HNF-1ß as an immunohistochemical marker for distinguishing chromophobe renal cell carcinoma and hybrid oncocytic tumors from renal oncocytoma.

The histologic features of renal oncocytoma (RO) are similar to those for the more aggressive chromophobe renal cell carcinoma (ChRCC). To assess immunohistochemical markers of the two, the sensitivity and specificity of cytokeratin 7 (CK7) and C-kit, as well as hepatocyte nuclear factor-1ß (HNF-1ß), were analyzed. Typical cases of ChRCC and RO at Severance Hospital between July 2014 and July 2018 were selected retrospectively. Among 44 cases, 17 were unanimously compatible with ChRCC, 16 were RO, and 11 cases were indeterminate. Samples from all selected cases were used for immunostaining with antibodies against CK7, C-kit, HNF-1ß, and CD10. Immunostaining demonstrated complete loss of HNF-1ß expression in 11 out of 17 (64.7%) ChRCC cases and a partial, but significant loss in > 50% of tumor cells in the remaining 6 cases (35.3%). In contrast, HNF-1ß expression was preserved in tumor cells of RO cases. Fourteen of 17 ChRCC cases (82.4%) were diffusely positive for CK7, whereas cases of RO were focal positive or negative. C-kit staining did not show a significant difference between ChRCC and RO. Two of five ChRCC cases showing diffuse immunoreactivity for CD10 had poor prognoses of local invasion, distant metastasis, or death. Loss of HNF-1ß expression is a useful marker with which to diagnose ChRCC, especially in cases with confusing histologic findings or equivocal CK7 staining. Additionally, CD10 staining in high-grade ChRCC aids in diagnosis and prediction of the clinical prognosis.

The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated with even more adverse outcome than classical PDTC cases, but its specific molecular features are largely unknown. Our aim was to explore the immune-related gene expression profile of oncocytic and classical PDTC, in correlation with clinical and pathological characteristics (including programmed death ligand 1 [PD-L1] expression) and outcome, and in comparison with a control group of well-differentiated follicular carcinomas (WDFCs), including conventional follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). METHODS: A retrospective series of 48 PDTCs and 24 WDFCs was analyzed by means of NanoString technology employing the nCounter PanCancer Immune Profiling panel. Gene expression data were validated using quantitative real-time polymerase chain reaction. RESULTS: Oncocytic PDTCs showed a specific immune-related gene expression profile, with higher expression of LAIR2, CD274, DEFB1, IRAK1, CAMP, LCN2, LY96, and APOE, and lower expression of NOD1, as compared to conventional PDTCs. This molecular signature was associated with increased intratumoral lymphocytic infiltration, PD-L1 expression, and adverse outcome. Three of these genes, CD274, DEFB1, and IRAK1, as well as PD-L1 expression, were also the hallmarks of HCCs as compared to FTCs. By contrast, the panel of genes differentially regulated in PDTCs as compared to WDFCs was unrelated to the oncocytic phenotype. CONCLUSIONS: Our results revealed a distinctive immune-related gene expression profile of oncocytic PDTC and confirmed a more aggressive outcome in this cancer subtype. These findings may provide guidance when exploring novel immunotherapeutic options for oncocytic PDTC patients.

Identification of Key Genes and Prognostic Analysis between Chromophobe Renal Cell Carcinoma and Renal Oncocytoma by Bioinformatic Analysis.

The present techniques of clinical and histopathological diagnosis hardly distinguish chromophobe renal cell carcinoma (ChRCC) from renal oncocytoma (RO). To identify differentially expressed genes (DEGs) as effective biomarkers for diagnosis and prognosis of ChRCC and RO, three mRNA microarray datasets (GSE12090, GSE19982, and GSE8271) were downloaded from the GEO database. Functional enrichment analysis of DEGs was performed by DAVID. STRING and Cytoscape were applied to construct the protein-protein interaction (PPI) network and key modules of DEGs. Visualized plots were conducted by the R language. We downloaded clinical data from the TCGA database and the influence of key genes on the overall survival of ChRCC was performed by Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) was utilized in exploring the function of key genes. A total of 79 DEGs were identified. Enrichment analyses revealed that the DEGs are closely related to tissue invasion and metastasis of cancer. Subsequently, 14 hub genes including ESRP1, AP1M2, CLDN4, and CLDN7 were detected. Kaplan-Meier analysis indicated that the low expression of CLDN7 and GNAS was related to the worse overall survival in patients with ChRCC. Univariate Cox analysis showed that CLDN7 might be a helpful biomarker for ChRCC prognosis. Subgroup analysis revealed that the expression of CLDN7 showed a downtrend with the development of the clinical stage, topography, and distant metastasis of ChRCC. GSEA analysis identified that cell adhesion molecules cams, B cell receptor signaling pathway, T cell receptor signaling pathway, RIG-I like receptor signaling pathway, Toll-like receptor signaling pathway, and apoptosis pathway were associated with the expression of CLDN7. In conclusion, ESRP1, AP1M2, CLDN4, PRSS8, and CLDN7 were found to distinguish ChRCC from RO. Besides, the low expression of CLDN7 was closely related to ChRCC progression and could serve as an independent risk factor for the overall survival in patients with ChRCC.

