Primary Renal Tumors Research Articles

Infiltrative Renal Malignancies: Imaging Features, Prognostic Implications, and Mimics.

Infiltrative renal malignancies are a subset of renal masses that are morphologically characterized by a poorly defined interface with the renal parenchyma. Infiltrative renal malignancies are less common but more aggressive than more typical renal malignancies and carry an overall worse prognosis. Although an infiltrative renal process often represents a malignant neoplasm, infiltrative masses include a wide spectrum of diseases including primary renal cortical, medullary, and pelvic tumors; lymphoproliferative processes; metastases; and various infectious, inflammatory, immune-mediated, and vascular mimics. The imaging features of these masses are often nonspecific, but with the appropriate history, laboratory results, and clinical context, the radiologist can help narrow the diagnosis and guide further treatment. An invited commentary by Lee is available online.Online supplemental material is available for this article. ©RSNA, 2021.

Atypical Presentation of Renal Cell Carcinoma: A Case Report

The most common form of malignant renal tumours is Renal cell carcinoma (RCC) which is considered for nearly 80-85% of primary renal tumors. Now a day renal tumours can usually be detected at primary stage due to the popularity of sonography. Clinical manifestations of RCC have a diverse range. Loin pain, hematuria and abdominal mass contemplate as a classical triad but only present in 4–17% of cases. Here, we present a unique case of RCC in a 65 years old elderly gentleman admitted to our hospital with upper gastrointestinal (GI) symptoms without any significant GI involvement.

Diffusion weighted imaging in differentiation of the clear cell RCC from the major non-clear cell RCC subtypes

Introduction. Renal cell carcinoma (RCC) is the most common malignant renal tumor in adults accounting for 80-90% of primary malignant adult renal neoplasms. RCC represents a very heterogenous groups of tumors with a number of distinct histological varieties, of which the major 3 subtypes are clear cell RCC (70-80%), papillary RCC (13-20%), and chromophobe RCC (5%). Imaging features are varied from solid and relatively homogenous appearance to markedly heterogenous appearance with cystic changes, hemorrhage and necrosis. The use of diffusion weighted imaging (DWI) for RCC subtyping and also for differentiation of high grade and low grade tumors has been showed to be useful in many studies in the literature. Aim. In this study, we aimed to determine the comparative contribution of DWI in differentiation of the clear cell RCC from the major non-clear cell RCC subtypes at standard high b-value (1000 s/mm2) versus low b-value (500 s/mm2). In addition, we also aimed to assess the diagnostic performance of DWI for differentiating high grade clear cell RCC from low grade clear cell RCC based on Fuhrman grades in our patients. Material and methods. 62 cases with a prediagnosis of RCC according to MRI findings including DWI sequence with histological verification and subtyping of renal cortical tumor following a total or partial nephrectomy were included in the study. Results. Among 62 cases, 46 were male and 16 were female, with mean age of 59.5 ± 15.7. Pathological diagnoses of 62 cases were as follows, clear cell RCC, (44) papillary cell RCC (14) and chromophobe cell RCC (4). They were divided into two groups as clear cell RCC group (44 cases) and non-clear cell RCC group (18 cases). There was no statistically significant difference between the mean ADC values of clear cell and non-clear cell groups at b-value of 1000 s/mm2 (p>0.05). However, the mean ADC level for clear cell RCC group at b-value of 500 s/mm2 were significantly higher than for non-clear cell RCC group (p<0.05). When a value of 0.99x10-3 mm2/s was set as cut-off for ADC at b-factor of 500 s/mm2, differentiation was achieved with a high sensitivity (91%) and specificity (56%). Regarding the diagnostic performance of DWI for differentiating high from low Fuhrman grades clear cell RCCs, there was no statistically significant difference between the ADC values of Grade I-II clear cell RCC cases and Grade III-IV clear cell RCC cases at b-factor of 1000 s/mm2 (p>0.05). However, ADC values for grade III-IV group was statistically significantly lower than ADC values for Grade I-II group at b-factor of 500 s/mm2 level. Conclusion. ADC measurements at moderate b-value of 500 s/mm2 were more sensitive in subtyping and grading of RCC cases. This technique can be used in clinical practice as a fast and additional sequence in abdominal MRI.

