Renal Oncocytoma Research Articles

Characteristics of renal oncocytomas and clinical novelties: Single center experience of 17 years.

To assess the characteristics of renal oncocytomas and the clinical outcomes of patients in the last 17 years in our institution. The medical records of the patients who underwent partial and radical nephrectomy from May 2004 to December 2021 were evaluated retrospectively. Radiology and pathology results were evaluated. Patients diagnosed with oncocytoma after surgery were included in the study. Out of 791 patients who were operated for renal masses, 55 patients with the diagnosis of oncocytoma were included in the study, 17 of them were female. The mean age of the patients was 64.77 ± 10.58 years. Open and laparoscopic methods were applied to patients. Partial nephrectomy was performed in 25 patients (46.2%). It was observed that none of the patients with a mean follow-up of 76 months developed recurrence or death due to oncocytoma. Oncocytoma is a benign and rare tumor of the kidney which distinguishing it from malign tumors preoperatively with recent techniques is impossible. Especially in small sized tumors, considering the possibility of oncocytoma, nephron sparing surgery should be preferred in terms of patients' benefit. Further research is needed for the novel imaging techniques and biomarkers proposed to be used in routine use to distinguish oncocytoma.

Renal Oncocytoma Presenting as a Huge Hypervascular Mass on Ultrasound

With the increasing use of ultrasonography, renal incidentaloma cases have also been rising. A solid renal mass observed incidentally will either be malignant or benign. Of malignant renal tumors, renal cell carcinoma (RCC) is the most common. The two most common benign tumors that need to be differentiated from RCC are oncocytoma and angiomyolipoma. It is difficult to differentiate benign from malignant tumors on ultrasonography. Furthermore, there are also difficulties distinguishing oncocytoma from RCC due to the nonspecific clinical presentation and overlapping imaging findings. Thus, renal oncocytomas are often removed by nephrectomy despite their benign nature. We report the case of a tumor that was suspected to be RCC preoperatively on ultrasonography and computed tomography but was diagnosed as oncocytoma postoperatively.

Endoscopic Endonasal Approach to Cavernous Sinus Hemangioma: A Report of Two Cases and Review of the Literature

Cavernous sinus hemangiomas (CSHs) are rare, benign, slow-growing neoplasms within the cavernous sinus. Laterally located to these lesions, the cranial nerves and carotid artery are subject to injury during removal of hemangiomas through a transcranial route. Therefore, forsurgi- cal management of cavernous sinus hemangiomas a medial corridor granted through an endoscop- ic endonasal approach may be less traumatic to the neurovascular bundle.
 Case-1 describes a 23-year old male who presented with intermittent blurred vision and very mild ptosis on the right side for two yearsbefore admission. Fundoscopic exam, visual acuity and perimetry tests were normal. With intense enhancement after contrastadministration, both brain MRI and CT scan demonstrated an extra-axial mass in the right cavernous sinus.
 Case-2 presents a 59-year-old male, a known case of renal oncocytoma who underwent nephrec- tomy a year before, with chief complain ofmoderate intermittent headaches. Imaging study of the brain by MRI revealed a sellar mass.
 Near-total resection for case-1 and gross total resection for case-2 were performed through the an extended endoscopic endonasal approach.
 We report two cases of near-total and gross total resection of CSHs via an extend- ed endoscopic endonasal approach substantiatingadvances in minimal access neurosurgery to the treatment of such grim lesions of an intricate vicinity of the skull base. At the same time, we focus to review extensively the growing yet heterogenous literature of the past twenty
 years on the broached topic. The evolution of extended endoscopic endonasal approach over the past two decades changes the dynamism of the surgical practices steeped in tradition and provides a safer alternate route for preserving cranial nerves of this anatomic region.

