Low-grade Renal Cell Carcinoma Research Articles

Stereotactic body radiation therapy for primary renal cell carcinoma: A review on behalf of the CC-AFU

IntroductionThe incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. Material and methodsWe conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. ResultsStudies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately −5 to −17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. ConclusionStereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited. Level of evidence5.

PD-L1 as a Urine Biomarker in Renal Cell Carcinoma-A Case Series and Proof-of-Concept Study.

Renal cell carcinoma (RCC) is among the most lethal urologic malignancies once metastatic. Current treatment approaches for metastatic RCC (mRCC) involve immune checkpoint inhibitors (ICIs) that target the PD-L1/PD-1 axis. High PD-L1 expression in tumor tissue has been identified as a negative prognostic factor in RCC. However, the role of PD-L1 as a liquid biomarker has not yet been fully explored. Herein, we analyze urine levels of PD-L1 in mRCC patients before and after either ICI therapy or surgical intervention, as well as in a series of patients with treatment-naïve RCC. The mid-stream urine of patients with mRCC (n = 4) or treatment-naïve RCC, i.e., prior to surgery from two centers (cohort I, n = 49: cohort II, n = 29) was analyzed for PD-L1 by ELISA. The results from cohort I were compared to a control group consisting of patients treated for non-malignant urologic diseases (n = 31). In the mRCC group, urine PD-L1 levels were measured before and after tumor nephrectomy (n = 1) or before and after ICI therapy (n = 3). Exosomal PD-L1 in the urine was analyzed in selected patients by immunoblotting. A strong decrease in urine PD-L1 levels was found after tumor nephrectomy or following systemic treatment with ICIs. In patients with treatment-naïve RCC (cohort I), urine PD-L1 levels were significantly elevated in the RCC group in comparison to the control group (median 59 pg/mL vs. 25.7 pg/mL, p = 0.011). PD-L1 urine levels were found to be elevated, in particular, in low-grade RCCs in cohorts I and II. Exosomal PD-L1 was detected in the urine of a subset of patients. In this proof-of-concept study, we show that PD-L1 can be detected in the urine of RCC patients. Urine PD-L1 levels were found to correlate with the treatment response in mRCC patients and were significantly elevated in treatment-naïve RCC patients.

The Effectiveness of Volumetric MRI Histogram Analysis in Renal Cell Carcinoma

This study investigated the utility of histogram parameters derived from diffusion-weighted imaging (DWI)for evaluating renal cell carcinoma (RCC)grading prior to surgery. This retrospective study included 88 patients who were histopathologically diagnosed with RCC and underwent magnetic resonance imaging (MRI)examinations. The patients were divided into two groups as well-differentiated (Group 1)and poorly differentiated (Group 2). Demographic data, preoperative MRI findings, MRI apparent diffusion coefficient (ADC) histogram analyzes, operation types, postoperative histopathological data and cancer stages of the patients were recorded. The histogram parameters of ADC values, comprising the mean, minimum, maximum, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles, as well as skewness, kurtosis, and variance, were calculated. The study included 59 males and 29 women with an average age of 56.21±1.33 years. There were 52 patients in Group 1 and 36 patients in Group 2. The ADCmin, ADCmean, ADCmax, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values of the poorly differentiated group were all lower than those of the well-differentiated group. ADCmin and the 5th percentile of ADC values, as well as ADCmean and the 10th, 25th, 50th, and 75th percentiles of ADC values, showed a statistically significant difference (p<0.05). The AUC, sensitivity, and specificity of the ADCmin value were 0.703, 56.3%, and 75.7%, respectively. The present study indicated that histogram parameters generated from DWI were capable of differentiating between high-grade and low-grade RCC.

Reliability and Management Outcomes Following a Percutaneous Biopsy Diagnosis of Oncocytoma: A 15-year Retrospective Analysis.