The N6 -methyladenosine (m6 A) erasers alkylation repair homologue 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) are prognostic biomarkers in patients with clear cell renal carcinoma.

OBJECTIVES: To comprehensively investigate the role of the N6 -methyladenosine (m6 A) erasers ALKBH5 and FTO in clear cell renal cell carcinoma (ccRCC), other RCC subtypes, and oncocytoma with respect to prognostic value and biomarker potential. PATIENTS AND METHODS: The collection of tissue samples was performed within the framework of the Biobank at the Centre for Integrated Oncology Cologne-Bonn. The gene expressions of alkylation repair homologue 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) were determined using quantitative real-time polymerase chain reaction. ALKBH5 and FTO expressions were further investigated in ccRCC, papillary RCC, chromophobe RCC, sarcomatoid RCC, oncocytoma, and benign renal tissue using tissue microarrays. RESULTS: ALKBH5 mRNA, as well as ALKBH5 and FTO protein expressions, was significantly downregulated in ccRCC compared to normal tissue and most of the other studied tumour entities. Decreased mRNA levels of ALKBH5 and FTO correlated with a shortened overall and cancer-specific survival following nephrectomy. CONCLUSIONS: Taken together, our present data indicate that the m6 A-demethylases ALKBH5 and FTO are dysregulated in ccRCC and could be used as prognostic biomarkers.

Survival with Follicular and Hurthle Cell Microcarcinoma Compared to Papillary Thyroid Microcarcinoma: A Population Study of 84,532 Patients.

BACKGROUND: This study compares survival in patients with the rare subtypes of follicular (FTmC) and Hurthle cell (HCmC) microcarcinoma compared to that of papillary thyroid (PTmC) microcarcinoma. METHODS: Patients with FTmC and HCmC were selected from the National Cancer Database 2004-2015 and compared with PTmC. Patient clinicopathological characteristics and overall survival (OS) were analyzed. Multivariable logistic and Cox regression analysis evaluated binary outcomes and predictors of survival. A propensity score matched analysis using age, gender, race, extrathyroidal extension (ETE), nodal status, distant metastasis, radiation, and operation was performed to evaluate the difference in OS with FTmC, HCmC, and PTmC. RESULTS: We identified 858 FTmC, 476 HCmC, and 82,056 PTmC. FTmC was less likely to have macroscopic ETE compared to PTmC (2.6% vs. 3.1% p = 0.03), but more likely to have distant metastasis (2.3% vs. 0.2%, p < 0.01). FTmC and HCmC were less likely to have nodal metastasis (2.7%, 2.5% vs. 10.9%, p < 0.01). Ten-year OS was decreased in patients with FTmC (91.4%, p = 0.04) and HCmC (89.8%, p < 0.01) compared to PTmC (93.5%). On multivariable analysis, histology was not associated with OS. With HCmC, older age (OR 1.13, p < 0.01) and male gender (OR 2.72, p = 0.03) were associated with decreased OS. In propensity matched analysis, there was no difference in 10-year OS with FTmC and PTmC (91.4% vs. 93.7%, p = 0.54), but HCmC had decreased OS compared to PTmC (89.8% vs. 94.3%, p = 0.04). CONCLUSIONS: Patients with FTmC have comparable OS to those with PTmC, but HCmC has decreased OS especially in older and male patients.

Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up.

Objective: The objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up. Methods: A retrospective review of medical records identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019. Results: In total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent prognostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively). Conclusions: WDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.

Comparing oncologic outcomes in patients undergoing surgery for oncocytic neoplasms, conventional oncocytoma, and chromophobe renal cell carcinoma.

