Benign Renal Tumors Research Articles

Quantitative Contour Analysis as an Image-based Discriminator Between Benign and Malignant Renal Tumors

To investigate whether morphologic analysis can differentiate between benign and malignant renal tumors on clinically acquired imaging. Between 2009 and 2014, 3-dimensional tumor volumes were manually segmented from contrast-enhanced computerized tomography (CT) images from 150 patients with predominantly solid, nonmacroscopic fat-containing renal tumors: 100 renal cell carcinomas and 50 benign lesions (eg, oncocytoma and lipid-poor angiomyolipoma). Tessellated 3-dimensional tumor models were created from segmented voxels using MATLAB code. Eleven shape descriptors were calculated: sphericity, compactness, mean radial distance, standard deviation of the radial distance, radial distance area ratio, zero crossing, entropy, Feret ratio, convex hull area and convex hull perimeter ratios, and elliptic compactness. Morphometric parameters were compared using the Wilcoxon rank-sum test to investigate whether malignant renal masses demonstrate more morphologic irregularity than benign ones. Only CHP in sagittal orientation (median 0.96 vs 0.97) and EC in coronal orientation (median 0.92 vs 0.93) differed significantly between malignant and benign masses (P = .04). When comparing these 2 metrics between coronal and sagittal orientations, similar but nonsignificant trends emerged (P = .07). Other metrics tested were not significantly different in any imaging plane. Computerized image analysis is feasible using shape descriptors that otherwise cannot be visually assessed and used without quantification. Shape analysis via the transverse orientation may be reasonable, but encompassing all 3 planar dimensions to characterize tumor contour can achieve a more comprehensive evaluation. Two shape metrics (CHP and EC) may help distinguish benign from malignant renal tumors, an often challenging goal to achieve on imaging and biopsy.

EZH2 Expression is increased in BAP1-mutant renal clear cell carcinoma and is related to poor prognosis.

Aim: BAP1 is frequently mutated in clear cell renal cell carcinoma (ccRCC) with a definitive role still unclear.Methods: In silico analysis of BAP1-mutant and wild-type gene enrichment and functional annotation in TCGA-KIRC dataset was performed. Target gene was studied based on functional clustering and was knowledge-based. Validation using in-house pathological sections were performed immunohistochemically. In vitro and in vivo studies on target gene were performed.Results: The TCGA ccRCC dataset included 534 ccRCC samples. BAP1 was frequently mutated and more frequently downregulated in ccRCC compared to normal kidney tissue or benign renal tumors. In the analysis between samples with BAP1 mutation (N = 33) and pan-negative (N = 33), we found that cancers with BAP1 mutation was significantly enriched for 14 pathways, of which 3 were DNA repair pathways, in which EZH2 played a role. CcRCC patients with lower BAP1 expression had poor prognosis and showed higher EZH2 expression, which also conferred worsened survival. Genetic and pharmaceutical inhibition of EZH2 not only inhibited BAP1-mutatn ccRCC cell viability and invasion but also abrogated genetic replenishing of BAP1 expression. Validation cohort encompassing 62 ccRCC samples confirmed the worsened phenotype for cases with higher EZH2 expression and significant positive correlation between expressions of EZH2 and BAP1. EZH2 inhibitor also inhibited tumor growth in xenograft mouse model with BAP1-mutated ccRCC cells with unremarkable toxicity.Conclusion: CcRCC with decreased BAP1 level has poor prognosis and is associated with higher EZH2 expression. Inhibition of EZH2 in BAP1-mutated entity holds promise for further investigation.

Potential clinical applications of microRNAs as biomarkers for renal cell carcinoma.