Background There is uncertainty in the management of renal masses diagnosed as oncocytomas with image-guided percutaneous biopsy. Purpose To assess the reliability of a diagnosis of oncocytoma based on image-guided percutaneous renal mass biopsy and evaluate patient outcomes following different management strategies. Materials and Methods In this retrospective study, image-guided percutaneous biopsy pathology reports from April 2004 to April 2019 were searched for keywords "oncocytoma" and "oncocytic neoplasm" and compared with surgical pathology or repeat biopsy results. Patients with at least 12 months of clinical follow-up and known cause of death were grouped according to management strategies, and disease-specific survival and metastatic renal cell carcinoma (RCC)-free survival were compared. Mass growth rates were calculated with use of a normal linear mixed model. Results The database yielded 160 biopsy reports of 149 renal masses in 139 patients; 149 masses were categorized as oncocytoma (n = 107), likely oncocytoma (n = 12), oncocytic neoplasm (n = 28), and indeterminate with oncocytoma in differential (n = 2). Biopsied masses categorized as oncocytoma or likely oncocytoma were oncocytomas in 16 of 17 masses (94%) based on surgical pathology or repeat biopsy; four of eight masses (50%) categorized as oncocytic neoplasms were low-grade RCCs. Outcome analysis included 121 patients (mean age ± SD, 68 years ± 9.1; 82 men); 80 patients initially underwent active surveillance (11 were later treated), 33 underwent ablation, and eight underwent surgery. Disease-specific survival and metastatic-free survival were 100% after each management strategy (median follow-up, 86.6 months; range, 14.2-207.9 months). Mass growth rate (mean, 1.7 mm per year) showed no evidence of a significant difference among biopsy result categories (P = .37) or initial (P = .84) or final management strategies (P = .11). Conclusion Image-guided percutaneous biopsy diagnosis of renal oncocytoma was reliable. Although some masses diagnosed as oncocytic neoplasms were low-grade renal cell carcinomas (RCCs) at final diagnosis, no patients died of RCC, including those managed with active surveillance. © RSNA, 2023 See also the editorial by Lockhart in this issue.

Advances in Imaging-Based Biomarkers in Renal Cell Carcinoma: A Critical Analysis of the Current Literature.

Cross-sectional imaging is the standard diagnostic tool to determine underlying biology in renal masses, which is crucial for subsequent treatment. Currently, standard CT imaging is limited in its ability to differentiate benign from malignant disease. Therefore, various modalities have been investigated to identify imaging-based parameters to improve the noninvasive diagnosis of renal masses and renal cell carcinoma (RCC) subtypes. MRI was reported to predict grading of RCC and to identify RCC subtypes, and has been shown in a small cohort to predict the response to targeted therapy. Dynamic imaging is promising for the staging and diagnosis of RCC. PET/CT radiotracers, such as 18F-fluorodeoxyglucose (FDG), 124I-cG250, radiolabeled prostate-specific membrane antigen (PSMA), and 11C-acetate, have been reported to improve the identification of histology, grading, detection of metastasis, and assessment of response to systemic therapy, and to predict oncological outcomes. Moreover, 99Tc-sestamibi and SPECT scans have shown promising results in distinguishing low-grade RCC from benign lesions. Radiomics has been used to further characterize renal masses based on semantic and textural analyses. In preliminary studies, integrated machine learning algorithms using radiomics proved to be more accurate in distinguishing benign from malignant renal masses compared to radiologists' interpretations. Radiomics and radiogenomics are used to complement risk classification models to predict oncological outcomes. Imaging-based biomarkers hold strong potential in RCC, but require standardization and external validation before integration into clinical routines.

Diagnostic Value of Contrast-Enhanced Ultrasound Features for WHO/ISUP Grading in Renal Cell Carcinoma.

By analyzing the differences of contrast-enhanced ultrasound (CEUS) features between low- and high-grade of WHO/ISUP grading, to explore the diagnostic value of CEUS in evaluating the prognosis of renal cell carcinoma (RCC). The qualitative and quantitative features of CEUS in 69 patients with RCC confirmed by surgical pathology in the Lanzhou University Second Hospital from March to October 2021 were retrospectively analyzed. Patients were categorized into two groups: low-grade group (n=22) and high-grade group (n=47), with surgical pathology as reference standard. The diagnostic performance of statistically significant CEUS features was evaluated by receiver operating characteristic (ROC) curves. There were statistically significant differences in enhancement degree (P=.032) and quantitative features such as slopelesion (P=.034), the differences between lesion and cortex in arrive time (∆AT=ATlesion - ATcortex , P=.013), peak intensity(∆PI=[PIlesion - PIcortex ]/PIcortex , P=.003), area under the curve (∆Area=Arealesion - Areacortex , P=.008) in two groups, and the sensitivity was 70.2% and specificity was 71.4% of ∆PI, which has a high diagnostic performance in the differentiation of low-grade group from high-grade group (P=.005). CEUS features such as ∆PI, may help differentiate low-grade RCC from high-grade RCC. CEUS has a promising application prospect in preoperative evaluation of the prognosis of RCC.

The Role of Focal Therapy and Active Surveillance for Small Renal Mass Therapy.

