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Cell Reports. Medicine May 2024Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early...
Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.
Topics: Humans; Proteogenomics; Kidney Neoplasms; Biomarkers, Tumor; Carcinoma, Renal Cell; Transcriptome; Male; Female; Middle Aged; Gene Expression Regulation, Neoplastic
PubMed: 38703764
DOI: 10.1016/j.xcrm.2024.101547 -
Frontiers in Oncology 2024This report delineates the clinical progression of a renal oncocytoma in a 38-year-old female, initially asymptomatic, over a three-year follow-up period following her...
This report delineates the clinical progression of a renal oncocytoma in a 38-year-old female, initially asymptomatic, over a three-year follow-up period following her treatment for papillary thyroid cancer. The timeline of this case is as follows: In 2016, the patient was treated with total thyroidectomy and I131 for thyroid cancer. During an annual follow-up, an incidental renal mass was detected via FDG PET/CT, initially characterized as a benign, non-FDG-avid renal oncocytoma. Over two years, this lesion demonstrated a remarkable increase in FDG uptake and a slight growth in size, coupled with new I131 uptake in subsequent scans. These findings led to a reassessment of the diagnosis, initially suggesting a potential small renal cell carcinoma (RCC). Histopathological analysis eventually confirmed the diagnosis of oncocytoma. This case is notable for the tumor's unusual metabolic evolution and the challenges it posed in differential diagnosis.
PubMed: 38496753
DOI: 10.3389/fonc.2024.1282508 -
Leukemia Research Reports 2024Intravascular large B cell lymphoma (IVLBCL) is exceedingly rare and difficult to diagnose. We describe a case of IVLBCL in a 56-year-old male which was identified after...
Intravascular large B cell lymphoma (IVLBCL) is exceedingly rare and difficult to diagnose. We describe a case of IVLBCL in a 56-year-old male which was identified after recurrent strokes. Right partial nephrectomy was then performed which demonstrated renal oncocytoma and IVLBCL. Chemotherapy was initiated with standard R-Hyper-CVAD which included intrathecal methotrexate and cytarabine. R-CHOP is largely considered the treatment of choice in IVLBCL, however low doses of chemotherapy in this regimen do not cross the blood brain barrier like in R-Hyper-CVAD. The patient achieved complete remission after completion of treatment and has remained in remission for 5 years after diagnosis.
PubMed: 38124760
DOI: 10.1016/j.lrr.2023.100401 -
Indian Journal of Pathology &... 2023Renal oncocytoma is a benign renal neoplasm which has mostly been reported in adults. Occurrence in children is infrequent. To date, there are only six pediatric cases... (Review)
Review
Renal oncocytoma is a benign renal neoplasm which has mostly been reported in adults. Occurrence in children is infrequent. To date, there are only six pediatric cases of renal oncocytoma reported previously. Herein, we report a 13-year-old girl presented with hematuria for a week. Abdominal computed tomography showed a well-defined heterogeneous solid mass with a stellate central scar in the left kidney. The patient underwent a nephron sparing surgery. Histopathological and immunohistochemical findings confirmed the diagnosis of renal oncocytoma. Though uncommon, renal oncocytoma should be considered as the differential diagnosis of renal tumor in children. In addition, intranuclear inclusions were firstly described in this pediatric patient with unclear significance, which need a large cohort to summarize and analyze.
Topics: Adolescent; Female; Humans; Adenoma, Oxyphilic; Diagnosis, Differential; Kidney Neoplasms; Tomography, X-Ray Computed
PubMed: 38084552
DOI: 10.4103/ijpm.ijpm_264_22 -
Clinical Proteomics Nov 2023This study investigates the proteomic landscapes of chromophobe renal cell carcinoma (chRCC) and renal oncocytomas (RO), two subtypes of renal cell carcinoma that...
BACKGROUND
This study investigates the proteomic landscapes of chromophobe renal cell carcinoma (chRCC) and renal oncocytomas (RO), two subtypes of renal cell carcinoma that together account for approximately 10% of all renal tumors. Despite their histological similarities and shared origins, chRCC is a malignant tumor necessitating aggressive intervention, while RO, a benign growth, is often subject to overtreatment due to difficulties in accurate differentiation.
METHODS
We conducted a label-free quantitative proteomic analysis on solid biopsies of chRCC (n = 5), RO (n = 5), and normal adjacent tissue (NAT, n = 5). The quantitative analysis was carried out by comparing protein abundances between tumor and NAT specimens. Our analysis identified a total of 1610 proteins across all samples, with 1379 (85.7%) of these proteins quantified in at least seven out of ten LC‒MS/MS runs for one renal tissue type (chRCC, RO, or NAT).
RESULTS
Our findings revealed significant similarities in the dysregulation of key metabolic pathways, including carbohydrate, lipid, and amino acid metabolism, in both chRCC and RO. Compared to NAT, both chRCC and RO showed a marked downregulation in gluconeogenesis proteins, but a significant upregulation of proteins integral to the citrate cycle. Interestingly, we observed a distinct divergence in the oxidative phosphorylation pathway, with RO showing a significant increase in the number and degree of alterations in proteins, surpassing that observed in chRCC.
