Papillary Renal Cell Carcinoma Type Research Articles

Papillary Renal Cell Carcinoma Type 1 Accompanied by Hemorrhagic Anemia: A Case Report

Background: Kidney cancer or renal cell carcinoma (RCC) accounts for 5% and 3% of all adult malignancies in men and women, respectively, thus representing the 7th most common cancer in men, and the 10th most common cancer in women. The incidence of kidney cancer in the last two decades has shown an increase, but in recent years the death rate due to kidney cancer has decreased because it is increasing.
 Case Presentation: A 27 year old male patient came with complaints of bloody urination. Patients also complain of body weakness. Every time they are active, the weakness decreases if the patient rests. The patient was stated to be suffering from anemia and a left kidney tumor. There was bilateral antebrachial pitting edema. There was bilateral pretibial edema. Cytological examination revealed papillary renal cell carcinoma type 1.
 Conclusion: Papillary cell carcinoma type 1 is a kidney tumor that has a good prognosis, especially if found at an early stage. The classic symptoms of type 1 pRCC are anemia, hematuria and kidney swelling.

Papillary renal neoplasm with reverse polarity—a comparative study with CCPRCC, OPRCC, and PRCC1

Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. In this study, we aimed to identify and analyze the clinicopathological, immunohistochemical (IHC), and molecular features of PRNRP in our center and to evaluate its differential diagnosis with other tumors with which it is easily confused: clear cell papillary renal cell carcinoma (CCPRCC), oncocytic papillary renal cell carcinoma (OPRCC), and papillary renal cell carcinoma type 1 (PRCC1). Nephrectomy specimens of PRNRP (n=15), CCPRCC (n=11), and OPRCC (n=12) were retrieved from our pathology archives. We also selected typical cases of PRCC1 (n=15) as a control group. PRNRP accounted for 3.05% (15/492) of all PRCC cases at our center. The median follow-up period was 41.3 months. All PRNRP cases were pT1N0M0, and only one involved recurrence (1 year after surgery). IHC analysis showed diffuse staining of CK7, EMA, and GATA3 but weak or negative staining of CD10, CD117, p504s, and vimentin in the PRNRP samples and distinctive IHC features in the other three tumor types. KRAS mutation was detected in 4/10 PRNRP cases. Among the 40 most commonly mutated genes identified, 5 (BCLAF1, PDE4DIP, NCOR1, PARP4, and PABPC1) have actionable alterations. Our study supports the suggestion that PRNRP is an entity distinct from CCPRCC, OPRCC, and PRCC1.

Papillary Type Renal Cell Carcinoma with Sarcomatoid Differentiation

Renal cell carcinoma is the most common renal tumor in adult population. Sarcomatoid differentiation of renal cell carcinoma is quite aggressive in nature and has poor prognosis. In this study, a case of 69-year-old female patient who initially presented with hematuria was discussed.

Differential Diagnosis of Type 1 and Type 2 Papillary Renal Cell Carcinoma Based on Enhanced CT Radiomics Nomogram.

ObjectivesTo construct a contrast-enhanced CT-based radiomics nomogram that combines clinical factors and a radiomics signature to distinguish papillary renal cell carcinoma (pRCC) type 1 from pRCC type 2 tumours.MethodsA total of 131 patients with 60 in pRCC type 1 and 71 in pRCC type 2 were enrolled and divided into training set (n=91) and testing set (n=40). Patient demographics and enhanced CT imaging characteristics were evaluated to set up a clinical factors model. A radiomics signature was constructed and radiomics score (Rad-score) was calculated by extracting radiomics features from contrast-enhanced CT images in corticomedullary phase (CMP) and nephrographic phase (NP). A radiomics nomogram was then built by incorporating the Rad-score and significant clinical factors according to multivariate logistic regression analysis. The diagnostic performance of the clinical factors model, radiomics signature and radiomics nomogram was evaluated on both the training and testing sets.ResultsThree validated features were extracted from the CT images and used to construct the radiomics signature. Boundary blurring as an independent risk factor for tumours was used to build clinical factors model. The AUC value of the radiomics nomogram, which was based on the selected clinical factors and Rad-score, were 0.855 and 0.831 in the training and testing sets, respectively. The decision curves of the radiomics nomogram and radiomics signature in the training set indicated an overall net benefit over the clinical factors model.ConclusionRadiomics nomogram combining clinical factors and radiomics signature is a non-invasive prediction method with a good prediction for pRCC type 1 tumours and type 2 tumours preoperatively and has some significance in guiding clinicians selecting subsequent treatment plans.

