Unclassified Renal Cell Carcinoma Research Articles

A pediatric and young adult case of unclassified renal cell carcinoma with medullary phenotype (RCCU-MP): Clinical course and treatment

Renal cell carcinoma (RCC) is the most common kidney tumor in adults. RCC is rare in children, although its incidence increases in the second decade of life. Renal medullary carcinoma (RMC) is a rare and often aggressive RCC subtype characterized by complete loss of SMARCB1/INI1, predominantly diagnosed in patients with sickle cell disease or -trait. Here, we describe a pediatric and a young adult patient with clinicopathological characteristics similar to RMC but without hemoglobinopathies. These tumors are currently classified as “RCC unclassified with medullary phenotype” (RCCU-MP). Both our patients had an infiltrating, rather small kidney tumor with SMARCB1/INI1 deficiency. Remarkably, the aggressiveness and clinical course and treatment differed greatly between these two cases. So far, only nine patients, predominantly adults, have been reported. In a literature overview, most cases were metastatic and progressed or relapsed after varying treatment approaches, with low survival. Whereas the classification of these tumors remains a topic of debate, case reports add to the current knowledge of RMCs without hemoglobinopathies, stressing the importance of sharing experience concerning rare renal neoplasms with often poor outcomes, also concerning younger age categories.

Abstract 4627: Metastatic renal cell carcinoma with occult primary: Clinical and biological evidence for a new entity of cancers of unknown primary that beneficiates from tissue-tailored treatment

Abstract Background: Cancers of unknown primary (CUP) is a heterogenous group of malignancies characterized by distant metastases in the absence of detectable primary. Specifics subgroups of CUP that share similarities with cancers of known primary beneficiate from tissue-tailored therapeutic strategies. The objective of this study was to characterize the clinical and biological presentation of a cohort of patients with suspected CUP of renal origin (rCUP) and to evaluate their optimal therapeutic management. Methods: All Patients with rCUP identified prospectively between 2020 and 2023 within the French National Multidisciplinary Tumor Board for CUP were included. Centralized pathological review and immunohistochemical stainings were performed. Whole Exome Sequencing (WES), whole transcriptomic sequencing (RNAseq) and application of the deep-learning based algorithm TransCUPtomics for prediction of tissue of origin, and DNA methylation analysis were performed and compared to public renal cell carcinomas (RCC). Progression Free Survival (PFS) and Overall Survival (OS) were calculated using Kaplan-Meier estimates. Results: 23 patients were included. The median age at diagnosis was 57 yo and 17/23 were male. The most common metastatic sites were the bones (N=17) and the lymph nodes (N=14). 19/23 patients presented with at least two distinct distant metastatic sites. Genomic analyses performed in 10 patients led to the identification of recurrent inactivating mutations in genes commonly altered in RCC, including NF2 (N=7), SETD2 (N=3), or VHL (N=1). 10/11 samples analyzed by RNAseq were predicted as RCC by the TransCUPtomics classifier based on their gene expression profiles. DNA methylation profiling performed in 7 samples showed major similarity with known RCC subtypes.Centralized pathological review and integration of molecular characteristics led to the final diagnoses of papillary RCC (N=2), clear cell RCC (N=7), renal medullary carcinoma (N=1), TFEB-amplified RCC (N=1) and unclassified RCC (N=12). 20/23 patients received at least one line of systemic treatment based on the renal origin, including anti-angiogenic TKI, anti-PD1/PDL1 antibody, anti-CTLA4 antibody or mTOR inhibitor. The median PFS under the first renal-oriented systemic treatment was 5 months and 10 patients remained progression-free for more than 6 months under tailored-treatment. The median OS was 31 months, and 11 patients are still alive in October 2023. Conclusions: This study shows that rCUP represent a new entity within CUPs that shares major similarities with classical RCC despite the more frequent presentation of unfavorable prognostic factors. Prolonged survival can be observed with renal-tailored systemic treatment, supporting the individualization of these patients within CUP. Citation Format: Nicolas Jacquin, Julien Masliah-Planchon, Guillaume Grisay, Ronan Flippot, Riwan Brillet, Célia Dupain, Maud Kamal, Isabelle Guillou, Nadège Gruel, Nicolas Servant, Pierre Gestraud, Jennifer Wong, Vincent Cockenpot, Andreia Goncalves, Janick Selves, Hélène Blons, Etienne Rouleau, Oliver Delattre, Christophe Le Tourneau, Ivan Bièche, Yves Allory, Laurence Albigès, Sarah Watson. Metastatic renal cell carcinoma with occult primary: Clinical and biological evidence for a new entity of cancers of unknown primary that beneficiates from tissue-tailored treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4627.

