Renal capillary hemangioma mimicking renal cell carcinoma: A diagnostic pitfall.

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

In order to identify the proteomic differences between renal cell carcinoma (RCC) and benign renal tumors, we analyzed 168 serum samples from 65 RCC patients, 34 patients with benign renal tumors, and 69 healthy persons using the IMAC-Cu2+ ProteinChip system by surface enhanced laser desorption/ionization mass spectrometry technology. Two decision trees were generated by Biomarker Pattern software to distinguish between RCC versus healthy and RCC versus patients with benign tumors, respectively. Although the sensitivity and specificity of the RCC vs. healthy decision tree were 97.6% and 95.7%, respectively, it could not be used to distinguish RCC from benign renal tumors. The sensitivity of a blind test process using RCC, benign tumors and healthy persons were 92%. The specificity of the test process was 35.3% for benign tumors and 95.5% for healthy persons. The sensitivity and specificity of the RCC-Benign tumors decision tree were 85.7% and 95.5%, respectively. The blind test process using RCC, benign tumors and healthy persons also showed significant results. The sensitivity was 90.0%. The specificity was 95.7% for healthy persons and 90.0% for benign tumors. Combining these data with the results of CT scanning, the sensitivity can be improved over the use of either CT and decision tree analysis and the specificity may reach 100%. Two peaks with molecular masses of 3887.11 Da and 11079.8 Da were detected that are potentially useful for the diagnosis or screening of RCC. It was found that these two peaks can be used, not only to distinguish the RCC vs. healthy cases, but also to distinguish RCC from benign renal tumors. In combination with CT scanning, the sensitivity and specificity of the diagnosis of renal tumors can be improved. However, the decision tree constructed for RCC and healthy persons may not present good specificity for use in distinguishing malignant from benign renal tumors.

Renal tumors originated from renal parenchyme or renal pelvis with different histological subtypes. The most common observed malign renal tumors are clear cell renal cell carcinoma (CCRCC), multilocular cystic renal cell carcinoma (MCRCC), papillary renal cell carcinoma (PRCC), chromophobe RCC and carcinoma of the collecting ducts of Bellini, respectively [1]. Primary squamous cell carcinoma (SCC) of the renal parenchyme or renal pelvis is very unusual and rare entity which accounts less than 1 % of renal malign tumors [2]. To our knowledge, there are only two renal parenchymal SCC cases reported until today [3]. This letter presents a case of metastatic renal parenchymal squamous cell carcinoma associated with hypercalcemia, which is not reported until now. A 53-year-old male patient was admitted to our clinic with severe left-sided flank pain and intermittent hematuria. The patient was non-smoker and had a history of intermittent flank pain due to nephrolithiasis. Laboratory evaluation revealed mild anemia and hypercalcemia with microscopic hematuria. Serum calcium level was 13.2 mg/ dl (normal range 8.6–10.2 mg/dl) and serum albumin was 2.9 g/dl (normal range 3.5–4.5 mg/dl) with suppressed parathyroid hormone levels and normal renal functions. Corrected calcium level was calculated as 14.1 mg/dl. By intense hydration and zoledronic acid treatment, serum calcium level was corrected to normal levels. Thoracic and abdominal computed tomography (CT) was performed, and multiple metastatic nodular lesions in both lung and multilocular metastatic hypodense masses with the largest 61 9 55 mm in the right posterior lobe of liver were revealed. Additionally, prominent parenchymal mass in the right kidney and perirenal multiple lymphadenopathies with the biggest size of 18 9 33 mm were found. The patient underwent cytoreductive nephrectomy and right hemicolectomy due to direct tumoral invasion. On the gross examination, the tumor measuring 6.2 9 4.2 9 3.1 cm diameter with multiple calculus was seemed as ulcerative and necrotic confined to the upper pole of right kidney. No tumoral invasion to the renal pelvis was found. Pathological examination of the surgical material revealed moderately differentiated SCC in the renal parenchyma directly invasive to the serosal surface of the right colon without mucosal involvement. Then, due to the extensive disease, patient was treated with six cycles of gemcitabine and carboplatin regimen every 3 weeks plus zoledronic acid. After six cycles of chemotherapy, the patient was progressively deteriorated and died. Squamous cell carcinomas are associated with chronic inflammatory conditions such as renal calculi, recurrent urinary tract infections and schistosomiasis. So, a patient with SCC should be evaluated for such predisposing risk factors that associated with squamous metaplasia and subsequently SCC [4]. In our case, renal calculi were established in both radiologic studies and gross examination of the surgical material. Due to the renal pelvis SCCs tend to be invasive and sessile, the diagnosis of the renal parenchymal SCC should be confirmed with the evaluation Y. Acikgoz Department of Internal Medicine, Ankara Numune Education and Research Hospital, Ankara, Turkey