IntroductionRenal cell carcinoma (RCC) accounts for 3% of adult malignancies and more than 90% of kidney neoplasms. High rates of undiagnostic percutaneous kidney biopsies and difficulties in reliable pre-operative differentiation between malignant and benign renal tumors using contemporary imaging techniques result in large numbers of redundant surgeries. Absence of specific biomarkers for early detection and monitoring complicates on-time diagnosis of the disease and relapse. For the patients followed up after having a nephrectomy, a noninvasive and sensitive biomarker enabling early detection of disease relapse would be extremely useful.Material and methodsThe study is a review of recent knowledge regarding potential clinical applications of microRNAs (miRNAs) as biomarkers of RCC.ResultsMicroRNAs are essential regulators of various processes such as cell proliferation, differentiation, development and death; they have been implicated in diverse biological and pathological processes in RCC. There is a class of miRNAs that promote RCC development (oncomirs) and a class of miRNAs that negatively regulate oncogenes, suppress tumor growth and invasion, and thus could be considered treatment agents (anti-oncomirs). Separate miRNAs and specific miRNAs expression profiles have been identified, enabling early detection of the disease, prediction of response to systemic therapy, or prognostication of biological behavior of the disease.ConclusionsThe miRNA network analysis and gene profiling may help to identify the most sensible molecular signatures of RCC that can be used for diagnostic purposes, as well as poor prognosis signatures and poor therapeutic response signatures in patients who undergo systemic therapy.

Mammalian target of rapamycin inhibitor and transarterial embolization for treatment of tuberous sclerosis complex patients with renal angiomyolipoma

Objective: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease that results in multiorgan hamartomas. Patients with TSC also frequently have renal angiomyolipomas, which are rare but benign renal tumors. However, the main causes of mortality in these patients are angiomyolipoma-related chronic kidney disease and acute tumor hemorrhage. Angiomyolipomas are mostly treated in our hospital using mammalian target of rapamycin (mTOR) inhibitor therapy or transarterial embolization (TAE). This study was undertaken to evaluate and compare the short-term outcomes of a combined therapy of mTOR inhibitor and TAE in patients with TSC-associated angiomyolipoma. Materials and Methods: This was a retrospective observational study based on collected data obtained from chart reviews. The single-center data set covered patients diagnosed, treated, and followed up from September 10, 2008, to March 17, 2016, at a specialist center. Patients with TSC-associated angiomyolipoma treated with monotherapy or combined treatment of mTOR inhibitor and TAE were included in this study. We compared the tumor size with image studies in the baseline and follow-up periods in both groups. Results: In total, 15 patients (3 males and 12 females) were included; 8 patients underwent mTOR inhibitor monotherapy and 7 received the combined mTOR inhibitor and TAE therapy. The mean patient age was 37.7 (17–72) years. The maximal diameters of renal angiomyolipomas ranged from 2 to 20.9 (10.2 ± 5.4) cm for all patients at the time of treatment intervention. During an average follow-up duration of 22 (2–56) months, the mean size of the angiomyolipomas decreased from 9.3 ± 5.6 to 8.5 ± 5.3 cm in the monotherapy group and 11.5 ± 5.4–10.0 ± 5.8 cm in the patients in the combined therapy (P = 0.014). Conclusions: In comparison with m-TOR inhibitor monotherapy, TAE combined with mTOR inhibitor therapy allows management of tumor bleeding with acceptable complications, and it also statistically reduces the tumor size in patients with TSC-associated renal angiomyolipomas.

A Rare Benign Tumor in a 14-Year-Old Girl

Background Oncocytomas are the second most common benign renal neoplasm but, unfortunately, they are difficult to differentiate from renal cell carcinoma. Renal oncocytomas are rare and have mostly been reported in adults. To our knowledge, this is only the sixth pediatric reported case of renal oncocytoma worldwide. Case Presentation A 14-year-old Yemeni girl with a recurrent history of urinary tract infections came to our clinic complaining of left flank pain with a frontal headache. Ultrasound showed a 3 cm, well-defined echogenic lesion with mild vascularity. This lesion increased in size on her subsequent follow-ups. Computed tomography showed no intralesional fat, vessels invasion, or enlarged lymph nodes. The patient underwent laparoscopic radical nephrectomy, and a pathology report confirmed the diagnosis of renal oncocytoma. Conclusion and Recommendations We present the rare occurrence of renal oncocytoma in a pediatric patient and highlight the importance of considering oncocytomas in the diagnosis of a renal mass.