CONCLUSIONS
This study underscores the value of integrating high-resolution mass spectrometry protein quantification to effectively characterize and differentiate the proteomic landscapes of solid tumor biopsies diagnosed as chRCC and RO. The insights gained from this research offer valuable information for enhancing our understanding of these conditions and may aid in the development of improved diagnostic and therapeutic strategies.
PubMed: 38017382
DOI: 10.1186/s12014-023-09443-8 -
The American Journal of Surgical... Feb 2024Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell...
Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients-A Tale of Two Cities: Sequencing Analysis Reveals Dual Lineage Markers Capturing the 2 Cellular Populations of HOT.
Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell carcinoma (chRCC). HOT exhibits heterogenous histologic features overlapping with chRCC and benign renal oncocytoma, posing challenges in diagnosis of HOT and renal tumor entities resembling HOT. In this study, we performed integrative analysis of bulk and single-cell RNA sequencing data from renal tumors and normal kidney tissues, and nominated candidate biomarkers of HOT, L1CAM, and LINC01187 , which are also lineage-specific markers labeling the principal cell and intercalated cell lineages of the distal nephron, respectively. Our findings indicate the principal cell lineage marker L1CAM and intercalated cell lineage marker LINC01187 to be expressed mutually exclusively in a unique checkered pattern in BHD-associated HOTs, and these 2 lineage markers collectively capture the 2 distinct tumor epithelial populations seen to co-exist morphologically in HOTs. We further confirmed that the unique checkered expression pattern of L1CAM and LINC01187 distinguished HOT from chRCC, renal oncocytoma, and other major and rare renal cell carcinoma subtypes. We also characterized the histopathologic features and immunophenotypic features of oncocytosis in the background kidney of patients with BHD, as well as the intertumor and intratumor heterogeneity seen within HOT. We suggest that L1CAM and LINC01187 can serve as stand-alone diagnostic markers or as a panel for the diagnosis of HOT. These lineage markers will inform future studies on the evolution and interaction between the 2 transcriptionally distinct tumor epithelial populations in such tumors.
Topics: Humans; Birt-Hogg-Dube Syndrome; Cities; Neural Cell Adhesion Molecule L1; Kidney Neoplasms; Carcinoma, Renal Cell; Adenoma, Oxyphilic
PubMed: 37994665
DOI: 10.1097/PAS.0000000000002152 -
Urology Case Reports Nov 2023Multifocality in renal tumors is a rare occurrence, but not unheard of. Commonly the different foci correspond to the same histological pathology, however co-existence...
Multifocality in renal tumors is a rare occurrence, but not unheard of. Commonly the different foci correspond to the same histological pathology, however co-existence with other renal lesions, including both malignant and benign tumors, have also been reported. Here we present a 57-year-old male, ex-smoker who exhibited four distinct histological tumors in an ipsilateral kidney; multilocular cystic clear cell renal cell carcinoma (RCC) of low malignant potential, clear cell papillary RCC, renal oncocytoma, and renomedullary interstitial cell tumor. To our knowledge this is the first time these four tumors were found in the same patient, let alone the same kidney.
PubMed: 37811540
DOI: 10.1016/j.eucr.2023.102574 -
Improving CNNs classification with pathologist-based expertise: the renal cell carcinoma case study.Scientific Reports Sep 2023The prognosis of renal cell carcinoma (RCC) malignant neoplasms deeply relies on an accurate determination of the histological subtype, which currently involves the...
The prognosis of renal cell carcinoma (RCC) malignant neoplasms deeply relies on an accurate determination of the histological subtype, which currently involves the light microscopy visual analysis of histological slides, considering notably tumor architecture and cytology. RCC subtyping is therefore a time-consuming and tedious process, sometimes requiring expert review, with great impact on diagnosis, prognosis and treatment of RCC neoplasms. In this study, we investigate the automatic RCC subtyping classification of 91 patients, diagnosed with clear cell RCC, papillary RCC, chromophobe RCC, or renal oncocytoma, through deep learning based methodologies. We show how the classification performance of several state-of-the-art Convolutional Neural Networks (CNNs) are perfectible among the different RCC subtypes. Thus, we introduce a new classification model leveraging a combination of supervised deep learning models (specifically CNNs) and pathologist's expertise, giving birth to a hybrid approach that we termed ExpertDeepTree (ExpertDT). Our findings prove ExpertDT's superior capability in the RCC subtyping task, with respect to traditional CNNs, and suggest that introducing some expert-based knowledge into deep learning models may be a valuable solution for complex classification cases.
Topics: Pregnancy; Humans; Female; Carcinoma, Renal Cell; Pathologists; Kidney Neoplasms; Adenoma, Oxyphilic; Neural Networks, Computer
PubMed: 37741835
DOI: 10.1038/s41598-023-42847-y -
Asian Journal of Surgery Dec 2023
Topics: Humans; Carcinoma, Transitional Cell; Adenoma, Oxyphilic; Urinary Bladder Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Kidney Pelvis; Neoplasms, Multiple Primary
PubMed: 37696701
DOI: 10.1016/j.asjsur.2023.08.230