Papillary Renal Cell Carcinomas Demonstrating Micropapillary Features: An Investigation Into the Diagnostic and Prognostic Implications.

Aims: Papillary renal cell carcinoma (PRCC) with micropapillary carcinoma (MC) has been rarely described. We conducted a retrospective descriptive evaluation of the association of MC with PRCC and the possible prognostic implications.Methods: A database search was made at the University of Southern California (USC) and Lenox Hill Hospital (LHH; New York City) in June 2016-June 2019 of PRCC cases with MC. Diagnosis of MC was made using routine histology, based on the presence of small clusters of cells without a vascular core. Features evaluated included: percent of MC, gross appearance, PRCC typing, nuclear grade, lymphovascular invasion, and lymph node metastasis.Results: 848 RCC cases (690 from USC and 157 from LHH); 70 cases PRCC (54 from USC, 16 from LHH) of these cases, 13 had an MC, 12 were from radical nephrectomy, and 12 cases were male. Mean age was 68.3 years; seven were located in the right kidney. Average tumor size was 8.6 cm. MC ranged from 10% to 80% (average 37.5%), nine cases were PRCC type 2 and four type 1. Nuclear grade: three cases (grade 2), nine cases (grade 3), and one case (grade 4); 11 out of 13 tumors presented with extrarenal extension; nine cases that had lymph nodes submitted had metastatic carcinoma.Conclusions: The presence of a micropapillary component in PRCC was found to be 18.5%, and it was predominantly associated with high pathologic stage and lymph node metastases. The clinical course of these tumors seems similar to MC in other tissues/organ systems. We advocate reporting this pattern when identified.

A prospective randomized parallel-controlled pilot trial of stereotactic body radiation therapy versus radiofrequency ablation for the management of small renal masses.

363 Background: The potential of ablative technologies as an alternative to surgery for the treatment of small renal masses (SRMs) ≤4cm is unclear. Our objective was to evaluate the feasibility and toxicity of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) for SRMs in a prospective randomized pilot trial. Methods: Patients scheduled for renal cell carcinoma (RCC) treatment at a single academic center were approached for the pilot trial, with the aim of recruiting 24 patients. Participants were assigned 1:1 to SBRT or RFA. Imaging (CT or MRI) using a renal tumor protocol is completed at 3, 6, 9, and 12 months post-procedure. Biopsies were completed prior to the procedure and at 12 months. Multiple clinical parameters were collected. Follow-up visits will occur at 6 month intervals following the trial up to 5 years. SBRT included an initial simulation session and a single image-guided treatment session with a prescribed dose of 25 Gy. RFA was conducted by either percutaneous or laparoscopic access with 2 cycles of 8 minutes duration each upon reaching target temperature. Results: Beginning in December 2019, 24 patients were recruited and randomized (SBRT = 11; RFA = 13). Eleven had SBRT, 8 RFA, 3 have not yet had treatment, and 2 became ineligible. Median age for all patients was 67 (53,85) and 17 were male. A total of 17 patients had clear cell RCC, 6 had papillary RCC (type 1), and 1 had chromophobe RCC. All patients had T1a disease. Mean procedure length (minutes) for SBRT and RFA was 15.5±7.4 and 10.5±3.9, respectively. Two patients (both SBRT) had a 12-month biopsy showing no evidence of recurrence or metastases, while two patients (1 RFA, 1 SBRT) had a 9-month CT showing no recurrence. Data are pending for the remaining patients. An early grade 2 flare-up occurred in one SBRT patient. Conclusions: Recruitment and randomization of patients with SRMs in a SBRT vs. RFA prospective trial is feasible on a timeline that allows for regular follow-up and imaging. To date, both treatment modalities have been shown to have excellent short-term safety profiles.

Novel germline MET pathogenic variants in French patients with papillary renal cell carcinomas type I.