Clinical research priorities in renal cell carcinoma: renal cell carcinoma chemoprevention strategies including target populations, proposed agents, and clinical trial designs--Workgroup No. 6. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC).

von Hippel-Lindau Exonic Methylation Analysis Using MALDI-TOF Mass Spectrometry

The purpose of our study was to differentiate subtypes of renal cell carcinoma on helical CT scans. We reviewed CT scans of four subtypes of renal cell carcinoma: 76 conventional (clear cell), 19 papillary, 13 chromophobe, and two collecting duct. Biphasic CT scans (unenhanced, corticomedullary, and excretory phase scans) were obtained in 61 patients, and monophasic CT scans (unenhanced and excretory phase scans) in 49. We compared patient age and sex; tumor size; degree and pattern (homogeneous, heterogeneous, predominantly peripheral) of enhancement; presence or absence of calcification; and tumor-spreading patterns including perinephric change, venous invasion, and lymphadenopathy in four subtypes. Conventional renal carcinoma showed stronger enhancement than the other subtypes (p < 0.05): 106 +/- 48 H (mean +/- SD) in the corticomedullary phase and 62 +/- 25 H in the excretory phase. The sensitivity and specificity for differentiating conventional renal carcinoma from the other subtypes were 74% and 100% when 84 H was used as the cutoff value in the corticomedullary phase and 84% and 91% when 44 H was used as the cutoff value in the excretory phase. Conventional (84%), papillary (74%), and collecting duct (100%) renal carcinomas tended to show heterogeneous or predominantly peripheral enhancement, whereas chromophobe renal carcinoma (69%) usually showed homogeneous enhancement. Calcification was more common in papillary (32%) and chromophobe (38%) renal carcinomas than in conventional renal carcinoma (11%) (p < 0.05). Perinephric change and venous invasion were not noted in chromophobe renal carcinoma, whereas both were common in collecting duct renal carcinoma. For the differentiation of the subtypes of renal cell carcinoma, degree of enhancement is the most valuable parameter; enhancement pattern, the presence or absence of calcification, and tumor-spreading patterns can serve supplemental roles in the identification of the subtype of renal cell carcinoma.

Long-Term Outcomes of Renal Tumor Radio Frequency Ablation Stratified by Tumor Diameter: Size Matters

miRNA Profiling for Clear Cell Renal Cell Carcinoma: Biomarker Discovery and Identification of Potential Controls and Consequences of miRNA Dysregulation

Claudin-5 is a tight junction protein expressed in endothelial cells and in some epithelial cells. It has been shown as a marker in canine angiosarcoma; however, data on human mesenchymal tumors are limited. In this study, we examined claudin-5 in selected normal tissues, in 280 benign and malignant vascular tumors, and in 448 other epithelial, mesenchymal, and neuroectodermal tumors. Early human embryos showed limited claudin-5 expression in endothelia of large truncal vessels, in liver sinusoids, and in the epidermis. In adult human tissues, claudin-5 was widely present in the endothelia of vessels of different calibers. However, neovascular capillaries in carcinomas and other tumors were often negative. Claudin-5 was also present in many glandular and ductal epithelia, hair shafts, and glomerular podocytes. Capillary and cavernous hemangiomas and lymphangiomas generally showed endothelial positivity; however, many vessels, especially those with poorly formed lumina, were negative in juvenile capillary hemangiomas, and fewer vessels were highlighted in lobular capillary hemangiomas. Hemangioendotheliomas of retiform, kaposiform, epithelioid, and epithelioid sarcoma-like types showed positivity, the latter in a diffuse cytoplasmic manner. Most angiosarcomas (115 of 119) and Kaposi sarcomas (28 of 29) showed strong labeling, but rare cases only contained positive cytoplasmic dots. Claudin-5 was commonly present in carcinomas (except in sarcomatoid ones), but most tumors showed heterogenous labeling weaker than that in angiosarcomas. Seminomas and renal cell, hepatocellular, and signet ring cell carcinomas were negative. Among non-vascular mesenchymal tumors, biphasic synovial sarcoma was the only tumor to contain claudin-5-positive nonvascular elements. In hemangiopericytomas, glomus tumor, and melanomas, claudin-5 was expressed in endothelial cells only. Claudin-5 is a promising new marker for angiosarcomas and hemangioendotheliomas, but widespread expression in carcinomas and biphasic synovial sarcoma should be considered in the differential diagnosis and addressed with the use of an antibody panel including keratins, especially the more epithelial-specific AE1/AE3 and epithelial membrane antigen.