Primary Renal Neuroendocrine tumor of kidney - Report of a rare case with literature review

Primary neuroendocrine tumours (NETs) of kidneys are extremely rare tumours. We report a case of a young female patient, who presented with complaints of hematuria and was diagnosed as a case of the right renal space-occupying lesion (SOL) on radiological imaging. She was advised for surgery, however, was lost to follow up. She remained asymptomatic and presented two years later again, pain abdomen, hematuria and abdominal mass. Imaging revealed a large space-occupying lesion in the right kidney pelvicalyceal system. In suspicion of urothelial malignancy of pelvis, she underwent a ureteroscopic biopsy which revealed malignancy of urothelial origin. The patient later underwent definitive surgery with radical nephroureterectomy, and immunohistochemistry of her nephrectomy specimen revealed poorly differentiated NET, which was positive for chromogranin A, synaptophysin and CD56 with a KI index of 25%. This case report highlights the importance of the indolent nature of disease along with diagnostic challenges requiring meticulous pathological examination and immunohistochemistry studies.

Cyclooxygenase -2 expression and antitumor activity of piroxicam in canine primary renal tumors

Cyclooxygenase -2 expression and antitumor activity of piroxicam in canine primary renal tumors

Renal Cancer Without Primary Cancer in the Kidney: Extra-Renal TFE3 Translocation Associated Renal Cell Carcinoma

We report a case of an isolated para-aortic retroperitoneal renal cell carcinoma (RCC) in the absence of a primary cancer in the kidney. Single case reports in the literature have described extra-renal RCC in different locations with no evidence of primary renal tumor. We present the initial presentation, diagnostic imaging, surgical treatment, and pathologic evaluation. Immunohistochemistry demonstrated positivity for TFE3 and TFEB, both of which are Microphthalmia associated transcription factors (MiT) associated with translocation RCCs. We hypothesize these few cases of extra-renal RCC represent rare forms of translocation RCC.

Soft tissue metastasis of renal cell carcinoma: A case report

Renal cell carcinoma (RCC) is the most common primary renal malignant neoplasm in adults, accounting for 90% of renal tumours and 2% of all adult malignancies. Distant metastasis has been reported commonly to bone, lung, abdomen, brain etc. Soft tissue and skeletal muscle metastasis is rare. This is the case of a 59 year old female, who presented with a left lower chest wall mass, which was proven to be a metastatic deposit from a clear cell RCC. The rare presentation in skeletal muscle should be suspected, which should also be differentiated from a benign soft tissue tumour. Keywords: Chest wall, Metastasis, RCC, Skeletal muscle.

Metastatic renal cell carcinoma of unknown primary site. Clinical follow-up

Renal cell cancer metastases without evidence of a primary tumor are extremely rare. These variants are usually showed as a spontaneous description of single clinical cases.
 Aim.This contribution is a clinical follow-up of synchronous renal cell cancer metastases of unknown primary site.
 Results.A 52-year-old patient U. with a history of increased blood pressure, up to 170/100 mmHg for the last 5 years, who had undergone many instrumental examinations, including ultrasound examination, because of this disease. The computed tomography of the abdomen showed a 4975 mm heterogeneous tumor in the right adrenal gland in October 2017. The combined positron emission and X-ray computed tomography showed a 795441 mm mass in the right adrenal gland, associated with elevated fluorodeoxyglucose metabolic activity SUVmax 7.25. Focal accumulation of the radiopharmaceutical SUVmax 4.31 in a 171124 mm mass was detected in the space of bifurcation in the mediastinum. The lytic lesion (1015 mm) was found in right superior L3 articular process. The patient underwent retroperitoneoscopic adrenalectomy and thoracoscopic removal of mediastinal tumor in November 2017 because of the oligometastatic nature of the process. The histological study identified clear-cell carcinoma with areas of papillary structure in the right adrenal gland. The immunohistochemical study showed carcinoma cells intensively expressing CD10, and some other cells RCC. The immune phenotype of the tumor was identified as clear-cell renal cell carcinoma. The immunohistological and immunohistochemical analysis reviled the metastases of the same variant of renal cell carcinoma in one of 9 lymph nodes. The patient was treated with pazopanib. The primary renal tumor was not detected during the dynamic observation, including the application of annual combined positron emission and X-ray computed tomography. The patient is alive without disease progression with a follow-up of 32 months.
 Conclusion.Metastases of clear-cell renal cell carcinoma, including adrenal gland, without evidence of a primary site are extremely rare. The main method of treatment is a combination of surgery and targeted therapy, providing long-term local control of the course of the disease.

