Treatment modalities and outcomes of granular cell tumors and spindle cell oncocytomas of the pituitary gland: an analysis of two national cancer databases.

BACKGROUND: Spindle cell oncocytomas (SCO) and granular cell tumors (GCT) are rare primary pituitary neoplasms; the optimal treatment paradigms for these lesions are unknown and largely unexplored. Thus, using national registries, we analyze the epidemiology, management patterns, and surgical outcomes of SCOs and GCTs. METHODS: The National Cancer Database (NCDB; years 2003-2017) and the Surveillance, Epidemiology, and End Results Program (SEER; years 2004-2018) were queried for patients with pituitary SCOs or GCTs. Incidence, extent of surgical resection, and rate of postoperative radiation use for subtotally resected lesions comprised the primary outcomes of interest. All-cause mortality was also analyzed via time-to-event Kaplan-Meier curves. RESULTS: SCOs and GCTs have an annual incidence of 0.017 and 0.023 per 1,000,000, respectively. They comprise 0.1% of the benign pituitary tumors registered in NCDB. A total of 112,241 benign pituitary tumors were identified in NCDB during the study period, of which 83 (0.07%) were SCOs and 59 (0.05%) were GCTs. Median age at diagnosis was 55 years, 44% were females, and median maximal tumor diameter at presentation was 2.1 cm. Gross total resection was achieved in 54% patients. Ten patients (7%) had postoperative radiation. Comparing patients with GCTs versus SCOs, the former were more likely to be younger at diagnosis (48.0 vs. 59.0, respectively; p < 0.01) and female (59% vs. 34%, p = 0.01). GCTs and SCOs did not differ in terms of size at diagnoses (median maximal diameter: 1.9 cm vs. 2.2 cm, respectively; p = 0.59) or gross total resection rates (62% vs. 49%, p = 0.32). After matching SCOs and GCTs with pituitary adenomas on age, sex, and tumor size, the former were less likely to undergo gross total resection (53% vs. 72%; p = 0.03). Patients with SCOs and GCTs had a shorter overall survival when compared to patients with pituitary adenomas (p < 0.01) and a higher rate of thirty-day mortality (3.1% vs 0.0%; p = 0.013). CONCLUSION: SCOs and GCTs are rare pituitary tumors, and their management entails particular challenges. Gross total resection is often not possible, and adjuvant radiation might be employed following subtotal resection.

Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.

Proteomic analysis of chromophobe renal cell carcinoma and benign renal oncocytoma biopsies reveals shared metabolic dysregulation.

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.

Low-grade oncocytic tumour of the kidney is characterised by genetic alterations of TSC1, TSC2, MTOR or PIK3CA and consistent GATA3 positivity.

Low-grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.

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.

Oncocytoma on renal mass biopsy: is it still the same histology when surgery is performed? Results from UroCCR-104 study.

PURPOSE: To describe clinical features of patients with oncocytoma on renal biopsy (RMB), correlation with final histology on surgically treated patients, and predictive factors of discrepancy between RMB and final histology. METHODS: This was a retrospective study conducted in the framework of the UroCCR project (NCT03293563). All tumors with oncocytoma on RMB were selected and all pathological reports were reviewed. Patients with the RMB simultaneously performed with a focal treatment, synchronous bilateral tumors and ambiguous RMB report were excluded. Discrepancy between RMB and definitive histology was evaluated using a uni- and multivariable logistic regression analyses model. RESULTS: Overall, 119 tumors with oncocytoma on RMB, from 15 centers, were included. Of those, 54 (45.4%) had upfront surgery and 65 (54.6%) had active surveillance (AS). In renal masses with initial active surveillance, with a median follow-up of 28 months, 23 (19.3%) underwent surgery, 4 (3.4%) received focal treatment and 38 (31.9%) remained on AS. On final pathology, only 51 of the 75 surgically treated tumors (68.0%) had oncocytoma, while 24 presented malignant tumors (mainly chromophobe carcinoma (19.2%), and hybrid oncocytic/chromophobe tumor (HOCT) (6.8%)) leading to a discrepancy of 32.0% between RMB and final pathology. The only predictive factor of a discrepancy between RMB and definitive histology was a biopsy done outside of the center (Odds ratio: 3.22 [95%-confidence interval: 1.08-9.61], p = 0.03). CONCLUSION: Despite the increase of RMB in more and more centers, histologic discrepancy between RMB and definitive histology remains significant. This information should be discussed with patients and taken into consideration before treatment decision.