Small and low-grade renal cell carcinomas have little potential for metastasis and disease-related mortality. As a consequence, the main problem remains the use of appropriately tailored treatment for each individual patient. Surgery still remains the gold standard, but many clinicians are questioning this approach and present the advantages of focal therapy. The choice of treatment regimen remains a matter of debate. This article summarizes the current treatment options in the management of small renal masses.

MP33-05 DIAGNOSTIC PARAMETERS OF 99m TC-SESTAMIBI SPECT/CT FOR RENAL ONCOCYTOMAS AND HYBRID ONCOCYTIC/CHROMOPHOBE TUMORS: COMBINED PROSPECTIVE TRIAL DATA

You have accessJournal of UrologyCME1 May 2022MP33-05 DIAGNOSTIC PARAMETERS OF 99mTC-SESTAMIBI SPECT/CT FOR RENAL ONCOCYTOMAS AND HYBRID ONCOCYTIC/CHROMOPHOBE TUMORS: COMBINED PROSPECTIVE TRIAL DATA Alexa Meyer, Hiten Patel, Lilja Solnes, Reema Goel, Mehrbod Javadi, Phillip Pierorazio, Christian Pavlovich, Mohamad Allaf, Michael Gorin, and Steven Rowe Alexa MeyerAlexa Meyer More articles by this author , Hiten PatelHiten Patel More articles by this author , Lilja SolnesLilja Solnes More articles by this author , Reema GoelReema Goel More articles by this author , Mehrbod JavadiMehrbod Javadi More articles by this author , Phillip PierorazioPhillip Pierorazio More articles by this author , Christian PavlovichChristian Pavlovich More articles by this author , Mohamad AllafMohamad Allaf More articles by this author , Michael GorinMichael Gorin More articles by this author , and Steven RoweSteven Rowe More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002587.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previously, we reported the results of our prospective trial of 50 patients imaged with 99mTc-sestamibi SPECT/CT prior to surgical resection, and showed that 99mTc-sestamibi SPECT/CT can aid in the differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) from other renal tumor histologies. Here, we present the following 75 patients in the prospective trial cohort. The objective of this study was to determine the diagnostic performance of this imaging test using data from the overall cohort. METHODS: Patients presenting with a solid T1 renal mass were imaged with 99mTc-sestamibi SPECT/CT prior to surgery. For the new 75 patients in the cohort, SPECT/CT scans were analyzed by two readers, and discrepancies were resolved by a third reader. Tumors were characterized as positive (i.e. “hot”) or negative (i.e. “cold”). Radiotracer uptake was quantified. Following surgical resection, the cases were reviewed by genitourinary pathologists. Diagnostic parameters were calculated for the novel patients, as well as for the overall cohort. True positive was defined as any tumor diagnosed as an oncocytoma or HOCT following surgical resection. RESULTS: In total, 125 patients were enrolled in the trial. 1 tumor was non-diagnostic on imaging secondary to bowel overlying the tumor, and was excluded from analysis. In the novel 74 patients, 99mTc-sestamibi SPECT/CT correctly identified 9/12 oncocytomas and HOCTs, resulting in sensitivity of 75.0% (95% CI 42.8-94.5). 10 tumors were false positives (FP), resulting in specificity of 83.9% (95% CI 72.3-92.0). These included 5 papillary renal cell carcinomas (RCC), 3 chromophobe RCC, 1 low grade RCC with oncocytic features, and 1 angiomyolipoma. The positive predictive value (PPV) was 47.4% (95% CI 24.4-71.1) and negative predictive value (NPV) was 94.5% (84.9-98.9%). For the combined cohort of 124 patients, 99mTc-sestamibi SPECT/CT correctly identified 16/20 oncocytomas and HOCTs, resulting in sensitivity of 80.0% (95% CI 56.3-94.3). 12 tumors were FP, resulting in specificity of 88.5% (95% CI 80.7-93.9). The additional 2 FP were chromophobe RCC. The overall PPV was 57.1% (95% CI 37.2-75.5) and NPV was 95.8% (89.7-98.9%). CONCLUSIONS: Data from this prospective trial shows that 99mTc-sestamibi SPECT/CT can aid in the risk stratification of small renal masses. A “hot” 99mTc-sestamibi SPECT/CT should proceed to biopsy for further work-up. A “cold” 99mTc-sestamibi SPECT/CT can avoid biopsy and proceed directly to surgery. Source of Funding: none © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e571 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexa Meyer More articles by this author Hiten Patel More articles by this author Lilja Solnes More articles by this author Reema Goel More articles by this author Mehrbod Javadi More articles by this author Phillip Pierorazio More articles by this author Christian Pavlovich More articles by this author Mohamad Allaf More articles by this author Michael Gorin More articles by this author Steven Rowe More articles by this author Expand All Advertisement PDF DownloadLoading ...