Clinicopathologic Features and Survival Outcomes for Primary Renal Neuroendocrine Neoplasms.

Primary renal neuroendocrine neoplasms (NENs) are exceedingly rare. We used the Surveillance, Epidemiology, and End Results (SEER) data to summarize clinicopathologic characteristics, treatment outcomes, and prognostic factors of primary renal NENs. Data were identified from the SEER database. Clinicopathologic characteristics were compared by the Pearson chi-square or correction test, in which continuous variables were analyzed by t test. Kaplan-Meier analyses and log-rank tests were used to compare the differences in overall survival (OS). Univariable and multivariable regression model analyses of OS were conducted using the Cox proportional hazard model. Also, we used directed acyclic graphs to guide the multivariable regression model and to try to determine the impact of each of surgery, chemotherapy, and radiotherapy on OS. A total of 132 patients were enrolled. There were significant differences in age, grade, tumor size, SEER stage, surgery, and chemotherapy between patients with carcinoid tumors and those with neuroendocrine carcinomas. Patients with disease with carcinoid tumors, younger age, smaller tumor size, and lower SEER exhibited better survival outcomes. Univariable and multivariable regression models analyses indicated that age, sex, tumor size, and SEER stage were independent prognostic factors for OS. Directed acyclic graphs guided the respective inclusion of variables in the multivariable regression model to assess the causal effect of surgery, chemotherapy, and radiotherapy on OS. The results showed that surgery, chemotherapy, and radiotherapy did not improve OS. Primary renal NENs are exceedingly rare and exhibit different biological behavior. Older age, male sex, larger tumor size, and tumors not confined to the renal parenchyma may indicate poor prognosis. Resection of all visible disease remains the reference-standard treatment of choice. Longer-term studies with a larger patient cohort are needed to determine systemic therapeutic options.

Circ_001504 promotes the development of renal cell carcinoma by sponging microRNA-149 to increase NUCB2.

Renal cell carcinoma (RCC) accounts for over 90% of primary renal tumors in adults. Although treatment approaches have steadily improved over the years, the prognosis outcome remains poor. With the aim of developing novel targets for RCC treatment, we explored the role of the circular RNA (circRNA) circ_001504 in the progression of RCC. We initially detected the expression of circ_001504 and microRNA (miRNA)-149 in RCC tissues and cells. RT-qPCR results showed that circ_001504 was highly expressed in RCC tissues, whereas miR-149 was poorly expressed. Interestingly, downregulation of circ_001504 suppressed malignant phenotypes in RCC cells, and upregulation of miR-149 exerted a similar effect. Bioinformatics analysis suggested potential binding sites between circ_001504 and miR-149, verified by a dual-luciferase reporter gene assay. Next, we identified nucleobindin 2 (NUCB2), a calcium-binding protein, as a target gene of miR-149. Furthermore, our data suggested that circ_001504 might serve as a competing endogenous RNA of miR-149, serving to elevate the expression of NUCB2. The silencing of circ_001504 resulted in decreased NUCB2 expression, which could be reversed by miR-149 inhibition. In addition, in vivo experiments demonstrated that circ_001504 depletion could suppress tumor growth in an established mouse RCC model. Collectively, reduced expression of circ_001504 lowered NUCB2 expression by sponging miR-149, thereby attenuating RCC progression, providing insight into circ_001504/miR-149/NUCB2 feedback loop into RCC treatment.