INTRODUCTION: Oncocytic neoplasms are renal tumors similar to oncocytoma, but their morphologic variations preclude definitive diagnosis. This somewhat confusing diagnosis can create treatment and surveillance challenges for the treating urologist. We hypothesize that these subtle morphologic variations do not drastically affect the malignant potential of these tumors, and we sought to demonstrate this by comparing clinical outcomes of oncocytic neoplasms to those of classic oncocytoma and chromophobe. METHODS: We gathered demographic and outcomes data for patients with variant oncocytic tumors. Oncologic surveillance was conducted per institutional protocol in accordance with NCCN guidelines. Descriptive statistics were used to compare incidence of metastasis and death against those for patients with oncocytoma and chromophobe. Three hundred and fifty-one patients were analyzed: 164 patients with oncocytoma, 28 with oncocytic neoplasms, and 159 with chromophobe tumors. RESULTS: Median follow-up time for the entire cohort was 32.4 months, (interquartile range 9.2-70.0). Seventeen total patients (17/351, 4.9%) died during the course of the study. In patients with oncocytoma or oncocytic neoplasm, none were known to metastasize or die of their disease. Only chromophobe tumors >6 cm in size in our series demonstrated metastatic progression and approximately half of these metastasized tumors demonstrated sarcomatoid changes. CONCLUSION: Variant oncocytic neoplasms appear to have a natural course similar to classic oncocytoma. These tumors appear to have no metastatic potential, and oncologic surveillance may not be indicated after surgery.

Evaluating the 2015 American Thyroid Association Risk Stratification System in High-Risk Papillary and Follicular Thyroid Cancer Patients.

Background: The 2015 American Thyroid Association (ATA) Risk Stratification System for differentiated thyroid cancer (DTC) is designed to predict recurring/persisting disease but not survival. Earlier studies evaluating this system evaluated the 2009 edition, comprised a low number of patients with ATA high-risk, had low numbers of patients with follicular thyroid cancer (FTC), or did not distinguish between papillary and FTC. Therefore, we evaluated the prognostic value of the 2015 ATA Risk Stratification System in a large population of high-risk thyroid cancer patients, which included a substantial proportion of FTC patients. Methods: We retrospectively studied adult patients with DTC who were diagnosed and/or treated at a Dutch university hospital between January 2002 and December 2015. All patients fulfilled the 2015 ATA high-risk criteria. Overall survival and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method. Logistic regression and Cox proportional hazards models were used to estimate the effects of DTC subtype and ATA high-risk criteria on response to therapy, recurrence, as well as survival. Results: We included 236 patients with high-risk DTC (32% FTC) with a mean age of 56 years. Median follow-up was 6 years. At final follow-up, 69 patients (29%) had excellent response, while 120 (51%) had structural disease. All high-risk criteria, except large pathologic lymph nodes, were inversely related to excellent response and positively related to structural disease at final follow-up. During follow-up, 14% of the 79 patients who achieved excellent response developed a recurrence. Finally, 10-year DSS was much higher in the initial excellent response than in the initial structural disease group (100% vs. 61%, respectively). Conclusions: In a population of high-risk DTC patients harboring a large subset of FTC patients, the 2015 ATA Risk Stratification System is not only an excellent predictor of persisting disease but also of survival. As much as 14% of the high-risk patients who had an excellent response upon dynamic risk stratification experienced a recurrence during follow-up. Clinicians should thus be aware of the relatively high recurrence risk in these patients, even after an excellent response to therapy.

Contemporary surgical management of renal oncocytoma: a nation's outcome.