Common Subtype of Small Renal Mass MR Imaging Characterisation: A Medical Center Experience in Taiwan

PurposeMany studies have shown that multiparametric magnetic resonance imaging (MRI) may be helpful for differentiating malignant renal cell carcinomas (RCCs) from benign lesions. However, the key imaging characteristics that differ between malignant and benign tumors still require further discussion.MethodsWe analyzed 60 adult patients diagnosed with 72 small renal masses (SRMs) who received preoperative MRI from 2014 to 2019 at a hospital in Taiwan. The MRI features included conventional MRI parameters, diffusion-weighted imaging (DWI) data, and dynamic contrast-enhanced (DCE) patterns, which were documented and compared among the four common subtypes: clear cell RCC (ccRCC), papillary RCC (pRCC), angiomyolipoma (AML) and other types of RCC. The apparent diffusion coefficient (ADC) values of high- and low-grade RCCs were also analyzed.ResultsThe results show that ccRCC had higher T2-weighted signal intensity than the other three subgroups, a higher arterial wash-in index (AWI) and ADC value than AML and pRCC, and manifested a plateau (n = 9, 25%) or washout (n = 27, 75%) enhancement pattern. AMLs exhibited more intravoxel fat than the other three subtype groups, and half of the AMLs (6 in 12) contained bulk fat. pRCC demonstrated a more progressive (n = 3, 60%) enhancement pattern than the other three subgroups. The ADC value of high-grade RCCs was significantly lower than that of low-grade RCCs.ConclusionThese findings may indicate that multiparametric MRI is useful in differentiating among four common pathological types of SRMs, and the ADC value may be helpful in evaluating the histological grade of malignancy.

Serum X Linked Inhibitor of Apoptosis Protein (XIAP) as a Biomarker for Predicting Recurrence of Low Grade Renal Cell Carcinoma

Serum X Linked Inhibitor of Apoptosis Protein (XIAP) as a Biomarker for Predicting Recurrence of Low Grade Renal Cell Carcinoma

Association between nuclear grade of renal cell carcinoma and the aorta-lesion-attenuation-difference

Several features noted on renal mass biopsy (RMB) can influence treatment selection including tumor histology and nuclear grade. However, there is poor concordance between renal cell carcinoma (RCC) nuclear grade on RMB compared to nephrectomy specimens. Here, we evaluate the association of nuclear grade with aorta-lesion-attenuation-difference (ALAD) values determined on preoperative CT scan. A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate low-grade (nuclear grade 1 and 2) and high-grade (nuclear grade 3 and 4) tumors was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using ROC analysis. Sub-group analysis by histologic sub-type was also performed. A total of 368 preoperative CT scans in patients with RCC on nephrectomy specimen were reviewed. Median patient age was 61years (IQR 52-68). The majority of patients were male, 66% (243/368). Tumor histology was chromophobe RCC in 7.6%, papillary RCC in 15.5%, and clear cell RCC in 76.9%. The majority, 69.3% (253/365) of tumors, were stage T1a. Nuclear grade was grade 1 in 5.46% (19/348), grade 2 in 64.7% (225/348), grade 3 in 26.2% (91/348), and grade 4 in 3.2% (11/348). Nephrographic ALAD values for grade 1, 2, 3, and 4 were 73.7, 46.5, 36.4, and 43.1, respectively (p = 0.0043). Nephrographic ALAD was able to differentiate low-grade from high-grade RCC with a sensitivity of 32%, specificity of 89%, PPV of 86%, and NPV of 36%. ROC analysis demonstrated the predictive utility of nephrographic ALAD to predict high- versus low-grade RCC with an AUC of 0.60 (95% CI 0.51-0.69). ALAD was significantly associated with nuclear grade in our nephrectomy series. Strong specificity and PPV for the nephrographic phrase demonstrate a potential role for ALAD in the pre-operative setting that may augment RMB findings in assessing nuclear grade of RCC. Although this association was statistically significant, the clinical utility is limited at this time given the results of the statistical analysis (relatively poor ROC analysis). Sub-group analysis by histologic subtype yielded very similar diagnostic performance and limitations of ALAD. Further studies are necessary to evaluate this relationship further.