“Outcome of primary renal tumors – A Single centre experience”

“Outcome of primary renal tumors – A Single centre experience”

Phase I/II Study of Stereotactic Body Radiation Therapy for Pulmonary Metastases in Pediatric Patients

PurposePulmonary metastases are common in many pediatric solid tumors; however, little is known about safety and efficacy of lung stereotactic body radiation therapy (SBRT) for pediatric patients. We conducted a phase I/II study to investigate the minimum effective dose level of SBRT with an acceptable safety profile in pediatric patients. Methods and MaterialsPatients with sarcoma and metastatic pulmonary lesions ≤3 cm in diameter and ≤21 years of age were enrolled. Dose levels 1, 2, and 3 were 24, 30, and 36 Gy in 3 fractions, respectively. Enrolled patients with metastases from primary renal tumors and sarcoma histologies were to begin at dose level 1 and 2, respectively. Exclusion criteria included receipt of whole-lung/hemi-thorax irradiation >12 Gy within 6 months of consent. Primary endpoints were tolerability and safety per Common Terminology Criteria for Adverse Events grading and disease response at 6 weeks post-SBRT per response evaluation criteria in solid tumors (RECIST) 1.1 criteria. Secondary endpoints included rates of local control and distant failure within the lung, but outside of the treatment volume. ResultsFive patients with median age of 13 years (range, 7-21) received SBRT at dose level 2. Primary tumor histologies included Ewing sarcoma (n = 3), anaplastic chordoma (n = 1), and osteosarcoma (n = 1). No grade ≥3 adverse events were observed. At 6 weeks after SBRT, 7/8 (87.5%) lesions achieved partial response. With median follow-up of 2.1 years (range, 1.4-2.5), 2-year local control and distant failure-free survival were 60% (n = 8) and 40% (n = 5), respectively. One patient developed widespread metastases and succumbed to disease 1.4 years after SBRT. ConclusionsSBRT for pulmonary metastases produces responses in pediatric patients with sarcoma at 6 weeks with acceptable toxicity; however, patients remain at risk of local and distant failure within the lung. Future prospective studies are needed to investigate whether higher doses of SBRT, possibly in combination with other therapies, are safe and provide more durable response.

Pathological features and outcomes of incidental renal cell carcinoma in candidate solid organ donors.

BackgroundWe report the findings of a single Italian center in the evaluation of renal lesions in deceased donors from 2001 to 2017. In risk evaluation, we applied the current Italian guidelines, which include donors with small (< 4 cm, stage pT1a) renal carcinomas in the category of non-standard donors with a negligible risk of cancer transmission.MethodsFrom the revision of our registries, 2,406 donors were considered in the Emilia Romagna region of Italy; organs were accepted from 1,321 individuals for a total of 3,406 organs.ResultsThe evaluation of donor safety required frozen section analysis for 51 donors, in which a renal suspicious lesion was detected by ultrasound. Thirty-two primary renal tumors were finally diagnosed 26 identified by frozen sections and 6 in discarded kidneys. The 32 tumors included 13 clear cell renal cell carcinomas (RCCs), 6 papillary RCCs, 6 angiomyolipomas, 5 oncocytomas, 1 chromophobe RCC, and 1 papillary adenoma. No cases of tumor transmission were recorded in follow-up of the recipients.ConclusionDonors with small RCCs can be accepted to increase the donor pool. Collaboration in a multidisciplinary setting is fundamental to accurately evaluate donor candidate risk assessment and to improve standardized protocols for surgeons and pathologists.

FOXI1 expression in chromophobe renal cell carcinoma and renal oncocytoma: a study of The Cancer Genome Atlas transcriptome-based outlier mining and immunohistochemistry.

FOXI1 is a forkhead family transcription factor that plays a key role in differentiation and functional maintenance for the renal intercalated cell (IC). The diagnostic utility of FOXI1 is rarely studied thus far. Comparative analyses of FOXI1 mRNA expression in normal kidney tissue and different renal neoplasms including chromophobe renal cell carcinoma (chRCC), renal oncocytoma (RO), and other renal cell carcinomas were conducted using transcriptomic data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and single-cell RNA-seq datasets, in combination with integrative analyses using mutant data, karyotype data, and digital slides for cases with anomalous FOXI1 expression in TCGA. Formalin-fixed, paraffin-embedded whole-tissue slides of varied primary renal neoplasms (n = 367) were subjected to FOXI1 staining for validating FOXI1 transcription levels. We confirmed that FOXI1 was significantly upregulated at mRNA levels in ICs, chRCCs, and ROs compared with other renal tubule cell and renal cell carcinoma subtypes. Furthermore, most of the cases with FOXI1 expression outliers were misclassified in the TCGA kidney cancer project. An underlying novel entity with frequent mutations involved in the mTOR pathway was also found. FOXI1 immunoreactivity was consistently noted in ICs of the distal nephron. FOXI1 staining was positive in 85 of 93 chRCCs and 13 of 18 ROs, respectively. FOXI1 staining was not seen in renal neoplasms (n = 254) derived from non-ICs. In conclusion, FOXI1 expression in normal kidney tissue is restricted to ICs. This cell type-specific expression is retained during neoplastic transformation from ICs to chRCCs or ROs. FOXI1 is thereby a potential biomarker of IC-related tumors.

