PTC.

Background: While most renal cell carcinomas (RCC) are of the clear cell subtype, other histologic subtypes are well described and have distinct clinical behavior. This study seeks to evaluate survival of clear and non-clear cell RCC retrospectively from a large, population-based cancer registry. Objectives: The key objectives of this study were to determine cancer-specific survival (CSS) and overall survival (OS) of RCC by histologic subtype and to examine survival by histologic subtype since the advent of anti-angiogenesis therapy in 2006. Methods: Within the California Cancer Registry (CCR), we used multivariable Cox proportional hazards models to assess the association of histologic subtype with CSS and OS, adjusted for sociodemographic and clinical factors. Results: In the CCR, 33,539 RCC patients were diagnosed between 2004 and 2014. The most common subtype, clear cell RCC, comprised 82.6% (n=27,717) of cases. The next most common subtypes were papillary (8.8%, 2,948) and chromophobe (5.2%, 1,759). RCC was more common in men (62.9%, 21,097) compared to women (37.1%, 12,442). Across histologic subtypes, patients with low neighborhood socioeconomic status had lower CSS (HR=1.07, 95% CI 1.02-1.13, p=0.011) and OS (HR=1.14, 95% CI: 1.10-1.19, p

Summary: Objective: Cervical lymph node (CLN) metastasis (CLNM) can be found in some patients with CLN-negative (cN0) papillary thyroid microcarcinoma (PTMC), while the risk factors are still unknown. This study aimed to examine the risk factors of CLNM in patients with cN0 PTMC, contributing to screening cN0 PTMC patients with high risk in CLNM for preventive CLN dissection (CLND). Methods: This retrospective study included consecutive patients pathologically diagnosed with cN0 PTMC and who underwent surgery at the General Surgery Department of China–Japan Friendship Hospital between 07/2016 and 01/2020. The patients were grouped according to whether CLNM was present. Factors associated with CLNM were analyzed, and a risk prediction model was established in logistic regression analysis, and their predictive power was evaluated by receiver operating characteristic curves (ROC). Results: Finally, 171 patients were included; among them, 71 (41.5%) had CLNM. There were 32 males and 139 females. The multivariable analysis showed that males (OR = 5.619, 95%CI: 2.186–14.446; P

Abstract Aims This study retrospectively investigated the morphological, immunohistochemical and molecular genetic features of papillary renal neoplasm with reverse polarity (PRNRP), a recently described renal tumor. Methods and results Eleven cases of PRNRP were collected, and 16 cases of type I and 9 cases of type II papillary renal cell carcinoma were included as a control series. Pathological features were evaluated based on HE staining and immunohistochemistry. KRAS exon 2 and BRAF V600E mutations were detected by Real-time PCR and Sanger sequencing. Fluorescence in situ hybridization was conducted for identification of chromosomal abnormalities. Hemosiderin deposition was found in a small amount of tumor cells in 6 cases. Multifocal or patchy necrosis (5/11), small focal invasion of the pseudocapsules or renal parenchyma (6/11), and breakthrough of renal capsule with nerve invasion (1/11) were revealed, inconsistent with the previous view that the tumor lacks necrosis and intercellular hemosiderin. Immunohistochemical staining (diffusely positive for CK7 and GATA3, negative for CD117 and vimentin, and negative to weakly positive for P504S) and high frequency of KRAS mutations in exon 2 (9/10) supported the identification and inclusion of our cases. Chromosome 7 trisomy (1/7), chromosome 17 trisomy (0/7) and chromosome Y deletion (0/5 male patients) were seldom detected in this tumor. All patients were alive without metastasis or recurrence at the end of the follow-up. Conclusion Our findings may highlight the possibility of a low malignant potential of this emerging entity. We suggest that the tumor be classified as a novel renal cell tumor subtype independent of papillary renal cell carcinoma.

Background: The most typical thyroid gland malignant lesion is papillary thyroid cancer (PTC). In many nations, the prevalence of thyroid cancer (TC) is rising, particularly papillary thyroid microcarcinoma (PTMC). Microwave ablation (MWA) has been gradually carried out in some patients with benign thyroid nodules, some low-risk PTMC, and metastatic lymph nodes in the neck. The role and safety of MWA remain controversial topics. So we conducted this study to provide the latest evidence of MWA for PTMC compared with surgery. Methods: Patients’ postoperative outcomes (duration of hospital stay and hospitalization expenditures), intraoperative outcomes (surgery time, blood loss, and incision size), and follow-up outcomes were all examined (complication rate, recurrence rate, and lymph node metastasis). The effectiveness and safety of MWA versus surgery for PTMC patients were compared using the weighted mean difference (WMD) and odds ratio (OR). Results: In total, we included 7 articles (7 trial comparisons) which contained 1, 567 PTMC patients. The results showed that MWA had significant advantages in operative time (WMD = -53.47, 95% CI: -67.62 to -39.32), postoperative hospital stay (WMD =-4.59, 95% CI: -6.40 to -2.77), hospitalization costs (WMD= -70.06, 95% CI: -90.93 to -49.19), blood loss (WMD =-28.07, 95% CI: -33.77 to -22.38), incisions size (WMD =-59.69, 95% CI: -67.79 to -51.59), and complication rates (OR = 0.28; 95% CI: 0.18 to 0.42) compared with surgery. It also showed that recurrence rates and risk of lymph node metastasis are similar to surgery. Conclusions: For PTMC patients, MWA could be an efficient, safe, and affordable therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Papillary renal cell carcinoma is the second most common type of kidney cancer, after clear cell kidney cancer. Given that it is relatively rare, studying this disease has been quite a challenge. New treatments and techniques for studying papillary kidney cancer have led to some meaningful improvements in therapy for this disease. In this review article, we summarize some of the historical studies in this space, and look ahead to three upcoming trials in papillary renal cell carcinoma. Papillary renal cell carcinoma (pRCC) is the second-most common subtype of kidney cancer following clear cell renal cell carcinoma (ccRCC), representing 15% of kidney cancers. Despite advances in therapy, including combination strategies with targeted therapies and immune checkpoint inhibitors, progress has lagged behind that of ccRCC. This is in part due to the heterogenous nature of the various subtypes of pRCC. More recently, investigators have turned efforts towards histology and biology-based trials. In this review, we outline some of the distinct biological characteristics of pRCC and discuss the most impactful clinical trials to date. Finally, we look ahead to several highly anticipated ongoing trials in pRCC. [ABSTRACT FROM AUTHOR]