OBJECTIVE: To report on the contemporary UK experience of surgical management of renal oncocytomas. PATIENTS AND METHODS: Descriptive analysis of practice and postoperative outcomes of patients with a final histological diagnosis of oncocytoma included in The British Association of Urological Surgeons (BAUS) nephrectomy registry from 01/01/2013 to 31/12/2016. Short-term outcomes were assessed over a follow-up of 60 days. RESULTS: Over 4 years, 32 130 renal surgical cases were recorded in the UK, of which 1202 were oncocytomas (3.7%). Most patients were male (756; 62.9%), the median (interquartile range [IQR]) age was 66.8 (13) years. The median (IQR; range) lesion size was 4.1 (3; 1-25) cm, 43.5% were ≤4 cm and 30.3% were 4-7 cm lesions. In all, 35 patients (2.9%) had preoperative renal tumour biopsy. Most patients had minimally invasive surgery, either radical nephrectomy (683 patients; 56.8%), partial nephrectomy (483; 40.2%) or other procedures (36; 3%). One in five patients (243 patients; 20.2%) had in-hospital complications: 48 were Clavien-Dindo classification grade ≥III (4% of the total cohort), including three deaths. Two additional deaths occurred within 60 days of surgery. The analysis is limited by the study's observational nature, not capturing lesions on surveillance or ablated after biopsy, possible underreporting, short follow-up, and lack of central histology review. CONCLUSION: We report on the largest surgical series of renal oncocytomas. In the UK, the complication rate associated with surgical removal of a renal oncocytoma was not negligible. Centralisation of specialist services and increased utilisation of biopsy may inform management, reduce overtreatment, and change patient outcomes for this benign tumour.

Tyrosine kinase inhibitors in iodine-refractory differentiated thyroid cancer: experience in clinical practice.

PURPOSE: The aim of this study is to describe our clinical experience with tyrosine kinase inhibitors (TKIs) and to evaluate their efficacy and tolerability in patients with iodine-refractory differentiated thyroid cancer (DTC). METHODS: There were 17 patients (47.1% women, mean age: 65.7) with DTC iodine-refractory (9 papillary, 2 follicular and 3 Hürthle cell), treated with TKIs: 16 with sorafenib and 1 with lenvatinib as first-line treatment; 7 required second-line treatment (4 lenvatinib and 3 axitinib). Primary endpoints were progression-free survival (PFS) and radiographic response (determinate at 3, 6, 12, 18, and 24 months after the initiation of treatment) and second endpoints were determining differences in baseline characteristics depending on clinical course and describing toxicities and tolerability. RESULTS: Median PFS was 18 months. During the first 24 months of treatment with TKIs PR rate was 35.3% (only 5.8% ≥ 6 months) and SD ≥ 6 months was observed in 58.8%. There were no significant differences in baseline characteristics between patients with good and poor evolution. Adverse events (AEs) were present in 100% of patients, but most of them were grade 1 and 2. CONCLUSIONS: In our population of patients with iodine-refractory DTC, treatment with sorafenib, lenvatinib, and axitinib allows the stabilization of the disease in a high percentage of cases, with acceptable tolerability.

Survival and prognostic factors for survival, cancer specific survival and disease free interval in 239 patients with Hurthle cell carcinoma: a single center experience.

BACKGROUND: Hurthle cell carcinoma makes up 3 to 5% of all thyroid cancers and is considered to be a true rarity. The aim of our study was to analyze clinical characteristics and survival rates of patients with Hurthle cell carcinoma. METHODS: Clinical data regarding basic demographic characteristics, tumor grade, type of surgical treatment and vital status were collected. Methods of descriptive statistics and Kaplan-Meier survival curves were used for statistical analysis. Cox proportional hazards regression was used to identify independent predictors. RESULTS: During the period from 1995 to 2014, 239 patients with Hurthle cell carcinoma were treated at our Institution. The average age of the patients was 54.3, with female to male ratio of 3.6:1 and average tumor size was 41.8 mm. The overall recurrence rate was 12.1%, with average time for relapse of 90.74 months and average time without any signs of the disease of 222.4 months. Overall 5-year, 10-year and 20-year survival rates were 89.4%, 77.2%, 61.9% respectively. The 5-year, 10-year and 20-year cancer specific survival rates were 94.6%, 92.5%, 87.4%, respectively. When disease free interval was observed, 5-year, 10-year and 20-year rates were 91.1%, 86.2%, 68.5%, respectively. The affection of both thyroid lobes and the need for reoperation due to local relapse were unfavorable independent prognostic factors, while total thyroidectomy as primary procedure was favorable predictive factor for cancer specific survival. CONCLUSION: Hurthle cell carcinoma is a rare tumor with an encouraging prognosis and after adequate surgical treatment recurrences are rare.

Favorable Outcome of Hurthle Cell Carcinoma of the Thyroid Treated With Total Thyroidectomy, Radioiodine, and Selective Use of External-Beam Radiotherapy.

