Chromophobe Renal Cell Carcinoma With Retrograde Venous Invasion and Gain of Chromosome 21: Potential Harbingers of Aggressive Clinical Behavior

2018 ◽  
Vol 26 (6) ◽  
pp. 536-541 ◽  
Author(s):  
Mohsin Jamal ◽  
Kanika Taneja ◽  
Sohrab Arora ◽  
Ravi Barod ◽  
Craig G. Rogers ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Aggressive Behavior ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Renal Vein ◽  
Clear Cell ◽  
Venous Invasion ◽  
Chromosome 21 ◽  
Chromophobe Rcc ◽  
Clear Cell Rcc

Occasionally, renal cell carcinoma (RCC) with renal vein extension spreads against the flow of blood within vein branches into the kidney, forming multifocal nodules throughout the renal parenchyma. These foci are not regarded as multiple tumors but rather reverse spread of tumor along the venous system. This intravascular spread has previously been reported in clear cell RCC and RCC unclassified. However, to our knowledge, this has never been reported in chromophobe RCC. Chromophobe RCC is a unique histologic subtype of renal cancer, generally thought to have less aggressive behavior. However, it nonetheless has the potential to undergo sarcomatoid dedifferentiation, which is associated with poor prognosis. We report a unique case of a 65-year-old man with chromophobe RCC (pT3a) showing classic morphology (nonsarcomatoid), yet presenting with retrograde venous invasion and hilar lymph node metastasis at the time of right radical nephrectomy. Fluorescence in situ hybridization revealed gain of chromosome 21 with loss of multiple other chromosomes. Partial hepatectomy was performed to resect metastatic RCC 7 months after nephrectomy, revealing chromophobe RCC with classic morphology. Bone biopsy confirmed skeletal metastases 38 months after initial diagnosis. Although invasion of the renal vein and retrograde venous invasion are characteristically seen in clear cell RCC, this unusual phenomenon may also occur in chromophobe RCC, despite its unique tumor biology. This and gain of chromosome 21, which was postulated to be associated with aggressive behavior in a previous report, were associated with adverse behavior in our patient, who had short-term progression to multi-organ metastatic disease.

scholarly journals Comparative Assessment of the WNT/β-Catenin Pathway, CacyBP/SIP, and the Immunoproteasome Subunit LMP7 in Various Histological Types of Renal Cell Carcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Żaneta Piotrowska ◽  
Michał Niezgoda ◽  
Grzegorz Młynarczyk ◽  
Magdalena Acewicz ◽  
Irena Kasacka
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Kidney Tissue ◽  
Renal Tumors ◽  
Histological Types ◽  
Chromophobe Rcc ◽  
Study Results ◽  
Clear Cell Rcc

ObjectiveThe Wnt/ß-catenin pathway plays an important role in pathogenesis of variety cancers. Most studies on changes in WNT/β-catenin pathway in renal cell carcinoma (RCC) apply only to clear cell RCC, while there are no comparative assessments of this signaling pathway in various histological types of renal tumors in the available literature. Additionally, considering the close relationship between WNT/β-catenin signaling, CacyBP/SIP and proteasomal activity, it seemed worth comparing WNT/β-catenin pathway, CacyBP/SIP and LMP7 immunoproteasome subunit in human samples of clear cell, papillary, and chromophobe RCC.MethodsTests were performed on sections of three types of kidney tumors together with surrounding unchanged tissue fragments collected from 50 patients. Samples were divided into three groups depending on the histological type of cancer: clear cell, papillary and chromophobe RCC. Immunohistochemistry and PCR methods were used to identify WNT10A, Fzd5, β-catenin, GSK-3ß, CacyBP/SIP, LMP7, and gene expression.ResultsImmunoreactivity and expression of WNT10A, Fzd5, β-catenin, GSK-3ß, CacyBP/SIP, LMP7 in clear cell RCC was markedly increased compared to non-cancerous kidney tissue. In papillary RCC, immunoreactivity and expression of WNT/β-catenin pathway, CacyBP/SIP, LMP7 was also increased compared to non-malignant kidneys, but it was less pronounced than in clear cell RCC. The least substantial increase in immunoreactivity and expression of WNT/β-catenin pathway, CacyBP/SIP, LMP7 was found in chromophobe RCC, compared to other RCC histological subtypes studied.ConclusionsStudy results suggest an important role of WNT/β-catenin pathway, CacyBP/SIP and LMP7 in RCC carcinogenesis, and may indicate new aspects of pathomechanisms leading to differences in the biology of clear cell, papillary and chromophobe RCC.