ODP049 Oncocytic adrenocortical carcinoma misdiagnosed as renal oncocytoma and use of urinary steroid profiling in disease monitoring after mitotane therapy

Abstract Introduction Oncocytic adrenocortical carcinoma (OAC) is a rare, more indolent variant of adrenocortical carcinoma (ACC). With fewer than 70 cases reported in the English literature, the biological behavior and its response to treatment are poorly characterized. The distinction of OAC from other oncocytic neoplasms (e. g., kidneys) and variants of renal cell carcinoma (RCC) may pose diagnostic challenge pathologically. Urine steroid profiling (USP) of OAC has not been previously reported. Case description A 65-year-old Chinese man was incidentally found to have a large left upper abdominal mass in September 2014. A CT urogram showed a 15×13×13cm solid mass in the upper pole of left kidney. Left radical nephrectomy and splenectomy was performed. Pathological examination of the 'nephrectomy' showed oncocytoma. He was managed as having a renal oncocytoma with complete resection with yearly follow-up. In December 2018, a surveillance chest X-ray showed multiple lung nodules over right lung base. PET-CT in June 2019 showed bilateral hypermetabolic lung nodules suggestive of lung metastases. CT guided fine needle aspiration biopsy of lung nodule showed oncocytoma. Pathology review of both the lung and 'nephrectomy' biopsy revealed identical cores of oncocytic tumor cells while immunohistochemical studies displayed positivity for SF-1 and Melan-A suggestive of adrenocortical origin. In the presence of lung metastases, a revised diagnosis of OAC was made with the original tumor classified as oncocytic adrenocortical neoplasm of uncertain malignant potential by the Lin-Weiss-Bisceglia system. Hormonally the tumor was non-functional with suppressible cortisol post 1mg overnight dexamethasone suppression test and normal renin, aldosterone, estradiol and DHEA-S levels. Twenty-four-hour urine steroid profiling showed elevated tetrahydro-11-deoxycortisol 788ug/day [RR 10-90µg /day], pregnanediol 374µg /day [RR 41-348µg/day] and pregnenetriol 487µg /day [RR 25-256µg /day]. Mitotane was started and titrated up to 1500mg daily, aiming at a serum mitotane level of 14- 20µg /ml. Resolution of lung metastases was noted 6 months later and the abnormal urinary steroid metabolites were also normalized. The patient remained in disease remission 18 months after commencement of mitotane. Conclusion Oncocytic adrenocortical carinoma may be mistaken as other oncocytic neoplasms or variants of RCC pathologically and is classified by the Lin-Weiss-Bisceglia system. An accurate diagnosis has significant impact on disease prognostication and management. OAC may respond more favorably to mitotane monotherapy in comparison to typical ACC. Urine steroid profiling is potentially useful in the surveillance and disease monitoring of OAC. Reference: (1) Harada et al. A rare case of oncocytic adrenocortical carcinoma clinically presented as an incidentaloma. Endocr J. 2020 Aug 28;67(8): 883-888. Presentation: No date and time listed

Differentiating Oncocytic Renal Tumors from Chromophobe Renal Cell Carcinoma: Comparison of Peak Early-phase Enhancement Ratio to Clinical Risk Factors and Rater Predictions

BackgroundMost surgically resected benign renal tumors are found to be oncocytomas or indolent hybrid oncocytic tumors, which are difficult to differentiate from chromophobe renal cell carcinoma (chRCC) on renal mass biopsy. Both often exhibit CD117+ staining. ObjectiveTo evaluate the ability of the peak early-phase enhancement ratio (PEER) to distinguish oncocytomas from chRCC and compare its discrimination to traditional clinical risk factors and blinded clinical raters. Design, setting, and participantsThis was a diagnostic case-control study of patients (2006–2020) with oncocytoma or chRCC according to surgical pathology. InterventionPartial or radical nephrectomy. Outcome measurements and statistical analysisThree clinical raters blinded to histology measured the PEER and the presence of stellate scar and predicted the final histology for each tumor. Averaged and individual PEER values were compared to surgical pathology and assessed for interobserver variability. Subanalyses were conducted for patients with confirmed CD117+ status. Results and limitationsFor the 76 patients identified, PEER was higher among the 32 (42.1%) oncocytomas than among the 44 (57.9%) chRCCs (median 0.81 vs 0.43; p < 0.001), with high correlation across raters (correlation coefficients ≥0.85). A PEER cutoff of <0.60 was strongly associated with identification of chRCC (OR 95.7 (95% CI 19.9–460.8), p < 0.001). In the overall and CD117+ cohorts, sensitivity was 93.2% and 97.0%, the negative predictive value was 90.3% and 95.5%, and the area under the receiver operating characteristic curve (AUC) on multivariable modeling was 95.0% and 98.1%, respectively. PEER outperformed models with clinical risk factors alone (AUC 70.4%) and histology predictions by three raters (AUC 51.6%, 62.5%, and 63.1%). Limitations include reliance on surgical pathology and inclusion of a mix of early contrast-enhanced phases. ConclusionsPEER reliably differentiated benign renal oncocytomas and indolent hybrid tumors from malignant chRCC with excellent diagnostic performance. A diagnostic pathway with biopsy, CD117 staining, and PEER deserves further study to potentially avoid unnecessary surgery for oncocytic renal tumors. Patient summaryWe assessed a measurement called PEER on computed tomography (CT) scans and found higher values for benign and lower values for malignant kidney masses, so we were able to tell these apart. PEER was reliable for identifying tumors with positive staining for the CD117 protein biomarker as well as in the overall patient group. Our results show that PEER could be considered for use with biopsy and CD117 staining to potentially avoid unnecessary surgery for benign kidney masses.

