Nonfamilial Bilateral Synchronous Renal Cell Carcinoma with Discordant Histology with Eventual Complete Response to Dual Immunotherapy
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ABSTRACT:
SUBMITTER: Robertson I
PROVIDER: S-EPMC10642977 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:We describe herein a patient presenting with bilateral estrogen-receptor-positive (ER+) breast tumors who was enrolled in a clinical trial exploring molecular aberrations associated with hormone-refractory tumor cell proliferation. Short-term (two week) hormonal therapy with the aromatase inhibitor letrozole substantially reduced proliferation as measured by Ki67 immunohistochemistry in one tumor, whereas the second was essentially unchanged. Extensive molecular and genetic work-up of the two tumors yielded divergent lesions in the two tumors: an activating KRAS mutation in the responsive tumor and an amplification of the fibroblast growth factor receptor-1 (FGFR1) locus in the treatment-refractory tumor. These findings provide an insight to possible mechanisms of resistance to antiestrogen therapy in ER+ breast cancers. First, they illustrate the necessity of clinically approved assays to identify FGFR1 gene amplification, which occur in approximately 5% of breast tumors and have been linked to antiestrogen resistance. It is quite possible that the addition of FGFR inhibitors to ER-targeted therapy will yield a superior antitumor effect and improved patient outcome. Second, they suggest that the role of activating mutations in RAS, although rare in breast cancer, may need to be explored in the context of ER+ breast tumors.
| S-EPMC3682668 | biostudies-literature
Project description:ObjectiveTo evaluate the presentation, management, pathology, and functional and oncological outcomes of patients undergoing retroperitoneoscopic treatment of bilateral synchronous sporadic RCC at our institution.MethodsWe retrospectively evaluated the records of 60 patients with bilateral synchronous sporadic RCC who underwent retroperitoneoscopic treatment at the General Hospital of People's Liberation Army from 2008 to 2014. The estimated glomerular filtration rate was calculated and compared among different surgical procedures. The overall survival and recurrence free survival were assessed based on information from recent follow-up.ResultsFifty-six patients underwent bilateral retroperitoneoscopic surgeries in staged procedures, and four patients underwent bilateral retroperitoneoscopic surgeries in simultaneous procedures. Among the former group of patients, 34 underwent bilateral partial nephrectomy, 12 underwent radical nephrectomy followed by partial nephrectomy, and 10 underwent partial nephrectomy followed by radical nephrectomy. Bilateral partial nephrectomy can better preserve renal function (p = 0.040) and the sequence of partial nephrectomy and radical nephrectomy did not affect functional outcomes (p = 0.790). One patient undergoing simultaneous procedures developed acute renal failure and required temporary hemodialysis. At 3 and 5 years, overall survival rates were 93.0% and 89.4%, and recurrence free survival rates were 90.5% and 81.6%. High nuclear grade (p = 0.014) was related to disease recurrence.ConclusionsStaged bilateral partial nephrectomy was efficient in preserving renal function. The survival of patients with bilateral synchronous sporadic renal tumors was similar to that of patients with unilateral nonmetastatic tumors. Nuclear grade was an independent prognostic factor of disease recurrence.
| S-EPMC4852891 | biostudies-literature
Project description:Renal cell carcinoma (RCC) is a malignant tumor that can metastasize easily. Hence, many patients have already developed metastasis when they are diagnosed. It is also one of the most common tumors that metastasize to the head and neck through extranodal disease. Herein, we reported a case of a 53-year-old man with cervical metastasis from bilateral RCC. Interestingly, whole exome sequencing (WES) and clonal evolution analysis revealed that bilateral renal tumor lesions and neck metastases (squamous cell carcinoma) share the same subclones and a large number of gene variants, while the pathological morphology is different (left nephrotic foci, a mixed pattern of mucinous tubular and spindle cell carcinoma (MTSCC) with papillary adenoma; right renal foci, papillary renal cell carcinoma (PRCC)). This was first reported in RCCs to the best of our knowledge. This case suggests that genotype analysis can be a powerful supplementary examination for clinical histopathological diagnosis. Gene detection has great significance for the accurate diagnosis and treatment of RCC metastasis or multiple lesions.
| S-EPMC8354027 | biostudies-literature
Project description:Bilateral renal cell carcinomas (RCCs) pose a challenge for clinical treatment and management. Most bilateral RCCs are sporadic, and do not show a hereditary pattern indicative of VHL syndrome or other inherited cancers. The origin and evolution of these sporadic bilateral RCCs remains elusive. We obtained normal and tumor samples from two male patients suffering from early stage synchronous bilateral clear cell RCC (ccRCC), and analyzed genomic DNA using whole exome sequencing and bisulfite pyrosequencing. We detected distinct 3p loss of heterozygosity (LOH) in both tumors in each patient. Two tumors within the same patient harbored distinct driver mutations and different CpG hypermethylation sites in the VHL promoter. Moreover, tumors exhibit independent evolutionary trajectories. Therefore, distinct 3p LOH, combined with contingent driver gene mutations and independent VHL hypermethylation, led to independent tumor origin and parallel evolution of bilateral ccRCC in these two patients. Our results indicate that tumors in these two cases were not due to common germline oncogenic mutations. They were results of multiple de novo mutations in each kidney, rather than primary ccRCC with contralateral renal metastasis. Therefore, histopathologic and genetic profiling from single tumor specimen may underestimate the mutational burden and somatic heterogeneity of bilateral ccRCCs.