Background: Some publications have recently been released on the safety of non-papillary access (NPA) in percutaneous nephrolithotomy (PCNL) by a Greek group. The purpose of this study was to prospectively examine the outcome of NPA during two years in a referral center. Methods: This prospective cohort study was conducted on PCNL operations performed from January 2020 to April 2022 in Labbafinejad Hospital. In cases in which obtaining papillary access (PA) was not obtainable after several attempts and NPA was obtained, or in cases in whom after entry to the pyelocalyceal system, a NPA was observed, the cases were categorized in the NPA group (n = 67). The control group (PA) was composed of patients who had undergone PCNL with papillary access with similar stone bulk (n = 67). The primary endpoints of interest were hemoglobin drop and transfusion frequency. The secondary endpoint included: stone free rate (SFR), operation duration, and complications. Results: A total of 134 patients were enrolled during the study period which included 33 female patients (25%). The mean ± SD age of patients was 49.6 ± 13.2 years. The frequency of transfusion and residual stones was not different between NPA and PA groups: 6 (9%) versus 8 (11%), P = 0.29; and 16 (24%) versus 12 (18%), P = 0.26. Likewise, the operation time (87.6 ± 25.8 versus 90.2 ± 22.6 min, P = 0.45), and the frequency of intraoperative and postoperative complications were not different between the NPA and PA groups. Conclusion: The results of this prospective study did not reveal a higher frequency of residual stones, transfusion, or complications in the NPA group. Nevertheless, our study is not powered enough to reveal complications of low frequency including delayed bleeding. [ABSTRACT FROM AUTHOR]

Hidden renal cell carcinoma (RCC) is not evident during severe inflammation such as acute pyelonephritis. We presented a 62‐year‐old male presenting with features of obstructive pyelonephritis managed with simple nephrectomy. However, the histopathology findings suggested unilateral papillary RCC. Our case showed that RCC might present with features of obstructive pyelonephritis. Severe inflammation, such as obstructive pyelonephritis, may masquerade RCC, which may delay the cancer diagnosis and lead to improper management. [ABSTRACT FROM AUTHOR]

Patients after kidney transplantation have a much higher risk of developing malignant tumors than the general population. And the native kidney is an organ relatively susceptible to malignant tumors after renal transplantation. However, the simultaneous development of bilateral renal tumors is very rare; especially the bilateral native kidneys harbor different pathological types of renal cell carcinoma (RCC). We report a case of a patient who developed malignant tumors in both native kidneys nearly 19 years after renal transplantation. This patient underwent bilateral laparoscopic radical nephrectomy, and postoperative pathological examination showed clear cell RCC on the left native kidney and papillary RCC on the right one. And the early detection and surgical treatment resulted in a good prognosis. The literature related to the diagnosis and treatment of bilateral RCC after renal transplantation is also reviewed. [ABSTRACT FROM AUTHOR]

Simple Summary: The analytic appropriateness and general applicability of lymph node-related risk factors used to predict long-term outcomes in patients with papillary thyroid carcinoma need to be validated. This study aimed to assess detailed lymph node-related risk factors and suggest new risk categories. In the present study, using the K-means clustering algorithm, we determined new cutoffs for lymph node variables besides extranodal extension: 0.2 cm and 1.1 cm for the maximal diameter of metastatic lymph node foci, 4 and 13 for the number of metastatic lymph nodes, and 0.28 and 0.58 for the metastatic lymph node ratio; new lymph node risk categories were suggested. The recurrence-free survival curves of each subgroup classified by these newly determined cutoffs showed significant differences. These newly developed risk categories might be considered when redefining risk stratification or staging systems. Background: Lymph node (LN)-related risk factors have been updated to predict long-term outcomes in patients with papillary thyroid carcinoma (PTC). However, those factors' analytic appropriateness and general applicability must be validated. This study aimed to assess LN-related risk factors, and suggest new LN-related risk categories. Methods: This multicenter observational cohort study included 1232 patients with PTC with N1 disease treated with a total thyroidectomy and neck dissection followed by radioactive iodine remnant ablation. Results: The median follow-up duration was 117 months. In the follow-up period, structural recurrence occurred in 225 patients (18.3%). Among LN-related variables, the presence of extranodal extension (p < 0.001), the maximal diameter of metastatic LN foci (p = 0.029), the number of retrieved LNs (p = 0.003), the number of metastatic LNs (p = 0.003), and the metastatic LN ratio (p < 0.001) were independent risk factors for structural recurrence. Since these factors showed a nonlinear association with the hazard ratio of recurrence-free survival (RFS) rates, we calculated their optimal cutoff values using the K-means clustering algorithm, selecting 0.2 cm and 1.1 cm for the maximal diameter of metastatic LN foci, 4 and 13 for the number of metastatic LN, and 0.28 and 0.58 for the metastatic LN ratio. The RFS curves of each subgroup classified by these newly determined cutoff values showed significant differences (p < 0.001). Each LN risk group also showed significantly different RFS rates from the others (p < 0.001). Conclusions: In PTC patients with an N1 classification, our novel LN-related risk estimates may help predict long-term outcomes and design postoperative management and follow-up strategies. After further validation studies based on independent datasets, these risk categories might be considered when redefining risk stratification or staging systems. [ABSTRACT FROM AUTHOR]