Characterization of Intercalated Cell Markers KIT and LINC01187 in Chromophobe Renal Cell Carcinoma and Other Renal Neoplasms.

Introduction. Chromophobe renal cell carcinoma (chromophobe RCC) is the third major subcategory of renal tumors after clear cell RCC and papillary RCC, accounting for approximately 5% of all RCC subtypes. Other oncocytic neoplasms seen commonly in surgical pathology practice include the eosinophilic variant of chromophobe RCC, renal oncocytoma, and low-grade oncocytic unclassified RCC. Methods. In our recent next-generation sequencing based study, we nominated a lineage-specific novel biomarker LINC01187 (long intergenic non-protein coding RNA 1187) which was found to be enriched in chromophobe RCC. Like KIT (cluster of differentiation 117; CD117), a clinically utilized chromophobe RCC related biomarker, LINC01187 is expressed in intercalated cells of the nephron. In this follow-up study, we performed KIT immunohistochemistry and LINC01187 RNA in situ hybridization (RNA-ISH) on a cohort of chromophobe RCC and other renal neoplasms, characterized the expression patterns, and quantified the expression signals of the two biomarkers in both primary and metastatic settings. Results. LINC01187, in comparison to KIT, exhibits stronger and more uniform expression within tumors while maintaining temporal and spatial consistency. LINC01187 also is devoid of intra-tumoral heterogeneous expression pattern, a phenomenon commonly noted with KIT. Conclusions. LINC01187 expression can augment the currently utilized KIT assay and help facilitate easy microscopic analyses in routine surgical pathology practice.

Eosinophilic solid and cystic renal cell carcinoma: a review of literature focused on radiological findings and differential diagnosis.

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a rare type of renal cell carcinoma with inert biological behavior that has not yet been included in the 2016 World Health Organization (WHO) classification, and its imaging manifestations are unclear due to its rarity. Although there have only been a few cases, the CT and MRI findings of ESC-RCC are characterized by its cystic solid structure, according to the proportion of cystic and solid components observed on images, ESC-RCC can be categorized into three types. Especially the Type I, when the cystic-solid components are almost equal, the imaging findings are illustrated as "lotus root-like," which may be helpful in the differential diagnosis of ESC-RCC from other types of renal tumors. In fact, ESC-RCC has diverse radiological appearances, and the differentiation of clear cell renal cell carcinoma, renal oncocytoma, chromophobe renal cell carcinoma, and renal angiomyolipoma remains challenging. This review aims to discuss ESC-RCC with a focus on the radiological findings and differential diagnosis of ESC-RCC.

CK7+/CD117- low grade oncocytic tumor of the kidney: a clinicopathological analysis

Objective: To investigate the clinicopathological, immunohistochemical and molecular characteristics of low grade oncocytic tumors (LOT) of the kidney with CK7+/CD117- staining pattern for enhancing the understanding of renal LOT. Methods: The clinical data, histological morphology and immunophenotypes of seven renal LOT cases diagnosed at the Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine from January 2017 to April 2021 were analyzed. The patients were followed up. Among the seven patients, five underwent high-throughput DNA targeted sequencing, and their molecular characteristics were analyzed. Results: The patients' age ranged 59-82 years, with an average of 70 years. There were 2 males and 5 females. The boundary of the tumor was clear. The tumor cells had homogeneous eosinophilic cytoplasm and round or oval nuclei, with a perinuclear halo. Small basophilic nucleoli were conspicuous (WHO/International Society of Urological Pathology grade 2). In the hypercellular areas, the tumor cells were mainly arranged in dense solid or nest. In the stroma, there were dilated veins, thick-walled arterioles and thick collagen fiber bundles that divided the cells into pseudonodules. In the sparsely cellular area, the tumor cells were arranged in the so-called "tissue culture" fashion. In addition, the stroma contained fresh hemorrhagic foci and lymphoid aggregates. High-throughput sequencing of 5 cases revealed that one case harbored mTOR gene missense mutation and another case harbored TSC1 frameshift mutation. Conclusions: LOT of the kidney is an indolent tumor with an overall good prognosis. Pathologists should not misdiagnose it as renal oncocytoma and chromophobe renal cell carcinoma.

