Cases Of Renal Cell Carcinoma Research Articles

Abscopal Effect Demonstrated on [18F]FDG PET/CT in a Case of Renal Cell Carcinoma Postnephrectomy

Renal cell carcinoma accounts for 3% of all malignancies with many of them presenting with metastasis at the time of presentation. The abscopal effect, a phenomenon characterized by systemic bystander effects on nontargeted lesions due to local therapy, has been extensively studied in the context of radiotherapy and immunotherapy. However, documentation of the abscopal effect following surgery remains limited. We present a case of a 67-year-old Indian male diagnosed with clear cell renal cell carcinoma (RCC), who underwent left radical nephrectomy. Baseline staging and postnephrectomy follow-up scans with fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) revealed an FDG-avid primary lesion in the left kidney with metastasis to the left lung. Surprisingly, the follow-up FDG PET-CT scan demonstrated the resolution of the left lung metastasis, indicating the occurrence of the abscopal effect resulting from the local nephrectomy. This rare clinical observation highlights the potential of surgery to induce immunogenic tumor neoantigens release and inflammatory factors, leading to systemic antitumor effects. While the abscopal effect has been extensively studied in the context of radiotherapy and immunotherapy, there is a scarcity of studies reporting nephrectomy promoting such systemic effects. The combination of radiotherapy and immunotherapy has shown promising results in enhancing tumor immunosuppression and facilitating the abscopal effect. We report a case of RCC with lung metastasis showing abscopal effect with resolution of lung nodule postnephrectomy on 18-F-FDG PET-CT.

Synchronous Carcinoma Cervix with Renal Cell Carcinoma: An Incidental Finding

Background In India, renal cell carcinoma (RCC) is the most frequent kidney cancer with an increasing tendency, whereas cervical cancer is the second most common disease among women. Synchronicity of RCC with other malignancies is not uncommon, but with the cervical cancer is rare.  Case description A 64-year-old, postmenopausal female, presented with complaint of bleeding per vagina and was diagnosed with carcinoma cervix and later on metastatic work-up also diagnosed with right RCC. After multidisciplinary discussion, patient planned for management for cervix then followed by renal lesion. Patient received radical external beam radiotherapy followed by brachytherapy for carcinoma cervix and underwent nephrectomy for right RCC.  Conclusion Synchronous cases of cervical cancer and renal cell carcinoma are very rare. Advancement in diagnostic protocol makes these kind of cases common and multidisciplinary team decisions are required for their management.

Anaesthetic challenges in a rare case of renal cell carcinoma with inferior vena cava tumor thrombus extension into right atrium under cardiopulmonary bypass with deep hypothermic circulatory arrest

Renal cell carcinoma, an epithelial tumour of the kidney, is the ninth most common cancer worldwide. It is uniquely associated with tumour thrombi extending into the renal vein and inferior vena cava, while rarely extending till the right atrium. This poses challenges in intra-operative and post-operative hemodynamic management as well as perioperative cardio and neuroprotection making it a challenging case from anaesthetic point of view. We report a rare case of Right renal cell carcinoma with thrombus extension into right renal vein, inferior vena cava and right atrium. Right radical nephrectomy with en-bloc tumor-thrombus excision under cardiopulmonary bypass with deep hypothermic circulatory arrest was performed. The case was suspected to have a difficult intraoperative and postoperative course with major hemodynamic instability, neuroprotection, and cardioprotection in mind, and was managed appropriately.

A case of synchronous phaeochromocytoma and renal cell carcinoma

A case of synchronous phaeochromocytoma and renal cell carcinoma

Programmed death ligand I (PDL-1) Expression in renal cell carcinoma: A retrospective cohort study