Differential diagnosis of the small renal masses: role of the apparent diffusion coefficient of the diffusion-weighted MRI.

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and more than 90% of neoplasms arising from the kidney. Uninformative percutaneous kidney biopsies vary from 10 to 23%. As a result, 7.5-33.6% of partial nephrectomies in patients with small renal masses (SRM) are performed on benign renal tumors. The aim of this study was to assess the feasibility of the apparent diffusion coefficient (ADC) of the diffusion-weighted imaging (DWI) of MRI, as RCC imaging biomarker for differentiation of SRM. Adult patients (n=158) with 170 SRM were enrolled into this study. The control group were healthy volunteers with normal clinical and radiologic findings (n=15). All participants underwent MRI with DWI sequence included. Mean ADC values of solid RCC (1.65±0.38×10-3mm2/s) were lower than healthy renal parenchyma (2.47±0.12×10-3mm2/s, p<0.05). There was no difference between mean ADC values of ccRCC, pRCC and chRCC (1.82±0.22×10-3 vs 1.61±0.07×10-3 vs 1.46±0.09×10-3 mm2/s, respectively, p=ns). An inverse relationship between mean ADC values and Fuhrman grade of nuclear atypia of solid ccRCCs was observed: grade I-1.92±0.11×10-3 mm2/s, grade II-1.84±0.14×10-3mm2/s, grade III-1.79±0.10×10-3mm2/s, grade IV-1.72±0.06×10-3mm2/s. This was significant (p<0.05) only between tumors of I and IV grades. Significant difference (p<0.05) between mean ADC values of solid RCCs, benign renal tumors and renal cysts was observed (1.65±0.38×10-3 vs 2.23±0.18×10-3 vs 3.15±0.51×10-3 mm2/s, respectively). In addition, there was a significant difference (p<0.05) in mean ADC values between benign cysts and cystic RCC (3.36±0.35×10-3 vs 2.83±0.21×10-3mm2/s, respectively). ADC maps with b values of 0 and 800s/mm2 can be used as an imaging biomarker, to differentiate benign SRM from malignant SRM. Using ADC value threshold of 1.75×10-3mm2/s allows to differentiate solid RCC from solid benign kidney tumors with 91% sensitivity and 89% specificity; ADC value threshold of 2.96×10-3mm2/s distinguishes cystic RCC from benign renal cysts with 90% sensitivity and 88% specificity. However, the possibility of differentiation between ccRCC histologic subtypes and grades, utilizing ADC values, is limited.

SETDB2 and RIOX2 are differentially expressed among renal cell tumor subtypes, associating with prognosis and metastization