scholarly journals Two Cases of Sporadic Eosinophilic Solid and Cystic Renal Cell Carcinoma in Manitoba Population

2021 ◽  
pp. 106689692199322
Author(s):  
Seyed Mohammad Mohaghegh Poor ◽  
Shivani Mathur ◽  
Karl Kassier ◽  
Janetta Rossouw ◽  
Robert Wightman ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Preoperative Imaging ◽  
Renal Neoplasm ◽  
Renal Masses ◽  
Cystic Renal Cell Carcinoma ◽  
Eosinophilic Cytoplasm ◽  
Clear Cell Rcc

Two sporadic cases of eosinophilic solid and cystic renal cell carcinoma (ESC RCC), at our institution, are presented in this study to contribute to the growing literature on this novel renal neoplasm. The first patient was a 38-year-old female with two synchronous renal masses measuring 3.5 and 1.9 cm on preoperative imaging. The second patient was a 44-year-old female with an incidental renal mass measuring 4 cm. Both patients underwent uncomplicated radical nephrectomies. The 1.9 cm mass in the first patient was consistent with clear cell RCC. The dominant mass in the first patient and the tumor in the second patient had microscopic and macroscopic findings in keeping with ESC RCC including a tan appearance, abundant eosinophilic cytoplasm, and CK20+ and CK7− staining. Both patients had an uncomplicated course following surgery with no evidence of local recurrence or distant metastatic disease for 1 and 2 years for the first and second patient accordingly. These cases contribute to a growing body of literature regarding ESC RCC including, to our knowledge, the first reported case of synchronous ESC RCC and clear cell RCC. Further research about this novel renal neoplasm is needed.

scholarly journals Detection of a peritumoral pseudocapsule in patients with renal cell carcinoma undergoing robot-assisted partial nephrectomy using enhanced MDCT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Makoto Toguchi ◽  
Toshio Takagi ◽  
Yuko Ogawa ◽  
Satoru Morita ◽  
Kazuhiko Yoshida ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Partial Nephrectomy ◽  
Renal Cell ◽  
Clear Cell ◽  
Robot Assisted ◽  
High Attenuation ◽  
Papillary Rcc ◽  
Clear Cell Rcc

AbstractTo investigate the detection of peritumoral pseudocapsule (PC) using multi-detector row computed tomography (MDCT) for tumors resected by robot-assisted laparoscopic partial nephrectomy (RAPN) for T1 renal cell carcinoma (RCC). Study participants included 206 patients with clinical T1 RCC who underwent RAPN between October 2017 and February 2018. Two radiologists who were blinded to the pathological findings evaluated the computed tomography (CT) images. Radiological diagnosis of a PC was defined by a combination of observations, including a low-attenuation rim between the tumor and renal cortex in the cortico-medullary phase and a high-attenuation rim at the edge of the tumor in the nephrogenic or excretory phase. A PC was detected on CT in 156/206 tumors (76%) and identified by pathology in 182/206 (88%) tumors including 153/166 (92%) clear cell RCC, 13/14 (93%) papillary RCC, and 7/16 (44%) chromophobe RCC. In the whole cohort, CT findings showed a sensitivity of 81.3% (148/182), specificity of 66.7% (16/24), and positive predictive value of 94.9% (148/156). When the data were stratified according to pathological subtypes, MDCT was observed to have a sensitivity of 86.9% (133/153) and specificity of 61.5% (8/13) in clear cell RCC, sensitivity of 38.5% (5/13) and specificity of 100% (1/1) in papillary RCC, and sensitivity of 44.4% (4/7) and specificity of 66.7% (6/9) in chromophobe RCC. A low or high-attenuation rim around the tumor in the cortico-medullary or nephrographic-to-excretory phase indicates a PC of RCC, though the accuracy is not satisfactory even with 64- or 320-detector MDCT.