Background and objectives: Inhibition of programed death -1and programed death ligand-1 pathway enhances antitumor activity of T lymphocytes, therefore, provides a new strategy for tumor treatment utilizing immunotherapy. The aim of this study to assess the frequency of programed death ligand-1 expression in renal cell carcinoma by using the immunohistochemistry and to correlate the results the clinicopathologic parameters. Methods: This is a cross sectional retrospective study performed in Duhok City from 2017-2022 on fifty-four formalin fixed paraffin embedded blocks of nephrectomy specimens diagnosed as renal cell carcinoma and collected from central lab of Duhok and some private labs. Two sections were prepared from each block, one section was stained with hematoxylin and eosin for histological analysis and the other one was used for immunohistochemical assessment of programed death ligand-1then the results were correlated with various clinicopathological parameters. Results: Programed death ligand -1; membranous expression was positive in 19 cases (35.2%) of renal cell carcinoma out of 54 cases. There was no significant correlation between programed death ligand -1 expression and age (p= 0.991), gender (p= 0.272), multifocality (p= 0.607), tumor size (p= 0.796), histological subtype (p= 0.107), tumor stage (p= 0.546), nuclear grade (p= 0.781), surgical margins involvement (p= 0.119) and lymphovascular invasion (p= 0.4), but there was statistically significant correlation with nodal metastases (p= 0.039). Conclusion: Programmed death ligand -1/ Combined positive score was ?1 in about one third (35.2%) of renal cell carcinoma cases and this result can be utilized for the provision of immune checkpoint inhibitor (ICIs), regardless the age, gender, histological type, stage, nuclear grade, and the presence of lymphovascular invasion (LVI).

The clinical significance of PRMT8 expression in esophageal squamous cell carcinoma and the influence on prognosis.

e16066 Background: Protein arginine methyltransferase 8 (PRMT8), a member of protein arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical post-translational modications (PTMs). Esophageal squamous cell carcinoma (ESCC) is the third most common cancer type of the gastrointestinal tract with poor prognosis. Abnormal arginine methylation modifications are closely associated with the development of ESCC and can exert oncogenic effects by regulating a variety of cellular processes. However, the expression of PRMT8 in ESCC and its influence on prognosis is currently unknown. Methods: After passing the application and obtaining the approval of the hospital ethics review committee and obtaining the informed consent of all patients and their families, we collected 46 cases of renal cell carcinoma diagnosed in the Fourth Hospital of Hebei Medical University from 2018 to 2023, and postoperative pathological reports of all patients confirmed to be ESCC. We followed the selected patients and obtained complete data. All the pathological specimens of the selected patients were resectioned and then subjected to immunohistochemical examination to observe the expression differences of PRMT8 in ESCC, and parallel semi-quantitative analysis. Finally, the data of the patients were statistically built. Results: PRMT8 is mainly stained on the plasma membrane of tumor cells. The difference in expression levels between ESCC and normal tissue adjacent to the cancer was statistically significant (P < 0.01). This study found that the patient’s gender, age, tumor side have no correlation with the expression levels of PRMT8 (P > 0.05), while the three indicators of tumor size, TNM stage, and lymph node metastasis are positively correlated with the expression levels of PRMT8 and the difference is statistically significant (P < 0.01). Moreover, the positive staining of PRMT1 in ESCC was significantly correlated with poor prognosis of ESCC patients. Conclusions: The expression of PRMT8 is highly expressed in ESCC and associated with aberrant clinicopathological characteristics and poor prognosis. PRMT8 is a potential target for the stratification and treatment of ESCC.

An analysis of AURKB's prognostic and immunological roles across various cancers.

Aurora kinase B (AURKB), an essential regulator in the process of mitosis, has been revealed through various studies to have a significant role in cancer development and progression. However, the specific mechanisms remain poorly understood. This study, therefore, seeks to elucidate the multifaceted role of AURKB in diverse cancer types. This study utilized bioinformatics techniques to examine the transcript, protein, promoter methylation and mutation levels of AURKB. The study further analysed associations between AURKB and factors such as prognosis, pathological stage, biological function, immune infiltration, tumour mutational burden (TMB) and microsatellite instability (MSI). In addition, immunohistochemical staining data of 50 cases of renal clear cell carcinoma and its adjacent normal tissues were collected to verify the difference in protein expression of AURKB in the two tissues. The results show that AURKB is highly expressed in most cancers, and the protein level of AURKB and the methylation level of its promoter vary among cancer types. Survival analysis showed that AURKB was associated with overall survival in 12 cancer types and progression-free survival in 11 cancer types. Elevated levels of AURKB were detected in the advanced stages of 10 different cancers. AURKB has a potential impact on cancer progression through its effects on cell cycle regulation as well as inflammatory and immune-related pathways. We observed a strong association between AURKB and immune cell infiltration, immunomodulatory factors, TMB and MSI. Importantly, we confirmed that the AURKB protein is highly expressed in kidney renal clear cell carcinoma (KIRC). Our study reveals that AURKB may be a potential biomarker for pan-cancer and KIRC.