CT features based preoperative predictors of aggressive pathology for clinical T1 solid renal cell carcinoma and the development of nomogram model

BackgroundWe aimed to identify preoperative predictors of aggressive pathology for cT1 solid renal cell carcinoma (RCC) by combining clinical features with qualitative and quantitative CT parameters, and developed a nomogram model.MethodsWe conducted a retrospective study of 776 cT1 solid RCC patients treated with partial nephrectomy (PN) or radical nephrectomy (RN) between 2018 and 2022. All patients underwent four-phase contrast-enhanced CT scans and the CT parameters were obtained by two experienced radiologists using region of interest (ROI). Aggressive pathology was defined as patients with nuclear grade III-IV; upstage to pT3a; type II papillary renal cell carcinoma (pRCC), collecting duct or renal medullary carcinoma, unclassified RCC or sarcomatoid/rhabdoid features. Univariate and multivariate logistic analyses were used to determine significant predictors and develop the nomogram model. To evaluate the accuracy and clinical utility of the nomogram model, we used the receiver operating characteristic (ROC) curve, calibration plot, decision curve analysis (DCA), risk stratification, and subgroup analysis.ResultsOf the 776 cT1 solid RCC patients, 250 (32.2%) had aggressive pathological features. The interclass correlation coefficient (ICC) of CT parameters accessed by two reviewers ranged from 0.758 to 0.982. Logistic regression analyses showed that neutrophil-to-lymphocyte ratio (NLR), distance to the collecting system, CT necrosis, tumor margin irregularity, peritumoral neovascularity, and RER-NP were independent predictive factors associated with aggressive pathology. We built the nomogram model using these significant variables, which had an area under the curve (AUC) of 0.854 in the ROC curve.ConclusionsOur research demonstrated that preoperative four-phase contrast-enhanced CT was critical for predicting aggressive pathology in cT1 solid RCC, and the constructed nomogram was useful in guiding patient treatment and postoperative follow-up.

Clear cell renal cell carcinoma cells show diffuse expression of phagocytotic markers through the identification of lysosome-rich eosinophilic granules.

Paneth cell-like granules (PCLG) in clear cell renal cell carcinomas (RCC) have previously been reported but were not found to express neuroendocrine markers. This study was to investigate if the eosinophilic granules (so called PCLG) were enlarged lysosomes. A retrospective review of 72 different renal tumors was conducted which included 42 clear cell RCC, 16 papillary RCC, 6 chromophobe RCC, 5 clear cell papillary RCC, 2 urothelial carcinomas and 1 unclassified RCC. All tumors were evaluated for the eosinophilic granules on hematoxylin and eosin-stained sections. In addition, PAS-D staining, immunohistochemical stains, and electron microscopy were performed. The eosinophilic granules were found in 19% (8 out of 42) clear cell RCC, but not in the other renal tumor types. The granules stained positively for PAS-D and were also positive for lysosomal protein markers CD68 and lysozyme. Electron microscopy revealed that the eosinophilic granules were smooth ball-shaped structures in the cytoplasm, ranging in size from 0.8 to 1.4µm. The overall findings indicate that the eosinophilic granules were best correlated with lysosomes. The eosinophilic granules in clear cell RCC are expanded lysosomes, and this may be used as a unique feature for confirming the pathologic diagnosis of clear cell RCC. The findings further support the view that clear cell RCC have phagocytic capacity due to their containing abundant lysosomes in the cytoplasm.

ORCHID: A phase II study of Olaparib in Metastatic Renal Cell Carcinoma Patients HarborIng a BAP1 or Other DNA Repair Gene Mutations

Abstract Background DNA damage repair genes alterations (DDRa) are frequent events in renal cell carcinoma (RCC), including BAP1 and other DDRa. Olaparib is a poly ADP ribose polymerase inhibitor (PARPi) that is FDA-approved for the treatment of several malignancies with DDRa. Preclinical models demonstrated synthetic lethality with PARPi in RCC cell lines including BAP1 mutant lines. Here we report an interim analysis of the ORCHID study investigating the clinical activity of single agent olaparib in patients (pts) with advanced RCC (aRCC) harboring BAP1 other select DDRa. Methods We conducted a single center, single arm, investigator-initiated Phase 2 trial of olaparib in pts with aRCC. Eligible pts harbored select DDRa and had prior therapy with immune checkpoint inhibitors (ICIs) and/or VEGF-TKI. Pts were treated with olaparib at an initial dose of 150mg twice which was increased to 300mg twice daily after one month if well tolerated. The primary endpoint is disease control rate (DCR) by RECIST v1.1 (including complete response (CR), partial response (PR), and stable disease (SD) >6 months). Secondary endpoints included objective response rate (ORR), progression free survival (PFS), and safety. Results Eleven pts were enrolled with a median age of 59 years (48-72) including 9 pts with clear cell RCC and 2 pts with unclassified RCC. Most pts had BAP1 mutations (Table). 36% of pts had history of brain metastasis. Median number of prior lines of therapies was 2 (1-6) and all pts received prior ICI. The study met the pre-specified Simon’s 2 stage design for the first stage with 22% DCR in the evaluable pts (2/9), including deep PR (>70% reduction in tumor volume) and SD of 10 months. Both pts harbored BAP1 mutations. An additional pt with BRCA1 mutation had 20% decrease in measurable disease. There were no treatment related adverse events resulting in study discontinuation. Conclusions This is the first study investigating single agent PARPi in RCC with the interim trial analysis indicating promising activity of olaparib in aRCC pts with BAP1 mutations including one pt with deep PR. These results support further development of PARPi in this setting.