Abstract 4702: DNA methylation enhances apoptosis resistance of renal cancer cells through the control of mitochondria related gene expression

Abstract Many gene alterations have been identified in the onset of renal carcinogenesis. However, molecular alterations might be added to renal cancer cells during the progression. In order to uncover additional molecular alterations, we established highly malignant cancer cells which possess identical background to original cancer cells, and analyzed them in the present study. Since our previous works demonstrated that interaction with cancer microenvironment aids cancer cells with malignant trait through “education” and “selection”, serial orthotopic transplantation was utilized. First, parental human clear cell renal cell carcinoma cells, OS-RC-2, were subjected to serial orthotopic transplantation. Then, novel derivatives were obtained from resulting primary renal tumors. These derivatives formed primary renal tumor faster than parental cells and exhibited increased lung metastasis, suggesting that these derivatives were defined as “highly malignant cancer cells”. Next, we tried to identify the underlying molecular mechanism(s) for renal cancer progression through the characterization of highly malignant cancer cells. Gene expressions in each cell were profiled using RNA-sequencing, and these analyses revealed that expression of several genes associated with mitochondrial functions were dramatically down-regulated in highly malignant cancer cells. Since mitochondrial electron transport chain triggers apoptotic cell death, decrease of these genes may contribute to suppression of apoptosis of highly malignant cancer cells. Cell culture and in vivo experiments demonstrated that mitochondrial dysfunction is responsible for increased survival of renal cancer cells and cancer metastasis. Finally, regulatory mechanism of downregulation of these mitochondria-related genes was analyzed. Bisulfite sequencing analysis revealed that the downregulation may occur by DNA hypermethylation of CpG islands in the promoter regions in renal cancer cells.Taken together, these findings suggested that renal cancer cells acquire additional anti-apoptotic ability through the DNA methylation during the interactions with renal microenvironment, which may in turn lead to the cancer progression and metastasis. We are currently investigating whether the effect of anti-cancer reagent is enhanced in the presence of DNA methylation inhibitors. Citation Format: Kosuke Miyakuni, Jun Nishida, Shogo Ehata, Kohei Miyazono. DNA methylation enhances apoptosis resistance of renal cancer cells through the control of mitochondria related gene expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4702.

The role of 18F-FAZA PET/CT in detecting lymph node metastases in renal cell carcinoma patients: a prospective pilot trial.

The accurate detection of nodal invasion is an unmet need in the clinical staging of renal cancer. Positron emission tomography (PET) with 18F-fluoroazomycin arabinoside (18F-FAZA), a hypoxia specific tracer, is a non-invasive imaging method that detects tumour hypoxia. The aim of this work was to evaluate the role of 18F-FAZA PET/CT in the identification of lymph node metastases in renal cancer. A proof-of-concept phase 2 study including 20 kidney cancer patients ( ClinicalTrials.gov Identifier: NCT03955393) was conducted. Inclusion criteria were one or more of the following three criteria: (1) clinical tumour size > 10cm, (2) evidence of clinical lymphadenopathies at preoperative CT scan and (3) clinical T4 cancer. Before surgery, 18F-FAZA PET/CT was performed, 2h after the intravenous injection of the radiotracer. An experienced nuclear medicine physician, aware of patient's history and of all available diagnostic imaging, performed a qualitative and semi-quantitative analysis on 18F-FAZA images. Histopathological analysis was obtained in all patients on surgical specimen. Fourteen/19 (74%) patients had a non-organ confined renal cell carcinoma (RCC) at final pathology (either pT3 or pT4). Median number of nodes removed was 12 (IQR 7-15). The rate of lymph node invasion was 16%. No patient with pN1 disease showed positive 18F-FAZA PET, thus suggesting the non-hypoxic behaviour of the lesions. In addition, neither primary tumour nor distant metastases presented a pathological 18F-FAZA uptake. No adverse events were recorded during the study. 18F-FAZA PET/CT scan did not detect RCC lymph neither nodal nor distant metastases and did not show any uptake in the primary renal tumour.