Long-term Outcome of Coronavirus Disease-associated Mucormycosis: 1-year Follow-up Study from India.

Invasive fungal infections have recently become a public health problem, particularly in India following the second wave of coronavirus disease 2019 (COVID-19). India harbors the world's largest population of patients suffering from diabetes. What prompted the sudden spike of mucormycosis infections in the COVID pandemic needs investigation. To determine if COVID-19 infection prompted the spike in invasive fungal infections in diabetic population. To determine the long-term outcome of COVID-associated mucormycosis. To determine if COVID-19 infection causes diabetes mellitus transiently. The study was a prospective cohort study comprising patients suffering from mucormycosis. The study was planned from 20 May 2021, until 30 November 2022, to investigate the long-term follow-up (1 year) of mucormycosis patients. The study setting was a referral hospital. All the consecutive patients admitted to this hospital for treatment of mucormycosis were included in the study who consented to it. Intervention(s) (for clinical trials) or exposure(s) (for observational studies): All patients suffering with mucormycosis underwent treatment at this hospital with surgery and injectable systemic antifungal drugs alongside diabetes management. Primary outcome measurement was in the form of survival with cure of mucormycosis. Hypothesis being tested was formulated during data collection. The data of 98 participants was collected, but analysis was done after excluding the case of cutaneous mucormycosis (infant patient). Mean age for patients was 55.5 years, varying from 28 to 88 years. In our study, 63.3% of patients with mucormycosis were males and 37.8% were females, of which 55.7% (34) and 58.3% (21) were known diabetics, respectively. Previous history of diabetes mellitus was identified as an underlying comorbid condition in 56.7% of patients, while the rest were diagnosed with new-onset diabetes mellitus. Sugar levels ranged (on admission) from 112 to 494 mg/dL (median 212 mg/dL) for known diabetics and from 132 to 356 mg/dL (median 204 mg/dL) for newly diagnosed diabetics. Other comorbidities included hypertension (19.5%), ischemic heart disease (8.2%), chronic renal illness (3.09%), and one case (1.03%) of postoperative renal cell carcinoma (disease-free). The majority of cases (91.8%) were not vaccinated for COVID-19, while only two patients reported a history of vaccination with two doses, and six others had received only a single dose. At the 1-year follow-up, 57.7% of cases were disease-free, 30.9% had expired, and 11.3% were lost to follow-up. The mean glycated hemoglobin (HbA1c) at the time of admission was found to be statistically significant when compared between known diabetics and newly diagnosed ones [confidence interval (CI)-95%, p ≤ 0.01]. A total of seven patients from the newly diagnosed diabetic group no longer required medicines for diabetes at the end of 1 year (CI-95%, p ≤ 0.01). Diabetes mellitus, particularly with poor glycemic control, was the single most important factor associated with and predictor of outcome. Contrary to the popular hypothesis, industrial oxygen and oxygen masks were not the reasons for the mucormycosis pandemic. Additionally, immunization against COVID provided protection not only from severe COVID but also from COVID-associated mucormycosis. It is recommended that patients with mucormycosis be followed for longer periods as a few patients could be suffering from transient diabetes, particularly against the backdrop of a pandemic.

Renal Cell Carcinoma of Variant Histology: New Biologic Understanding Leads to Therapeutic Advances.