Distinguishing common renal cell carcinomas from benign renal tumors based on machine learning: comparing various CT imaging phases, slices, tumor sizes, and ROI segmentation strategies.

OBJECTIVES: To determine whether a CT-based machine learning (ML) can differentiate benign renal tumors from renal cell carcinomas (RCCs) and improve radiologists' diagnostic performance, and evaluate the impact of variable CT imaging phases, slices, tumor sizes, and region of interest (ROI) segmentation strategies. METHODS: Patients with pathologically proven RCCs and benign renal tumors from our institution between 2008 and 2020 were included as the training dataset for ML model development and internal validation (including 418 RCCs and 78 benign tumors), and patients from two independent institutions and a public database (TCIA) were included as the external dataset for individual testing (including 262 RCCs and 47 benign tumors). Features were extracted from three-phase CT images. CatBoost was used for feature selection and ML model establishment. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the ML model. RESULTS: The ML model based on 3D images performed better than that based on 2D images, with the highest AUC of 0.81 and accuracy (ACC) of 0.86. All three radiologists achieved better performance by referring to the classifier's decision, with accuracies increasing from 0.82 to 0.87, 0.82 to 0.88, and 0.76 to 0.87. The ML model achieved higher negative predictive values (NPV, 0.82-0.99), and the radiologists achieved higher positive predictive values (PPV, 0.91-0.95). CONCLUSIONS: A ML classifier based on whole-tumor three-phase CT images can be a useful and promising tool for differentiating RCCs from benign renal tumors. The ML model also perfectly complements radiologist interpretations. KEY POINTS: • A machine learning classifier based on CT images could be a reliable way to differentiate RCCs from benign renal tumors. • The machine learning model perfectly complemented the radiologists' interpretations. • Subtle variances in ROI delineation had little effect on the performance of the ML classifier.

Oncocytic adrenocortical neoplasm of borderline uncertain malignant potential diagnosed after robot-assisted adrenalectomy case report.

BACKGROUND: Adrenal incidentalomas are radiologically discovered tumors that represent a variety of pathologies, with the diagnosis clinched only on surgical pathology. These tumors may be clinically monitored, but triggers for surgery include size > 4 cm, concerning features on radiology, or hormonally functioning. Adrenal oncocytic neoplasms (AONs) are notably rare and typically nonfunctional tumors that are discovered as incidentalomas and exist on a spectrum of malignant potential. CASE PRESENTATION: We discovered an exceptionally large (15 cm in the greatest dimension) incidentaloma in a 73-year-old man with left back pain and he was treated with robotic-assisted adrenalectomy. Surgical pathology was consistent with AON of borderline uncertain malignant potential; adjuvant mitotane and radiation were omitted based on shared decision-making. CONCLUSION: Large AONs are rare, usually benign tumors that can be safely treated with robotic-assisted adrenalectomy. Surgical pathology is the crux of diagnosis and post-operative management, as it informs both the initiation of adjuvant therapy and the stringency of post-operative surveillance.

CT differentiation of the oncocytoma and renal cell carcinoma based on peripheral tumor parenchyma and central hypodense area characterisation.