DNA methylation signature to define cell ontogeny of renal cell carcinomas.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 536-536
Author(s):  
Gabriel G. Malouf ◽  
Xiaoping Su ◽  
Jianping Zhang ◽  
Thai Huu Ho ◽  
Yue Lu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Covalent Modification ◽  
Tissue Type ◽  
Gene Promoters ◽  
Type Definition ◽  
Clear Cell Rcc

536 Background: DNA methylation is a heritable covalent modification that is developmentally regulated and is critical in tissue-type definition. Although genotype-phenotype correlations have been described for different subtypes of renal cell carcinoma (RCC), it is unknown if DNA methylation profiles correlate with morphological or ontology based phenotypes. Here we test the hypothesis that DNA methylation signatures can discriminate between putative precursor cells in the nephron. Methods: We performed deep profiling of DNA methylation in diverse histopathological RCC subtypes and validated DNA methylation and transcriptome signatures in The Cancer Genome Atlas Clear Cell and Chromophobe Renal Cell Carcinoma Datasets. Results: Our data provide the first mapping of methylome epi-signature and indicates that RCC subtypes can be grouped into two major epi-clusters: C1 which encompasses clear cell RCC, papillary RCC, mucinous and spindle cell carcinomas and translocation RCC; C2 which comprises oncocytoma and chromophobe RCC. Interestingly, C1 epi-cluster displayed three fold more hypermethylation as compared to C2 epi-cluster. Of note, differentially methylated regions between C1 and C2 epi-clusters occur in gene bodies and intergenic regions, instead of gene promoters. Transcriptome analysis of C1 epi-cluster suggests a functional convergence on Polycomb targets, whereas C2 epi-cluster displays DNA methylation defects. Furthermore, we find that our epigenetic ontogeny signature is associated with worse outcomes of patients with clear-cell RCC. Conclusions: Taken together, our data defines the epi-clusters that can discriminate between distinct RCC subtypes and for the first time, to our knowledge, define the epigenetic basis for proximal versus distal tubule derived kidney tumors.

Correlation of insulin-receptor expression with efficacy of axitinib in patients with advanced renal cell carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 442-442
Author(s):  
Masayuki Takahashi ◽  
Kei Daizumoto ◽  
Megumi Tsuda ◽  
Yoshito Kusuhara ◽  
Hidehisa Mori ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Insulin Receptor ◽  
Cell Carcinoma ◽  
Primary Tumor ◽  
Renal Cell ◽  
Clear Cell ◽  
Advanced Renal Cell Carcinoma ◽  
Second Line ◽  
Gene Set ◽  
Clear Cell Rcc

442 Background: Axitinib has demonstrated high efficacy with well-controlled adverse events (AEs) for advanced renal cell carcinoma (RCC). Recently, nivolumab has been approved for advanced RCC. However, it is very expensive in Japan and may cause severe immune-related AEs. There is no clue to choose axitinib or nivolumab as the second-line for advanced RCC. Previously we identified the gene set which may predict poor prognosis of RCC patients (Takahashi m et.al., Proc Natl Acad Sci U S A., 98: 9754, 2001) and have sought to elucidate whether insulin receptor (INSR) expression in the gene set may predict the resistance for axitinib as a biomarker. Methods: Axitinib was administered in 36 patients in our department between January 2008 and April 2015. Median age was 70 (36-84) years old with 22 males and 14 females. Histological subtype included clear cell RCC (n=27, 75.0%), clear cell + sarcomatoid component (n=3), collecting duct carcinoma (n=2), papillary, sarcomatoid, mucinous tubular and spindle cell carcinoma (MTSCC), and unknown in each one. Axitinib was administered in two patients as the first line, 21 patients as the second line, and 13 patients as ≥ the third line. Tissue of primary tumor was available in 20/36 patients, including 16 clear cell RCC and 4 other subtypes. Immunohistochemical INSR expression was examined and correlated with survival of the patients with axitinib. Results: Objective response rate was 27.6%, progression-free survival (PFS) was 16.3 months, and overall survival (OS) was 41.9 months in clear cell RCC patients. Patients with low INSR expression (n=7) had significantly shorter PFS (68 vs. 586 days, p<0.001) and OS (169 vs. 1027 days, p=0.004) compared with those with high INSR expression (n=13). If only clear cell RCC was evaluated, patients with low INSR expression (n=3) had significantly shorter PFS (77 vs. 586 days, p=0.008) and OS (294 vs. 1027 days, p=0.016) compared with those with high INSR expression (n=13). Conclusions: Axitinib was highly effective for advanced clear cell RCC. However, immunohistochemically low expression of INSR in the primary tumor may predict the resistance for axitinib and those patients may be more suitable for immune checkpoint inhibitors.