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging: Diagnostic Pathways and Metabolites for Renal Tumor Entities

Background: Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone. Nevertheless, some diagnoses are difficult, and further investigations are needed for correct tumor subtyping. Besides histochemical investigations, high-mass-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can detect new diagnostic biomarkers and hence improve the diagnostic. Patients and Methods: Formalin-fixed paraffin embedded tissue specimens from clear cell renal cell carcinoma (ccRCC, n = 552), papillary renal cell carcinoma (pRCC, n = 122), chromophobe renal cell carcinoma (chRCC, n = 108), and renal oncocytoma (rO, n = 71) were analyzed by high-mass-resolution MALDI fourier-transform ion cyclotron resonance (FT-ICR) MSI. The SPACiAL pipeline was executed for automated co-registration of histological and molecular features. Pathway enrichment and pathway topology analysis were performed to determine significant differences between RCC subtypes. Results: We discriminated the four histological subtypes (ccRCC, pRCC, chRCC, and rO) and established the subtype-specific pathways and metabolic profiles. rO showed an enrichment of pentose phosphate, taurine and hypotaurine, glycerophospholipid, amino sugar and nucleotide sugar, fructose and mannose, glycine, serine, and threonine pathways. ChRCC is defined by enriched pathways including the amino sugar and nucleotide sugar, fructose and mannose, glycerophospholipid, taurine and hypotaurine, glycine, serine, and threonine pathways. Pyrimidine, amino sugar and nucleotide sugar, glycerophospholipids, and glutathione pathways are enriched in ccRCC. Furthermore, we detected enriched phosphatidylinositol and glycerophospholipid pathways in pRCC. Conclusion: In summary, we performed a classification system with a mean accuracy in tumor discrimination of 85.13%. Furthermore, we detected tumor-specific biomarkers for the four most common primary renal tumors by MALDI-MSI. This method is a useful tool in differential diagnosis and biomarker detection.

LOT and HOT … or not. The proliferation of clinically insignificant and poorly characterised types of renal neoplasia

The classification of malignant tumours is influenced by both immunohistochemical and molecular genetic findings. This is highlighted in the latest World Health Organization classification of renal neoplasia, which has a tumour category of 'tumours that are molecularly defined'. This implies that the defining molecular features are integral to tumourigenesis, which may not necessarily be the case. Renal oncocytoma is recognised as a benign tumour with variable morphology and immunoexpression. A variant of these tumours is hybrid oncocytic chromophobe tumour, which has features of both oncocytoma and chromophobe renal cell carcinoma and may, on rare occasions, show malignant behaviour. Recent reports have proposed two further entities with eosinophilic cytoplasm and varying nuclear pleomorphism, designated low grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT), formally known as high grade oncocytic tumour (HOT). The diagnosis of these apparently benign tumours was made on the basis of morphological and immunohistochemical features. More recently it has been claimed that the mutations in the mTOR pathway are also a diagnostic feature and it is further suggested that these mutations are key to the pathogenesis of these tumours. As is seen in oncocytoma, immunohistochemical expression of tumours included in series of LOT and EVT is variable. The mutations in the mTOR pathway, where detected, were not constant, with any combination of mTOR, TSC1 and/or TSC2 being involved. A major issue is that in many of the studies full comparative genomic hybridisation results are not presented. In addition it is well recognised that mTOR mutations are seen in a variety of renal tumours. In view of these conflicting results, the rarity of these tumours and their apparent benign nature, raises questions as to why these tumours should be considered specific entities.

Algorithm-Based Approach to the Histological Routine Diagnosis of Renal Oncocytic Tumors in Core Biopsy Specimens.