Hereditary papillary renal cell carcinoma (HPRC) is a rare inherited renal cancer syndrome characterized by bilateral and multifocal papillary type 1 renal tumors (PRCC1). Activating germline pathogenic variants of theMET gene were identified in HPRC families. We reviewed the medical and molecular records of a large French series of 158 patients screened for MET oncogenic variants. MET pathogenic and likely pathogenic variants rate was 12.4% with 40.6% among patients with familial PRCC1 and 5% among patients with sporadic PRCC1. The phenotype in cases with MET pathogenic and likely pathogenic variants was characteristic: PRCC1 tumors were mainly bilateral (84.3%) and multifocal (87.5%). Histologically, six out of seven patients with MET pathogenic variant harbored biphasic squamoid alveolar PRCC. Genetic screening identified one novel pathogenic variant MET c.3389T>C, p.(Leu1130Ser) and three novel likely pathogenic variants: MET c.3257A>T, p.(His1086Leu); MET c.3305T>C, p.(Ile1102Thr) and MET c.3373T>G, p.(Cys1125Gly). Functional assay confirmed their oncogenic effect as they induced an abnormal focus formation. The genotype-phenotype correlation between MET pathogenic variants and PRCC1 presentation should encourage to widen the screening, especially toward nonfamilial PRCC1. This precise phenotype also constitutes a strong argument for the classification of novel missense variants within the tyrosine kinase domain when functional assays are not accessible.

Characterizing the tumor microenvironment in rare renal cancer histological types.

The tumor microenvironment (TME), including immune cells, cancer‐associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high‐grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial‐to‐mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann–Whitney and Kruskal–Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53–4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22–5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42–3.9]). Spatial analysis revealed CD3+ T‐cell and CD20+ B‐cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance‐dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies.

A rare association in a patient with non-muscle invasive bladder cancer: ureteral fibroepithelial polyp and ipsilateral renal cell carcinoma: a case report

BackgroundFibroepithelial polyps located in the ureter constitute 2–6% of all benign tumors in the urinary system. Distinguishing these lesions from transitional cell carcinoma is essential to avoid unnecessary nephroureterectomy.Case presentationA 59-year-old asymptomatic caucasian male patient was enrolled in follow-up for Ta low-grade transitional cell bladder cancer 4 years ago in our clinic. A suspicious, solid, contrast-enhancing mass 15 × 9 mm in diameter in the anteromedial mid-section of the left kidney, which was causing minimal washout and largely located in the parenchyma, was reported as renal cell carcinoma on computed tomography during routine controls. In the excretory phase, soft-tissue densities of approximately 30 mm in length, which were located in the distal part of the left ureter at a distance of 40 mm from the ureterovesical junction, extending towards the lumen suggested a urethral carcinoma. Urothelial lesion was reported as fibroepithelial polyp after histopathological examination. Partial nephrectomy for the mass, which was reported as renal cell carcinoma in the left kidney, was performed in the first postoperative month. Histopathological examination revealed Fuhrman grade 1 papillary type renal cell carcinoma. No recurrence was observed in the first year after treatment.ConclusionsAlthough our patient had a bladder transitional cell carcinoma and a suspicious renal cell carcinoma mass of 15 mm in the ipsilateral kidney, the patient was safeguarded from unnecessary nephroureterectomy early on by cross-sectional and endoscopic imaging of the ureter.

Expression of transient receptor potential melastatin 4 in differential diagnosis of eosinophilic renal tumors.

Immunohistochemical and molecular studies to differentiate eosinophilic kidney tumors are gradually increasing. The present study investigated the role of transient receptor potential cation channel subfamily M member 4 (TRPM4), a non-selective cation channel associated with migration, proliferation and invasion in cancer cells, in this differentiation. The aim was to investigate the effectiveness of TRPM4 in differentiation of eosinophilic kidney tumors. The study included a total of 112 patients, including 97 eosinophilic kidney tumors with the diagnoses of 33 eosinophilic clear cell renal cell carcinoma (CCRCC), 35 eosinophilic chromophobe renal cell carcinoma (ChRCC), 8 papillary renal cell carcinoma type 2 (P2RCC), 21 renal oncocytoma (RO), as well as 15 papillary renal cell carcinoma type 1 to differentiate from P2RCC. For TRPM4, diffuse staining (>10%) was observed in 2 CCRCC, 15 ChRCC, 20 RO and 4 P2RCC cases. There was a significant difference between eosinophilic CCRCC and other eosinophilic tumors (P<0.05). While basolateral staining was observed in papillary tumors, membrane staining was observed in other stained cases. It was hypothesized that the use of TRPM4 along with morphological findings, cytokeratin 7 and other markers may be useful for the differentiation of eosinophilic kidney tumors.