A Case of Renal Cell Carcinoma and Pheochromocytoma Due to Germline Inactivating Mutation in Fumarate Hydratase (FH)

A 60-year-old female with a history of well-controlled hypertension, prediabetes, status post hysterectomy for fibroids, presented for evaluation of hematuria and unintentional weight loss. She denied palpitations, headaches, tremors, and diaphoresis. Initial CT demonstrated a right renal mass suspicious for renal cell carcinoma and an adrenal mass. Magnetic resonance imaging (MRI) confirmed a hypervascular, right adrenal mass (6.7 x 6 x 5 cm) without loss of signal.Laboratory Testing: elevated 24-hour urine vanillylmandelic acid (VMA) 17.5 mg/24 h (<6), and urine normetanephrines 2276 ug/24 h (122-676) with normal urine metanephrines 158 ug/24 h (90-315). 24-hour urine free cortisol was normal. The patient underwent a right adrenalectomy and partial nephrectomy. Pathology confirmed a low-grade renal cell carcinoma (RCC) and a 6.8 cm pheochromocytoma (PCC). Genetic analysis revealed an inherited mutation in the fumarate hydratase (FH) gene, which is diagnostic of hereditary leiomyomatosis and renal cell cancer (HLRCC). Wildtype FH codes for an enzyme that converts fumarate to malate in the mitochondrial Krebs cycle. Inactivating mutations in FH trigger the hypoxia pathway by activating hypoxia-inducible factor (HIF) thereby promoting tumor growth and angiogenesis.In PCC, 30-40% are hereditary and another 40-50% are found to have somatic mutations in 1 of 20 PCC susceptibility genes. Several autosomal dominant heritable syndromes, including Neurofibromatosis type 1 (NF-1), von Hippel-Lindau (VHL), Multiple Endocrine Neoplasia Type 2 (MEN 2), and Paraganglioma Syndromes Types 1–5, have an increased incidence of PCC, most of which modulate hypoxia pathways. FH mutations are similarly inherited in an autosomal dominant fashion and cause HLRCC.HLRCC is associated with 75-80% risk for cutaneous and uterine leiomyomas, and a 10-16% risk for type II papillary renal cell carcinoma. The risk of RCC in patients with FH mutations is much greater than in the general population, where the prevalence is ~2% in those who lack the mutation. In one study, FH deficiencies attribute between 19-41% of all RCC cases. Rare families with PGL/PCC have also been found to carry this germline FH mutation. This FH mutation is associated with increased risk of metastasis in patients with PGL/PCC by a similar mechanism of carcinogenesis via the hypoxia pathway. Currently, there are no strict guidelines for surveillance in individuals with HLRCC, however, patients should have a yearly abdominal MRI, skin examination every 2 years, and an annual gynecological evaluation for leiomyosarcoma. Each first-degree relative should be offered genetic testing of the FH mutation, as 50% of relatives may carry the gene. This case underscores the importance of genetic workups in patients with PCC, especially if associated with other tumors.

Touch preparation for rapid onsite evaluations of renal mass biopsies: concordance rate, pearls, and pitfalls

Core needle biopsy (CNB) of renal masses has not been commonly performed because of the perceived low sensitivity until recent years. Rapid onsite evaluation (ROSE) using touch preparations (TPs) has the potential to improve the yield of CNB, although it can be challenging because of the diverse morphology of various types of renal tumors and native cells. We retrospectively reviewed percutaneous CNBs of renal masses with ROSE using TPs. ROSE findings were correlated with diagnoses on CNBs. Among the 165 cases identified between August 2016 and August 2019, CNB led to definitive diagnoses in 82.4% (136 of 165) cases. These included renal cell carcinomas (RCCs) (n = 113, 68.5%), benign neoplasms (n = 14, 8.5%), urothelial carcinomas (n = 6, 3.6%), metastatic carcinomas (n = 2, 1.2%) and 1 case of lymphoma (0.6%). Eight cases were indeterminate, including 2 cases positive for oncocytic neoplasm, 2 cases suspicious for RCC, and 4 cases with atypical features. Twenty-one (12.7%) CNBs were negative for tumor. ROSE interpretations for these cases were: malignant (n = 18, 10.8%); positive for neoplasm (n = 6, 3.6%); atypical/lesional/adequate not otherwise specified (n = 113, 68.5%); negative (n = 19, 11.5.0%); and unsatisfactory (n = 9, 5.5%). The overall concordance rate between ROSE and the final CNB diagnoses was 87.3%. Renal mass CNBs revealed a subset of non-surgical conditions in addition to RCCs. ROSE using TPs showed a high concordance rate with CNB results. Proximal tubular cells, macrophages, and angiomyolipomas are common pitfalls, whereas vacuolated cytoplasm and background are helpful features to confirm low-grade RCCs.