Evaluation of the clinical behavior of unclassified renal cell carcinoma and its imaging findings on computed tomography and magnetic resonance imaging based on World Health Organization (WHO) 2022

ObjectivesTo ascertain the clinical behaviors of unclassified renal cell carcinoma (RCC) and its characteristic imaging findings on CT and MRI.MethodsSubjects in this retrospective study were 10 patients who had received a histological diagnosis of unclassified RCC based on World Health Organization (WHO) 2022 and who had undergone CT and/or MRI prior to surgery. In terms of clinical behaviors, TNM classification, stage, postoperative recurrence, time to recurrence, and postoperative survival were evaluated. In terms of imaging findings, tumor size, growth pattern, CT density, dynamic contrast-enhancement (DCE) pattern, internal appearance, presence of a pseudocapsule, and signal intensity on MRI were evaluated. We compared clinical behaviors and imaging findings, and investigated associations between them.ResultsOne patient could not be followed-up due to death from other causes. Postoperative recurrence was observed in 4 patients, all of whom had Stage 3 RCC. In the remaining 5 patients without recurrence, all 5 patients showed Stage 2 or below. On imaging, unclassified RCC tended to be large (58.7 mm) and solid (100%), and heterogeneous interiors (80%), cystic degeneration (80%) and high intensity on diffusion-weighted imaging (DWI) (71.4%) were common. Comparing patients with and without recurrence, the following findings tended to differ between recurrence and recurrence-free groups: tumor size (73.4 ± 33.9 mm vs. 50.2 ± 33.9 mm, P = 0.286), growth pattern (invasive: 100% vs. 0%, expansive: 0% vs. 100%, P = 0.008 each), DCE pattern (progressive enhancement pattern, 66.7% vs. 0%, washout pattern, 0% vs. 66.7%, P = 0.135 each) and presence of a pseudocapsule (25% vs. 80%, P = 0.167).ConclusionThe clinical behavior of unclassified RCC varies widely. Although imaging findings are also variable, findings of large, heterogeneous tumors with cystic degeneration and high intensity on DWI were common. Several imaging findings such as large size, invasive growth, progressive enhancement pattern and no pseudocapsule may enable prediction of prognosis in unclassified RCC.

Abstract B022: Clinical outcomes in NF2-mutated RCC treated with contemporary immunotherapy regimens

Abstract Background: Neurofibromin-2 (NF2) encodes the cell scaffolding protein merlin, which is involved in the Hippo tumor suppressor pathway. Somatic loss of function NF2 alterations in renal cell carcinoma (RCC) are associated with poor prognosis and can also molecularly define a subset of unclassified renal cell carcinomas without a standard of care treatment. While immuno-oncology (IO) combination regimens such as ipilimumab/nivolumab (IO/IO) or PD-1 inhibitor with a VEGFR-targeted therapy (IO/VEGFR) are the standard of care for clear cell RCC, efficacy of IO-based regimens for NF2 mutated RCC remains unknown. We report the first comparison of clinical responses to IO/IO, IO/VEGFR, or other systemic therapies for NF2-mutated RCC. Methods: NF2-mutated RCC patients receiving systemic therapy at Memorial Sloan Kettering Cancer Center were retrospectively identified by screening of our targeted exome sequencing (MSK-IMPACT) database. Groups are defined by 1st line systemic therapy regimens: IO/IO, IO/VEGFR, and other (VEGFR-targeted monotherapy, IO monotherapy, everolimus/bevacizumab, and chemotherapy). PFS-2 is defined as time from start of 1st line to progression on next therapy, or death. ORR, PFS, and PFS-2 were measured by an independent RECIST radiologist (CD). PFS, PFS-2, and OS are estimated using the Kaplan-Meier method. Results: Histologic subtypes in the overall cohort were unclassified (N=25), clear cell (N=7), and papillary (N=3). ORR of IO containing regimens in any line of treatment (N=29) was 57% (95% CI 37, 75). In the 1st line setting, 8 patients received IO/IO, 12 received IO/VEGFR, and 15 received other regimens with an ORR of 38% (95% CI 9, 76), 75% (95% CI 43, 95), and 23% (95% CI 5, 54), respectively. Thirty-three patients were included for PFS and PFS-2 analysis and 34 for OS with a median duration of follow-up of 40 months. Median PFS is 11 months (95% CI 4, 19; 26 events), median PFS-2 is 14 months (95% CI 9, 25; 25 events) and median OS is 27 months (95% CI 13, 65; 21 events). PFS, PFS2, and OS did not differ by 1st line treatment group. Among patients who received any IO exposure in the 1st line versus patients who received non-IO-based therapy, there was no significant difference in median PFS (12 (95% CI 5, 22) vs 5 (95% CI 2,21) months, p=0.39), PFS2 (17 (95% CI 9, 28) vs 13 (95% CI 3, 25) months, p=0.49), or OS (27 (95% CI 13, 73) vs 26 (95% CI 4, NE), p=0.90). OS did not differ by tumor histologic subtype; however, sample size limits power to detect differences. Conclusion: In comparison to clear cell RCC, prognosis for patients with NF2-mutated RCC remains poor. IO-based therapy has activity in treating NF2-mutated RCC; patients may derive benefit even if first exposure to IO occurs ≥2nd treatment line. There was no significant difference in PFS, PFS2, or OS based on 1st line regimen for patients with NF2-mutated RCC. Further investigation of inhibitors specifically targeting downstream effectors of the Hippo pathway are warranted. Citation Format: Kelly N. Fitzgerald, Cihan Duzgol, Andrea Knezevic, Rachel Jacobi, Ritesh R. Kotecha, David H. Aggen, Maria I. Carlo, Neil J. Shah, Martin H. Voss, Darren R. Feldman, Robert J. Motzer, Chung-Han Lee. Clinical outcomes in NF2-mutated RCC treated with contemporary immunotherapy regimens [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr B022.