OBJECTIVES: There is controversy about the prognosis of Hurthle cell carcinoma of the thyroid. The purpose of this project is to report the outcome of a well-defined group of patients treated at a single institution in the modern era. METHODS: Sixteen patients met the following inclusion criteria: Treatment with curative intent at our institution between January 1, 1997, and December 31, 2010. Primary treatment with total thyroidectomy with or without neck dissection. Age >18 years at the time of thyroidectomy. Confirmation by a pathologist of the diagnosis of a primary Hurthle cell carcinoma of the thyroid based on ≥75% Hurthle cells with extension through the tumor capsule. No areas of poorly differentiated (insular) or undifferentiated (anaplastic) carcinoma. Stage T1-3, NX-1b, M0. All patients received radioiodine immediately after thyroidectomy (remnant ablation, n=14) or as adjuvant for a recurrence (n=2). External-beam radiotherapy to the neck as adjuvant therapy after thyroidectomy was used in 2 patients and after resection of a neck recurrence in 1 patient. RESULTS: Five-year actuarial rates with a median 6 years of follow up on surviving patients were as follows:Overall and cancer-specific survival: 92% (1 death from Hurthle cell carcinoma). Relapse-free survival (no visible tumor and unstimulated thyroglobulin ≤1.0): 65%. CONCLUSIONS: Our experience suggests that the outcome of Hurthle cell carcinoma of the thyroid is favorable in adults with stage T1-3 NX-1b M0 disease who are managed with total thyroidectomy, radioiodine, and-in selected cases-external-beam radiotherapy. We do not have the ability to compare our results to other management strategies.

Nuclear localization of the CK2α-subunit correlates with poor prognosis in clear cell renal cell carcinoma.

Protein kinase CK2α, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2α expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC). Also the kinase activity of CK2 was significantly increased in ccRCC compared to normal renal cortex. Nuclear protein expression of CK2α correlated in univariate analysis with poor Progression Free Survival (HR = 8.11, p = 0.016). Functional analyses (cell proliferation assay) revealed an inhibitory effect of Caki-2 cell growth following CK2 inhibition with CX-4945. Our results suggest that CK2α promotes migration and invasion of ccRCC and therefore could serve as a novel prognostic biomarker and molecular therapeutic target in this type of cancer.

Renal oncocytoma with vascular invasion: a series of 22 cases.

Renal oncocytomas are benign neoplasms that are often excised, as clinically they cannot be distinguished with certainty from renal cell carcinoma. One of the least common findings in oncocytomas is vascular invasion, and their behavior is not well characterized with only reports of isolated examples and smaller case series. Whether vascular invasion is acceptable for the diagnosis of oncocytoma still remains controversial, even amongst genitourinary pathologists with expertise in renal tumor pathology. Of 1474 cases of renal oncocytoma identified at 3 large medical centers, 22 (1.5%) had vascular invasion. Patients included 12 men and 10 women with an average age at diagnosis of 67.5 years (range, 48-91 years). Thirteen cases showed large vessel invasion, and the remainder involved medium or small vessels. Tumor was grossly visible in the renal vein in 2 cases. Clinical data were available on 16 of the 22 cases with an average follow-up time of 29.9 months (range, 7.5-94.5 months). Of the cases with clinical follow-up, all but one individual was alive. All living individuals were free of recurrence or metastatic disease at the time of last follow-up. Our cohort showed no metastasis or recurrence and overall survival of 94.7% at 2.5 years following diagnosis, supporting the finding that vascular invasion does not alter the favorable prognosis of oncocytoma. The presence of vascular invasion should not lead to any uncertainty about the diagnosis in an otherwise typical oncocytoma.

Active surveillance is suitable for intermediate term follow-up of renal oncocytoma diagnosed by percutaneous core biopsy.

OBJECTIVES: To evaluate the intermediate outcome of conservative management in patients with biopsy-proven oncocytoma. PATIENTS AND METHODS: Patients with oncocytoma diagnosed on percutaneous core biopsy between January 2000 to December 2014 were identified from the renal biopsy database of a large specialist urologic pathology laboratory. After review of patient clinical records, the study cohort comprised only of patients enrolled in active surveillance. Clinicopathological and follow-up details were reviewed for each case, in particular: type and interval of surveillance imaging, tumour growth, definitive intervention and reason for intervention. Where possible, correlation was made between the final surgical and the initial biopsy specimens. RESULTS: Fifty three patients diagnosed with oncocytoma on core biopsy were initially placed on active surveillance with median follow-up of 34 months (range 6-109). The median age at diagnosis was 65 years (range 20-85) and median tumour size was 30 mm (range 13-87). Mean average tumour growth was 1.4 mm per annum (median 0 mm/year) with the majority (36 of 53, 68%) exhibiting minimal growth (less than 2 mm per annum) or partial regression. Forty seven of the 53 patients remained on active surveillance with no significant progression. Six patients elected to undergo definitive intervention (five surgical excision, one ablation). Renal oncocytoma was confirmed in all five patients who underwent surgical excision of their lesions. CONCLUSIONS: The majority of oncocytomas in this study showed minimal growth rate or regression. Patients with biopsy proven oncocytoma can be conservatively managed with active surveillance.