The incidence of differentiated thyroid cancer (DTC) has been increasing worldwide, mostly, as an increase in the incidental detection of micro papillary thyroid carcinomas (microPTCs), many of which are potentially overtreated, as suggested by the unchanged mortality. Several international guidelines have suggested a less aggressive approach. More recently, it has been shown that active surveillance or minimally invasive treatments (MIT) are good alternatives for the management of these patients. In this context, patient participation in the decision-making process is paramount. The Endocrine Task Force of the European Organisation for Research and Treatment of Cancer (EORTC) has undertaken the task to establish consensus and define its position based on the scientific evidence concerning, 1) the current state of diagnostic and management options in microPTCs, including the current opinion of physicians about shared decision making (SDM), 2) the available evidence concerning patients' needs and the available decision instruments, and 3) to provide practical suggestions for implementation of SDM in this context. To improve SDM and patients' participation, knowledge gaps and research directions were highlighted. • New management approaches for patients with low-risk microPTC have been introduced. • For all available options, scientific evidence is weak, resulting in clinical equipoise. • SDM to carefully discuss these treatment options with patients is paramount. [ABSTRACT FROM AUTHOR]

Introduction The identification of thyroid cancer may be conducted through clinical detection, imaging method, and histopathological examination. Both solitary nodules and multinodular goiter are associated with malignancy. Objective To assess the risk factors for malignancy among patients with multinodular goiter submitted to total thyroidectomy. Methods A series of 712 consecutive patients, submitted to total thyroidectomy between 2005 and 2016 with multinodular goiter regarding clinical, ultrasound, and pathological variables, was retrospectively evaluated. Results There were 408 cases of papillary carcinoma (57.3%), with the remaining being benign. Gender had no statistical significance (p = 0.169) for malignancy, unlike the Bethesda index, higher age group (p = 0.005), shorter clinical history time (p = 0.036), smaller number of nodules (p < 0.0001), and smaller nodule size (p < 0.0001), which were related to malignancy. Conclusion The Bethesda index, older age group, shorter clinical history, smaller number of nodules, and smaller size of nodule were related to the diagnosis of papillary carcinoma. [ABSTRACT FROM AUTHOR]

Non-clear cell renal cell carcinoma (nccRCC) is an entity comprised of a heterogeneous constellation of RCC subtypes. Genomic profiling has broadened our understanding of molecular pathogenic mechanisms unique to individual nccRCC subtypes. To date, clinical trials evaluating the use of immunotherapies and targeted therapies have predominantly been conducted in patients with clear cell histology. A comprehensive review of the literature has been undertaken in order to describe molecular pathogenic mechanisms pertaining to each nccRCC subtype, and concisely summarise findings from therapeutic trials conducted in the nccRCC space. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland and early stages are curable. However, a subset of PTCs shows an unusually aggressive phenotype with extensive lymph node metastasis and higher incidence of locoregional recurrence. In this study, we investigated a large cohort of PTC cases with an unusual aggressive phenotype using a high-throughput RNA sequencing (RNA-Seq) to identify differentially regulated genes associated with metastatic PTC. All metastatic PTC with mutated BRAF (V600E) but not BRAF wild-type expressed an up-regulation of R-Spondin Protein 4 (RSPO4) concomitant with an upregulation of genes involved in focal adhesion and cell-extracellular matrix signaling. Further immunohistochemistry validation confirmed the upregulation of these target genes in metastatic PTC cases. Preclinical studies using established PTC cell lines support that RSPO4 overexpression is associated with BRAF V600E mutation and is a critical upstream event that promote activation of kinases of focal adhesion signaling known to drive cancer cell locomotion and invasion. This finding opens up the potential of co-targeting B-Raf, RSPO and focal adhesion proteins as a pharmacological approach for aggressive BRAF V600E PTC. [ABSTRACT FROM AUTHOR]