Functional magnetic resonance imaging for distinguishing type of papillary renal cell carcinoma: a preliminary study.

To investigate the feasibility of magnetic resonance diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) for distinguishing Type 1 and 2 of papillary renal cell carcinoma (PRCC). A total of Type 1 (n = 20) and Type 2 (n = 16) of PRCC were examined by pathology. For DKI and IVIM, mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK), kurtosis anisotropy (KA), radial kurtosis (RK), diffusivity (D), pseudodiffusivity (D*) and perfusion fraction (f) were performed in assessment of type of PRCC. The mean SNRs of IVIM and DKI images at b = 1500 and 2000 s/mm2 were 8.6 ± 0.8 and 7.8 ± 0.6. Statistically significant differences were observed in MD and D values (1.11 ± 0.23 vs 0.73 ± 0.13, 0.91 ± 0.24 vs 0.49 ± 0.13, p < 0.05) between Type 1 and Type 2 of PRCC, while comparable FA, RK, D* and f values were found between Type 1 and Type 2 of PRCC (p > 0.05). Statistically significant differences were observed in MK and KA values (1.23 ± 0.16 vs 1.91 ± 0.26, 1.49 ± 0.19 vs 2.36 ± 0.39, p < 0.05) between Type 1 and Type 2 of PRCC. Areas of MD, MK, KA and D values under ROC curves for differentiating Type 1 and Type 2 of PRCC were 0.836, 0.818, 0.881 and 0.766, respectively. Using MD, MK, KA and D values of 0.93, 1.64, 1.94, 0.68 as the threshold value for differentiating Type 1 from Type 2 of PRCC, the best result obtained had a sensitivity of 85.0%, 80.0%, 90.0%, 85.0%, a specificity 75.0%, 68.7%, 87.5%, 81.2%, and an accuracy of 83.3%, 80.5%, 88.9%, 86.1%, respectively. DKI and IVIM are feasible techniques for distinguishing type of PRCC, given an adequate SNR of IVIM and DKI images. 1. MD and D values are higher for Type 1 of PRCC and lower for Type 2 of PRCC.2. MK and KA values are higher for Type 2 of PRCC and lower for Type 1 of PRCC.3. DKI and IVIM can be used as clinical biomarker for PRCC type's differential diagnosis, given an adequate SNR.

Treatment of allograft renal cell carcinoma with partial nephrectomy in a pediatric kidney transplant.

Renal cell carcinoma (RCC) is a common malignancy among kidney transplant recipients that often occurs in the native kidney. The incidence of RCC in the renal allograft is rare and carries the double risk of returning to dialysis and the development of metastatic cancer. The majority of reported cases of RCC in transplanted kidneys are in adult recipients and its occurrence in the pediatric age group is an uncommon event. There are currently no established guidelines on the treatment of RCC in transplant recipients.We report our experience of a 15-year-old male who developed allograft RCC 12 years later after transplantation. MRI confirmed the presence of the mass near the hilum of the renal allograft and biopsy revealed a Papillary Renal Cell Carcinoma (PRCC) type I. A partial allograft nephrectomy was successfully performed with negative tumor margins. The patient’s serum creatinine 12 months post-operation was 1.9 mg/dL and presently he has no evidence of residual disease, recurrence, or metastasis.Partial nephrectomy is an effective treatment option for renal allograft RCC as it spares the patient from returning to dialysis until retransplantation is possible and necessary.