ABSTRACTIncreasing detection of small renal masses by imaging techniques entails the need for accurate discrimination between benign and malignant renal cell tumors (RCTs) as well as among malignant RCTs, owing to differential risk of progression through metastization. Although histone methylation has been implicated in renal tumorigenesis, its potential as biomarker for renal cell carcinoma (RCC) progression remains largely unexplored. Thus, we aimed to characterize the differential expression of histone methyltransferases (HMTs) and histone demethylases (HDMs) in RCTs to assess their potential as metastasis biomarkers. We found that SETDB2 and RIOX2 (encoding for an HMT and an HDM, respectively) expression levels was significantly altered in RCTs; these genes were further selected for validation by quantitative RT-PCR in 160 RCTs. Moreover, SETDB2, RIOX2, and three genes encoding for enzymes involved in histone methylation (NO66, SETD3, and SMYD2), previously reported by our group, were quantified (RT-PCR) in an independent series of 62 clear cell renal cell carcinoma (ccRCC) to assess its potential role in ccRCC metastasis development. Additional validation was performed using TCGA dataset. SETDB2 and RIOX2 transcripts were overexpressed in RCTs compared to renal normal tissues (RNTs) and in oncocytomas vs. RCCs, with ccRCC and papillary renal cell carcinoma (pRCC) displaying the lowest levels. Low SETDB2 expression levels and higher stage independently predicted shorter disease-free survival. In our 62 ccRCC cohort, significantly higher RIOX2, but not SETDB2, expression levels were depicted in cases that developed metastasis during follow-up. These findings were not apparent in TCGA dataset. We concluded that SETDB2 and RIOX2 might be involved in renal tumorigenesis and RCC progression, especially in metastatic spread. Moreover, SETDB2 expression levels might independently discriminate among RCC subgroups with distinct outcome, whereas higher RIOX2 transcript levels might identify ccRCC cases with more propensity to endure metastatic dissemination.

Urokinase-type plasminogen activator (uPA) is critical for progression of tuberous sclerosis complex 2 (TSC2)-deficient tumors

Lymphangioleiomyomatosis (LAM) is a fatal lung disease associated with germline or somatic inactivating mutations in tuberous sclerosis complex genes (TSC1 or TSC2). LAM is characterized by neoplastic growth of smooth muscle-α-actin-positive cells that destroy lung parenchyma and by the formation of benign renal neoplasms called angiolipomas. The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin slows progression of these diseases but is not curative and associated with notable toxicity at clinically effective doses, highlighting the need for better understanding LAM's molecular etiology. We report here that LAM lesions and angiomyolipomas overexpress urokinase-type plasminogen activator (uPA). Tsc1-/- and Tsc2-/- mouse embryonic fibroblasts expressed higher uPA levels than their WT counterparts, resulting from the TSC inactivation. Inhibition of uPA expression in Tsc2-null cells reduced the growth and invasiveness and increased susceptibility to apoptosis. However, rapamycin further increased uPA expression in TSC2-null tumor cells and immortalized TSC2-null angiomyolipoma cells, but not in cells with intact TSC. Induction of glucocorticoid receptor signaling or forkhead box (FOXO) 1/3 inhibition abolished the rapamycin-induced uPA expression in TSC-compromised cells. Moreover, rapamycin-enhanced migration of TSC2-null cells was inhibited by the uPA inhibitor UK122, dexamethasone, and a FOXO inhibitor. uPA-knock-out mice developed fewer and smaller TSC2-null lung tumors, and introduction of uPA shRNA in tumor cells or amiloride-induced uPA inhibition reduced tumorigenesis in vivo These findings suggest that interference with the uPA-dependent pathway, when used along with rapamycin, might attenuate LAM progression and potentially other TSC-related disorders.

Peroxisome proliferator-activated receptor gamma (PPARγ) is central to the initiation and propagation of human angiomyolipoma, suggesting its potential as a therapeutic target.

Abstract Angiomyolipoma (AML), the most common benign renal tumor, can result in severe morbidity from hemorrhage and renal failure. While mTORC1 activation is involved in its growth, mTORC1 inhibitors fail to eradicate AML, highlighting the need for new therapies. Moreover, the identity of the AML cell of origin is obscure. AML research, however, is hampered by the lack of in vivo models. Here, we establish a human AML‐xenograft (Xn) model in mice, recapitulating AML at the histological and molecular levels. Microarray analysis demonstrated tumor growth in vivo to involve robust PPARγ‐pathway activation. Similarly, immunostaining revealed strong PPARγ expression in human AML specimens. Accordingly, we demonstrate that while PPARγ agonism accelerates AML growth, PPARγ antagonism is inhibitory, strongly suppressing AML proliferation and tumor‐initiating capacity, via a TGFB‐mediated inhibition of PDGFB and CTGF. Finally, we show striking similarity between AML cell lines and mesenchymal stem cells (MSCs) in terms of antigen and gene expression and differentiation potential. Altogether, we establish the first in vivo human AML model, which provides evidence that AML may originate in a PPARγ‐activated renal MSC lineage that is skewed toward adipocytes and smooth muscle and away from osteoblasts, and uncover PPARγ as a regulator of AML growth, which could serve as an attractive therapeutic target.‡