BACKGROUND: Although the central scar is an essential imaging characteristic of renal oncocytoma (RO), its utility in distinguishing RO from renal cell carcinoma (RCC) has not been well explored. The study aimed to evaluate whether the combination of CT characteristics of the peripheral tumor parenchyma (PTP) and central hypodense area (CHA) can differentiate typical RO with CHA from RCC. METHODS: A total of 132 tumors on the initial dataset were retrospectively evaluated using four-phase CT. The excretory phases were performed more than 20 min after the contrast injection. In corticomedullary phase (CMP) images, all tumors had CHAs. These tumors were categorized into RO (n = 23), clear cell RCC (ccRCC) (n = 85), and non-ccRCC (n = 24) groups. The differences in these qualitative and quantitative CT features of CHA and PTP between ROs and ccRCCs/non-ccRCCs were statistically examined. Logistic regression filters the main factors for separating ROs from ccRCCs/non-ccRCCs. The prediction models omitting and incorporating CHA features were constructed and evaluated, respectively. The effectiveness of the prediction models including CHA characteristics was then confirmed through a validation dataset (8 ROs, 35 ccRCCs, and 10 non-ccRCCs). RESULTS: The findings indicate that for differentiating ROs from ccRCCs and non-ccRCCs, prediction models with CHA characteristics surpassed models without CHA, with the corresponding areas under the curve (AUC) being 0.962 and 0.914 versus 0.952 and 0.839 respectively. In the prediction models that included CHA parameters, the relative enhancement ratio (RER) in CMP and enhancement inversion, as well as RER in nephrographic phase and enhancement inversion were the primary drivers for differentiating ROs from ccRCCs and non-ccRCCs, respectively. The prediction models with CHA characteristics had the comparable diagnostic ability on the validation dataset, with respective AUC values of 0.936 and 0.938 for differentiating ROs from ccRCCs and non-ccRCCs. CONCLUSION: The prediction models with CHA characteristics can help better differentiate typical ROs from RCCs. When a mass with CHA is discovered, particularly if RO is suspected, EP images with longer delay scanning periods should be acquired to evaluate the enhancement inversion characteristics of CHA.

Spindle cell oncocytoma of the neurohypophysis with metastasis to the sphenoparietal sinus and immunohistochemical negativity for S100 and epithelial membrane antigen (EMA).

We report the case of a 61-year-old male with spindle cell oncocytoma of the hypophysis. On presentation to the Department of Neurosurgery at the German Armed Forces Hospital of Ulm, the patient reported a history of several years of left sixth nerve palsy, right ptosis, increased sensitivity to light, and a bilateral retrobulbar pressure sensation. Pituitary function was normal. A chromophobe non-functioning pituitary adenoma was initially suspected. The diagnosis was established on the basis of examination at a histopathology reference laboratory using immunohistochemistry to identify cell surface markers. During two years of follow-up, there were two clinical recurrences requiring surgery. To our knowledge, this is the 35th documented case of spindle cell oncocytoma of the pituitary gland and the first that was immunohistochemically negative for epithelial membrane antigen (EMA) and S100; and the first that displayed haematogenous metastasis to the right sphenoparietal sinus. The three surgical procedures were associated with massive intraoperative bleeding and thus resulted in subtotal tumor resection. Following surgery for the recurrences, the patient underwent radiotherapy.

[Morphological and molecular portrait hybrid renal tumors].

A hybrid tumor is not officially included in the latest International Histological Classification of Kidney Tumors (WHO, 2022), however, according to the literature, a number of researchers still consider a hybrid tumor as an independent nosological unit. In this regard, the development of morphological and molecular genetic criteria for a hybrid tumor, today, is the main task in the differential diagnosis of oncocytic renal tumors. AIM: Our aim was to carry out to identify immunohistochemical, ultrastructural features and determine the molecular profile of hybrid renal tumors. PATIENTS AND METHODS: The study was performed on the surgical material of 12 patients with a hybrid tumor of the kidney. Immunohistochemical study was carried out on paraffin sections according to the standard protocol. Antibodies CK7, CD117, Cyclin D1, EpCAM, Caveolin1, EABA, and S100A1 were used. To study tumor tissues on semi-thin and ultra-thin sections, an electron microscope Philips TECNAI 12 BioTwinD-265 is used. For in situ fluorescent diagnostic detection, defined centromere probes, LSI 13/21, LSI N25 /LSI ARSA and TelVysion telomeric probe. RESULTS: In some cases, a hybrid tumor is represented by a solid structure of monomorphic oxyphilic cells with a characteristic immuno-, ultraphenotype and molecular profile. CONCLUSION: The results of a comprehensive study confirm that the hybrid tumor is an intermediate link in the process of malignant transformation of oncocytoma into chromophobe renal cell carcinoma.

Technetium-99 m-sestamibi single-photon emission computerised tomography (CT)/CT in the prediction of malignant versus benign small renal masses.

