Variant Of Renal Cell Carcinoma Research Articles

Rapid Examination of Nonprocessed Renal Cell Carcinoma Using Nonlinear Microscopy.

Histology, the traditional method of examining surgical tissue under a microscope, is a time-consuming process involving the fixation of tissue in formalin, dehydration, embedding in paraffin, and cutting into thin sections for hematoxylin-eosin (H&E) staining. Frozen section analysis is a faster alternative used in surgery to quickly evaluate tissue, but it has limitations, such as the size of the specimens that can be analyzed and difficulties with fatty and bony tissues. To rapidly examine nonprocessed kidney tumors using nonlinear microscopy (NLM), a fluorescence microscopy technique that can rapidly visualize fresh or fixed, rapidly stained, nonprocessed tissue resembling H&E histology. This technology eliminates the need for fixation, embedding, microtome sectioning, or slide preparation. In this study, a total of 190 tissue specimens were collected from 46 patients who underwent partial or radical nephrectomy. Two genitourinary pathologists confirmed that diagnostically important features present in the H&E images could also be identified in the NLM images. The results of this study demonstrated that NLM had a high degree of correspondence with H&E staining for the classical variants of renal cell carcinoma. NLM offers several clinical benefits, such as facilitating rapid renal cell carcinoma diagnosis, assessment of targeted kidney biopsies for both tumor and medical kidney diseases, and collection of fresh renal cell carcinoma tissue for molecular studies.

Investigating the prognostic role of lncRNAs associated with disulfidptosis-related genes in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a grave malignancy that poses a significant global health burden with over 400,000 new cases annually. Disulfidptosis, a newly discovered programmed cell death process, is linked to the actin cytoskeleton, which plays a vital role in maintaining cell shape and survival. The role of disulfidptosis is poorly depicted in the clear cell histologic variant of RCC (ccRCC). Three sets of ccRCC cohorts, ICGC_RECA-EU (n =91), GSE76207 (n =32) and TCGA-KIRC (n =607), were included in our study, the batch effect of which was removed using the "combat" function. Correlation was calculated using the "rcorr" function of the "Hmisc" package for Pearson analysis, which was visualized using the "pheatmap" package. Principal component analysis was performed by the "vegan" package, visualized using the "scatterplot3d" package. Long non-coding RNAs (lncRNAs) associated with disulfidptosis were screened out using least absolute shrinkage and selection operator (LASSO) and COX analysis. Tumor mutation, immune landscaping and immunotherapy prediction were performed for further characterization of two risk groups. A total of 1822 disulfidptosis-related lncRNAs was selected, among which 308 lncRNAs were found to be significantly associated with the clinical outcome of ccRCC patients. We retained 11 disulfidptosis-related lncRNAs, namely, AP000439.3, RP11-417E7.1, RP11-119D9.1, LINC01510, SNHG3, AC156455.1, RP11-291B21.2, EMX2OS, AC093850.2, HAGLR and RP11-389C8.2, through LASSO and COX analysis for prognosis model construction, which displayed satisfactory accuracy (area under the curve, AUC, values all above 0.6 in multiple cohorts) in stratification of ccRCC prognosis. A nomogram model was constructed by integrating clinical factors with risk score, which further enhanced the prediction efficacy (AUC values all above 0.7 in multiple cohorts). We found that patients of male gender, higher clinical stages and advanced pathological T stage were inclined to have higher risk score values. Dactinomycin_1911, Vinblastine_1004, Daporinad_1248 and Vinorelbine_2048 were identified as promising candidate drugs for treating ccRCC patients of higher risk score value. Moreover, patients of higher risk value were prone to be resistant to immunotherapy. We developed a prognosis predicting model based on 11 selected disulfidptosis-related lncRNAs, the efficacy of which was verified in different cohorts. Furthermore, we delineated an intricate portrait of tumor mutation, immune topography and pharmacosensitivity evaluations within disparate risk stratifications.

The Role of Morphology in Predicting Fumarate Hydratase-deficient Uterine Leiomyomas in Young Women.