Renal Cell Carcinoma with Clear Cell Papillary Features: Perspectives of a Differential Diagnosis

Thirty-one cases of low-grade renal cell carcinoma (RCC) with clear cells and tubulopapillary/papillary architecture were analyzed retrospectively with immunohistochemical and genetic markers to gain more experience with the differential diagnosis of such cases. All samples coexpressed CK7 and CA9; the TFE3 or TFEB reactions were negative; the CD10 and the AMACR stainings were negative in 27 cases and 30 cases, respectively. The FISH assays for papillary RCC, available in 27 cases, and deletion of chromosome 3p, available in 29 cases, gave negative results. The results for 3p deletion, VHL gene mutation or VHL gene promoter region hypermethylation testing, along with the diffuse CD10-positivity in 2 cases confirmed 21 cases as clear cell papillary RCC (CCPRCC; CK7+, CA9+; no 3p loss, no VHL abnormality) and 10 cases as clear cell RCC (CCRCC; CK7+, CA9+; no 3p loss, VHL abnormality mutation/hypermethylation present). In CCPRCCs, the representative growth pattern was branching tubulo-acinar, commonly accompanied by cyst formation. The linear nuclear arrangement or cup-shaped staining of CA9 did not necessarily indicate CCPRCC, and the absence of these did not exclude the diagnosis of CCPPRC. One tumor infiltrated the renal sinus; the others exhibited pT1 stage; and metastatic outcome was not recorded. The CCRCC cases were in pT1 stage; 6 exhibited cup-shaped staining of CA9, and 1 displayed lymph node metastasis at the time of surgery. Distant metastatic disease was not observed. In summary, the VHL abnormalities distinguished the subset of CCRCC with diffuse CK7-positivity and no 3p loss from cases of CCPRCC.

Prognostic significance of extensive necrosis in renal cell carcinoma

Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000 and 2015. Patients' mean age was 59 years (43-77) with 16 men (76%); 12 cases (57%) were papillary RCC, 4 clear cell papillary RCC (19%), 4 clear cell RCC (19%), and 1 unclassified with sarcomatoid differentiation (5%). International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3, and 1 case was grade 4. Pathological stage was low (pT1-2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3 cm (1.2-17). In 52% (11) of cases, it was difficult to identify viable tumor, requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 cases (81%) with a mean follow-up of 59 months. Thirteen patients (62%) are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer, and 2 died due to causes unrelated to cancer. One patient (5%) with low-grade clear cell RCC developed metastases but had a contralateral RCC. In the setting of a low-grade RCC, extensive necrosis does not have an adverse prognosis. In summary, our data, together with a prior study from our institution, comprise one of the largest cohorts of extensively (>90%) necrotic RCCs and suggests that in the setting of a low-grade RCC, it portends a good prognosis (only 2/36 cases showing progression (6%) on follow-up). However, we did identify a single case of high-grade RCC with an adverse prognosis and therefore, careful attention to tumor grade and classification is critical. The presence of tumor necrosis as a prognosticator in RCCs is complex, and despite its well-accepted role as an indicator of poor prognosis, our data would suggest otherwise under specific conditions. Importantly, in diagnosing a renal mass with extensive cystic necrosis, careful and extensive sampling to identify small foci of viable tumor or "ghost" architecture may be necessary for classification. As such, evaluation of its presence should not only be quantitative, but critical attention should be made to tumor grade and stage, whereby in high-grade carcinomas, necrosis likely imparts a worse prognosis; however, in low-grade carcinomas with extensive necrosis, the histological subtype, grade, and stage drive prognosis.

Solid Renal Masses in Transplanted Allograft Kidneys: A Closer Look at the Epidemiology and Management.

