Durable Remission with Immunotherapy in a Patient with Sarcomatoid Renal Cell Carcinoma
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ABSTRACT:
SUBMITTER: Nwabundo A
PROVIDER: S-EPMC8557255 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSarcomatoid carcinoma is a rare, high-grade malignancy with epithelial and mesenchymal components. It may be a good candidate for immunotherapy because it is associated with overexpression of programmed cell death ligand 1. Sarcomatoid urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Here we report the first case of sarcomatoid UC of the renal pelvis that responded to immunotherapy.Case presentationA 79-year-old man was referred to our hospital complaining of various symptoms, including anorexia and abdominal pain. A computed tomography scan revealed a right atrial tumor, a 9 cm left renal mass with a renal vein tumor thrombus, para-aortic lymphadenopathy, and multiple small lung nodules. The patient underwent resection of the right atrial tumor. Pathological analysis of the tumor did not lead to an accurate diagnosis even after several rounds of immunohistochemistry. He underwent a needle biopsy of the left kidney and was initially diagnosed with collecting duct carcinoma, a rare subtype of renal cell carcinoma (RCC). Following the initial diagnosis, immunotherapy with nivolumab and ipilimumab commenced. Thereafter, almost all lesions, including the left renal tumor, were reduced in size. However, he underwent a left nephrectomy approximately a year after beginning immunotherapy due to repeated left renal bleeding. Histological examination of the nephrectomy specimen revealed two forms of cancer-sarcomatoid UC and conventional high-grade UC. Two months after surgery, the patient was found to have new lung metastases. He underwent chemotherapy with gemcitabine and cisplatin, followed by immunotherapy with pembrolizumab. However, both treatments were ineffective. The patient died of cancer 19 months after his first admission.ConclusionsThe presented case of sarcomatoid UC of the renal pelvis that partially responded to immunotherapy suggests that immunotherapy can be a promising treatment for sarcomatoid UC.
| S-EPMC10024438 | biostudies-literature
Project description:Cardiac metastasis from renal cell carcinoma (RCC) without inferior vena cava (IVC) involvements is extremely rare with few reported cases. Sarcomatoid RCC with rhabdoid feature is a rare pathologic type of RCC having aggressive behavior due to great metastatic potential. Here, we report a case of rapidly growing cardiac metastasis of RCC which brought on right ventricular outflow tract (RVOT) obstruction without IVC and right atrial involvement in a 61-year-old woman. Cardiac arrest occurred during radical nephrectomy and echocardiography revealed mass nearly obstructing the RVOT which was not recognized by preoperative echocardiography 1 month ago. Postoperative immunohistochemical evaluation of renal mass revealed sarcomatoid RCC with rhabdoid feature.
| S-EPMC5234337 | biostudies-literature
Project description:Sarcomatoid dedifferentiation is an uncommon feature that can occur in most histological subtypes of renal cell carcinomas (RCCs) and carries a decidedly poor prognosis. Historically, conventional treatments for sarcomatoid RCCs (sRCCs) have shown little efficacy, and median survival is commonly 6-13 months. Despite being first described in 1968, the mechanisms driving sarcomatoid dedifferentiation remain poorly understood, and information and treatment options available to physicians and patients are limited. When diagnosed at an early stage, surgical intervention remains the treatment of choice. However, preoperative identification through routine imaging or biopsy is unreliable and most patients present with advanced disease and systemic symptoms. For these patients, the role of cytoreductive nephrectomy is disputed. The expansion of immunotherapies approved for RCCs has generated a search for biomarkers that might be indicative of treatment response in sRCCs, although a proven effective systemic agent remains elusive. PDL1 expression is increased in sarcomatoid dedifferentiated renal tumours, which suggests that patients with sRCCs could benefit from PD1 and/or PDL1 immune checkpoint blockade therapy. Treatment outcomes for sarcomatoid tumours have remained relatively consistent compared with other RCCs, but further investigation of the tumour-immune cell microenvironment might yield insights into further therapeutic possibilities.
| S-EPMC7551522 | biostudies-literature
Project description:The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.
| S-EPMC4776463 | biostudies-literature
Project description:Sarcomatoid renal cell carcinoma is a de-differentiated form of kidney cancer with an extremely poor prognosis. Genes associated with sarcomatoid differentiation may be closely related to the prognosis of renal cell carcinoma. The prognosis of renal cell carcinoma itself is extremely variable, and a new prognostic model is needed to stratify patients and guide treatment. Data on clear cell renal cell carcinoma with or without sarcomatoid differentiation were obtained from TCGA database, and a sarcomatoid-associated gene risk index (SAGRI) and column line graphs were constructed using sarcomatoid-associated genes. The predictive power of the SAGRI and column line graphs was validated using an internal validation set and an independent validation set (E-MTAB-1980). The SAGRI was constructed using four sarcoma-like differentiation-related genes, COL7A1, LCTL, NPR3, ZFHX4, and had a 1-year AUC value of 0.725 in the training set, 0.712 in the internal validation set, and 0.770 in the independent validation set for TCGA training cohort, with high model reliability. The molecular characteristics among the SAGRI subgroups were analyzed by multiple methods, and results suggested that the SAGRI-HIGH subgroup may benefit more from immunotherapy to improve prognosis. SAGRI satisfactorily predicted the prognosis of patients with clear cell renal cell carcinoma with or without sarcomatoid differentiation.