MP04-05 NF2-MUTANT RENAL CELL CARCINOMA: A CLINICAL AND GENOMIC CHARACTERIZATION OF AN UNCLASSIFIED CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023MP04-05 NF2-MUTANT RENAL CELL CARCINOMA: A CLINICAL AND GENOMIC CHARACTERIZATION OF AN UNCLASSIFIED CARCINOMA Stephen W. Reese, Mark Zucker, Lennert Eismann, Katiana Vazquez-Rivera, Arnold Oparanozie, Robert Motzer, Martin H. Voss, Chung-Han Lee, Maria Carlo, Ritesh R. Kotecha, Victor Reuter, Jonathan Coleman, Paul Russo, Eduard Reznik, Ari A. Hakimi, and Yingbei Chen Stephen W. ReeseStephen W. Reese More articles by this author , Mark ZuckerMark Zucker More articles by this author , Lennert EismannLennert Eismann More articles by this author , Katiana Vazquez-RiveraKatiana Vazquez-Rivera More articles by this author , Arnold OparanozieArnold Oparanozie More articles by this author , Robert MotzerRobert Motzer More articles by this author , Martin H. VossMartin H. Voss More articles by this author , Chung-Han LeeChung-Han Lee More articles by this author , Maria CarloMaria Carlo More articles by this author , Ritesh R. KotechaRitesh R. Kotecha More articles by this author , Victor ReuterVictor Reuter More articles by this author , Jonathan ColemanJonathan Coleman More articles by this author , Paul RussoPaul Russo More articles by this author , Eduard ReznikEduard Reznik More articles by this author , Ari A. HakimiAri A. Hakimi More articles by this author , and Yingbei ChenYingbei Chen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003215.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The use of genomic and molecular classification of renal cell carcinoma has led to an increasing appreciation of tumor biology and as well as characterization of previously unclassified subset of tumors. The importance of identifying specific drivers of tumorigenesis has wide-ranging implications for clinical care including risk stratification and treatment decision in the localized and systemic setting. We present a series of previously unclassified renal cell carcinoma patients that are primarily driven by a mutation in the NF2 gene. METHODS: We queried the MSK Clinical Sequencing Cohort, a database containing 95,499 samples who were sequenced using MSK-IMPACT, a DNA sequencing platform that captures 505 whole exome cancer genes. We found 37 patients with an NF2 mutation who had tumors designated as “unclassified” based on their pathology report. We also identified patients in our prospectively maintained surgical registry if they had undergone extirpative kidney surgery. RESULTS: Our cohort was notable for a median age at presentation of 64 years, male predominance (64.58%) and normal body habitus (BMI 25.5). At the time of presentation, mass size was noted to be small at 4.7 cm, however 25 (67.5%) of patients had metastatic disease a presentation. 14 patients underwent surgical resection of primary tumor, 9 of which were performed in the cytoreductive setting and most patients (n=10, 71.4%) had evidence of non-localized disease on surgical pathology. The median overall survival for the cohort was 29.6 months. We performed an additional stratification of patients with an NF2 mutation and concurrent 3p mutations (SETD2, PBRM1, BAP1). Median overall survival in the cohort was 28.2 mo. (95% CI: 15.5-NR). Survival amongst patients with an NF2 mutation alone was 29.6 mo. (95% CI: 19.6-NR) and patients with a concurrent 3p mutation had an overall survival of 16.5 mo. (95% CI: 6.2-NR). There was a non-specific trend for tumors with 3p mutations to have worse outcomes, however the log-rank differences between the two groups was not significant (p=0.06). Genomic analysis of sequenced tumors demonstrated that the NF2 mutant tumors have a low median MSI score (0.12) and low TMB score (3.9). CONCLUSIONS: We provide clinical and genomic characterization of a group of patients who were previously found to be unclassified renal cell carcinoma, however now found to have NF2 mutation as the putative driver of tumorigenesis. NF2 mutated renal cell carcinoma is an aggressive histology that undergoes early metastatic spread at small tumor size. Greater awareness of this tumor histology can lead to early identification and can help guide treatment decisions. Source of Funding: No funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e35 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stephen W. Reese More articles by this author Mark Zucker More articles by this author Lennert Eismann More articles by this author Katiana Vazquez-Rivera More articles by this author Arnold Oparanozie More articles by this author Robert Motzer More articles by this author Martin H. Voss More articles by this author Chung-Han Lee More articles by this author Maria Carlo More articles by this author Ritesh R. Kotecha More articles by this author Victor Reuter More articles by this author Jonathan Coleman More articles by this author Paul Russo More articles by this author Eduard Reznik More articles by this author Ari A. Hakimi More articles by this author Yingbei Chen More articles by this author Expand All Advertisement PDF downloadLoading ...