P0633 - Papillary renal cell carcinoma type I and II: Two distinct diseases with different clinical and therapeutical implications

P0633 - Papillary renal cell carcinoma type I and II: Two distinct diseases with different clinical and therapeutical implications

Morphological, immunohistochemical, and genomic analyses of papillary renal neoplasm with reverse polarity

Papillary renal neoplasm with reverse polarity (PRNRP) is a recently proposed entity of renal tumor. It shows a far better prognosis than papillary renal cell carcinoma (PRCC) and frequently has KRAS missense mutation. In this study, we compared 14 cases of PRNRP and 10 cases of PRCC type 1 (PRCC1) and type 2 (PRCC2) from clinical, morphological, immunohistochemical, and molecular biological perspectives. We subjected all PRNRP and PRCC cases to immunohistochemical analysis. Whole-exome sequencing using next-generation sequencing (NGS) was performed for six cases of PRNRP, three cases of PRCC1, and four cases of PRCC2. A search for KRAS gene mutation in the remaining eight cases of PRNRP was performed by polymerase chain reaction (PCR) sequencing. The results showed that all cases of PRNRP were pT1N0M0, none of which followed a course of recurrence or tumor-related death. Immunohistochemical analysis revealed diffuse staining of CK7, EMA, PAX8, and GATA3 but weak or negative staining of CD10, CD15, and AMACR in PRNRP. By NGS and PCR, KRAS missense mutation was detected in 11 of 14 PRNRP cases, although pathogenic KRAS mutation was not observed in PRCC1 and PRCC2. NGS analysis revealed less tumor mutation burden in PRNRP than in PRCC. PRNRP also showed no specific chromosomal copy number abnormalities, including gains of 7 and 17. In conclusion, we propose that PRNRP is a distinct condition from PRCC.

Integrated Analysis Revealed the MicroRNA-Based Prognostic Predicting Signature for Papillary Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is one of the most frequently occurring tumors worldwide. Herein, we established a microRNA (miRNA) predicting signature to assess the prognosis of papillary-type RCC (PRCC) patients. miR-1293, miR-34a, miR-551b, miR-937, miR-299, and miR-3199-2 were used in building the overall survival (OS)-related signature, whereas miR-7156, miR-211, and miR-301b were used to construct the formula of recurrence-free survival (RFS) with the help of LASSO Cox regression analysis. The Kaplan-Meier and receiver operating characteristic curves indicated good discrimination and efficiency of the two signatures. Functional annotation for the downstream genes of the OS/RFS-related miRNAs exposed the potential mechanisms of PRCC. Notably, the multivariate analyses suggested that the two signatures were independent risk factors for PRCC patients and had better prognostic capacity than any other classifier. In addition, the nomogram indicated synthesis effects and showed better predictive performance than clinicopathologic features and our signatures. We validated the OS and RFS prediction formulas in clinical samples and met our expectations. Finally, we established two novel miRNA-based OS and RFS predicting signatures for PRCC, which are reliable tools for assessing the prognosis of PRCC patients.

Treatment strategy for papillary renal cell carcinoma type 2: a case series of seven patients treated based on next generation sequencing data.

BackgroundPapillary renal cell carcinoma type 2 (PRCC2) is refractory to systemic treatment and has a dismal prognosis. Previous studies showed that genetic alterations in PRCC2 were heterogeneous regardless of germline or somatic mutations. In this study, we aimed to perform precision treatment of PRCC2 based on genetic information.MethodsWe performed exome and genome sequencing of tumor tissues and matched normal samples. Based on sequencing data, we treated patients with metastatic PRCC2 using precision oncology.ResultsFour patients underwent curative surgery of PRCC2 and three patients had metastatic PRCC2. All PRCC2 heterogeneously harbored own driver mutations. Two out of the three patients with metastatic disease had fumarate hydratase (FH) germline mutations. One patient with a germline FH mutation was diagnosed with hereditary leiomyomatosis RCC. He was treated with bevacizumab and erlotinib combination and showed a durable response. The other metastatic PRCC2 patient harboring a germline FH mutation had an additional somatic FH mutation and was durably controlled with pazopanib. Other metastatic PRCC2 patient with somatic PBRM1 and SETD2 mutations had over 5 years of overall survival with axitinib treatment.ConclusionsWe performed precision systemic treatment based on genetic information. Genome sequencing could help identify candidates for targeted therapy in PRCC2, a genetically heterogeneous disease.