A growing number of tumor entities with badly defined limits are enlarging in the last years the family of oncocytic tumors in the kidney. Chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO) are classically well-known tumors, but the borderland between them, and their precise connection, remains a matter of debate. Aside from that, other emerging and provisional entities, like eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumor (EVT), low-grade oncocytic tumor (LOT), and papillary renal neoplasm with reverse polarity (PRRP), have been recently described. This spectrum of tumors remains a diagnostic challenge in renal pathology, especially if the specimen obtained is scarce. This review focuses on practical diagnostic problems when managing core biopsies and proposes a diagnostic algorithm maximizing the information provided by both morphology and immunohistochemistry. So, a combination of morphologic features on hematoxylin-eosin and six antibodies (CK7, CD117, CK20, CD10, GATA-3, and cathepsin K) is advised to be used in a stepwise fashion.

A triple-classification for differentiating renal oncocytoma from renal cell carcinoma subtypes and CK7 expression evaluation: a radiomics analysis

BackgroundTo investigate the value of computed tomography (CT)-based radiomics model analysis in differentiating renal oncocytoma (RO) from renal cell carcinoma subtypes (chromophobe renal cell carcinoma, clear cell carcinoma) and predicting the expression of Cytokeratin 7 (CK7).MethodsIn this retrospective study, radiomics was applied for patients with RO, chRCC and ccRCC who underwent surgery between January 2013 and December 2019 comprised the training cohort, and the testing cohort was collected between January and October 2020. The corticomedullary (CMP) and nephrographic phases (NP) were manually segmented, and radiomics texture parameters were extracted. Support vector machine was generated from CMP and NP after feature selection. Shapley additive explanations were applied to interpret the radiomics features. A radiomics signature was built using the selected features from the two phases, and the radiomics nomogram was constructed by incorporating the radiomics features and clinical factors. Receiver operating characteristic curve was calculated to evaluate the above models in the two sets. Furthermore, Rad-score was used for correlation analysis with CK7.ResultsA total of 123 patients with RO, chRCC and ccRCC were analyzed in the training cohort and 57 patients in the testing cohort. Subsequently, 396 radiomics features were selected from each phase. The radiomics features combining two phases yielded the highest area under the curve values of 0.941 and 0.935 in the training and testing sets, respectively. The Pearson’s correlation coefficient was statistically significant between Rad-score and CK7.ConclusionWe proposed a non-invasive and individualized CT-based radiomics nomogram to differentiation among RO, chRCC and ccRCC preoperatively and predict the immunohistochemical protein expression for accurate clinical diagnosis and treatment decision.

99mTc-Sestamibi SPECT/CT and histopathological features of oncocytic renal neoplasia

Background 99mTc-Sestamibi Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) contributes to the non-invasive differentiation of renal oncocytoma (RO) from renal cell carcinoma (RCC) by characterising renal tumours as Sestamibi positive or Sestamibi negative regarding their 99mTc-Sestamibi uptake compared to the non-tumoral renal parenchyma. Purpose To determine whether 99mTc- Sestamibi uptake in renal tumour and the non-tumoral renal parenchyma measured using Standard Uptake Value (SUV) SPECT, has a beneficial role in differentiating RO from RCC. Material and Methods Fifty-seven renal tumours from 52 patients were evaluated. In addition to visual evaluation of 99mTc-Sestamibi uptake, SUVmax measurements were performed in the renal tumour and the ipsilateral non-tumoral renal parenchyma. Analysis of the area under the receiver operating characteristic curve identified an optimal cut-off value for detecting RO, based on the relative ratio of 99mTc- Sestamibi uptake. Results Semiquantitative evaluation of 99mTc-Sestamibi uptake did not improve the performance of 99mTc- Sestamibi SPECT/CT in detecting RO. 99mTc- Sestamibi SPECT/CT identifies a group of mostly indolent Sestamibi-positive tumours with low malignant potential containing RO, Low-Grade Oncocytic Tumours, Hybrid Oncocytic Tumours, and a subset of chromophobe RCCs. Conclusion The imaging limitations for accurate differentiation of Sestamibi-positive renal tumours mirror the recognised diagnostic complexities of the histopathologic evaluation of oncocytic neoplasia. Patients with Sestamibi-positive renal tumours could be better suited for biopsy and follow-up, according to the current active surveillance protocols.