The value of superb microvascular imaging in differentiating benign renal mass from malignant renal tumor: a retrospective study

This study is to evaluate the value of superb microvascular imaging (SMI) in assessing renal tumour vascularity and in differentiating benign from malignant renal tumours. Patients with pathologically confirmed renal mass who underwent colour Doppler flow imaging (CDFI) and SMI examination between October 2016 and March 2017 were retrospectively analysed. Patients were classified into benign renal mass group and malignant tumour group according to their pathological results. The vascularity, vascular distribution and vessel morphology obtained from the two scanning methods were analysed and compared between the two groups. 53 patients with renal tumour were enrolled into the study, including 11 cases of benign renal tumours and 42 cases of malignant ones. SMI showed significant difference in vascularity between the two groups; CDFI showed no statistical difference. Compared with CDFI, SMI showed significantly higher grade in malignant tumour (p < 0.001), and no significant difference (p = 0.421) in benign mass. According to CDFI, there is no statistical difference in vascular distribution and vessel morphology (p = 0.432, p = 0.122) between the two groups, while SMI method showed significant difference (p < 0.05) between the two groups. SMI was significantly more sensitive and accurate than CDFI. Comparing with CDFI, SMI could effectively detect vascularity, vascular characteristics and distribution and annular blood flow in renal tumour. SMI appears more sensitive and precise in distinguishing benign renal mass from malignant tumour. Advances in knowledge: SMI seems potentially valuable in evaluating renal tumour vascularity and in differentiating benign from malignant renal tumours.

Les volumineuses tumeurs rénales nécrotiques et hémorragiques ne sont pas toutes malignes même en pédiatrie : à propos d’un cas chez un enfant de 7 mois

We report the case of a large tumor in the left kidney with necrotic and hemorrhagic features in a 7-month-old child, which was clinically and radiologically suggestive of a nephroblastoma. The tumor was a nodular mass measuring 8cm in diameter occupying two thirds of the kidney and presenting areas of necrosis and hemorrhage. No capsular rupture or renal sinus infiltration were found. Adjacent renal parenchyma appeared mascroscopically normal. Histologically, the tumor showed a strictly tubulopapillary architectural pattern with numerous psammomas. The initial hypothesis was a purely epithelial nephroblastoma. However, this hypothesis was rejected due to some immunohistochemical and histological characteristics and the final diagnosis was a metanephric adenoma. Metanephric adenoma is an exceptionally rare benign renal tumor in children. However, pathologists need to keep it in mind because simple surgical excision is curative.