Predicting the probability of malignant pathological type of kidney cancer based on mass size: A retrospective study

Different degrees of malignancy of renal cell carcinoma (RCC) correspond to dissimilar therapies, and the prediction of malignancy of kidney cancer based on tumor size is still not fully studied. We evaluated a total of 50,776 patients with T1-T2, N0, M0 RCC diagnosed between 2004 to 2015 based on the Surveillance, Epidemiology, and End Results database. Three and four fuhrman grade clear cell RCC, three and four fuhrman grade papillary RCC, collecting duct RCC, sarcomatoid differentiation RCC and unclassified RCC were classified as aggressive RCC. The other RCC was classified as indolent RCC. The probability of aggressive and indolent was estimated according to tumor size using a logistic regression model. Differences in survival between subgroups were assessed using the Kaplan-Meier method. There were 38,003 cases of indolent tumor and 12,773 cases of aggressive tumor totally. As tumor size increases, the predicted probability of an aggressive tumor also increases. Concretely, kidney cancers of 2cm, 3cm and 4cm were estimated to be 19.6%, 21.6% and 23.7% more likely to be aggressive. And for the same tumor size, clear cell RCC in men is more likely to be invasive relative to women and other kidney cancer pathology types. In addition, both the overall and tumor-specific survival are longer for indolent tumors than for aggressive tumors. We evaluated the degree of malignancy of different sizes RCC in a retrospective study. This result may be helpful in the choice of initial therapy strategies for kidney cancer patients.

Approach for reclassification of collecting duct carcinoma and comparative histopathological analysis with SMARCB1/INI1-deficient renal cell carcinoma and fumarate hydratase-deficient renal cell carcinoma

Collecting duct carcinoma (CDC) is a rare subset of high-grade renal cell carcinoma (RCC). To diagnose CDC, it is necessary to rule out other renal tumors including renal medullary carcinoma and fumarate hydratase (FH)-deficient RCC. However, there is overlap in the morphology of these three tumors, which all have poor outcomes. There is also still a need to sufficiently examine the therapeutic strategies for each of these tumors. In this study, we retrospectively reclassified invasive/infiltrating high-grade RCC and investigated its pathological features. We reviewed 18 cases previously diagnosed as "CDC," "FH-deficient RCC," and "unclassified RCC," which were reclassified as SMARCB1/INI1-deficient RCC, FH-deficient RCC, and CDC by SMARCB1/INI1, FH, and 2SC immunohistochemistry (IHC) and FH gene mutational status. As the result, 18 cases were reclassified into 2 cases of SMARCB1/INI1-deficient RCC, 7 cases of FH-deficient RCC, and 9 cases of CDC. The morphological features of each group overlapped, and no specific immunohistochemical expression except for SMARCB1/INI1, FH, and 2SC was detected. These results suggest that invasive/infiltrating high-grade RCC should be diagnosed by the combination of immunohistochemistry and molecular biological technique.

Unclassified Oncocytic Renal Neoplasm with Rib and Liver Metastases: Metastatic Oncocytoma?

Renal tumors with oncocytic or chromophobe-like morphology can be a common source of diagnostic difficulty. In some series, they constitute the largest group of unclassified renal cell carcinomas, a term used for neoplasms that do not fit the current classification of renal tumors. We describe the histological, immunohistochemical, and molecular findings of an eosinophilic renal neoplasm which presented with rib and liver metastases, and provide a review of the literature. The possibility of a renal oncocytoma with metastases was initially considered but excluded on the basis of several morphological and immunohistochemical features. Additionally, the tumor did not correspond with other traditional or newly emerging categories of renal neoplasms. It was therefore regarded as an unclassified oncocytic renal neoplasm which demonstrated evidence of malignant potential due to the presence of multiple metastases.