Radioactive Iodine Treatment Is Associated with Improved Survival for Patients with Hürthle Cell Carcinoma.

BACKGROUND: Hürthle cell carcinoma (HCC) is not typically iodine avid, raising questions regarding postoperative use of radioactive iodine (RAI). The aims of this study were to describe current practice patterns regarding the use of RAI for HCC and to assess its association with survival. METHODS: The National Cancer Data Base 1998-2006 was queried for all patients with HCC who underwent total thyroidectomy. Inclusion was limited to T1 tumors with N1/M1 disease, and T2-4 tumors with any N/M disease. Patients were divided into two treatment groups based on receipt of RAI. Baseline patient characteristics were compared between the two groups. Survival was examined using Kaplan-Meier and Cox regression analyses. RESULTS: A total of 1909 patients were included. Of these, 1162 (60.9%) received RAI, and 747 (39.1%) did not. Patients treated with RAI were younger (57 vs. 61 years for no RAI, p < 0.001), more often had private insurance (61.7% vs. 53.5% for no RAI, p < 0.003), and were more likely to be treated at an academic center (40.0% vs. 33.1% for no RAI, p < 0.001). Five- and 10-year survival rates were improved for patients who received RAI compared with those who did not (88.9 vs. 83.1% and 74.4 vs. 65.0%, respectively, p < 0.001). RAI administration was associated with a 30% reduction in mortality (hazard ratio = 0.703, p = 0.001). CONCLUSION: Present guidelines are inconsistent with regard to indications for using RAI for HCC. This could explain why nearly 40% of HCC patients did not receive RAI. RAI is associated with improved survival, suggesting that it should be advocated for HCC patients with tumors >2 cm and those with nodal and distant metastatic disease.

Characteristics of the Peritumoral Pseudocapsule Vary Predictably With Histologic Subtype of T1 Renal Neoplasms.

OBJECTIVE: To determine characteristics of the peritumoral pseudocapsule (PC) between renal tumor subtypes. METHODS: The peritumoral PCs of 160 pT1 renal tumors were examined, including 60 clear cell renal cell carcinomas (RCCs), 50 papillary RCCs, 25 chromophobe RCCs, and 25 oncocytoma. Pathologic features (presence or absence of PC, mean thickness, continuity, and invasion by tumor) were analyzed. PC thickness was measured using an ocular micrometer to the nearest 1/10 mm. RESULTS: A complete PC was found in 77% of clear cell tumors, 74% of papillary, 28% of chromophobe, and 4% of oncocytomas. Tumor PC was present but incomplete in 18% of clear cell, 18% of papillary, 44% of chromophobe, and 56% of oncocytoma. The PC was entirely absent in no clear cell tumors, 6% of papillary, 28% of chromophobe, and 40% of oncocytoma. Mean PC thickness and presence of invasion beyond the PC differed significantly by tumor subtype. Clear cell RCC possessed the thickest PC showing invasion through the capsule in 8% of tumors compared to 30% of papillary tumors. Complete PC invasion was not seen in chromophobe RCC or renal oncocytoma. Oncocytoma and chromophobe RCC characteristically exhibited an incomplete or absent PC. CONCLUSION: The characteristics of peritumoral PC vary predictably with histologic subtype of renal neoplasms. Clear cell RCC shows the most consistent PC, with a lower rate of invasion beyond it compared to papillary RCC. Chromophobe and oncocytoma characteristically have an incomplete or absent PC.

Localized non-conventional renal cell carcinoma: prediction of clinical outcome according to histology.