| S-EPMC4935960 | biostudies-literature
Project description:BackgroundBilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy.MethodsA total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers.ResultsGrade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs.ConclusionOur study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC.Clinical trial registrationhttps://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159.
| S-EPMC9642914 | biostudies-literature
Project description:This clinical case resulted from an ongoing trial at Vanderbilt University and abroad where ER+ breast cancer patients are administered 2-3 weeks of aromatase inhibitor therapy leading up to definitive surgical resection of the tumor. In this case, we describe a study patient presenting with bilateral primary ER+ breast tumors. Short term hormonal therapy substantially reduced proliferation in one tumor, while the second was essentially unchanged. Extensive molecular and genetic workup of the two tumors yielded divergent lesions in the two tumors; an activating KRAS mutation in the responsive tumor, and an amplification of the FGFR1 locus in the treatment-refractory tumor. Surgical tumor specimens from ER+ breast cancer patient 7603 who was administered letrozole for 16 days leading up to definitive surgery were utilized for RNA extraction and hybridization to Affymetrix Gene expression microarrays.
2012-07-16 | E-GEOD-39387 | biostudies-arrayexpress
Project description:This clinical case resulted from an ongoing trial at Vanderbilt University and abroad where ER+ breast cancer patients are administered 2-3 weeks of aromatase inhibitor therapy leading up to definitive surgical resection of the tumor. In this case, we describe a study patient presenting with bilateral primary ER+ breast tumors. Short term hormonal therapy substantially reduced proliferation in one tumor, while the second was essentially unchanged. Extensive molecular and genetic workup of the two tumors yielded divergent lesions in the two tumors; an activating KRAS mutation in the responsive tumor, and an amplification of the FGFR1 locus in the treatment-refractory tumor.
2012-07-17 | GSE39387 | GEO
Project description:PurposeSynchronous bilateral renal masses (SBRM) account for a low percentage of kidney tumors, and there is no current recommendation for their management. The objective was to review evidence regarding the best surgical approach for SBRM in terms of type and timing of surgery.MethodsA broad literature search was performed on 28th January 2023 using Scopus, PubMed, and EMBASE. Only English papers dealing with adults were included. Meeting abstracts were excluded.ResultsTwenty-four papers were accepted and included. SBRM behave less aggressively than metachronous tumors, and partial nephrectomy (PN) is the preferred therapeutic option to preserve renal function. Open, laparoscopic, and robot-assisted approaches were found to be similar in oncological outcomes, though robot-assisted surgery resulted in lower comorbidities. Same-sitting PN was demonstrated to be a safe approach, particularly in the robotic-assisted one. Finally, the same-siting and staged NSS were similar in preserving renal function.ConclusionsPN should be the desirable treatment for SBRM whenever feasible and if patients are fit, but surgeon expertise should also be taken into the account.
| S-EPMC10415478 | biostudies-literature
Project description:Bilateral synchronous paratesticular leiomyoma (BSPL) is a rare tumor that originates from smooth muscle cells in the paratesticular region. Four BSPL cases have been reported sporadically, starting with the 1991 report by Aus and Boiesen. Herein, we report the case of a 60-year-old male with a bilateral scrotal mass with a maximum size of 7.5 cm. Histological examination revealed oval to spindle-shaped tumor cells with a fascicular growth pattern. Immunohistochemically, the tumor cells were positive for α-smooth muscle actin. The pathological diagnosis was a leiomyoma. Based on the simultaneous bilateral nature of the disease, BSPL was diagnosed. In conclusion, we encountered a rare case of BSPL, and our report may contribute to the understanding of this disease.
| S-EPMC9938400 | biostudies-literature
Project description:This clinical case resulted from an ongoing trial at Vanderbilt University and abroad where ER+ breast cancer patients are administered 2-3 weeks of aromatase inhibitor therapy leading up to definitive surgical resection of the tumor. In this case, we describe a study patient presenting with bilateral primary ER+ breast tumors. Short term hormonal therapy substantially reduced proliferation in one tumor, while the second was essentially unchanged. Extensive molecular and genetic workup of the two tumors yielded divergent lesions in the two tumors; an activating KRAS mutation in the responsive tumor, and an amplification of the FGFR1 locus in the treatment-refractory tumor. Surgical tumor specimens from ER+ breast cancer patient 7603 who was administered letrozole for 16 days leading up to definitive surgery were utilized for RNA extraction and hybridization to Affymetrix Gene expression microarrays.
| S-ECPF-GEOD-39387 | biostudies-other