Eosinophilic vacuolated tumour of the kidney

Eosinophilic vacuolated tumour (EVT) is one of the emerging entities of renal cell carcinoma. We present a case which we believe is second ever reported case of eosinophilic and vacuolated renal tumour (EVT) arising in setting of tuberous sclerosis syndrome. A 44-year-old male patient with past history (2017) of unclassified renal cell carcinoma of left kidney and known tuberous sclerosis syndrome receiving ongoing tyrosine kinase inhibitor therapy and undergoing radiological surveillance was found to have a 3 cm right renal mass.

Role of multidetector ct in quantitative enhancement- washout analysis of solid renal masses

BackgroundEnhancement washout technique in solid renal masses using multidetector computed tomography (MDCT) can differentiate different type of lesions. 99 Patients who are presenting with suspected renal masses or renal tumour for staging are included in this study. CT examination are carried out at urology and nephrology centre using MDCT. The attenuation values (Hounsfield Unit) will be assesed for each lesion on the pre enhanced, corticomedullary, nephrographic and delayed phases. Washout ratio will be calculated for each phase of enhancement in comparison to the unenhanced attenuation value. The characteristics of enhancement-washout will be correlated with the final histopathological diagnosis.ResultsEarly enhancement and washout pattern was noted in 54 renal lesions (54.5%) representing 4 types of renal lesions; Oncocytoma (n = 13), clear cell renal cell carcinoma (n = 16), Chromophobe renal cell carcinoma (n = 15) and unclassified renal cell carcinoma (n = 10).Prolonged enhancement pattern was noted 45 lesions (45.4%); PRCC (n = 14), 10 case of lipid poor AML (n = 10), metanephric adenoma (n = 10) and Xp11 RCC (n = 11). High pre-contrast attenuation was noted in Xp 11RCC showing attenuation value 41.7 ± 6.823HU. The highest CMP values were noted in CCRCC (151.9 ± 20.4) followed by oncocytomas (137.6 ± 19.15HU) and then CHRCC (123.6 ± 16.6 HU)while the lowest values were noted in Metanephric adenoma)57.1 ± 17.4HU)and followed by PRCC (59.9 ± 4.8)and followed by lipid poor AML (79.17 ± 13.666) and RCC unclassified (89.06 ± 18.1).ConclusionsFour-phase MDCT (the unenhanced, corticomedullary, nephrographic, and excretory phases) evaluate role of MDCT in differentiation of solid renal masses.

Germline Variants Identified in Patients with Early-onset Renal Cell Carcinoma Referred for Germline Genetic Testing

BackgroundDespite guidelines recommending genetic counseling for patients with early-onset renal cell carcinoma (RCC), studies interrogating the spectrum of germline mutations and clinical associations in patients with early-onset RCC are lacking. ObjectiveTo define the germline genetic spectrum and clinical associations for patients with early-onset RCC diagnosed at age ≤46 yr who underwent genetic testing. Design, setting, and participantsWe retrospectively identified patients with early-onset RCC who underwent germline testing at our institution from February 2003 to June 2020. Outcome measurement and statistical analysisThe frequency and spectrum of pathogenic/likely pathogenic (P/LP) variants were determined. Clinical characteristics associated with mutation status were analyzed using two-sample comparison (Fisher’s exact or χ2 test). Results and limitationsOf 232 patients with early-onset RCC, 50% had non–clear-cell histology, including unclassified RCC (12.1%), chromophobe RCC (9.7%), FH-deficient RCC (7.0%), papillary RCC (6.6%), and translocation-associated RCC (4.3%). Overall, 43.5% had metastatic disease. Germline P/LP variants were identified in 41 patients (17.7%), of which 21 (9.1%) were in an RCC-associated gene and 20 (8.6%) in a non–RCC-associated gene, including 17 (7.3%) in DNA damage repair genes such as BRCA1/2, ATM, and CHEK2. Factors associated with RCC P/LP variants include bilateral/multifocal renal tumors, non–clear-cell histology, and additional extrarenal primary malignancies. In patients with only a solitary clear-cell RCC, the prevalence of P/LP variants in RCC-associated and non–RCC-associated genes was 0% and 9.9%, respectively. ConclusionsPatients with early-onset RCC had high frequencies of germline P/LP variants in genes associated with both hereditary RCC and other cancer predispositions. Germline RCC panel testing has the highest yield when patients have clinical phenotypes suggestive of underlying RCC gene mutations. Patients with early-onset RCC should undergo comprehensive assessment of personal and family history to guide appropriate genetic testing. Patient summaryIn this study of 232 patients with early-onset kidney cancer who underwent genetic testing, we found a high prevalence of mutations in genes that increase the risk of cancer in both kidneys and other organs for patients and their at-risk family members. Our study suggests that patients with early-onset kidney cancer should undergo comprehensive genetic risk assessment.