Vascular Neoplasms and Related Lesions of Kidney

Vascular tumors arising in the kidney are distinctly uncommon occurrences and have not been well-characterized in the literature; most cases have been documented in single reports or small case series. These tumors often exhibit nonspecific clinical and radiologic features and may mimic malignant epithelial tumors such as renal cell carcinoma (RCC) on imaging studies, necessitating nephrectomy with pathologic examination for definitive diagnosis. In addition, since primary renal vascular tumors are rare and infrequently encountered in surgical pathology specimens, they are often not considered in the differential diagnosis and therefore may be systematically under-diagnosed. In this review, we discuss the clinical and morphologic features of benign, borderline, and malignant vascular neoplasms and related lesions arising in the kidney, with a focus on recent, clinically relevant advances in imaging, histopathologic diagnosis, and treatment.

Incidence, treatment, and outcomes of primary and recurrent Non-Wilms renal tumors in children: Report of 109 patients treated at a single institution

Non-Wilms renal tumors represent a compelling subset of childhood renal tumors. However, their relative rarity renders accurate diagnosis, and therapy challenging which in some instance is inferred from their adult counterparts. To describe the incidence and analyze the diagnostic challenges, therapies and, outcomes of non-Wilms renal tumors at the largest tertiary cancer centre in India. All patients with histologically confirmed non-Wilms renal tumours diagnosed in the paediatric oncology unit of Tata Memorial Hospital between 2006 and 2019 were included. Data regarding clinical and radiological features and treatment outcomes were retrieved from the prospectively maintained institutional database. At the outset, histological types were categorised into a high and low-risk group depending on anticipated survival. Survival analysis was performed utilising the Kaplan-Meier method on SPSS software version 24.0. Of the 569 patients with renal tumors, 109 (19%) patients with primary (n=97) or recurrent (n=12) non-Wilms renal tumors were included. Histological high-risk group included clear cell sarcoma (CCSK) (39.4%), renal cell carcinoma (RCC) (19.3%), malignant rhabdoid tumor (MRTK) (12.8%), Ewing's sarcoma (rES) (15.6%), synovial sarcoma (2%), and undifferentiated sarcoma (2%). The low-risk group comprised of congenital mesoblastic nephroma (CMN) (4.6%), cystic partially differentiated nephroblastoma (2%), and other rare tumors (3%). Diagnostic error occurred in 2 patients in the high-risk group. All low-risk tumours were treated with surgery alone and most (97%) high-risk tumors were operated either upfront (61.5%) or after preoperative chemotherapy (38.4%). Adjuvant therapy based on histology was offered to 70%. The recurrent tumors received various salvage treatments including chemotherapy; radiotherapy; surgery and immunotherapy, however, only 2 patients could be salvaged. The 3-year overall survival for the entire cohort with primary tumors was 59%, and the survival rates were 76.7%, 77.9%, 0.0%, and 52% for CCSK, RCC, MRTK, and rES (summary figure). Low-risk tumors had 100% survival while the recurrent tumors had a median survival of 10.5 months. Non-Wilms renal tumors constitute a heterogeneous group of tumors, accounting for less than 20% of all renal tumors. Low-risk tumors are associated with excellent outcomes following surgery alone while the high-risk tumours have a variable outcome. MRTK and recurrent non-Wilms tumour have the worst survival. Favourable outcomes for CCSK and RCC and worst outcomes for MRTK were observed in this study. Renal ES have higher incidence of treatment failure and unsatisfactory outcomes. Recurrent non-Wilms tumours have an extremely poor outcome and more alternative or innovative approaches are needed for their treatment.