Abstract D121: Predicting African American and European American patient response to kidney cancer immunotherapy by stage using the tumor microenvironment

Abstract Background Kidney cancer ranks as a top ten leading site of new cancer cases (~64,000) in the US each year. Renal Cell Carcinoma (RCC) is the predominant type of kidney cancer (~90% cases). The most common RCC subtypes include clear cell RCC (ccRCC, 75%), papillary RCC types I and II (pRCC I and II, 5% and 10%), and chromophobe RCC (chRCC, 5%). RCC subtypes have distinct responses to immunotherapy. Combination checkpoint inhibitors are the first-line treatment for advanced stage ccRCC. Unfortunately, response varies in advanced stage patients, suggesting stage-specific differences in tumor biology. Tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) have been shown to directly influence checkpoint inhibitor response. African Americans (AAs) have higher RCC incidence rates than European Americans (EAs) for reasons that are unclear. Biological determinants of this cancer health disparity have been largely understudied. To our knowledge, no study to date has profiled the TME by stage in AA and EA RCC patients and explored its usefulness as a predictor of checkpoint inhibitor response. Hypothesis TIL abundances and composition varies by stage between AAs and EAs with RCC. Methods Downloaded mRNA-sequencing and clinical data for 531 ccRCC patients, 52 Type I pRCC patients, 66 Type II pRCC patients, and 66 chRCC patients in the TCGA discovery cohort. Differential expression analyses for checkpoint inhibitor drug targets (PD-1, PD-L1, and CTLA-4) were carried out. CIBERSORT, a computation tool that quantifies abundances for 22 TILs based on gene expression, was used to characterize the TME. 1-way ANOVAs between Stages I-IV were performed with GraphPad Prism 8. Significant racial differences for relevant TILs were determined using two-tailed unpaired Welch t tests. Kidney cancer immunotherapy drug responses were inferred based on published clinical studies. Results PD-1 and CTLA-4 significantly increased in advanced stage ccRCC patients. 6/22 TILs showed stage-specific increases and decreases in ccRCC patients. Interestingly, three of these (follicular helper T cells, regulatory T cells, and CD8+ T cells) showed the same trend as the checkpoint inhibitor targets. In pRCC I and II, some TILs also demonstrated a linear increase by stage (Both: regulatory T cells, M1 macrophages; Type II only: naive B cells). M2 macrophage abundance increased significantly by stage in chRCC patients. When comparing AA (n=55) and EA (n=461) ccRCC patients, follicular helper T cells and regulatory T cells increased by stage in EA only. CD8+ T cells increased in abundance in both racial groups. Regulatory T cells and M2 macrophages have been reported to mediate clinical response to checkpoint inhibitor immunotherapy. Conclusions/Future Directions Our data suggests AA and EA RCC patients with advanced stage disease will respond differently to kidney cancer immunotherapy due to TME differences, namely TIL abundance and composition. Future studies include validating these findings in the expO cohort. Citation Format: Jacquelyn Cobb, Heinric Williams, Khadijah A. Mitchell. Predicting African American and European American patient response to kidney cancer immunotherapy by stage using the tumor microenvironment [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 D121.

De novo chromophobe renal cell carcinoma in the graft three decades after renal transplantation in a patient with a history of three renal transplants

De novo renal allograft tumors were reported sporadically. Most of them were small, low-grade, and papillary renal cell carcinoma (RCC) type. A 46-year-old male presented with hematuria three decades after the first transplant. The patient had a history of three renal transplants. A tumor (12 cm × 13 cm) was diagnosed in the nonfunctioning first transplanted kidney. Radical nephrectomy of the graft harboring the tumor with preservation of the adjacent functioning graft was done and identified to be chromophobe RCC. After two-year follow-up, the patients had a perfect graft function with no evidence of oncological failure. We suggest that allograft tumor be considered in patient evaluation for hematuria. Regular follow-up imaging of transplanted kidney is mandatory even after graft failure for early detection of graft tumors.