Comparative Analysis for the Distinction of Chromophobe Renal Cell Carcinoma from Renal Oncocytoma in Computed Tomography Imaging Using Machine Learning Radiomics Analysis.

Simple SummaryChromophobe renal cell carcinoma (ChRCC) is the 3rd most common subtype of renal cell carcinoma (RCC), which is difficult to differentiate from benign renal oncocytoma (RO) using conventional imaging techniques. The aim of this study was to differentiate chromophobe renal cell carcinoma and renal oncocytoma non-invasively using radiomics features extracted from pre-operative computed tomography (CT) scan images in combination with machine learning (ML) techniques for classification. This would help in providing “virtual biopsy” and may prevent unnecessary surgical resection for benign renal oncocytoma tumors.Background: ChRCC and RO are two types of rarely occurring renal tumors that are difficult to distinguish from one another based on morphological features alone. They differ in prognosis, with ChRCC capable of progressing and metastasizing, but RO is benign. This means discrimination of the two tumors is of crucial importance. Objectives: The purpose of this research was to develop and comprehensively evaluate predictive models that can discriminate between ChRCC and RO tumors using Computed Tomography (CT) scans and ML-Radiomics texture analysis methods. Methods: Data were obtained from 78 pathologically confirmed renal masses, scanned at two institutions. Data from the two institutions were combined to form a third set resulting in three data cohorts, i.e., cohort 1, 2 and combined. Contrast-enhanced scans were used and the axial cross-sectional slices of each tumor were extracted from the 3D data using a semi-automatic segmentation technique for both 2D and 3D scans. Radiomics features were extracted before and after applying filters and the dimensions of the radiomic features reduced using the least absolute shrinkage and selection operator (LASSO) method. Synthetic minority oversampling technique (SMOTE) was applied to avoid class imbalance. Five ML algorithms were used to train models for predictive classification and evaluated using 5-fold cross-validation. Results: The number of selected features with good model performance was 20, 40 and 6 for cohorts 1, 2 and combined, respectively. The best model performance in cohorts 1, 2 and combined had an excellent Area Under the Curve (AUC) of 1.00 ± 0.000, 1.00 ± 0.000 and 0.87 ± 0.073, respectively. Conclusions: ML-based radiomics signatures are potentially useful for distinguishing ChRCC and RO tumors, with a reliable level of performance for both 2D and 3D scanning.

Succinate dehydrogenase B-deficient renal cell carcinoma with a germline variant in a Japanese patient: a case report

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare renal cancer. A 75-year-old Japanese female presented with gross hematuria. Computed tomography revealed two tumors in the left kidney, which were resected. Immunohistochemistry indicated negative staining for the B subunit of SDH (SDHB) in the resected specimen, leading to a final diagnosis of SDHB-deficient RCC. Genetic testing for SDHB showed a RCC germline variant in exon 6 (NM_003000.3:c.642 G > C) that was previously reported but associated with a novel phenotype (i.e., RCC). Twenty-six years prior, her daughter, who was 25 years old at the time, had undergone radical nephrectomy for a pathologic diagnosis of renal oncocytoma of the right kidney; SDHB immunostaining of her daughter’s tumor was also negative retrospectively. We confirmed that her daughter carried the germline variant in SDHB exon 6, similar to the patient. The patient had no evidence of disease progression at 15 months after surgery.

Development of a Single Molecule Counting Assay to Differentiate Chromophobe Renal Cancer and Oncocytoma in Clinics.