Background: The tall cell variant papillary thyroid carcinoma (TCV‐PTC) shows aggressive behaviour. Thus far, the diagnosis of TCV‐PTC can only be confirmed using the postoperative specimen. This study aims to evaluate whether fine‐needle aspiration (FNA) or core needle biopsy (CNB) could diagnose TCV‐PTC preoperatively. Methods: This is a retrospective cohort study. We included adult patients diagnosed with TCV‐PTC or PTC with tall cell features (TCF) at final surgical pathology between January 2015 and December 2018. Preoperative histology was reviewed for six cytomorphologic features suggesting TCV‐PTC in FNA or the percentage of tall cells in the CNB specimen. The postoperative pathology was also reviewed to confirm the percentage of tall cells. Results: A total of 119 patients were included in this study; 35 (29%) patients with PTC with TCF served as controls. The most frequent cytomorphological feature in FNA samples of TCV‐PTC was tall columnar cells, including single tombstone‐like cells (70%). Among 43 TCV‐PTC evaluated by FNA, 3 FNA (7%) revealed the absence of any of the six cytomorphologic features suggesting TCV‐PTC. When we defined 30% of tall cells in CNB specimens as a cutoff suggesting TCV‐PTC, only 16 (41%) TCV‐PTCs could be preoperatively detected, and 3 (7%) TCV‐PTCs did not have any tall cells. The proportion of tall cells was not associated with the postoperative percentage of tall cells. Conclusion: Both cytomorphologic features in FNA and the percentage of tall cells in CNB present limitations for use as accurate preoperative diagnostic tools of TCV‐PTC. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most frequent endocrine cancer representing 1-1.5% of all cancers. Approximately 90% of these are differentiated thyroid carcinomas (DTC) with a favorable prognosis and cure rate. DTC has recently witnessed an increase in incidence with a relatively stable mortality rate, mostly due to intensive screening. Despite being considered indolent and the 10-year survival rate being above 90%, local or distant recurrence can be observed in up to 20% of cases. Mutations in BRAF, RET, RAS, NTRK1, PAX8-PPARG are commonly found in DTC but studies show that genetic alterations with apparently no correlation to DTC might improve or aggravate prognosis. Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms is consider to be one of these factors, due to the fact that it exerts immunological and antineoplastic functions thought its antiproliferative and pro-differentiating actions. FokI gene polymorphism has been associated with later stage and negative prognosis in different studies. Also, polymorphisms of genes involved in folate metabolism (MTHFR, MTR, RFC1) may be incriminated in carcinogenesis, folate being an extremely important factor in DNA synthesis. Studies suggest that through correction and avoidance of incriminated neoplastic agents, thyroid cancer incidence, evolution and prognosis might improve significantly. For this to be possible we need to be aware of the molecular pathways these environmental factors use to exert their carcinogenic effects.

Background: Recent guidelines in the management of papillary thyroid microcarcinoma (PTMC) recommend limiting surgery. However, trends in the characteristics and management of PTMC from the Middle East and North Africa region is lacking. Objectives: To determine the clinical features, management strategy, and outcomes of PTMC in a large tertiary care center in the United Arab Emirates (UAE). Patients and Methods: This retrospective study included all patients diagnosed with PTMC (i.e., size ≤10 mm) at Tawam Hospital, Al Ain, UAE, between 2008 and 2019. Tumor histopathology, management strategy, and outcomes were the primary analyzed variables. Results: A total of 213 patients with PTMC met the inclusion criteria, of which 83.6% were women and 58.7% were Emiratis. The majority had the classical tumor subtype (76.1%) and tumor of size 5–10 mm (71.4%). Multifocal disease was present in 41.1% and lymph node metastasis (LNM) in 16.6% of the patients. According to the 2015 American Thyroid Association categorization, the majority (93.9%) had a low-risk disease, and all except one patient had Stage 1 disease. Total thyroidectomy was performed in 91.1% of the patients, and 47.9% received radioiodine (RAI) therapy. None of the patients were under active surveillance strategy. RAI treatment was used more often in patients with non-incidental tumors, larger tumor size, multifocal disease, positive LNM, tumors in the intermediate/high ATA category, and those who underwent total thyroidectomy or neck dissection (for all, P < 0.05). After a median follow-up of 32.4 months, about 73% had an excellent response to dynamic risk stratification assessment, and only one patient had disease recurrence. Conclusions: The majority of the patients had low-risk PTMC, yet most patients underwent total thyroidectomy, and almost 50% were treated with RAI ablation. Further studies are needed to determine if these trends are also present regionally and to explore reasons for not adopting a less aggressive approach in this indolent tumor.

Aim:As a frequent finding of prenatal second trimester ultrasound screening, echogenic intracardiac focus (EIF) may have a relationship with serum calcium and magnesium levels instead of major fetal abnormalities. This study was conducted to assess the relationship between the EIF and serum calcium and magnesium levels in women who had undergone mid-trimester screening ultrasound and had no other soft markers or fetal malformations.Methods:This cross-sectional study was performed in a tertiary center experienced in maternal, fetal, and neonatal care, and included 206 patients who had undergone prenatal screening at 18-25 weeks of pregnancy with isolated EIF or without other laboratory abnormalities from July 2020 to June 2021. Serum calcium and magnesium levels were collected from the electronic health records of our institution.Results:Overall, although there were remarkable changes in some of the clinical characteristics of patients with or without EIF, in general, the study groups were found comparable in terms of these variables. No significant differences were found between the study groups regarding serum calcium and magnesium levels.Conclusions:Serum calcium and magnesium levels did not show a significant increase in cases with EIF. Therefore, measurement of serum calcium and magnesium levels in EIF cases was not found to be explanatory of the cause.

Abstract Hidden renal cell carcinoma (RCC) is not evident during severe inflammation such as acute pyelonephritis. We presented a 62‐year‐old male presenting with features of obstructive pyelonephritis managed with simple nephrectomy. However, the histopathology findings suggested unilateral papillary RCC. Our case showed that RCC might present with features of obstructive pyelonephritis.