Renal cell carcinoma (RCC) is one of the 10 most commonly diagnosed solid tumors. Most RCCs are histologically defined as clear cell, comprising approximately 75% of diagnoses. However, the remaining RCC cases are composed of a heterogeneous combination of diverse histopathologic subtypes, each with unique pathogeneses and clinical features. Although the therapeutic approach to both localized and metastatic RCCs has dramatically changed, first with the advent of antiangiogenic targeted therapies and more recently with the approval of immune checkpoint inhibitor (ICI)-based combinations, these advances have primarily benefited the clear cell RCC patient population. As such, there remains critical gaps in the optimization of treatment regimens for patients with non-clear cell, or variant, RCC histologies. Herein, we detail recent advances in understanding the biology of RCC with variant histology and how such findings have guided novel clinical studies investigating precision oncology approaches for these rare subtypes. Among the most common variant histology RCCs are papillary RCC, comprising approximately 15%-20% of all diagnoses. Although a histopathologically diverse subset of tumors, papillary RCC is canonically associated with amplification of the MET protooncogene; recently completed and ongoing trials have investigated MET-directed therapies for this patient population. Finally, we discuss the unique biology of RCC with sarcomatoid dedifferentiation and the recent clinical findings detailing its paradoxical sensitivity to ICIs.

Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). This study included young adult patients aged 18-40years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. A total of 300 RCC patients aged 18-40years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4±6.1years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p<0.001). There was no statistically significant difference observed in overall survival (OS) (p=0.069). Pathological stage was a significant independent predictor for OS (p=0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p=0.020; p=0.005). The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Laparoscopic nephron-sparing surgery for complex renal cystic lesions: a single-center experience.

This study aimed to explore the feasibility and safety of laparoscopic nephron-sparing surgery (LNSS) for complex renal cystic lesions. A retrospective study was conducted on 83 cases of complex renal cystic lesions treated with LNSS in our hospital. There were 32 men and 51 women, ranging in age from 24 to 73years (average, 47.22±9.03years). The diameter of the cysts was 1.5-5.9cm (average, 3.44±0.86cm). According to the Bosniak classification, there were 15 cases of type II, 23 cases of type IIF, 29 cases of type III, and 16 cases of type IV complex renal cystic lesions. According to clinical classification based on the difficulty of laparoscopic partial nephrectomy and the depth of the lesion, the 83 complex renal cystic lesions were divided into 48 cases of the extra-renal type, 15 cases of the centrally located type, seven cases of the renal sinus type, and 13 cases of the renal hilum type. Laparoscopic partial nephrectomy was successful in all 83 patients. The surgical time was 35-102min (average, 52.13±14.38min), the intraoperative bleeding volume was 10-200ml (average, 27.25±12.26ml), and the renal artery occlusion time was 12-28min (average, 12.46±4.45min). There was no significant change in creatinine before and after surgery. The postoperative pathological results showed 71 cases of renal clear cell carcinoma, five cases of low malignant potential multilocular cystic renal tumors, and seven cases of pure renal cysts with all margins negative. There is potential for the malignant transformation of complex renal cysts into renal cell carcinoma. For complex renal cysts classified as Bosniak IIF or higher, surgical intervention is recommended, and LNSS is safe and effective. The complexity of the surgical procedure varies depending on the location classification of the complex renal cysts.

Fumarate hydratase-deficient renal cell carcinoma: an oncology care institutional experience.

Renal cell carcinoma (RCC) accounts for 2% of all cancer cases worldwide, and majority are sporadic. The latest World Health Organization (WHO) classification of renal cell tumors (fifth edition, 2022) has molecularly defined renal tumor entities, which includes fumarate hydratase (FH)-deficient RCC. FH-deficient RCC is an aggressive carcinoma caused by pathogenic alterations in FH gene, seen in 15% of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) syndrome. These tumors occur more frequently at a younger age and present at an advanced stage, carrying a dismal prognosis. We report a series of 10 cases of FH-deficient RCC. The mean age was 49.8 years, and all cases presented in advanced stages (III and IV). Morphologically, the cases had varied architectural patterns with characteristic eosinophilic macronucleoli and perinucleolar halo. On immunohistochemistry (IHC), all showed diffuse nucleo-cytoplasmic expression of S-(2-succino)-cysteine (2-SC), with loss of FH in seven cases. FH-deficient RCCs are aggressive neoplasms and can be diagnosed using specific IHC markers (FH and 2-SC). These patients should undergo germline testing for FH gene mutation, genetic counseling, and surveillance of family members.