Hereditary leiomyomatosis and renal cell carcinoma is caused by germline mutations in the fumarate hydratase (FH) gene and is associated with an increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma. Pathologic evaluation of uterine leiomyoma can provide an opportunity for early recognition of the syndrome. We reviewed all archived slides of the cases to identify the characteristic morphologic features described for FH-deficient leiomyomas. We performed immunohistochemistry on whole sections of patients with uterine leiomyoma to evaluate for both FH and 2-succinocysteine (2SC) expression. Of the 106 cases, 19 showed the characteristic eosinophilic nucleoli with perinuclear halos, and 24 revealed a characteristic eosinophilic cytoplasmic inclusion consisting of pink globules present within the cytoplasm. Both of these morphologic findings were present together in 15 cases, and hemangiopericytomatous vessels were detected in 23 cases. The loss of FH protein expression was detected in 14 out of 106 cases (13%), and 13 out of 106 cases (12%) were positive for 2SC. We detected 10 cases with both 2SC-positive and FH expression loss. The presence of eosinophilic nucleoli with perinuclear halos and eosinophilic cytoplasmic inclusion was associated with both loss of FH protein expression and 2SC positivity ( P < 0.001). These findings underscore the importance of hematoxylin and eosin-based predictive morphology in FH-deficient uterine leiomyomas. Therefore, morphologic assessment of uterine leiomyomas for features of FH deficiency can serve as a screening tool for hereditary leiomyomatosis and renal cell carcinoma syndrome, allowing patients to be divided according to their hereditary risk assessment.

Appendiceal collision tumor presented as acute appendicitis: A dissonant scenario

Renal cell carcinoma arises from the epithelium of the renal tubules and accounts for approximately 3% of adult malignancies. Tumours occur most often in older individuals usually in sixth and seventh decades of life. Bilateral multifocal papillary type of RCC is rare and its presence should prompt the suspicion of some underlying hereditary genetic predisposition thus thorough cytogenetic evaluation and detailed family history could help in finding the etiology. Bilateral RCC could be synchronous or metachronous. We hereby present the autopsy findings of a case of sudden death of a 65 years old male. On histopathological evaluation, both kidneys showed papillary variant of renal cell carcinoma as an incidental finding.

Bilateral multifocal papillary renal cell carcinoma on autopsy: A case report

Renal cell carcinoma arises from the epithelium of the renal tubules and accounts for approximately 3% of adult malignancies. Tumours occur most often in older individuals usually in sixth and seventh decades of life. Bilateral multifocal papillary type of RCC is rare and its presence should prompt the suspicion of some underlying hereditary genetic predisposition thus thorough cytogenetic evaluation and detailed family history could help in finding the etiology. Bilateral RCC could be synchronous or metachronous. We hereby present the autopsy findings of a case of sudden death of a 65 years old male. On histopathological evaluation, both kidneys showed papillary variant of renal cell carcinoma as an incidental finding.

Histological pattern of nephrectomy specimens: A fifteen-year review

Background: Nephrectomy is the surgical removal of all or part of a diseased kidney in a living person. Pathological assessment of the tissue specimen is required in most cases for eventual diagnosis and disease prognostication. Objective: To demonstrate the pathological patterns of nephrectomy specimens in Nnewi, South East Nigeria. Methods: The data of all the nephrectomy specimens submitted to the Department of Histopathology of the Nnamdi Azikiwe University Teaching Hospital, Nnewi, as well as Triple Green Diagnostic Clinics Ltd, Nnewi, from 2007 to 2021 were retrospectively reviewed. Their pathological features were analyzed. Results: Of the 153 nephrectomy specimens, 141 that had complete data were used for the study. Those that had neoplastic lesions were 84(59.6%), while 57(40.4%) were non-neoplastic. Of the neoplastic lesions, 79 (94%) were malignant and renal cell carcinoma (RCC) accounted for 60%, with a mean age of 48.8±18.1 years and median age 52.5 years. RCC occurred commonly in the sixth decade of life (26%) with male preponderance (56%) and predominantly involving the left kidney (64%). Clear cell variant of renal cell carcinoma was the most common (52%), followed by papillary variant (34%). Nephroblastoma was the most common malignancy in the first decade with a modal age of 2years. Chronic pyelonephritis was the most common non-neoplastic lesions. Conclusion: Nephrectomy is done for a wide range of renal pathology, with more done for neoplastic conditions than non-neoplastic ones.