Simple SummaryWe previously reported a gene signature, “Chromophobe-Oncocytoma Gene Signature” (COGS), to differentiate chromophobe renal cell carcinoma from oncocytoma. Current clinical workflow with histology and immunohistochemistry can fail to distinguish these two renal cancers. We have evaluated the potential of COGS genes to classify these two renal tumors, on a single-molecule counting platform by measuring the expression of the COGS genes in archival tissue at Augusta University Medical Center. We show the expression level difference of the COGS signature in these tumors is able to classify these cancers accurately using machine learning. The assay has the potential to be instituted in clinically complex cases to differentiate these renal tumors.Malignant chromophobe renal cancer (chRCC) and benign oncocytoma (RO) are two renal tumor types difficult to differentiate using histology and immunohistochemistry-based methods because of their similarity in appearance. We previously developed a transcriptomics-based classification pipeline with “Chromophobe-Oncocytoma Gene Signature” (COGS) on a single-molecule counting platform. Renal cancer patients (n = 32, chRCC = 17, RO = 15) were recruited from Augusta University Medical Center (AUMC). Formalin-fixed paraffin-embedded (FFPE) blocks from their excised tumors were collected. We created a custom single-molecule counting code set for COGS to assay RNA from FFPE blocks. Utilizing hematoxylin-eosin stain, pathologists were able to correctly classify these tumor types (91.8%). Our unsupervised learning with UMAP (Uniform manifold approximation and projection, accuracy = 0.97) and hierarchical clustering (accuracy = 1.0) identified two clusters congruent with their histology. We next developed and compared four supervised models (random forest, support vector machine, generalized linear model with L2 regularization, and supervised UMAP). Supervised UMAP has shown to classify all the cases correctly (sensitivity = 1, specificity = 1, accuracy = 1) followed by random forest models (sensitivity = 0.84, specificity = 1, accuracy = 1). This pipeline can be used as a clinical tool by pathologists to differentiate chRCC from RO.

Nomogram predictive model for differentiation between renal oncocytoma and chromophobe renal cell carcinoma at multi-phasic CT: a retrospective study

To develop a predictive model to discriminate renal oncocytoma (RO) from chromophobe renal carcinoma (chRCC) using multiphase computed tomography (CT). Two hundred and five cases of renal tumours were analysed retrospectively regarding attenuation values during four CT phases, in addition to age, size, and sex. Then, logistic analysis was applied and a nomogram model developed to predict the most significant variables that can be used to differentiate between both tumour types. The cases were histopathologically proven as 81 cases of RO and 124 cases of chRCC. There was no association between the sex of the patient and the tumour types (p=0.41); however, there was a significant positive association between RO and the age of the patient (odds ratio 1.05; 95% confidence interval 1.02-1.08; p=0.001)) and a significant negative association between tumour size and RO (odds ratio 0.81; 95% confidence interval 73-90; p<0.001). There was a significant difference between tumour types in the contrast-enhanced phases. Logistic regression showed that absolute arterial enhancement (AAE) and absolute venous enhancement (AVE) are the most significant predictors for discriminating between tumour types. Combining these variables, size, AAE, and AVE were the best classifiers to discriminate between tumour types with an area under the curve of 0.90. A nomogram model was developed using these variables to predict RO probability in different case scenarios. The nomogram can predict the probability of RO from chRCC by using the best predictors, size, AAE, and AVE, with high accuracy.

A Metastatic Papillary Thyroid Carcinoma Could be Confused Clinically with a Primary Renal Neoplasm; A Case Report and Literature Review

Background: Papillary thyroid carcinoma is the most common thyroid neoplasm. It has a very high incidence of regional lymph node metastasis at the initial presentation. However, vascular spread is a very uncommon event. Lungs and bones are the most frequent sites of vascular metastasis from papillary thyroid carcinoma. Case concerns: The currently discussed case was obtained from the archive of Pathology laboratory, Sohag University. A 46-year-old female patient admitted to Urology Department, Sohag University, in 2015. The patient had a left loin pain, no other clinical data included in her referral sheet . Radiological findings revealed a renal mass and left radical nephrectomy was performed. Histopathological evaluation revealed a circumscribed neoplasm, formed of densely packed acini with scanty stroma. The patient was diagnosed as renal oncocytoma. On re-evaluation of the Hematoxylin and Eosin-stained slides; the nuclear features were different from those described in renal oncocytomas. So, a panel of immunohistochemical markers was performed (anti-CK7, anti-EMA, anti-Vimentin, anti-Thyroglobulin and anti-TTF1). Results: The neoplastic cells showed strong and diffuse cytoplasmic expression for Thyroglobulin and CK7 and nuclear expression for TTF1. The neoplastic cells didn’t express EMA or Vimentin. Based on the characteristic nuclear features detected by Hematoxylin and Eosin-stained slides and the obtained immunohistochemical results; the diagnosis of metastatic papillary thyroid carcinoma to the kidney was confirmed. Conclusions: Papillary thyroid carcinoma may metastasize to the kidney and form a solitary mass, that could be confused as a primary renal neoplasm.

Molecular characterization of the tumor microenvironment in chromophobe renal cell carcinoma (ChRCC) and related oncocytic neoplasms.