The role of miRNA-15a in diagnostics of renal cell carcinoma

Renal cell carcinoma (RCC) – is the most common primary tumor of the kidney. The part of nondiagnostic percutaneous core biopsy (PCB) of the kidney varies from 5 to 40%. The application of imaging methods of examination, such as CT or MRI don’t guarantee 100% sensitivity and specificity for diagnosis of RCC, remaining within 88–96%. The objective: the goal of the investigation was to estimate the value of application of the miRNA-15a expression in urine as a biomarker of RCC. Patients and methods. The study enrolled 67 adult patients with solid renal neoplasms: RCC (n=58), benign renal tumors (n=15). The medium age was 60,19±6,36 years, the medium size of the tumor was 7,01±2,08 sm. All patients were treated by surgery. One day before and after the 8th day after the surgery in all patients and once in 30 healthy volunteers without renal pathology 100–150 ml of urine was collected with further definition of expression by using reverse transcription and PCR in real time. Results. For the first time significant difference (р<0,05) was detected between medium values of miR-15a expression in urine of the patients with RCC, benign renal tumors and healthy people: 2,50E-01±2,72E-01 УО vs 1,32E-03±3,90E-03 vs 3,36E-07±1,04E-07 УО accordingly. The strong correlation between the size of RCC and the level of miR-15a expression was observed (r=0,87). The sensitivity and specificity during differentiation of RCC and benign renal tumors using the threshold 03±5,18E-03 УО were 98,1% and 100% accordingly. Conclusion. Application measured in urine miR-15a expression may be used as a biomarker of RCC. Further studies are required with inclusion of bigger quantity of patients with different histological subtypes of RCC and grades of differentiation, benign renal tumors for more depth analysis of diagnostic value of miR-15a Further studies are needed for finding out the reason of miR-15a upregulation in urine of the patients with RCC, considering its tumor-protective features, which are described in literature.

Incidence and histologic features of mixed renal tumors.

Guidelines for management of renal cell carcinoma (RCC) incompletely address the implications of mixed renal tumor histology. We investigate the incidence of mixed renal tumors identified at renal surgery and determine the association with pathologic features. Institutional kidney tumor database was reviewed to identify 536 patients who underwent partial or radical nephrectomy. Clinical, demographic, and pathologic data were collected. A linear fixed effects model and logistic regression determined the association of mixed tumor histology with tumor size, stage, grade, and nephrometry score. Three hundred and eighteen men and 218 women with a median BMI of 31 and median tumor size of 3.5 cm were included. 469 (87.5%) patients had pathologic kidney cancer with the most common histologies being clear cell carcinoma in 343 (73.1%) patients, papillary in 81 (17.3%) patients, and chromophobe in 25 (5.3%) patients. Twenty (4.3%) patients had mixed tumors on final pathology. Clear cell RCC was the most common primary pathology in patients with mixed tumor histology (n = 14, 75%) with additional primary tumor histologies included papillary and chromophobe. When considering secondary histologies, 85% were coexistent primary renal cancers while 15% (n = 3) were benign renal tumors. No association of mixed tumor histology and adverse pathologic features was noted. Mixed tumor histology is an uncommon entity that is not associated with adverse features in a solitary renal mass. These results are especially relevant in discussing the role of renal mass biopsy, and provide further evidence that renal sampling is a valuable tool in the appropriate clinical context.

Modern Pathologic Diagnosis of Renal Oncocytoma.

Oncocytoma is a well-defined benign renal tumor, with classic gross and histologic features, including a tan or mahogany-colored mass with central scar, microscopic nested architecture, bland cytology, and round, regular nuclei with prominent central nucleoli. As a result of variations in this classic appearance, difficulty in standardizing diagnostic criteria, and entities that mimic oncocytoma, such as eosinophilic variant chromophobe renal cell carcinoma and succinate dehydrogenase-deficient renal cell carcinoma, pathologic diagnosis remains a challenge. This review addresses the current state of pathologic diagnosis of oncocytoma, with emphasis on modern diagnostic markers, areas of controversy, and emerging techniques for less invasive diagnosis, including renal mass biopsy and advanced imaging.

Value of triphasic MDCT in the differentiation of small renal cell carcinoma and oncocytoma.