OBJECTIVES: To determine the effectiveness of technetium-99m (99m Tc)-sestamibi single-photon emission computerised tomography/computerised tomography (SPECT/CT) in distinguishing between malignant and benign renal lesions. PATIENTS AND METHODS: Between June 2018 and October 2020 all patients with new indeterminate small renal masses (SRMs) underwent 99m Tc-sestamibi renal SPECT/CT before biopsy or surgery. The accuracy of 99m Tc-sestamibi imaging diagnoses was assessed against histopathology. Receiver operating characteristic (ROC) analysis was used to determine the optimum cut-off for the tumour:normal uptake ratio. Logistic regression was used to determine if quantitative analysis significantly added to visual interpretation alone. RESULTS: A total of 74 patients with SRMs were investigated with 99m Tc-sestamibi SPECT/CT. The SPECT/CT correctly identified 49 malignant tumours and 11 benign tumours, resulting in a sensitivity of 0.89 (95% confidence interval [CI] 0.77-0.95) and a specificity of 0.73 (95% CI 0.45-0.91). The ROC analysis of uptake ratios demonstrated that a tumour:normal uptake ratio of 0.41 provided optimal diagnostic accuracy (sensitivity 0.81, specificity 0.88, area under the curve 0.883 [95% CI 0.794-0.971]). The uptake ratio was also highly significant in excluding malignancy on univariate logistic regression analysis whereby the higher the uptake ratio, the lower the chances were for malignancy (odds ratio 0.009, 95% CI 0.001-0.118, P < 0.001). However, this did not improve diagnostic accuracy when compared to visual interpretation alone. CONCLUSION: 99m Tc-sestamibi SPECT/CT is a non-invasive technique with good accuracy in determining if a SRM is benign or malignant.

Diagnostic Performance and Interreader Agreement of the MRI Clear Cell Likelihood Score for Characterization of cT1a and cT1b Solid Renal Masses: An External Validation Study.

BACKGROUND. The clear cell likelihood score (ccLS) has been proposed for the noninvasive differentiation of clear cell renal cell carcinoma (ccRCC) from other renal neoplasms on multiparametric MRI (mpMRI), though further external validation remains needed. OBJECTIVE. The purpose of our study was to evaluate the diagnostic performance and interreader agreement of the ccLS version 2.0 (v2.0) for characterizing solid renal masses as ccRCC. METHODS. This retrospective study included 102 patients (67 men, 35 women; mean age, 56.9 ± 12.8 [SD] years) who underwent mpMRI between January 2013 and February 2018, showing a total of 108 (≥ 25% enhancing tissue) solid renal masses measuring 7 cm or smaller (83 cT1a [≤ 4 cm] and 25 cT1b [> 4 cm and ≤ 7 cm]), all with a histologic diagnosis. Three abdominal radiologists independently reviewed the MRI examinations using ccLS v2.0. Median reader sensitivity, specificity, and accuracy were computed for predicting ccRCC by ccLS of 4 or greater, and individual reader AUCs were derived. The percentage of masses that were ccRCC was calculated, stratified by ccLS. Interobserver agreement was assessed by the Fleiss kappa statistic. RESULTS. The sample included 45 ccRCCs (34 cT1a, 11 cT1b), 30 papillary renal cell carcinomas (RCCs), 13 chromophobe RCCs, 14 oncocytomas, and six fat-poor angiomyolipomas. Median reader sensitivity, specificity, and accuracy for predicting ccRCC by ccLS of 4 or greater were 85%, 82%, and 83% among cT1a masses and 82%, 100%, and 92% among cT1b masses. The three readers' AUCs for predicting ccRCC by ccLS for cT1a masses were 0.90, 0.84, and 0.89 and for cT1b masses were 0.99, 0.97, and 0.92. Across readers, the percentage of masses that were ccRCC among cT1a masses was 0%, 0%, 20%, 68%, and 93% for ccLS of 1, 2, 3, 4, and 5, respectively; among cT1b masses, the percentage of masses that were ccRCC was 0%, 0%, 32%, 90%, and 100% for ccLS of 1, 2, 3, 4, and 5, respectively. Interobserver agreement among cT1a and cT1b masses for ccLS of 4 or greater was 0.82 and 0.83 and for ccLS of 1-5 overall was 0.65 and 0.62, respectively. CONCLUSION. This study provides external validation of the ccLS, finding overall high measures of diagnostic performance and interreader agreement. CLINICAL IMPACT. The ccLS provides a standardized approach to the noninvasive diagnosis of ccRCC by MRI.