4549 Background: ChRCC represents about 5% of all kidney cancer and has a dismal prognosis in the metastatic setting, with limited response to immune checkpoint inhibitors (ICI) and targeted therapy. We evaluated the molecular properties of ChRCC and related oncocytic neoplasms to define the tumor immune microenvironment and identify potential therapeutic strategies. Methods: ChRCC, renal oncocytoma (RO) and low-grade oncocytic tumor (LOT) samples with matched normal kidney specimens were evaluated using single-cell RNA sequencing (scRNA-seq) and single-cell T-cell receptor sequencing (scTCR-seq). T-cell antigenic specificities from scTCR-seq were inferred using a comprehensive database of annotated T-cell receptor sequences (VDJdb). The infiltration of CD45+ immune cells in renal oncocytic tumors and ccRCC samples was quantified using immunohistochemistry (IHC). Bulk RNA-sequencing (RNA-seq) data of clear cell RCC (ccRCC) and ChRCC were further analyzed using The Cancer Genome Atlas (TCGA) KIRC and KICH cohorts, respectively, with immune cell fractions calculated using CIBERSORTx. Results: After quality-control, 46,817 cells from 5 tumor (ChRCC: n = 3, RO: n = 1 and LOT: n = 1) and 4 normal samples were isolated for scRNA-seq analysis. Renal oncocytic tumors (ChRCC, RO, and LOT) had a low density of CD45+ cells (mean: 739 ± 114 cells/mm2; n = 5) compared to ccRCC (mean: 3,420 ± 1,979 cells/mm2; n = 5) (p &lt; 0.05). Across all tumors, CD8+ T-cell clusters displayed a low expression of immune exhaustion markers (i.e. PDCD1 [PD-1], CTLA4, LAG3, HAVCR2 [TIM-3], and TIGIT). Analysis of TCGA bulk RNA-seq data after adjustment for CD8 T-cell fraction showed no difference in the expression of most immune exhaustion markers (i.e. PDCD1, CTLA4, LAG3) in ChRCC compared to normal samples (p &gt; 0.05), contrasting with a substantially higher expression in ccRCC versus normal kidney (p &lt; 0.05). Analysis of the T-cell repertoire (scTCR-seq) of ChRCC, RO and LOT samples did not identify a pattern of clonal expansion, and a considerable proportion of clonotypes were inferred to have specificity for viral antigens (range: 1.3 to 34.4% among all samples; 11.3 to 34.4% after filtering out two samples with a low ( &lt; 300) number of T-cells). Conclusions: Renal oncocytic tumors, including ChRCC, exhibit a low infiltration of immune cells, a non-exhausted immune phenotype and, a lack of clonally expanded tumor-specific T-cells. These findings may partially explain the molecular basis for the lack of response to ICIs in advanced ChRCC and outline the unique exhaustion phenotype of renal oncocytic tumors.

A review of 99mTc-sestamibi SPECT/CT for renal oncocytomas: A modified diagnostic algorithm.

99mTc-sestamibi SPECT/CT is a promising nuclear medicine imaging investigation for benign renal lesions such as renal oncocytomas. The purpose of this article is to i) review the current literature on 99mTc-sestamibi SPECT/CT, ii) to review to current application of 99mTc-sestamibi SPECT/CT for indeterminate renal lesion imaging, and iii) to discuss present limitations and areas for future research. The literature has been reviewed up to April 2022 for articles relating to the application of 99mTc-sestamibi SPECT/CT for benign renal lesions including a recently published systematic review and meta-analysis performed by the authors. One study evaluating 99mTc-sestamibi SPECT alone and five studies evaluating 99mTc-sestamibi SPECT/CT have been performed to date. 99mTc-sestamibi SPECT/CT demonstrates high sensitivity and specificity for detecting benign renal lesions, particularly renal oncocytomas. 99mTc-sestamibi SPECT/CT demonstrates near-perfect specificity for benign and low-grade renal lesions. The optimal quantified threshold ratio for tumor-to-background renal parenchyma radiotracer uptake for a positive result is > 0.6. In this article, we propose a modified diagnostic algorithm for small enhancing renal masses measuring 1-4 cm in which suspected benign lesions after conventional imaging are considered for 99mTc-sestamibi SPECT-CT. In this algorithm, positive studies can be monitored with active surveillance rather than requiring invasive biopsy and/or targeted therapy.