OBJECTIVE: A wide variety of parameters have been investigated in the prognostic significance of non-conventional clear cell renal cell carcinoma. Aim of the present study was to compare its clinical outcome and to determine the independent prognostic factors according to the histology. METHODS: This retrospective study enrolled localized non-conventional clear cell renal cell carcinomas (T1a-T4N0M0), including Xp11.2 translocation (Xp11.2t), all surgically treated in a single institution between 1988 and 2011. The study statistically analyzed the clinicopathological parameters to compare the prognostic outcomes among the different histological subtypes of non-conventional clear cell renal cell carcinoma and to define any independent prognostic factors. RESULTS: A total of 374 cases were examined, including 126 papillary (33.7%), 164 chromophobe (43.9%), eight collecting duct (2.1%), 40 unclassified (10.7%), 16 Xp11.2t (4.3%), seven mucinous tubular and spindle cell (1.8%) renal cell carcinomas and 13 oncocytomas (3.5%). The mean follow up was 56.4 months, with s mean tumor size of 4.9 ± 3.4 cm. The 4-year recurrence-free survival, overall survival and cancer-specific survival were inversely related to the increase of pathological T stages (P < 0.001). For histological type other than 13 oncocytomas and seven mucinous tubular and spindle cell renal cell carcinomas, the chromophobe showed the best prognosis of survival, followed by papillary, Xp11.2t, unclassified and collecting duct renal cell carcinomas, in this order. All survival rates were significantly different, as according to the histology (P = 0.009). The significant prognostic factors were preoperative body mass index (hazard ratio 0.76), serum albumin (hazard ratio 0.64), T stage (hazard ratio 2.28), the sarcomatoid differentiation (hazard ratio 33.45) and lymphovascular invasion (hazard ratio 12.40) in pathology (P < 0.05). CONCLUSIONS: Different non-conventional clear cell renal cell carcinoma subtypes have significantly different clinical characteristics of prognosis with many suggestive predictive factors of survival.

Iatrogenic splenectomy during nephrectomy for renal tumors.

OBJECTIVES: To evaluate risk factors associated with iatrogenic splenectomy during nephrectomy and to assess outcomes among patients undergoing nephrectomy for renal tumors. METHODS: Of 4323 patients who underwent nephrectomy at Mayo Clinic between 1992 and 2008, 33 (0.8%) had an iatrogenic/unplanned splenectomy. In a case-control study design, controls without splenectomy were matched 1:3 based on age, sex, surgical date, side of the renal tumor, surgical approach and surgeon. Perioperative features and survival were evaluated using conditional logistic and Cox regression. RESULTS: Among the 33 iatrogenic splenectomy patients, the majority (94%) underwent radical, open and left-sided nephrectomy. Primary tumor classification ≥T3 was the only clinicopathological risk factor significantly associated with splenectomy (odds ratio 3.4; P = 0.02). Compared with controls, patients with an iatrogenic splenectomy were more likely to have longer operative time (205 vs 171 min; P = 0.02), higher estimated blood loss (1.3 vs 0.3 L; P = 0.001), longer length of stay (median 7 vs 5 days; P = 0.03) and a higher likelihood for postoperative complications (odds ratio 5.3; P = 0.002). With a median of 9.8 years of follow up, splenectomy patients tended to have greater all-cause mortality (hazard ratio 1.6; P = 0.07), although this difference approached statistical significance. CONCLUSIONS: Iatrogenic splenectomy is a rare complication during nephrectomy and is associated with locally advanced tumors (≥pT3). It also carries prognostic significance for adverse perioperative outcomes and possibly diminished survival, although this warrants further study.

Poorly differentiated oncocytic thyroid carcinoma--diagnostic implications and outcome.

AIMS: Poorly differentiated thyroid carcinomas (PDTC) are an ongoing diagnostic challenge. Although the Turin consensus criteria for PDTC excluded consideration of oncocytic tumours, the World Health Organization (WHO) classification does recognise an oncocytic variant of conventional PDTC. The aims of this study were to establish whether the Turin criteria can be applied to oncocytic PDTC, and to determine if there are prognostic differences between conventional and oncocytic PDTC. METHODS AND RESULTS: We applied the Turin criteria to 129 thyroid carcinomas. We identified 18 oncocytic PDTC and 16 conventional PDTC. Kaplan-Meier analysis revealed a significantly worse outcome for oncocytic PDTC with regard to overall and tumour-specific survival but no difference for relapse-free survival, all of which were confirmed by multivariate analysis. There was no association of survival with gender, age or tumour stage. CONCLUSIONS: The Turin criteria can be applied to oncocytic PDTC and patients with this variant have a decreased survival using conventional radioiodine treatment compared to conventional PDTC and might therefore be candidates for novel treatment modalities.