| S-EPMC9493111 | biostudies-literature
Project description:Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC.
| S-EPMC7865061 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-06-18 | GSE59266 | GEO
Project description:Background: Clear cell renal cell carcinoma (ccRCC) constitutes the commonest kidney malignancy. Immunogenic cell death (ICD) is a type of regulated cell death (RCD), which sufficiently activates adaptive immunity. However, ICD's involvement in cancer development is unclear, as well as the associations of ICD effectors with ccRCC prognosis. Methods: RNA-sequencing expression profiles of ccRCC in The Cancer Genome Atlas (TCGA) and normal samples in Gene Expression Omnibus (GEO) were comprehensively investigated. Consensus clustering analysis was employed to determine subgroup members linked to ICD-related genes. Functional enrichment analysis was utilized for the examination of TLR4's biological role, and in vitro cellular assays were utilized for further confirmation. We also used Kaplan-Meier (KM) and Cox regression analyses to assess TLR4's prognostic value. Finally, "CIBERSORT" was employed for immune score evaluation. Results: The associations of ICD effectors with ccRCC prognosis were examined based on TCGA, and 12 genes showed upregulation in ccRCC tissue specimens. Meanwhile, ccRCC cases with upregulated ICD-related genes had increased overall survival. Among these ICD-related genes, TLR4 was selected for subsequent analysis. TLR4 was upregulated in ccRCC samples and independently predicted ccRCC. TLR4 also enhanced the proliferative, migratory and invasive abilities in cultured ccRCC cells. Moreover, TLR4 had close relationships with immune checkpoints and infiltrated immune cells. ccRCC cases with elevated TLR4 expression had prolonged overall survival, suggesting a prognostic value for TLR4. Finally, a pan-cancer analysis demonstrated TLR4 had differential expression in various malignancies in comparison with normal tissue samples. Conclusions: This study revealed prognostic values for ICD-associated genes, particularly TLR4, and experimentally validated the inducing effects of TLR4 on ccRCC progression in vitro. We also demonstrated the associations of TLR4 with immune cell infiltration, providing a novel strategy for prognostic evaluation and a novel therapeutic target in ccRCC.
| S-EPMC10414050 | biostudies-literature
Project description:Tubulocystic carcinoma of the kidney (TC-RCC) is a rare renal tumor and has been recently included as a distinct entity in WHO classification of renal neoplasms. We report the case of a patient with metastatic tubulocystic RCC whose disease progressed through standard of care treatment for nonclear RCC. However, genetic analysis revealed a germline pathogenic variant of fumarate hydratase (FH) gene, and the patient had a sustained and durable response to pazopanib.
| S-EPMC10105324 | biostudies-literature
Project description:ObjectiveTo evaluate MRI features of sarcomatoid renal cell carcinoma (RCC) and their association with survival.MethodsThis retrospective single-center study included 59 patients with sarcomatoid RCC who underwent MRI before nephrectomy during July 2003-December 2019. Three radiologists reviewed MRI findings of tumor size, non-enhancing areas, lymphadenopathy, and volume (and percentage) of T2 low signal intensity areas (T2LIA). Clinicopathological factors of age, gender, ethnicity, baseline metastatic status, pathological details (subtype and extent of sarcomatoid differentiation), treatment type, and follow-up were extracted. Survival was estimated using Kaplan-Meier method and Cox proportional-hazards regression model was used to identify factors associated with survival.ResultsForty-one males and eighteen females (median age 62 years; interquartile range 51-68) were included. T2LIAs were present in 43 (72.9%) patients. At univariate analysis, clinicopathological factors associated with shorter survival were: greater tumor size (> 10 cm; HR [hazard ratio] = 2.44, 95% CI 1.15-5.21; p = 0.02), metastatic lymph nodes (present; HR = 2.10, 95% CI 1.01-4.37; p = 0.04), extent of sarcomatoid differentiation (non-focal; HR = 3.30, 95% CI 1.55-7.01; p < 0.01), subtypes other than clear cell, papillary, or chromophobe (HR = 3.25, 95% CI 1.28-8.20; p = 0.01), and metastasis at baseline (HR = 5.04, 95% CI 2.40-10.59; p < 0.01). MRI features associated with shorter survival were: lymphadenopathy (HR = 2.24, 95% CI 1.16-4.71; p = 0.01) and volume of T2LIA (> 3.2 mL, HR = 4.22, 95% CI 1.92-9.29); p < 0.01). At multivariate analysis, metastatic disease (HR = 6.89, 95% CI 2.79-16.97; p < 0.01), other subtypes (HR = 9.50, 95% CI 2.81-32.13; p < 0.01), and greater volume of T2LIA (HR = 2.51, 95% CI 1.04-6.05; p = 0.04) remained independently associated with worse survival.ConclusionT2LIAs were present in approximately two thirds of sarcomatoid RCCs. Volume of T2LIA along with clinicopathological factors were associated with survival.
| S-EPMC9930281 | biostudies-literature