ABSTRACT Research from the last 20 years has provided important insights into the molecular pathogenesis of craniopharyngiomas (CPs). Besides the well-known clinical and histological differences between the subtypes of CPs, adamantinomatous (ACP) and papillary (PCP) craniopharyngiomas, other molecular differences have been identified, further elucidating pathways related to the origin and development of such tumors. The present minireview assesses current knowledge on embryogenesis and the genetic, epigenetic, transcriptomic, and signaling pathways involved in the ACP and PCP subtypes, revealing the similarities and differences in their profiles. ACP and PCP subtypes can be identified by the presence of mutations in CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively. Therefore, β-catenin accumulates in the nucleus-cytoplasm of cell clusters in ACPs and, in PCPs, cell immunostaining with specific antibody against the V600E-mutated protein can be seen. Distinct patterns of DNA methylation further differentiate ACPs and PCPs. In addition, research on genetic and epigenetic changes and tumor microenvironment specificities have further clarified the development and progression of the disease. No relevant transcriptional differences in ACPs have emerged between children and adults. In conclusion, ACPs and PCPs present diverse genetic signatures and each subtype is associated with specific signaling pathways. A better understanding of the pathways related to the growth of such tumors is paramount for the development of novel targeted therapeutic agents.

Introduction The identification of thyroid cancer may be conducted through clinical detection, imaging method, and histopathological examination. Both solitary nodules and multinodular goiter are associated with malignancy. Objective To assess the risk factors for malignancy among patients with multinodular goiter submitted to total thyroidectomy. Methods A series of 712 consecutive patients, submitted to total thyroidectomy between 2005 and 2016 with multinodular goiter regarding clinical, ultrasound, and pathological variables, was retrospectively evaluated. Results There were 408 cases of papillary carcinoma (57.3%), with the remaining being benign. Gender had no statistical significance (p = 0.169) for malignancy, unlike the Bethesda index, higher age group (p = 0.005), shorter clinical history time (p = 0.036), smaller number of nodules (p

BackgroundIn an era of rising differentiated thyroid cancer incidence, the rate and impact of neck reoperation may inform the intensity of earlier interventions and surveillance. This study sought to define predictors of neck reoperation and to assess its impact on survival.MethodsUsing the California Cancer Registry linked to the California Office of Statewide Health Planning and Development records, a retrospective cohort study was performed of 24,230 patients with total or near-total thyroidectomy for papillary or follicular thyroid cancer between 1991 and 2008 and follow-up through 2013. The primary outcome was neck reoperation 91 days to 5 years after the initial thyroid surgery. Using logistic and Cox proportional hazards regression, the impact of sociodemographics, tumor staging, and hospital thyroid cancer surgery volume on neck reoperation and survival was determined.ResultsNeck reoperation was identified in 1231 (5.1%) patients in increasing odds from 1991 to 2008. In multivariable models, male sex, papillary thyroid cancer, and advancing tumor stage were associated with neck reoperation. Among men, neck reoperation was associated with Asian/Pacific Islander (odds ratio [OR] = 1.44 [confidence interval (CI) 1.07-1.94]) race/ethnicity. Among women, neck reoperation was associated with younger age (15-34 years; OR = 1.50 [CI 1.17-1.92] versus ≥55 years), and Asian/Pacific Islander (OR = 1.24 [CI 1.02-1.51]) or Hispanic (OR = 1.20 [CI 1.00-1.44]) race/ethnicity. After controlling for baseline characteristics, neck reoperation predicted worse thyroid cancer-specific survival (hazard ratio = 4.26 [CI 3.50-5.19]). The effect differed between men and women, and was most pronounced among women who received radioiodine in initial treatment (hazard ratio = 8.32 [CI 6.14-11.27]).ConclusionsNeck reoperation is becoming increasingly frequent and is strongly predictive of mortality. Advancing tumor stage, Asian/Pacific Islander race/ethnicity, male sex, as well as younger age and Hispanic ethnicity among women predict a higher risk for neck reoperation and subsequent mortality, reflecting a higher risk of persistent or more biologically aggressive disease.

The newly introduced pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) will result in less bilateral thyroid surgery as well as deescalation in T4 suppressive and radioactive iodine treatment. Although, NIFTP is a nonmalignant lesion that has nuclear features of some papillary malignancies, the challenge for the surgeon is to identify a lesion as possibly NIFTP before the pathologic diagnosis. NIFTP, due to its reduction of overall rates of malignancy, will result in the initial surgical pendulum swinging toward lobectomy instead of initial total thyroidectomy. This American Head and Neck Society endocrine section consensus statement is intended to inform preoperative evaluation to attempt to identify those patients whose final pathology report may ultimately harbor NIFTP and can be offered a conservative surgical plan to assist in cost-effective, optimal management of patients with NIFTP.

Purpose: Sixty percent of papillary thyroid cancers (PTC) have an oncogenic (V600E) BRAF mutation. Inhibitors of BRAF and its substrates MEK1/2 are showing clinical promise in BRAFV600E PTC. PTC progression can be decades long, which is challenging in terms of toxicity and cost. We previously found that MEK1/2 require copper (Cu) for kinase activity and can be inhibited with the well-tolerated and economical Cu chelator tetrathiomolybdate (TM). We therefore tested TM for antineoplastic activity in BRAFV600E -positive PTC.Experimental Design: The efficacy of TM alone and in combination with current standard-of-care lenvatinib and sorafenib or BRAF and MEK1/2 inhibitors vemurafenib and trametinib was examined in BRAFV600E-positive human PTC cell lines and a genetically engineered mouse PTC model.Results: TM inhibited MEK1/2 kinase activity and transformed growth of PTC cells. TM was as or more potent than lenvatinib and sorafenib and enhanced the antineoplastic activity of sorafenib and vemurafenib. Activated ERK2, a substrate of MEK1/2, overcame this effect, consistent with TM deriving its antineoplastic activity by inhibiting MEK1/2. Oral TM reduced tumor burden and vemurafenib in a BrafV600E -positive mouse model of PTC. This effect was ascribed to a reduction of Cu in the tumors. TM reduced P-Erk1/2 in mouse PTC tumors, whereas genetic reduction of Cu in developing tumors trended towards a survival advantage. Finally, TM as a maintenance therapy after cessation of vemurafenib reduced tumor volume in the aforementioned PTC mouse model.Conclusions: TM inhibits BRAFV600E -driven PTC through inhibition of MEK1/2, supporting clinical evaluation of chronic TM therapy for this disease. Clin Cancer Res; 24(17); 4271-81. ©2018 AACR.