Although differentiation between benign and malignant small renal tumors (≤4 cm) is still difficult, it is a demand for decision making and determining the treatment strategy. Our aim is to evaluate the role of multidetector row computed tomography (MDCT) in the differentiation of small renal clear cell carcinoma (RCC) and renal oncocytoma (RO). We reviewed triphasic computed tomographic (CT) scans performed in 43 patients diagnosed with RCC (n = 23) and RO (n = 21). After an unenhanced CT phase of the upper abdomen, triple-phase acquisition included a cortico-medullary phase (CMP), a nephrographic phase (NP), and a pyelographic phase (PP), and lesions were evaluated both qualitatively and quantitatively. RCCs were hypervascular in 13 cases and hypovascular in 10 cases, while ROs were hypervascular in nine cases and hypovascular in 12 cases. Mean attenuation values (MAVs) for hypervascular RCCs and hypervascular ROs on unenhanced examination were 34.0 ± 7.1 and 31.3 ± 8.1 HU, respectively. Enhancement in CMP was 173.1 ± 45.2 HU for RCCs and 151.1 ± 36.0 HU for ROs and a gradual wash-out in NP (148.8 ± 34.3 and 137.1 ± 33.9 HU for RCCs and ROs, respectively) and in PP (98.2 ± 36.0 HU for RCCs and 79.4 ± 21.5 HU for ROs) was observed. MAV for hypovascular RCCs and hypovascular ROs on unenhanced examination were 32.4 ± 12.0 and 28.9 ± 8.0 HU, respectively. Both hypovascular RCCs and ROs showed a statistically significant difference in each post contrastographic phase. Absolute attenuation and the quantitative amount of the enhancement were not strong predictors for RO and RCC differentiation.

Metanephric Adenoma of the Kidney: A Case Report and Literature Review

Metanephric Adenoma is a rare benign renal epithelial tumor, only a few reports are found in the literature. Reported a 48-year-old female with a palpable mass at left flank, pain and microscopic haematuria. Radiological imaging shows a mass on left Kidney suspected of Renal Cell Carcinoma. Transperitoneal left radical nephrectomy was done. Histopathological results revealed a Metanephric adenoma. The patient is repatriated from the hospital four days after surgery. The patient is in good health, and there is no sign of recurrence on 48 months follow up after surgery.

MTORC1 Inhibition Is an Effective Treatment for Sporadic Renal Angiomyolipoma

IntroductionRenal angiomyolipoma (AML) is the most common benign renal tumor. Despite a generally benign histology, AML can result in significant morbidity, from intra-abdominal hemorrhage and reduction in kidney function. While classically associated with the autosomal dominant disorder tuberous sclerosis complex (TSC) or with pulmonary lymphangioleiomyomatosis, most AMLs are sporadic. Mammalian target of rapamycin complex 1 (mTORC1) inhibitors (e.g., sirolimus) have been found to be effective in treating TSC- or lymphangioleiomyomatosis-associated AML, but to date it is unknown whether this strategy is effective for sporadic AML.MethodsWe stained tumor specimens of sporadic AML patients for pS6 to assess for mTORC1 activation.ResultsWe detected strong activation of the mTORC1 pathway, similar to TSC-associated AML. Consequently, we showed that in vitro treatment with sirolimus results in significant growth inhibition of the human sporadic AML cell line SV7Tert, similar to the effect seen when the same treatment is applied to the human TSC-associated AML cell line UMBSV-tel. To further investigate the potential of mTORC1 inhibition for treating sporadic AML and assess whether the in vitro results are clinically relevant, we identified a patient with sporadic, bilateral AMLs, showing continued tumor growth following a partial nephrectomy. Using immunostaining, we detected strong mTORC1 activation in the patient's AML tissue. Accordingly, upon treatment with sirolimus, we noted significant reduction in the patient's tumor volume and resolution of hydronephrosis, without any significant side effects.ConclusionWe propose mTORC1 inhibition as an effective treatment option for patients with sporadic AML, which represents the vast majority of patients with this tumor.

Metanephric adenoma treated with laparoscopic nephrectomy: A case report.