Statin use and risk of renal cell carcinoma in three prospective cohort studies.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 679-679
Author(s):  
Kathryn M. Wilson ◽  
Alejandro Sanchez ◽  
Rebecca E. Graff ◽  
Sabina Signoretti ◽  
Toni K. Choueiri ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cox Proportional Hazards ◽  
Health Study ◽  
P Value ◽  
Increased Risk ◽  
Clear Cell Rcc ◽  
Statin Use

679 Background: Evidence on statin use and incidence of renal cell carcinoma (RCC) is mixed. Previous results from the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) found a suggestive protective effect in women but not in men (Liu et al, Cancer 2012). We conducted an updated analysis of statin use and risk of total and fatal RCC in the NHS, HPFS, and NHS 2 cohorts, with more than twice as many cases. Methods: We examined the associations between statin use and risk of RCC from 1990 to 2016 in HPFS (men), 1994 to 2016 in NHS (women), and 1999 to 2015 in NHS 2 (women). Information on statin use was collected every two years. We used Cox proportional hazards models, adjusting for known and suspected risk factors, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for use of statins and risk of total and fatal RCC, RCC by stage at diagnosis, and clear cell RCC. We pooled results across cohorts using a random effects model. Results: We documented 661 cases of RCC (310 in HPFS, 255 in NHS, 96 in NHS 2), of which 132 (20%) were fatal. Of the 661 cases, 458 (69%) were clear cell. The pooled multivariable HR for total RCC was 1.01 (95% CI 0.84-1.21) for current statin use, updated over time. Current use was not associated with risk of fatal, advanced (stage T3 or higher), or localized (stage T1 or T2) disease. There were no associations between duration of statin use and risk of RCC; compared to never users, those with less than four years of total use had an HR of 0.91 (95% CI 0.71-1.18), and those with four or more years of use had an HR of 1.03 (95% CI 0.84-1.27). Among men, statin use was associated with increased risk of clear cell RCC (HR for current use: 1.48, 95% CI 1.04-2.11; HR for 4 or more years of use: 1.58, 95% CI 1.05-2.36). Statins were not associated with risk of clear cell RCC in women (HR for current use: 0.77, 95% CI 0.58-1.03; p-value for heterogeneity across cohorts = 0.02). Conclusions: Overall, statin use was not associated with risk of RCC in three large, prospective cohorts of US women and men. Statin use was associated with increased risk of clear cell RCC among men.

Nivolumab in metastatic nonclear cell renal cell carcinoma: First results of the AcSe prospective study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 699-699
Author(s):  
Laurence Albiges ◽  
Damien Pouessel ◽  
Marie Beylot-Barry ◽  
Guido Bens ◽  
Diane Pannier ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prospective Study ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Type I ◽  
Cell Renal Cell Carcinoma ◽  
Duct Carcinoma ◽  
Clear Cell Rcc

699 Background: AcSe Nivolumab (N), is a non-randomised, open-label, multicentric study to investigate the efficacy and safety of nivolumab monotherapy in patients (pts) with specific rare cancers (NCT03012581). We report on the non-clear cell renal cell carcinoma (RCC) cohort. Methods: Primary endpoint was objective response rate (ORR) at 12 weeks according to RECIST1.1. All pts receives N at 240mg IV every 2 weeks. Secondary endpoints included progression free survival (PFS), overall survival (OS), best response, and safety. Results: Between 07/2017 and 02/2019, 50 pts have been enrolled across 13 institutions. Median age was 61.4 years old, 70% were male. ECOG PS was 0, 1, 2, in 29%, 63% and 8% of pts respectively. Histological types were papillary (pRCC) type 2 (41%), chromophobe (18%), pRCC type I (10%), pRCC unclassified (8%), collecting duct carcinoma (CDC) (8%), and others (including predominant sarcomatoid, renal medullary carcinoma, MITF associated RCC, unclassified RCC). N was used in first line in 16%, second line in 54% and third line or beyond in 30%. IMDC risk group was 14%, 70% and 16% for good, intermediate and poor risk respectively. With a median follow up of 10.4 months (mo), 42 pts had discontinued N. The 12 weeks-ORR was 6% (3 PR), with stable disease in 49% and PD in 44% of pts. The best ORR was 10%. Median PFS was 3.9 mo (IC95% [2.9; 8.3]). At time of analysis, 25 pts (50%) had died and 12-months OS rate was 47.7% (IC95% [33.5; 67.8]). Overall, 31 pts (62%) have presented at least one grade ≥ 3 AE. No new safety signal with N was reported. 12 weeks-ORR and best ORR according to distinct histology are presented in table 1. Pts with PR were 1pRCC type 2, 1pRCC type 1, 1 CDC, 1 MITF RCC and 1 unclassified. Conclusions: We report the first prospective study of N single agent in non-clear cell RCC. N demonstrates limited activity in a pretreated and heterogeneous non- clear cell RCC population. Interestingly 1/4 CDC developed PR while no response was noted in chromophobe RCC. Clinical trial information: NCT03012581. [Table: see text]

scholarly journals Case of renal cell carcinoma with immunotherapy effect mimicking xanthogranulomatous pyelonephritis