PD16-07 NEUTROPHIL-TO-LYMPHOCYTE RATIO IN UNCLASSIFIED RENAL CELL CARCINOMA IS ASSOCIATED WITH OUTCOME AND DIFFERS BETWEEN MOLECULAR SUBGROUPS

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy II (PD16)1 Sep 2021PD16-07 NEUTROPHIL-TO-LYMPHOCYTE RATIO IN UNCLASSIFIED RENAL CELL CARCINOMA IS ASSOCIATED WITH OUTCOME AND DIFFERS BETWEEN MOLECULAR SUBGROUPS Julian Marcon, Renzo G. DiNatale, Stanley Weng, Mazyar Ghanaat, Andrew W. Silagy, Roy Mano, Kyle A. Blum, Kyrollis Attalla, Ed Reznik, Maria I. Carlo, Robert J. Motzer, Jonathan A. Coleman, Paul Russo, A. Ari Hakimi, and Ying-Bei Chen Julian MarconJulian Marcon More articles by this author , Renzo G. DiNataleRenzo G. DiNatale More articles by this author , Stanley WengStanley Weng More articles by this author , Mazyar GhanaatMazyar Ghanaat More articles by this author , Andrew W. SilagyAndrew W. Silagy More articles by this author , Roy ManoRoy Mano More articles by this author , Kyle A. BlumKyle A. Blum More articles by this author , Kyrollis AttallaKyrollis Attalla More articles by this author , Ed ReznikEd Reznik More articles by this author , Maria I. CarloMaria I. Carlo More articles by this author , Robert J. MotzerRobert J. Motzer More articles by this author , Jonathan A. ColemanJonathan A. Coleman More articles by this author , Paul RussoPaul Russo More articles by this author , A. Ari HakimiA. Ari Hakimi More articles by this author , and Ying-Bei ChenYing-Bei Chen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001998.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Unclassified renal cell carcinoma (uRCC) is a rare non-clear cell RCC variant. Next-generation sequencing studies have reported molecular subgroups to be associated with better (MTOR/PI3K) and worse (HIPPO/TP53/DNA damage repair) outcome. High neutrophil-to-lymphocyte ratio (NLR) is a biomarker of inflammatory response and has been shown to be associated with worse prognosis. We aimed to explore the role of NLR in this setting and further assessed the differences in NLR between genomic subgroups. METHODS: After IRB approval a total of 112 patients with uRCC, who underwent molecular profiling, were identified from our internal database. 85 patients with a preoperative complete blood count obtained at the time of diagnosis and comprehensive follow-up data were included. NLR was computed by dividing the absolute neutrophil count by the absolute lymphocyte count (in K/µl). We performed non-parametric hypothesis testing with p≤0.05 defining statistical significance. Cancer-specific survival (CSS) was calculated from the time of pathological diagnosis to the time of death or last follow-up. Survival estimates were calculated using uni- and multivariable Cox regression models. RESULTS: The study cohort comprised 51 men and 34 women, the median age was 60.5 years (IQR: 51.5-70). The median NLR was 3.05 K/µl (IQR: 2.04-4.2). Patients with higher NLR showed poor CSS (Cox p<0.001, HR 1.23, 95%CI: 1.12-1.36). After accounting for pT and M stage, molecular subgroups and the number of driver mutations at multivariable analysis, higher NLR remained significantly associated with poor CSS (p=0.012, HR 1.18, CI: 1.04-1.34 – Fig. 1A). MTOR/PI3K pathway related subgroups were detected in 17 (20.0%) patients, while in 30 cases mutations in genes of other major pathways (HIPPO/TP53/DNA damage repair/cell cycle) were found. There was a significant difference in NLR between genomic subgroups (Kruskal-Wallis p=0.002, Fig. 1B). CONCLUSIONS: NLR is significantly associated with clinical outcome in uRCC. Further studies are warranted to investigate its value as a biomarker of disease aggressiveness. Moreover, distinct genomic subgroups of uRCC vary considerably with respect to this parameter. Source of Funding: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e281-e281 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Julian Marcon More articles by this author Renzo G. DiNatale More articles by this author Stanley Weng More articles by this author Mazyar Ghanaat More articles by this author Andrew W. Silagy More articles by this author Roy Mano More articles by this author Kyle A. Blum More articles by this author Kyrollis Attalla More articles by this author Ed Reznik More articles by this author Maria I. Carlo More articles by this author Robert J. Motzer More articles by this author Jonathan A. Coleman More articles by this author Paul Russo More articles by this author A. Ari Hakimi More articles by this author Ying-Bei Chen More articles by this author Expand All Advertisement Loading ...

Predictors of postoperative recurrence in patients with non-metastatic pT3a renal cell carcinoma.