Metanephric adenoma is an uncommon benign renal tumor that occurs predominantly in adult females and rarely in children. Its histomorphology resembles that of epithelial Wilms' tumor and papillary renal cell carcinoma. From a diagnostic and therapeutic perspective, recognition of this entity is important as it has a more favorable clinical outcome compared with Wilms' tumor and renal cell carcinoma. Metanephric adenoma should not be treated with nephrectomy if the tumor size is small. However, preoperative diagnosis of this disease is extremely challenging. The present study describes a case of this rare disease, which was treated with laparoscopic nephrectomy. The tumor was not clearly enhanced in the early phase on contrast-enhanced computed tomography imaging. The immunohistochemical analysis revealed positive immunoreactivity for vimentin and Wilms' tumor 1, and partial positivity for cytokeratin (CK) AE1/AE3, CK56, and CK34, consistent with metanephric adenoma. Although metanephric adenoma is difficult to diagnose preoperatively, this rare disease must be considered in order to avoid unnecessary surgical procedures in these patients.

Association of decreased mean platelet volume with renal cell carcinoma.

Renal cell carcinoma (RCC) is the third most common genitourinary cancer. Activated platelets play a pivotal role in cancer development and progression. Altered mean platelet volume (MPV) has been reported in several malignancies. The aim of the present study was to investigate the association of MPV with RCC. The study consisted of 145 patients with RCC, 110 patients with benign renal tumor and 132 healthy control subjects between January 2015 and December 2015. All participants' clinical and laboratory characteristics at initial diagnosis were collected. The odds ratios (ORs) for RCC were calculated using multivariate logistic regression analysis after adjusting for confounding variables across MPV quartiles. The patients with RCC had decreased pre-operative MPV compared to the patients with benign renal tumor and healthy control subjects. Furthermore, pre-operative MPV was reduced in benign renal tumor compared with healthy control subjects. Surgical tumor resection resulted in a significant increase in MPV levels (8.7 fL vs. 9.0 fL; p=0.011). After adjusting for other risk factors, the ORs (95% CIs) for RCC in each MPV quartile were 25.725 (7.556-87.585), 7.447 (2.701-20.537), 0.703 (0.245-2.019), and 1.000, respectively. RCC patients have remarkably reduced MPV compared to patients with benign renal tumor and healthy control subjects. Moreover, decreased MPV was independently associated with RCC. Our results suggest that detection of MPV may be useful to assess the risk of RCC.

The frequency of a novel KANK1 and NTRK3 translocation and BRAFV600E mutation in patients diagnosed with metanephric adenoma utilizing molecular mechanisms.

1537 Background: Renal metanephric adenoma (MA) is a very rare benign renal tumor, which is frequently misclassified when microscopic features alone are applied. Despite the classification of adenoma as a benign tumor, it is difficult to differentiate from other renal carcinomas such as malignant papillary renal cell carcinomas and in children it can be mistaken with Wilms tumor. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, there is limited data available regarding the genetic alterations critical to the metanephric adenoma development. Recent data suggest that 90% of MA have BRAFV600Emutations; the genetics of the remaining 10 % are unclear. Methods: This study was conducted on 13 FFPE specimens from patients who were diagnosed with renal metanephric adenoma. H&amp;E stained slides from all cases were reviewed by study pathologist, and representative tissue blocks were further selected for BRAFV600E sequencing and fluorescent in situ hybridization was adapted to detect chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3). Results: In this study, we identified a novel chromosomal translocation t(9;15)(p24;q24) between KANK1 and NTRK3, and provided new insights into molecular mechanisms which might identify a subset of metanephric adenomas. Such findings imply that recurrent cytogenetic aberrations may be of prognostic significance as well. Interestingly, our data suggested mutual exclusivity of BRAFV600Eand t(9;15) aberrations. Conclusions: Molecular and cytogenetic analyses have allowed us to elucidate a genetic aberration, which may be specific to metanephric adenoma. Aberrant expression of the KANK1-NTRK3 gene fusion may be one mechanism by which functionally relevant genes are altered in the development of metanephric adenoma, and thus mark a subgroup of metanephric adenomas with particular clinicopathological features. Also, our study adds KANK1 and NTRK3 to the list of candidate genes that may play a role in the 10% of renal metanephric adenomas that lack a BRAFV600E mutation.