BACKGROUND:Papillary thyroid carcinoma with squamous differentiation (PTC-SD) is a poorly understood pathologic finding of unknown clinical significance. Selected case reports have suggested that PTC-SD is an aggressive tumor with a poor prognosis. Here we present the largest case series of PTC-SD reported in the United States. MATERIALS AND METHODS:The cancer registry at our tertiary care referral center was reviewed to identify all patients from 1995-2015 who had been diagnosed with PTC-SD on initial total thyroidectomy or lymph node dissection for recurrent disease. All cases were reviewed by an endocrine pathologist to confirm the diagnosis. Patient demographic, pathology, and outcomes data were collected and reviewed. RESULTS:During the study period, ten patients were diagnosed with PTC-SD, six in the primary tumor at the time of initial surgery, and four in lymph node metastases during surgery for recurrent disease. The median age at diagnosis was 56 y and half of the patients were male. Aggressive features such as multifocality (67%), extrathyroidal extension (67%), positive margin (89%), lymph node metastases (80%), and extranodal extension (60%) were far more prominent than is typically seen in classic PTC. Long-term follow-up (median 56.5 mo) demonstrated high rates of locoregional recurrence (60%), pulmonary metastases (30%), and mortality (10%). CONCLUSIONS:Squamous differentiation is a rare finding in PTC that is associated with aggressive pathologic features and poor long-term outcomes. This phenomenon may represent a step in progression toward dedifferentiation; thus, patients with PTC-SD should have close, life-long surveillance and should be treated according to evidence-based guidelines for high-risk thyroid cancers.

The incidence of intraductal papillary mucinous neoplasms (IPMNs) has been increasing over the past decade, mainly owing to increased awareness and the increased use of cross-sectional imaging. The Sendai and Fukuoka consensus guidelines provide us with clinical management guidelines and algorithms; however, the clinical management of IPMNs continues to be challenging. Our incomplete understanding of the natural history of the disease, and the events and pathways that permit progression to adenocarcinoma, result in difficulties predicting which tumors are high risk and will progress to invasive disease. In this review, we summarize the current management guidelines and describe ongoing efforts to more clearly stratify IPMNs by risk of malignancy and identify IPMNs with malignant potential or ongoing malignant transformation.

Purpose: This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center. Methods: Patients with histologically confirmed PTC who underwent surgic al treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short-and long-termed, were collected. Results: A total of 128 patients (68% females) were included in this st udy with a mean age of 38 years (±13.8). The median follow-up period was 50 mon ths. The BRAF V600E mutation was found in 71% of patients. The tumour size for pati ents with a negative BRAF V600E mutation was significantly larger in comparison to pa tients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0–168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3–142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall surviva l rates, positive = 94.5% (median 56 months (0–228)) compared to 94.6% for the neg ative BRAF V600E mutation (median 43 months (3–157)) (P = 0.941, HR = 0.940). Conclusion: BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attr ibuted to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.

Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6–12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. Results: A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19–87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 − 7.45), male sex (OR, 2.48; 95% CI, 1.47 − 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 − 3.27) were independently significant. Conclusions: The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinical trial registration: Clinicaltrials.gov NCT02938702. [ABSTRACT FROM AUTHOR]

Background: Prophylactic central lymph node dissection (CLND) in papillary thyroid carcinoma (PTC) is still controversial. This study aimed to analyze the factors related to the patient and tumor characteristics affecting central lymph node metastasis (CLNM) in PTC patients and to evaluate the contribution of the results to shaping the surgical treatment algorithm. Methods: Two hundred and fifty-five PTC patients who underwent total thyroidectomy and CLND were evaluated retrospectively. Histopathology reports were examined to reveal tumor characteristics. The CLNM ratio and the relationship between CLNM with clinicopathological and demographic characteristics were analyzed. Results: The incidence of CLNM was 54.9% (95 CI%: 49-60.8). Male gender (P = 0.027), age < 45 years (P = 0.016), tumor size ≥ 9.5 mm (P < 0.001), lymphovascular invasion (P < 0001) and extracapsular invasion (P = 0.007) were factors that increased the risk of metastasis. The follicular variant decreased the risk (P = 0.010). There was no relationship between CLNM and focality (P = 0.054). A low-to-moderate correlation was found between tumor diameter and the metastatic lymph node (MLN) number/total lymph node number ratio (r = 0.396, P < 0.001). Conclusion: A selective prophylactic CLND strategy can be applied in cN0 patients. As the tumor diameter increases in PTC, both the risk of CLNM and the number of MLN increase. Lymphovascular and extracapsular invasion are other factors that increase the risk. The follicular variant is associated with a lower risk of CLNM. Male patients who are under the age of 45 and have a tumor diameter of 9.5 mm or more are definite candidates for prophylactic CLND. [ABSTRACT FROM AUTHOR]