The objective of this review is to explore the available literature on solid renal masses (SRMs) in transplant allograft kidneys to better understand the epidemiology and management of these tumors. A literature review using PubMed was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Fifty-six relevant studies were identified from 1988 to 2015. A total of 174 SRMs in 163 patients were identified, with a mean tumor size of 2.75 cm (range 0.5-9.0 cm). Tumor histology was available for 164 (94.3%) tumors: clear cell renal cell carcinoma (RCC; 45.7%), papillary RCC (42.1%), chromophobe RCC (3%), and others (9.1%). Tumors were managed by partial nephrectomy (67.5%), radical nephrectomy (19.4%), percutaneous radiofrequency ablation (10.4%), and percutaneous cryoablation (2.4%). Of the 131 patients (80.3%) who underwent nephron-sparing interventions, 10 (7.6%) returned to dialysis and eight (6.1%) developed tumor recurrence over a mean follow-up of 2.85 years. Of the 110 patients (67.5%) who underwent partial nephrectomy, 3.6% developed a local recurrence during a mean follow-up of 3.12 years. The current management of SRMs in allograft kidneys mirrors management in the nontransplant population, with notable findings including an increased rate of papillary RCC and similar recurrence rates after partial nephrectomy in the transplant population despite complex surgical anatomy.

Pulmonary metastasis from renal epithelioid angiomyolipoma in the setting of breast cancer

A 68-year-old woman presented with visible haematuria. Ultrasonography and triphasic CT revealed a 2.6 cm mass in the lower pole of the left kidney. A biopsy suggested low-grade renal cell...

PD52-08 CAN LOOKS DECEIVE? NOT ALL CLINICALLY “CYSTIC” RENAL MASSES HARBOR INDOLENT BIOLOGY

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging III1 Apr 2017PD52-08 CAN LOOKS DECEIVE? NOT ALL CLINICALLY “CYSTIC” RENAL MASSES HARBOR INDOLENT BIOLOGY Benjamin Ristau, Lyudmila DeMora, Eric Ross, Randall Lee, Michael Haifler, Shreyas Joshi, Andres Correa, David Chen, Richard Greenberg, Rosalia Viterbo, Marc Smaldone, Robert Uzzo, and Alexander Kutikov Benjamin RistauBenjamin Ristau More articles by this author , Lyudmila DeMoraLyudmila DeMora More articles by this author , Eric RossEric Ross More articles by this author , Randall LeeRandall Lee More articles by this author , Michael HaiflerMichael Haifler More articles by this author , Shreyas JoshiShreyas Joshi More articles by this author , Andres CorreaAndres Correa More articles by this author , David ChenDavid Chen More articles by this author , Richard GreenbergRichard Greenberg More articles by this author , Rosalia ViterboRosalia Viterbo More articles by this author , Marc SmaldoneMarc Smaldone More articles by this author , Robert UzzoRobert Uzzo More articles by this author , and Alexander KutikovAlexander Kutikov More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2196AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cystic renal cell carcinomas (RCC) are suggested to be clinically indolent. As such, a distinct pathologic staging category for these lesions was recently proposed. While not without merit, these recommendations fail to account for limitations in the ability of modern imaging to differentiate cystic RCC from more biologically aggressive mimics. We evaluated the frequency of high grade kidney cancer in the highly selected cohort of surgically resected renal masses having cystic appearance on pre-operative radiographic imaging. METHODS A prospectively maintained institutional database was queried for clinically cystic renal masses that underwent surgery from January 2000 - June 2016 (n=2,729 kidney surgeries). Patient and tumor characteristics including age at surgery, smoking history, Charlson comorbidity index (CCI), gender, race, BMI, surgery date, laterality, Bosniak classification, histology, grade, size, and nearness to the collecting system were tabulated. Associations between tumor grade and patient/tumor characteristics were evaluated using generalized estimating equations. RESULTS Eighty-nine patients (n=101 cystic lesions) met strict inclusion criteria; the majority (77%) were older than 50 years of age and the mean Charlson comorbidity index was 1.15 (SD1.48) (Table 1). Of the 101 clinically cystic renal masses, 23% were confirmed pathologically as high grade RCC while 77% were low grade RCC (n=56) or benign (n=22). CCI was associated with high grade surgical pathology (OR 1.37, 95% CI 1.05-1.79, p = 0.02). There was no association between tumor grade and the remainder of the patient/tumor characteristics analyzed. CONCLUSIONS Recently proposed changes to the kidney cancer staging system define a tumor's cystic nature based on pathologic examination. Proceeding with surgery for a radiographically “cystic” renal mass was a rare event in our cohort; however, among those that went onto surgery, nearly a quarter harbored high grade pathology. Before making changes to the clinical RCC staging system, a better understanding of the limitations inherent to radiographic determination of low malignant potential, cystic renal masses is necessary. © 2017FiguresReferencesRelatedDetailsCited byRistau B and Kutikov A (2017) Editorial CommentJournal of Urology, VOL. 199, NO. 3, (639-640), Online publication date: 1-Mar-2018. Volume 197Issue 4SApril 2017Page: e992 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Benjamin Ristau More articles by this author Lyudmila DeMora More articles by this author Eric Ross More articles by this author Randall Lee More articles by this author Michael Haifler More articles by this author Shreyas Joshi More articles by this author Andres Correa More articles by this author David Chen More articles by this author Richard Greenberg More articles by this author Rosalia Viterbo More articles by this author Marc Smaldone More articles by this author Robert Uzzo More articles by this author Alexander Kutikov More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The Usefulness of Serum X-linked Inhibitor of Apoptosis Protein (XIAP) for Predicting Recurrence of Low-Grade Renal Cell Carcinoma