CORRELATION BETWEEN CONTRAST ENHANCED ABDOMINAL COMPUTERIZED TOMOGRAPHY SCAN AND HISTOPATHOLOGY IN EVALUATION OF RENAL MASSES Mustafa Saleh Mutar Al-Sukainy*, Rana Tahseen Mehsen@, Muthanna Habeeb Abid Al-Athari$ & Inaam Abduljabbar Mussa# *MB,ChB, FIBMS(Radiodiagnosis), Radiologist Specialist, Al-Sadar Teaching Hospital, Basrah Health Directorate. @MB,ChB, FIBMS(Radiodiagnosis), Jabir Ibn hayan College of Medicine. $MB,ChB, FIBMS(Urology), College of Medicine, Kufa University. #MB,ChB, DMRD, Karbala Health Directorate. Abstract Renal tumors are divided into benign and malignant. The most common malignant renal tumor is renal cell carcinoma (RCC) with a rising incidence of about 3% per year since 1975, RCC accounts for nearly 3% of all solid tumors in the body and 65% of all renal tumors. According to contrast enhancing computerized tomography (CECT), The enhancing masses are classified as solid or complex cystic, 85% percent of solid masses are malignant. Contrast medium rapidly redistributes from the vascular to the interstitial spaces of the organs, the more vascular the organ or pathologic mass the more enhanced one. Therefore, a solid, enhancing mass must be considered malignant until proved otherwise. The aim of this study is to evaluate the role of contrast enhanced CT scan in the assessment of renal masses and its correlation with the histopathological type. Over a period of eight months (from February 2013 to September 2013) 45 patients presented with renal masses (diagnosed by ultrasound) submitted to abdominal CECT scan, then the renal masses radiologicaly evaluated in the form of site, size, degree and pattern of enhancement, then the radiological findings were correlated with the postoperative specimen histopathological results. Different histopathological types of renal tumors have different degree and patterns of enhancement. Regarding the degree of enhancement: The enhancement in Hounsfield units in order of frequency are as follows: Conventional renal cell carcinoma (Clear cell carcinoma) (27HU). Chromophobe renal cell carcinoma (19 HU). Onchocytoma (18.5 HU). Wilms (16.66HU). Transitional cell carcinoma (9.75 HU). Angiomyolipoma (5.33 HU). According to the homogeneity of enhancement: There is difference between type of tumors and homogeneity of enhancement, as follows: Conventional renal cell carcinoma (clear cell carcinoma) have heterogeneous in 75% and homogenous in 25% of tumors. Chromophobe renal cell carcinoma, 50% have homogenous, while other 50% have heterogeneous pattern. Oncocytomas and Transitional cell carcinoma have 100% homogenous enhancement. Wilms tumors have 100% heterogeneous patterns. Angiomyolipomas have homogenous pattern in 66.7 % while heterogeneous enhancement seen in 33.3 %. In conclusion, contrast enhanced CT Scan is highly valuable in differentiating types of renal masses in correlation with histopathological results.