Context: It is not known how underlying subclinical papillary thyroid cancer (PTC) differs by age. This meta-analysis of autopsy studies investigates how subclinical PTC prevalence changes over the lifetime. Methods: We searched PubMed, Embase, and Web of Science databases from inception to May 2021 for studies that reported the prevalence of PTC found at autopsy. Two investigators extracted the number of subclinical PTCs detected in selected age groups and extent of examination. A quality assessment tool was used to assess bias. Logistic regression models with random intercepts were used to pool the age-specific subclinical PTC prevalence estimates. Results: Of 1773 studies screened, 16 studies with age-specific data met the inclusion criteria (n = 6286 autopsies). The pooled subclinical PTC prevalence was 12.9% (95% CI 7.8-16.8) in whole gland and 4.6% (2.5-6.6) in partial gland examination. Age-specific prevalence estimates were =40 years, 11.5% (6.8-16.1); 41-60 years, 12.1% (7.6-16.5); 61-80 years, 12.7% (8-17.5); and 81+ years, 13.4% (7.9-18.9). Sex did not affect agespecific prevalence and there was no difference in prevalence between men and women in any age group. In the regression model, the OR of prevalence increasing by age group was 1.06 (0.92-1.2, P = .37). Conclusion: This meta-analysis shows the prevalence of subclinical PTC is stable across the lifespan. There is not a higher subclinical PTC prevalence in middle age, in contrast to higher observed incidence rates in this age group. These findings offer unique insights into the prevalence of subclinical PTC and its relationship to age. [ABSTRACT FROM AUTHOR]

Objective: Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid carcinoma, and is prone to cervical lymph node metastases (CLNM). We aim to evaluate the association between sonographic characteristics of PTC and CLNM before the initial surgery. Methods: Clinical information as well as ultrasonographic measurements and characteristics for 2376 patients from three hospitals were acquired in this retrospective cohort study. Univariate and multivariate logistic analysis were performed to predict CLNM in unifocal PTC patients. Receiver operating characteristic (ROC) curve was created to evaluate diagnostic performance. Results: Univariate analysis showed that gender, age, maximum tumor diameter and volume, cross-sectional and longitudinal aspect ratio, location, echogenicity, margin, and echogenic foci were independently associated with CLNM metastatic status (P < 0.05). Multivariate logistic analysis showed that gender, age, maximum tumor diameter and volume, cross-sectional aspect ratio (CSAR), location, echogenicity, margin, and echogenic foci were independent correlative factors; CSAR showed a significant difference for PTC2 to predict CLNM. The area under the curve (AUC) of the maximum tumor diameter, tumor volume, margin, and echogenic foci was 0.70, 0.69, 0.65, and 0.70, respectively. The multiple-variable linear regression model was constructed with an AUC of 0.77, a specificity of 73.4%, and a sensitivity of 72.3%. Kruskal-Wallis analysis for positive subgroups, maximum tumor diameter and volume, cross-sectional and longitudinal aspect ratio, margin, and echogenic foci showed statistical significance (P < 0.05). Conclusions: Younger age (< 55 years), male, larger tumor, and echogenic foci were high risk factors for CLNM in patients with unifocal PTC. CSAR had a more effective predictive value for CLNM in patients with larger thyroid tumors. A larger tumor with irregular and punctate echogenic foci was also more prone to the lateral neck, and both central and lateral neck metastasis. [ABSTRACT FROM AUTHOR]

Background: Florida Firefighters experience a higher risk of thyroid cancer than non-firefighters. This study examines whether the histologic types and tumor stage of thyroid cancer is different among firefighters compared to other occupational groups. Methods: Eligible cases were firefighters (n = 120) identified in a linkage of Florida Cancer Data System (FCDS) registry records (1981–2014) and Florida State Fire Marshal's Office employment and certification records, and non-firefighters classified into: blue-collar (n = 655), service (n = 834), white-collar (n = 4,893), and other (n = 1,789). Differences in thyroid histologic type (papillary, follicular, and rare/other less common forms of thyroid cancer), tumor stage, and age at diagnosis were evaluated using multinomial logistic regression models comparing blue-collar, service, white-collar, and other occupational groups with firefighters. Univariate odds ratios as well as odds ratios adjusted for age, gender, race, tumor stage, and year of diagnosis (aOR) and 95% confidence intervals (95%CI) were reported. Results: Service (aOR = 4.12; 95%CI: 1.25—13.65), white-collar (aOR = 3.51; 95%CI: 1.08—11.36), and blue-collar (aOR = 4.59; 95%CI: 1.40—15.07) workers had significantly higher odds of being diagnosed with rare histologic types of thyroid cancer vs papillary type compared to firefighters. Service (aOR = 0.42; 95%CI: 0.27—0.66), white-collar (aOR = 0.39; 95%CI: 0.26—0.59), blue-collar (aOR = 0.36; 95%CI: 0.23—0.56), and other (aOR = 0.34; 95%CI: 0.22—0.53) occupational groups have a significantly lower odds of being diagnosed with rare vs papillary type at a younger age (30—49 years) vs 50—69 years compared to firefighters. However, stage at diagnosis was not significantly different among occupational groups. Conclusion: Firefighters diagnosed with thyroid cancer experience a higher odds of papillary compared to rare histologic types of thyroid cancer relative to other workers; there is no evidence of an increased odds of late-stage diagnosis in firefighters relative to other worker groups. Firefighters may benefit from routine screening and active surveillance of suspected thyroid tumors especially given the excellent treatment outcomes available for those diagnosed with early-stage papillary thyroid tumors. [ABSTRACT FROM AUTHOR]