Abstract A004: Introducing single-cell sequencing genomic DNA copy number analysis to study cancer heterogeneity in renal cell carcinoma and its potential benefits in cancer health disparities research

Abstract Renal cell carcinoma (RCC) is one of the most lethal urological malignancies and is responsible for around 80 percent of all primary renal neoplasms. In the US, every year are reported approximately 74,000 new cases and almost 15,000 deaths. It has been reported significant racial disparities in survival for renal cell carcinoma (RCC) between African Americans patients (AA), Hispanics and Caucasians Americans (CA) but more efforts are needed in order to have a high resolution genomic profile of the tumor. Currently, RCC has been characterized by extensive cancer heterogeneity using bulk sequencing. In order to get new insight in the study of RCC cancer heterogeneity, we applied DNA single cell sequencing since it has the potential to improve our understanding of this genetic feature by providing sub-clonal and variant information in high resolution. To this end, we studied cancer heterogeneity applying single cell copy number analysis and clonotype detection in four RCC tumors. 10x Chromium™ Technology was used for processing single cells. This technology provides 100 Kb CNV events, calling clonotypes down to 10 of 1000 cell inputs. The most representative sample resulted with more than 50% of tumor content. Analysis of the tumor cells showed variable median ploidies. In addition, regional copy number was estimated by processing our data in 20 Kb cases of reads. Multiple sub-clones were identified in sample number one where four clusters of sub-clones characterized cancer heterogeneity. By using Fast maximum-likelihood and Bayesian Information Criterion, the clustering process were implemented on the most representative sample to select the optimal clustering solution. This allowed us to provide a better insight of sub-clonal evolution. We detected copy number changes on entire chromosome arms and mutations at variant detection level. For this last, we identified previously reported VHL gene mutations that have been reported in RCC samples as signatures of clinical prognosis. The use of single cell copy number analysis has the potential to uncover and characterize the evolution of hidden sub-clones, highlighting their important uses in cancer health disparities research to identify genomic racial differences in RCC risk and progression of AA, Hispanics and CA patients. Citation Format: Enrique I. Velazquez Villarreal, David W. Craig, John D. Carpten. Introducing single-cell sequencing genomic DNA copy number analysis to study cancer heterogeneity in renal cell carcinoma and its potential benefits in cancer health disparities research [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A004.

CT-based radiomic classifier of primary renal tumors to distinguish between metastatic and non-metastatic disease.

5074 Background: Existing clinicopathological tools are unable to accurately identify renal cell carcinoma (RCC) patients who will develop metastases after surgery. As a result, it is unclear how long and how often to follow-up patients post-operatively. Tumor macropathology, as assayed by CT scanning, represents the sum product of tumor biology and microenvironment. We hypothesized that quantitative tumor features extracted from CT scans (termed radiomics) could discriminate between metastatic and non-metastatic RCCs. Methods: This retrospective study incorporated three cohorts of clear-cell RCC patients (n = 279, from TCGA, CPTAC and KiTS19 datasets) treated with nephrectomy. The study cohort was sub-divided into metastatic (n = 54, M1 at diagnosis or recurrence after surgery), high metastatic risk/HMR (n = 85, N1, T3-4, T2G3/4, T1G4) or low metastatic risk/LMR (n = 140, absence of these features) subsets. 3D primary tumor segmentation of arterial contrast CT scans was performed by trained investigators. Features were extracted using pyRadiomics 2.2.0 (n = 839) with gray value and voxel size normalization. For random forest (RF) model training, the cohort was randomly split into training (75%) and validation (25%) sets. Results: Multidimensional clustering of radiomic features by t-SNE analysis showed that metastatic and HMR tumors predominantly cluster together, while LMR tumors cluster separately. Consistent with this, there were no differentially regulated radiomic features (DR-features) between HMR and metastatic tumors. In contrast, we identified 26 DR-features (adjusted p-value &lt; 0.05) between presumed-metastatic (n = 139, HMR and metastatic tumors) and LMR tumors, which were then used as input to a RF binary classifier. In the training set, the trained classifier discriminated between presumed-metastatic and LMR tumors with bootstrapped AUC = 0.81. In the validation set, the classifier discriminated subsets with AUC = 0.80. Conclusions: High-risk and metastatic tumors have similar radiomic properties, suggesting common biology driving metastasis in RCC. We propose a novel radiomic classifier that accurately distinguishes between presumed-metastatic and low-risk tumors. Further work will assess whether this tool can identify patients with micrometastatic disease at diagnosis, who may benefit from adjuvant therapy or closer, long-term surveillance.