Clinico-pathological correlation of lacrimal caruncle tumors: a retrospective analysis over 22 years at the University Eye Hospital Bonn.

PURPOSE: The lacrimal caruncle is composed of numerous structures including different glands as well as hair follicles. Accordingly, the spectrum of benign and malignant lesions is broad, and the clinical diagnosis is often challenging. Here we systematically analyzed excised caruncular tumors over the past 22 years with special emphasis on the clinico-pathological correlation to provide a guidance for clinicians. METHODS: Retrospective evaluation with clinico-pathologic correlation of surgically removed caruncular tumors between 1998 and 2020 at a tertiary referral center. RESULTS: Eighty-two caruncular tumors were identified in the respective period. The patients were between 11 and 85 years of age (mean, 46.8 years; median, 49 years). Nevi (n = 35), cystic lesions (n = 14), oncocytoma (n = 9), papilloma (n = 8), sebaceous gland hyperplasia (n = 8), and reactive lymphoid hyperplasia (n = 4) were observed most frequently. Besides, we are the first reporting herniated orbital fat accompanied by a pyogenic granuloma. 2.4% (n = 2) were malignant tumors (sebaceous gland carcinoma, conjunctival intraepithelial neoplasia with pyogenic granuloma). CONCLUSION: Caruncular tumors show a broad spectrum of mostly benign tumors. They can occur in patients of any age. However, 8/9 oncocytomas and both malignant lesions were detected in patients older than 60 years. Although the clinical diagnosis was confirmed in only 68.3% by the histopathological analysis, the two malignant lesions were identified as such already clinically. Caruncular lesions with a history of growth or other signs of malignancy should be excised followed by detailed histopathological examination to allow a final diagnosis and exclude rare malignant tumors with lethal potential.

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

BACKGROUND: To 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). METHODS: In 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. RESULTS: A 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. CONCLUSION: We 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.

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

PURPOSE OF REVIEW: A growing number of tumor entities with badly defined limits are enlarging in the last years the family of oncocytic tumors in the kidney. RECENT FINDINGS: 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.

Differential diagnosis of renal oncocytoma and chromophobe renal cell carcinoma using CT features: a central scar-matched retrospective study.

BACKGROUND: Renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC) have a common cellular origin and different clinical management and prognosis. PURPOSE: To explore the utility of computed tomography (CT) in the differentiation of RO and chRCC. MATERIAL AND METHODS: Twenty-five patients with RO and 73 patients with chRCC presenting with the central scar were included retrospectively. Two experienced radiologists independently reviewed the CT imaging features, including location, tumor size, relative density ratio, segmental enhancement inversion (SEI), necrosis, and perirenal fascia thickening, among others. Interclass correlation coefficient (ICC, for continuous variables) or Kappa coefficient test (for categorical variables) was used to determine intra-observer and inter-observer bias between the two radiologists. RESULTS: The inter- and intra-reader reproducibility of the other CT imaging parameters were nearly perfect (>0.81) except for the measurements of fat (0.662). RO differed from chRCC in the cortical or medullary side (P = 0.005), relative density ratio (P = 0.020), SEI (P < 0.001), and necrosis (P = 0.045). The logistic regression model showed that location (right kidney), hypo-density on non-enhanced CT, SEI, and perirenal fascia thickening were highly predictive of RO. The combined indicators from logistic regression model were used for ROC analysis. The area under the ROC curve was 0.923 (P < 0.001). The sensitivity and specificity of the four factors combined for diagnosing RO were 88% and 86.3%, respectively. The correlation coefficient between necrosis and tumor size in all tumors including both of RO and chRCC was 0.584, indicating a positive correlation (P < 0.001). CONCLUSION: The CT imaging features of location (right kidney), hypo-density on non-enhanced CT, SEI, and perirenal fascia thickening were valuable indicators in distinguishing RO from chRCC.

Renal Oncocytoma: The Diagnostic Challenge to Unmask the Double of Renal Cancer.