Purpose of Review: Historically, kidney cancer was diagnosed as either clear cell renal carcinoma (ccRCC) or non-clear cell renal carcinoma (nccRCC). With further research into the pathophysiology of nccRCC, multiple distinct subtypes have emerged creating distinct diagnosis, such as papillary renal cell carcinoma (PRCC), chromophobe renal cell carcinoma (crRCC), or unclassified carcinoma (cRCC). Many other kidney cancer subtypes are now included in the WHO classification system. Recent Findings: The prognosis for each of the more frequently diagnosed types is discussed here along with treatment recommendations. The available clinical trial results and salient retrospective studies of each subtype are reviewed here to guide clinicians on the optimal treatment selection for patients with these rare histologic types or RCC. Summary: Many nccRCC types are now recognized and each has unique molecular drivers which are different than ccRCC. The optimal treatment strategy is different for each subtype. The prognosis also differs based on the histology. [ABSTRACT FROM AUTHOR]

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Renal cell carcinoma with papillary and oncocytic features (RCC-PO) are poorly understood, partially due to conflicting results in multiple studies. The histological features that predict behavior of RCC-PO have not been elucidated. The aim is to review clinicopathologic features and to correlate clinical outcomes of patients with RCC-PO to further expand our knowledge on these heterogeneous tumors. An archival search was done for "RCC" and "papillary," and tumors with >50% papillary and oncocytic features were included. Clinicopathologic data including tumor size, grade, stage, molecular and immunohistochemical testing when performed, and follow-up data were collected. Using multivariate analyses, correlation between histological features, tumor stage and prognosis were analyzed. Sixty-one patients with RCC-PO were identified of which 49 (80%) were male with a median age of 65 (range: 36-93) years, and a mean tumor size of 5.2 (range: 1-21.5) cm. Micropapillary features were seen in 4, bizarre nuclei (at least 3 times larger or with irregular shape) in 6, multinucleated tumor cells (MTC) in 15, single or small clusters (SSC) (made of 2-3 tumor cells) located away from areas of necrosis in 16, and striking eosinophilic cytoplasmic inclusions in 3 tumors, respectively. Thirty-six (59%) tumors were high-grade (WHO/ISUP grade 3-4), and 23 (38%) had a high stage (≥pT3 or pN1). Tumors were positive for AMACR (15/16) and CK7 (13/17), with preserved FH (7/7) staining and were all negative for CD117 (0/7), ALK, TFE3, cathepsin K, Melan A, and HMB45 (0/4, each). Three tumors underwent chromosomal microarray (CMA) plus gene fusion assay, and FISH and germline testing for FLCN and MET gene alterations by PCR were done on 1 each. Ten (16%) patients had a local recurrence (LR) or metastasis after nephrectomy; 4 died of disease (2 had tumors with micropapillary features), with a median follow-up of 7 (range: 0.01-19) years. Tumors with micropapillary features showed significantly higher RCC-PO-related mortality (50% vs. 3.5%, p < 0.001). In multivariable analysis, SSC correlated with a higher stage (HR: 11.95; p = 0.005); micropapillary features (HR: 18.42; p = 0.017) and MTC (HR: 180.22; p = 0.036) with presence of metastasis/LR; and micropapillary features with a higher RCC-PO-related mortality (HR: 60.35; p = 0.036). RCC-PO are cytogenetically heterogeneous with overlapping features of various renal neoplasms. Micropapillary features and MTC appear to be independent predictors of poor outcomes in these tumors., Competing Interests: Declaration of competing interest Nothing to declare., (Copyright © 2024. Published by Elsevier Inc.)

In this case report, we describe a diagnosis of papillary renal cell carcinoma in a 76-year-old male patient who was incidentally found to have a left adrenal mass during routine aneurysm surveillance. Computed tomography demonstrated a left adrenal mass and left renal structure which was concerning for renal cell carcinoma. He underwent left adrenalectomy and initial histopathology demonstrated papillary renal cell carcinoma. He subsequently underwent left radical nephrectomy with lymph node dissection. Histopathological analysis of the removed left renal and nodal specimens revealed papillary renal cell carcinoma with lymph node metastasis. However, re-review of the adrenal pathology slides determined the specimen as represented by primary kidney tumor and not adrenal metastasis. This report reviews the presentation and radiological findings of synchronous papillary renal cell carcinoma and differential diagnosis for indeterminate adrenal mass on computed tomography., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objectives: The present study aims to characterize immunohistochemical features of markers associated with Epithelial-Mesenchymal Transition (EMT) and proliferative activity that could lead to death in Papillary Thyroid Cancer (PTC)., Methods: Clinical data and tumor material were retrospectively collected. The patients were separated into death from PTC (Group 1), metastatic cases with indolent behavior (Group 2) and non-metastatic indolent PTC (Group 3). Immunohistochemical assessment of E-cadherin, β-catenin, Vimentin, ZEB-1 and Ki-67 was performed in each tumor and a semiquantitative estimation of the percentage of expression was fulfilled on the best marking area at high of the tumor invasion front., Results: 31 patients were included, 15 that died from PTC (Group 1), 6 in Group 2 and 10 in Group 3. The proliferative marker Ki-67 showed a significant difference in its expression in the tumor invasion front between the groups, specifically between groups 1 and 3 (p = 0.006). On the other hand, EMT-related immunohistochemical markers did not show significant difference in their percentage of expression, since loss of E-cadherin, β-catenin and Vimentin was observed in most cases at the invasion front., Conclusion: Patients that died from PTC had a significantly higher Ki-67 labelling index compared to patients with indolent disease (cutoff of 11%). Ki-67 may have a role as a prognostic marker and could be considered for routine use in PTC., (Copyright © 2024. Published by Elsevier España S.L.U.)