Construction of a Model for Predicting the Risk of pT3 Based on Perioperative Characteristics in cT1 Renal Cell Carcinoma: A Retrospective Study at a Single Institution

IntroductionThis study explored the predictors of upstaging and multiple sites of extension, and constructed a predictive model based on perioperative characteristics to calculate the risk of upstaging of cT1 renal cell carcinoma to pT3. MethodsWe retrospectively reviewed 1012 patients diagnosed with cT1 renal cell carcinoma who underwent surgical treatment at the Affiliated Hospital of Qingdao University between June 2016 and August 2021. The continuous and categorical variables were analyzed using the Mann–Whitney U test and Chi-square test, respectively. After randomly dividing patients into a training set and an internal validation set with a ratio of 7:3, univariate and multivariate logistic regression analyses were used to explore the predictors of upstaging and multiple sites of extension. A nomogram model was established based on the predictors of upstaging and was validated. ResultsNinety-one cases (8.99%) of renal cell carcinoma were upstaged to pT3. In the training set, multivariate logistic regression identified the following predictors of upstaging: maximum tumor diameter, hilus involvement, tumor necrosis, tumor edge irregularity, symptoms, smoking, and platelet–lymphocyte ratio. A nomogram model was established based on the predictors. The area under the receiver operating characteristic curve was 0.810 in the training set, and 0.804 in the validation set. A 10-fold internal cross-validation conducted 200 times showed that the mean area under the curve was 0.797. The calibration curve and decision curve analysis suggested that the nomogram had robust clinical predictive power. Analyses showed higher neutrophil–lymphocyte ratio and tumor necrosis were associated with multiple sites of extrarenal extension in patients with pT3a renal cell carcinoma. ConclusionsWe identified 7 predictors of upstaging to pT3 and 2 predictors of multiple sites of extension. A nomogram model was constructed with satisfactory accuracy for predicting upstaging to pT3.

Detection of two synchronous histologically different renal cell carcinoma subtypes in the same kidney:a case report and review of the literature.

Renal cell carcinoma (RCC) is the dominant primary renal malignant neoplasm, encompassing a significant portion of renal tumors. The presence of synchronous yet histologically distinct ipsilateral RCCs, however, is an exceptionally uncommon phenomenon that is rather under-described in the literature regarding etiology, diagnosis, management, and later outcomes during follow-up. We aim to present the 9th case of a combination chromophobe RCC (ChRCC) and clear cell RCC (ccRCC) in literature, according to our knowledge, for a 69-year-old North African, Caucasian female patient who, after complaining of loin pain and hematuria, was found to have two right renal masses with preoperative computed tomography (CT) and underwent right radical nephrectomy. Pathological examination later revealed the two renal masses to be of different histologic subtypes. The coexistence of dissimilar RCC subtypes can contribute to diverse prognostic implications. Further research should focus on enhancing the complex, yet highly crucial, preoperative detection and pathological examination to differentiate multiple renal lesions. Planning optimal operative techniques (radical or partial nephrectomy), selecting suitable adjuvant regimens, and reporting long-term follow-up outcomes of patients in whom synchronous yet different RCC subtypes were detected are of utmost importance.