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S71-S71
Author(s):  
Y Wang ◽  
S Ganesan ◽  
R Rayes-Danan ◽  
S Williamson
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Left Kidney ◽  
Xanthogranulomatous Pyelonephritis ◽  
Eosinophilic Cytoplasm ◽  
Golden Yellow ◽  
Clear Cell Rcc

Abstract Introduction/Objective The histologic features of renal cell carcinoma (RCC) after immunotherapy are not fully established. We report the pathologic findings of one case of clear cell RCC after treatment with pembrolizumab which is a humanized monoclonal anti-PD1 antibody. Methods/Case Report 46-year-old man completed three cycles of pembrolizumab for recurrent basal cell carcinoma. A 5.0 cm mass was incidentally found within left kidney during staging CT scan. He subsequently had left radical nephrectomy. Pathologic examination of nephrectomy specimen identified one 5.0 cm, well-circumscribed, solid mass in the upper pole, confined to the kidney with predominantly hemorrhagic, focally golden-yellow soft cut surface. The remaining parenchyma appears unremarkable. The pelvicalyceal system is not dilated. Sections of tumor show predominance of foamy histiocytes, lymphoplasmacytic infiltrate, and scattered cells having pale or eosinophilic cytoplasm, conspicuous nucleoli and low nuclear: cytoplasm ratio. Cholesterol clefts and hemosiderin deposits are noted. The immunostaining profile highlights areas suspicious for viable tumor cells by using pan-keratin, CK8/18, EMA, CA9 and CD10. Focal positivity in the same area is noted by the stains of PAX 8 and AMACR. However, with numerous histiocytes, it is difficult to determine if the tumor cells are positive for Vimentin. Moreover CD 117 is negative in the tumor cells. Results (if a Case Study enter NA) NA Conclusion Differential diagnosis includes renal cell carcinoma and xanthogranulomatous pyelonephritis. The overall findings support a clear cell RCC affected by the immunotherapy. With immunotherapy-based combinations becoming standard of care in advanced malignancies, it makes the pathological diagnosis more challenging and difficult, especially for incidental tumors.

scholarly journals Decreased Expression of Inhibitor of Caspase-Activated DNase (ICAD) in Renal Cell Carcinoma – Tissue Microarray of Human Samples

2016 ◽  
Vol 3 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Retnagowri Rajandram ◽  
Azad H. A. Razack ◽  
Keng Lim Ng ◽  
Glenda C Gobe
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tissue Microarray ◽  
Renal Cell ◽  
Clear Cell ◽  
Normal Kidney ◽  
Down Regulation ◽  
Caspase Activated Dnase ◽  
Clear Cell Rcc ◽  
Metastatic Rcc

Although primary localised tumours of renal cell carcinoma (RCC) can be treated relatively successfully with surgery, metastatic RCC has poor prognosis because of late diagnosis and resistance to therapies. In the present study, we were interested in profiling the protein expression of “inhibitor of caspase-activated DNase” (ICAD), an apoptosis inhibitor, in kidney cancer and its paired normal kidney. Immunohistochemistry with automated batch staining and morphometry using digital pathology were used to compare ICAD in 121 RCC specimens with their paired normal kidney tissue. Tissue microarray of formalin-fixed, paraffin-embedded archival tissue was used. Intensity and localisation of ICAD were compared between normal and cancer samples, and against grading within the cancers. The results demonstrated that, in this cohort, ICAD was highly expressed in the proximal tubular epithelium of normal kidney, and significantly decreased in clear cell RCC tissue (p < 0.05) as well as other subtypes of RCC (p < 0.01) compared with normal kidney. There was a tendency towards nuclear localisation of ICAD in clear cell RCC, but not in other subtypes of RCC. No significant association was found between ICAD intensity and grade of RCC. In summary, down-regulation of ICAD occurs in RCC. ICAD normally inhibits DNA fragmentation and apoptosis; thus, its down-regulation was unexpected in a cancer known for its resistance to apoptosis. However, these RCC samples were from primary, not metastatic, RCC sites, and down-regulated ICAD may be part of a progressive pathway that promotes RCC metastasis.

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