Papillary renal cell carcinoma with prominent spindle cell stroma - tumor mimicking mixed epithelial and stromal tumor of the kidney: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 6 cases

Papillary renal cell carcinoma (PRCC) is currently a well-studied type of RCC. In addition to PRCC type 1, there are a number of other subtypes and variants of PRCCs which have been reported. We describe a series of 6 PRCCs with papillary, micropapillary and/or tubulopapillary architecture and prominent spindle cell stroma, resembling stroma in mixed epithelial and stromal tumor of the kidney (MESTK) or sarcomatoid RCC.Clinicopathologic, morphologic, immunohistochemical and molecular features were analyzed.All patients were males with an age range of 44–98 years (mean 65.3, median 65.5 years). Tumor size ranged from 2.4–11.4 cm (mean 5.8, median 4.5 cm). Follow-up data were available for 4 patients, ranging from 3 to 96 months (mean 42.75, median 36 months). Epithelial cells were mostly cylindrical with eosinophilic cytoplasm, showing nuclear grade 2 and 3 (ISUP/WHO).In all cases, loose to compact prominent stroma composed of spindle cells, without malignant mesenchymal heterologous elements was detected. No atypical mitoses were found, while typical mitoses were rare in both epithelial and stromal components.Epithelial cells were positive for CK7, AMACR, and vimentin in all cases, while negative for TFE3, HMB45, desmin, CD34, and actin. The stroma was positive for vimentin, actin and focally for CD34, while negative for CK7, AMACR, TFE3, HMB45, and desmin. Estrogen and progesterone receptors were completely negative. FH and SDHB expression was retained in all analyzable cases. Proliferative index was barely detectable in stromal component and low in epithelial component, ranging 0 to 5% positive stained cells/high power field.Copy number variation was variable with no distinct pattern. No mutations in CDKN2A, BAP1, MET were detected.PRCC with MESTK-like features is a distinct variant of PRCC mimicking MESTK. Our findings add to the body of literature on ever expanding variants of PRCCs. Both epithelial and stromal components lacked true Müllerian features, which was also proven by immunohistochemistry.

Papillary Renal Neoplasm With Reverse Polarity: A Morphologic, Immunohistochemical, and Molecular Study.

We evaluated the clinicopathologic and chromosomal characteristics of a distinct subset of papillary renal tumors and compared them to a control series of papillary renal cell carcinoma types 1 and 2. Of the 18 patients, 9 were women and 9 were men, ranging in age from 46 to 80 years (mean, 64 y; median, 66 y). The tumors ranged in diameter from 0.6 to 3 cm (mean, 1.63 cm; median, 1.4 cm). Fourteen tumors were WHO/ISUP grade 2 and 4 were grade 1. All were stage category pT1. The tumors had branching papillae with thin fibrovascular cores, covered by cuboidal to columnar cells with granular eosinophilic cytoplasm, smooth luminal borders, and mostly regular and apically located nuclei with occasional nuclear clearing and inconspicuous nucleoli. Tubule formation and clear cytoplasmic vacuoles were observed in 5 and 9 tumors, respectively. Ten tumors had pseudocapsules. Psammoma bodies, necrosis, mitotic figures and intracellular hemosiderin are absent from all tumors. In contrast, papillary renal cell carcinoma type 1 consisted of delicate papillae covered by a single layer of cells with scanty pale cytoplasm with nuclei generally located in a single layer on the basement membrane of the papillary cores, while type 2 tumors had broad papillae covered by pseudostratified cells with eosinophilic cytoplasm and more randomly located nuclei. Both had occasional psammoma bodies, foamy macrophages and intracellular hemosiderin. Immunohistochemically, all were positive for pancytokeratin AE1/AE3, epithelial membrane antigen, MUC1, CD10, GATA3, and L1CAM. Cytokeratin 7 was positive in 16 tumors (1 had <5% positivity). CD117 and vimentin were always negative. α-methylacyl-CoA-racemase (AMACR/p504s) showed variable staining (range, 10% to 80%) in 5 tumors. However, all tumors in the control group were negative for GATA3 and positive for AMACR/p504s and vimentin immunostains. Fluorescence in situ hybridization analysis of the study group demonstrated chromosome 7 trisomy in 5 tumors (33%), trisomy 17 in 5 tumors (33%), and trisomy 7 and 17 in 3 tumors (20%). Chromosome Y deletion was found in 1 of 7 male patients and chromosome 3p was present in all tumors. No tumor recurrence or metastasis occurred. In summary, we propose the term papillary renal neoplasm with reverse polarity for this entity.