An epidemiological and clinicopathological study of type 1 vs. type 2 morphological subtypes of papillary renal cell carcinoma– results from a nation-wide study covering 50 years in Iceland

IntroductionPapillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10–15% of cases. Traditionally, pRCC is divided into type 1 and type 2, although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period.Materials and methodsA Population based retrospective study including consecutive cases of RCC in Iceland from 1971–2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan–Meier method and Cox regression were used for outcome analysis.ResultsA total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p < 0.001). Age standardized cancer specific mortality (ASCSM) of pRCC was 0.6/100.000 and 0.19/100.000 for males and females, respectively. The annual average increase in ASI was 3.6% for type 1 pRCC, but the ASI for type 2 pRCC and ASCSM for both subtypes did not change significantly. Male to female ratio was 4.4 for type 1 pRCC and 2.3 for type 2. The average tumor size for type 1 and 2 was 58.8 and 73.7 mm, respectively. Metastasis at diagnosis was found in 8.7% in the type 1 pRCC, compared to 30.0% of patients with type 2 pRCC (p < 0.001). Estimated 5-year cancer-specific survival (CSS) were 94.4%, 80.7%, and 69.3% for chRCC, pRCC and ccRCC, respectively (p < 0.001). For the pRCC subtypes, type 1 was associated with better 5-year CSS than type 2 (86.3% vs. 66.0%, p < 0.001), although this difference was not significant after adjusting for cancer stage and grading.ConclusionspRCC histology was slightly less common in Iceland than in other countries. Males are more than three times more likely to be diagnosed with pRCC, compared to other RCC histologies. The subtype of pRCC was not found to be an independent risk factor for worse survival, and as suggested by the most recent WHO Classification of Urinary Tumors, grade and TNM-stage seem to be the most important factors for estimation of survival for pRCC patients.

Acetylation- and ubiquitination-regulated SFMBT2 acts as a tumor suppressor in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (RCC) is the most common kidney tumor. The analysis from medical database showed that Scm-like with four MBT domains protein 2 (SFMBT2) was decreased in advanced clear cell RCC cases, and its downregulation was associated with the poor prognosis. This study aims to investigate the role of SFMBT2 in clear cell RCC.MethodsThe expression of SFMBT2 in clear cell RCC specimens were determined by immunohistochemistry staining and western blot. The overexpression and knockdown of SFMBT2 was realized by infection of lentivirus loaded with SFMBT2 coding sequence or silencing fragment in 786-O and 769-P cells, and its effects on proliferation and metastasis were assessed by MTT, colony formation, flow cytometry, wound healing, transwell assay, xenograft and metastasis experiments in nude mice. The interaction of SFMBT2 with histone deacetylase 3 (HDAC3) and seven in absentia homolog 1 (SIAH1) was confirmed by co-immunoprecipitation.ResultsIn our study, SFMBT2 exhibited lower expression in clear cell RCC specimens with advanced stages than those with early stages. Overexpression of SFMBT2 inhibited the growth and metastasis of clear cell RCC cells, 786-O and 769-P, in vitro and in vivo, and its silencing displayed opposites effects. HDAC3 led to deacetylation of SFMBT2, and the HDAC3 inhibitor-induced acetylation prevented SFMBT2 from SIAH1-mediated ubiquitination modification and proteasome degradation. K687 in SFMBT2 protein molecule may be the key site for acetylation and ubiquitination.ConclusionsSFMBT2 exerted an anti-tumor role in clear cell RCC cells, and HDAC3-mediated deacetylation promoted SIAH1-controlled ubiquitination of SFMBT2. SFMBT2 may be considered as a novel clinical diagnostic marker and/or therapeutic target of clear cell RCC, and crosstalk between its post-translational modifications may provide novel insights for agent development.

The effectiveness of the combination of lenvatinib and everolimus in metastatic renal cell carcinoma in patients with resistance to targeted treatment in real clinical practice

Every year, 400,000 new cases of renal cell carcinoma (RCC) and 175,000 deaths are registered worldwide. Currently available advanced treatments for RCC have less toxicity than previously used therapeutic agents, but drug resistance remains a clinically significant problem. Drug resistance occurs as a result of angiogenic transition through activation of pathways that do not depend on VEGF targets of most first-line treatments. Lenvatinib with everolimus can fight resistance to increase both progression-free survival and overall survival in patients with metastatic RCC according to clinical studies.