Renal oncocytoma represents the most common type of benign neoplasm that is an increasing concern for urologists, oncologists, and nephrologists due to its difficult differential diagnosis and frequent overtreatment. It displays a variable neoplastic parenchymal and stromal architecture, and the defining cellular element is a large polygonal, granular, eosinophilic, mitochondria-rich cell known as an oncocyte. The real challenge in the oncocytoma treatment algorithm is related to the misdiagnosis due to its resemblance, at an initial radiological assessment, to malignant renal cancers with a completely different prognosis and medical treatment. Unfortunately, percutaneous renal biopsy is not frequently performed due to the possible side effects related to the procedure. Therefore, the majority of oncocytoma are diagnosed after the surgical operation via partial or radical nephrectomy. For this reason, new reliable strategies to solve this issue are needed. In our review, we will discuss the clinical implications of renal oncocytoma in daily clinical practice with a particular focus on the medical diagnosis and treatment and on the potential of novel promising molecular biomarkers such as circulating microRNAs to distinguish between a benign and a malignant lesion.

A case of a borderline adrenal oncocytoma in a 62-year old female.

INTRODUCTION: Adrenal oncocytomas are a rare pathology and only about 160 cases have been reported in the literature. CASE DESCRIPTION: We describe the case of a 62-year old female with an incidentaloma found in the right adrenal gland on a CT scan. Endocrine testing showed a non-secreting lesion. An MRI was performed to get a more precise diagnosis. It excluded a simple adenoma and a malignant tumor had to be suspected. Open adrenalectomy was performed, and pathology results confirmed a borderline adrenal oncocytoma. DISCUSSION: Oncocytomas are usually found in the kidneys, salivary glands, parathyroid, lung, pituitary gland, and ovaries. It is important to differentiate them from, for example, pheochromocytomas, adrenal cortical carcinoma, and metastasis. Most oncocytomas are non-functioning (17% are functional). Usually, they are found as incidentalomas on a CT or MRI scan. The only way to confirm the diagnosis at present is pathological examination. Bisceglia and his colleagues have proposed a new system to classify adrenal oncocytomas. The presence of one major criterion indicates malignancy, the presence of one to four minor criteria is indicative of uncertain potential. The absence of all major and minor criteria indicates benign behavior. Treatment options are open surgery, laparoscopic surgery and rarely robotic surgery. CONCLUSION: An adrenal oncocytoma remains a rare diagnosis and has a wide array of differential diagnosis. It should be treated by surgical removal and a close follow up is suggested. More research should be done regarding diagnosis, treatment and follow-up.

Renal Cell Carcinoma or Oncocytoma? The Contribution of Diffusion-Weighted Magnetic Resonance Imaging to the Differential Diagnosis of Renal Masses.

Background and Objectives: Renal Cell Carcinoma (RCC) accounts for 85% and oncocytomas constitute 3-7% of solid renal masses. Oncocytomas can be confused, especially with hypovascular RCC. The purpose of this research was to evaluate the contribution of diffusion-weighted imaging (DWI) and contrast-enhanced MRI sequences in the differential diagnosis of RCC and oncocytoma Materials and Methods: 465 patients with the diagnosis of RCC and 45 patients diagnosed with oncocytoma were retrospectively reviewed between 2009 to 2020. All MRI acquisitions were handled by a 1.5 T device (Achieva, Philips Healthcare, Best, The Netherlands) and all images were evaluated by the consensus of two radiologists with 10-15 years' experience. The SPSS package program version 15.0 software was used for statistical analysis of the study. Chi-square test, Mann-Whitney U test or the Kruskal-Wallis tests were used in the statistical analysis. A receiver operating characteristic (ROC) curve was used to calculate the cut-off values Results: The results were evaluated with a 95% confidence interval and a significance threshold of p < 0.05. ADC values (p < 0.001) and enhancement index (p < 0.01) were significantly lower in the RCC group than the oncocytoma group. Conclusion: DWI might become an alternative technique to the contrast-enhanced MRI in patients with contrast agent nephropathy or with a high risk of nephrogenic systemic fibrosis, calculation of CI of the oncocytoma and RCCs in the contrast-enhanced acquisitions would contribute to the differential diagnosis.