Additional renal masses were found in the same or contralateral kidney in 41 of 131 patients with renal cell carcinoma. In 35 of the patients the additional renal masses were simple renal cysts situated in the kidney contralateral to the renal cell carcinoma in 16 patients, in the same kidney in 11 and bilaterally in 8 patients. Four patients had bilateral renal cell carcinomas. One patient had polycystic kidney disease as well as renal cell carcinoma and another patient had a benign tumour in the contralateral kidney. In 3 of the 30 patients with additional renal masses in the kidney contralateral to the renal cell carcinoma the radiologic examinations were insufficient to exclude malignancy. Only explorative surgery could establish a true diagnosis of these masses.

Primary cardiac tumours are rare, accounting for only 0.002-0.03% at autopsy. Cardiac haemangiomas are benign vascular tumours and constitute for 0.28% of all primary cardiac tumours. Cavernous haemangiomas, capillary haemangiomas, and arteriovenous haemangiomas are three distinct types. Cardiac haemangiomas are often misdiagnosed as myxomas and must be differentiated from malignant angiosarcomas. We present a 44-year-old Mediterranean male patient with a cavernous haemangioma in the inferior vena cava and right atrium, detected on transthoracic echocardiography. The patient experienced palpitations and dyspnoea on exertion. Computed tomography (CT) angiography revealed a 7.5 × 6 × 5 cm mass suspected to be perfused by the distal right coronary artery. A watch-and-wait approach was suggested, leading to a cardiac magnetic resonance imaging (MRI) with contrast 6 months later. T1 mapping exhibited a prolonged relaxation time and isointensity to the myocardium. T2 mapping revealed a homogenous hyperintense mass with heterogenous late enhancement. Surgical excision was performed using a bicaval cannulation technique on cardiopulmonary bypass. Intraoperatively, no connection to the coronaries was noted. At 1 year follow-up, the patient reported restored physical resilience, with no evidence of tumour recurrence. Clinical symptoms of cardiac cavernous haemangiomas are unspecific and become evident once the tumour grows. To investigate the nature and vascular involvement of the tumour, a contrast-enhanced CT angiography or MRI can be performed. Cardiac haemangiomas are often misdiagnosed and must be differentiated from malignant angiosarcomas. Clear guidelines for the treatment of cardiac haemangiomas in adult patients are lacking. Primary cardiac tumours require thorough investigation, and surgical intervention should be tailored to the individual's case.

Renal cell carcinoma: Children’s hospital Boston experience

Guideline for Management of the Clinical T1 Renal Mass

Background Cytokine therapies show promise in treating renal cell carcinoma (RCC). Transforming growth factor beta 1 (TGF-β1) is a cytokine whose downstream Smad2/3 signaling activity is inhibited by the protein phosphatase Mg2+/Mn2+-dependent 1 A (PPM1A). Here, we hypothesized that PPM1A may be involved in suppressing RCC cell aggressiveness through its negative regulation of Smad2/3. Methods We quantified PPM1A expression from RCC tumors and matching healthy tissue and performed a Kaplan-Meier survival analysis. In silico analysis on PPM1A was performed using Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma and Clinical Proteomic Tumor Analysis Consortium RCC cohort data. We tested four RCC cell lines and selected the ACNH and A498 cells lines as expressing the greatest PPM1A levels. We assayed the effects of RNAi-mediated PPM1A silencing on invasiveness, proliferation, colony formation, and Smad2/3 phosphorylation in untreated and TGF-β1-stimulated ACNH and A498 cells. A nude mouse A498 xenograft tumor model was constructed to validate PPM1A’s effects in vivo. Results PPM1A levels are reduced in RCC tumors and are negatively correlated with RCC grade and stage. Below-median PPM1A expression is associated with reduced overall survival in RCC patients. PPM1A silencing promoted cellular invasiveness, proliferation, colony formation, and Smad2/3 phosphorylation under TGF-β1-stimulated conditions but not under untreated conditions. These effects of PPM1A were shown to be dependent on Smad2/3. Intratumor PPM1A overexpression inhibited A498 xenograft tumor growth. Conclusions This study establishes a direct link between PPM1A’s suppression of Smad2/3 signaling and RCC cell aggressiveness. PPM1A could potentially serve as a biomarker for RCC cell aggressiveness.