A pediatric and young adult case of unclassified renal cell carcinoma with medullary phenotype (RCCU-MP): Clinical course and treatment

Renal cell carcinoma (RCC) is the most common kidney tumor in adults. RCC is rare in children, although its incidence increases in the second decade of life. Renal medullary carcinoma (RMC) is a rare and often aggressive RCC subtype characterized by complete loss of SMARCB1/INI1, predominantly diagnosed in patients with sickle cell disease or -trait. Here, we describe a pediatric and a young adult patient with clinicopathological characteristics similar to RMC but without hemoglobinopathies. These tumors are currently classified as “RCC unclassified with medullary phenotype” (RCCU-MP). Both our patients had an infiltrating, rather small kidney tumor with SMARCB1/INI1 deficiency. Remarkably, the aggressiveness and clinical course and treatment differed greatly between these two cases. So far, only nine patients, predominantly adults, have been reported. In a literature overview, most cases were metastatic and progressed or relapsed after varying treatment approaches, with low survival. Whereas the classification of these tumors remains a topic of debate, case reports add to the current knowledge of RMCs without hemoglobinopathies, stressing the importance of sharing experience concerning rare renal neoplasms with often poor outcomes, also concerning younger age categories.

Fumarate Hydratase-Deficient Renal Cell Carcinoma—A Clinicopathological Study of a Series of 11 Cases

Abstract Introduction Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare, molecularly defined renal tumor with aggressive behavior. The diagnosis of these tumors is challenging because of varied morphology and limited access to molecular testing and immunohistochemistry (IHC) for FH and 2-succinocysteine. We aim to elucidate the histomorphology, clinical presentation, and follow-up of this tumor in this first series of cases of FH-deficient RCCs from India. Objectives This article aims to understand and elucidate the clinical presentation, pathologic findings, treatment options, and outcomes of FH-deficient RCC. Materials and Methods Diagnosed cases of FH-deficient RCC between January 2021 and January 2023 including clinical details were retrieved from the electronic medical record database. Histopathological and immunohistochemical slides were reviewed. Results Out of 11 cases of FH-deficient RCC, 36% had been referred with a diagnosis of type 2 papillary RCC. One patient presented with metastatic disease. All had mixed histologic patterns with the predominant pattern being papillary and showed FH loss on IHC. The classically described inclusion like nucleoli was present only focally in most cases. A subset of tumors had low-grade solid-nested morphology and these patients presented at an earlier stage (T2a). Two patients on multikinase inhibitors are alive with disease at 14 months' follow-up. Conclusion FH-deficient RCCs can have varied histologic patterns within the same tumor and show loss of FH expression by IHC. A subset has low grade morphology and tends to have a more indolent course. It is important to have a high index of suspicion for this diagnosis due to its varied histological appearance and aggressive behavior.

Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes.

Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses. Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have clear cell RCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository, of whom 184 had RCC. We assessed the relationship between pKIM-1, surgical pathology, and clinical outcomes. In Cohort 1, pKIM-1 distinguished RCC versus benign masses with area under the receiver operating curve (AUC-ROC, 0.81 [95% CI, 0.76 to 0.86]). In Cohort 2 (cT1a only), pKIM-1 distinguished RCC versus benign masses (AUC-ROC, 0.74 [95% CI, 0.67 to 0.80]) and the addition of pKIM-1 to an established nomogram for predicting malignancy improved the model AUC-ROC (0.65 [95% CI, 0.57 to 0.74] v 0.78 [95% CI, 0.72 to 0.85]). A pKIM-1 cutpoint identified using Cohort 2 demonstrated sensitivity of 92.5% and specificity of 60% for identifying RCC in Cohort 1. In long-term follow-up of RCC cases (Cohort 1), higher prenephrectomy pKIM-1 was associated with worse metastasis-free survival (multivariable MFS hazard ratio [HR] 1.29 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.53) and overall survival (multivariable OS HR 1.31 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.54). In long-term follow-up of Cohort 2, no metastatic events occurred, consistent with the favorable prognosis of resected cT1a RCC. Among patients with renal masses, pKIM-1 is associated with malignant pathology, worse MFS, and risk of death. pKIM-1 may be useful for selecting patients with renal masses for intervention versus surveillance.