To analyze the effect of patterns of extrarenal tumor extension with other pathological factors on postoperative recurrence in patients with non-metastatic pT3a renal cell carcinoma. We retrospectively reviewed 587 non-metastatic renal cell carcinoma patients who underwent radical surgery between 2006 and 2017 at Kansai Medical University Hospital, Hirakata, Osaka, Japan. We extracted a subset of 114 patients with pT3a of predominant histological types: 93 with clear cell renal cell carcinoma (81.6%), 13 with unclassified renal cell carcinoma (11.4%), six with chromophobe renal cell carcinoma (5.3%) and two with papillary renal cell carcinoma. The primary end-point was recurrence-free survival. The Kaplan-Meier method and Cox proportional hazards model were used for statistical analysis. Of the 114 patients with pT3a renal cell carcinoma, 42 patients (36.8%) experienced recurrence. Multivariate analysis showed that perinephric fat invasion (hazard ratio 2.36, P=0.009), sarcomatoid or rhabdoid component (hazard ratio 2.88, P=0.022) and necrosis (hazard ratio 2.34, P=0.030) were independent factors for recurrence-free survival. The high-risk pT3a group, which had more than two independent predictors, had poor prognosis. Recurrence-free survival of the high-risk pT3a group and the pT3b or greater group were similar (median recurrence-free survival 23.0 and 10.8months, respectively). Perinephric fat invasion, sarcomatoid or rhabdoid component and necrosis are independent predictors of recurrence-free survival in patients with pT3a-predominant renal cell carcinoma. Patients with more than two of these predictors have poor oncological outcomes. These findings will aid in risk stratification for predicting recurrence and provide prognostic information for patient counseling.

P0613 - Neutrophil-to-lymphocyte ratio in unclassified renal cell carcinoma is associated with clinical outcome and varies between genomic subgroups

P0613 - Neutrophil-to-lymphocyte ratio in unclassified renal cell carcinoma is associated with clinical outcome and varies between genomic subgroups

Postoperative and Mid-term Outcomes of Unclassified Renal Cell Carcinoma

Postoperative and Mid-term Outcomes of Unclassified Renal Cell Carcinoma

A Case of Unclassified Renal Cell Carcinoma Initially Considered as Translocation RCC and Review of Literature

A Case of Unclassified Renal Cell Carcinoma Initially Considered as Translocation RCC and Review of Literature

Racial Comparison of Patients Undergoing Minimally Invasive Partial Nephrectomy for Renal Masses at a Large Volume Tertiary Center.

Introduction and Objective: African American (AA) race has been identified to have a higher incidence of chronic kidney disease (CKD) and worse renal cancer survival compared with Caucasian Americans (CA), irrespective of tumor size, pathologic type, and surgical procedure. We aimed to compare the outcomes between CA and AA patients undergoing minimally invasive partial nephrectomy (PN) at our high-volume center. Materials and Methods: We queried our PN data repository from 2007 to 2017. We identified 981 cases of PN (robotic n = 943 and laparoscopic n = 38), of which there were 852 CA and 129 AA patients. We compared age, sex, body mass index (BMI), operative time, estimated blood loss (EBL), nephrometry score, tumor size, pre- and postoperative estimated glomerular filtration rate (eGFR), length of stay, Charlson Comorbidity Index (CCI), tumor characteristics, and 30-day complication rate. We then estimated the overall survival and disease-specific survival. Results: Age, BMI, operative time, EBL, nephrometry score, tumor size, CCI, length of stay, and sex were not statistically different. The mean preoperative eGFR was higher in the AA cohort (91.4 mL/min/1.73 m2 vs 86.1 mL/min/1.73 m2, p = 0.007); however, at 1 year, there was no mean difference (76.8 mL/min/1.73 m2 vs 74.5 mL/min/1.73 m2, p = 0.428). There was a higher percentage of Fuhrman Grade 3/4 in the AA cohort (33.3% vs 22.5%, p = 0.044). The AA cohort had a 2.66 × higher incidence of papillary renal cell carcinoma (RCC) (34.9% vs 13.1%, p < 0.001) and unclassified RCC (3.9% vs 0.4%, p = 0.001). There was no difference in tumor stage (p = 0.260) or incidence of benign histology (15.3% vs 11.6%, p = 0.278). There were no differences in 30-day complications (p = 0.330). The median follow-up was 43.2 months. By using Kaplan-Meier curves, there was no observed difference in overall survival (p = 0.752) or disease-free survival (p = 0.403). Conclusions: Our cohort of AA and CA patients with intermediate follow-up showed no worse outcomes for CKD or survival when undergoing laparoscopic or robotic PN. For low-stage renal cancer, there was no difference in overall survival and disease-free survival at a median follow-up of 43.2 months among AA patients, despite having higher grade tumors and a higher percentage of unclassified RCC. Our cohort of AA patients did have a higher incidence of papillary RCC. The equivalent overall survival and disease-free survival could be due to the earlier discovery of lower stage renal masses incidentally identified on imaging studies performed equally for other reasons in both AA and CA patients.