The X-linked Inhibitor of Apoptosis Protein (XIAP) has been associated with cell survival because it blocks caspase-mediated apoptosis. The expression of XIAP and its prognostic significance in Renal Cell Cancer (RCC) have rarely been studied. Objective: To evaluate the usefulness of serum XIAP levels in RCC patients as a biomarker for predicting recurrence after surgery. Methods: Peripheral blood samples were obtained from 88 patients (67 males and 21 females; median age, 60.0 years) with RCC before surgery. All of the patients underwent radical or partial nephrectomy. Blood samples were also collected from 52 healthy controls. The serum XIAP levels were measured by ELISA. The cut-off value was calculated by ROC analysis. Recurrence-free survival was evaluated in all patients. Results: The mean serum XIAP levels in patients with RCC were higher than those of normal control individuals (239.8 pg/ml vs. 156.2 pg/ml, P<0.001). At a median follow-up of 48 months (3-105 months), tumors with low serum XIAP showed significantly longer recurrence-free survival than those with high serum XIAP in the Grade 1-2 group (n=75) (P<0.05). Conclusion: Serum XIAP level is associated with recurrence and prognosis of RCC patients, especially in patients with the lower nuclear grade of 1 and 2. These results suggest that it may be used as a novel biomarker for predicting prognosis.

TFEB-amplified Renal Cell Carcinomas: An Aggressive Molecular Subset Demonstrating Variable Melanocytic Marker Expression and Morphologic Heterogeneity.

Renal cell carcinomas (RCCs) with the t(6;11)(p21;q12) chromosome translocation are low-grade RCC which often occur in young patients. They typically feature an unusual biphasic morphology characterized by nests of larger epithelioid cells surrounding intraluminal collections of smaller cells clustered around basement membrane material. The t(6;11)(p21;q12) translocation fuses the Alpha (MALAT1) gene with the TFEB transcription factor gene, resulting in upregulated expression of intact native TFEB that drives the aberrant expression of melanocytic markers which is a hallmark of this distinctive neoplasm. We now report 8 cases of RCC, which demonstrate TFEB gene amplification (6 without TFEB rearrangement, 2 with concurrent TFEB rearrangement) and demonstrate downstream consequences of TFEB overexpression. Like the unamplified t(6;11) RCC, all TFEB-amplified RCC were associated with aberrant melanocytic marker expression. However, several differences between TFEB-amplified RCC and the usual unamplified t(6;11) RCC are evident. First, TFEB-amplified RCC occurred in older patients (median age, 64.5 y) compared with unamplified t(6;11) RCC (median age, 31 y). Second, the morphology of TFEB-amplified RCC is not entirely distinctive, frequently featuring nests of high-grade epithelioid cells with eosinophilic cytoplasm associated with pseudopapillary formation and necrosis, or true papillary formations. These patterns raise the differential diagnosis of high-grade clear cell and papillary RCC. Third, TFEB and melanocytic marker expression was more variable within the TFEB-amplified RCC. TFEB protein expression by immunohistochemistry was detectable in 6 of 8 cases. While all 8 cases expressed melan-A, only 5 of 8 expressed cathepsin K and only 3 of 8 expressed HMB45. Fourth, the TFEB-amplified RCC were associated with a more aggressive clinical course; 3 of 8 cases presented with advanced stage or metastatic disease, 2 subsequently developed metastatic disease, whereas the other 3 cases had minimal/no follow-up. Our results are corroborated by scant data reported on 6 TFEB-amplified RCC in the literature, gleaned from 1 case report, 1 abstract, and 4 individual cases identified within 2 genomic studies of large cohorts of RCC. In summary, TFEB-amplified RCC represent a distinct molecular subtype of high-grade adult RCC associated with aggressive clinical behavior, variable morphology, and aberrant melanocytic marker expression.