Application of perfusion computed tomography in renal diseases (review of literature)

Purpose. To analyze the literature data on the use of CT perfusion in kidney diseases and to assess the future prospects of using the technique in clinical practice.Materials and methods. In electronic databases (PubMed, E-library, Web of Science, Google Scholar), a search was conducted for published studies evaluating the possibilities of using CT perfusion in both neoplastic and non-neoplastic kidney diseases. The article analyzes the results of 40 most relevant works of Russian and foreign researchers devoted to this topic.Results. According to the analysis of the data obtained, perfusion CT is an effective diagnostic tool in oncology: the technique allows noninvasively assessing the nature of the tumour, including differentiating benign nodes (fat-poor angiomyolipoma and oncocytoma) from renal cell carcinoma; to establish the histological variant of renal cell carcinoma and Fuhrman grade, to characterize the effectiveness of ablative techniques and systemic treatment of renal cell carcinoma. Based on the correlation of CT kidney perfusion data and the results of various methods for determining organ function, the possibility of using perfusion CT as one of the prognostic factors for determining the tactics of treatment of patients with obstructive uropathies, aortomesenteric compression, and also shows the potential of using the technique in transplantology both in patients after surgery and during the examination of donors.Conclusions. Despite the fact that the role of CT kidney perfusion in various fields of urology and nephrology has been sufficiently studied, some important aspects of the likely application of this technique remain underestimated. Taking into account the high incidence rates and a significant percentage of localized forms of tumors, the study of the role of CT perfusion in planning and evaluating the results of nephron-sparing treatment of renal cell carcinoma may open up new prospects in optimizing surgical tactics.

Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance.

The clear cell variant of renal cell carcinoma (ccRCC) is the most common renal epithelial malignancy and responsible for most of the deaths from kidney cancer. Patients carrying inactivating mutations in the Von Hippel-Lindau (VHL) gene have an increased proclivity to develop several types of tumors including ccRCC. Normally, the Hypoxia Inducible Factor alpha (HIF-α) subunits of the HIF heterodimeric transcription factor complex are regulated by oxygen-dependent prolyl-hydroxylation, VHL-mediated ubiquitination and proteasomal degradation. Loss of pVHL function results in elevated levels of HIF-α due to increased stability, leading to RCC progression. While HIF-1α acts as a tumor suppressor, HIF-2α promotes oncogenic potential by driving tumor progression and metastasis through activation of hypoxia-sensitive signaling pathways and overexpression of HIF-2α target genes. One strategy to suppress ccRCC aggressiveness is directed at inhibition of HIF-2α and the associated molecular pathways leading to cell proliferation, angiogenesis, and metastasis. Indeed, clinical and pre-clinical data demonstrated the effectiveness of HIF-2α targeted therapy in attenuating ccRCC progression. This review focuses on the signaling pathways and the involved genes (cyclin D, c-Myc, VEGF-a, EGFR, TGF-α, GLUT-1) that confer oncogenic potential downstream of the VHL-HIF-2α signaling axis in ccRCC. Discussed as well are current treatment options (including receptor tyrosine kinase inhibitors such as sunitinib), the medical challenges (high prevalence of metastasis at the time of diagnosis, refractory nature of advanced disease to current treatment options), scientific challenges and future directions.

Метастаз светлоклеточного варианта почечно-клеточного рака в корне языка

This article presents a rare clinical case of metastasis of a clear cell variant of renal cell carcinoma in the root of the tongue 4 years after right-sided nephrectomy. The patient underwent supporting laryngoscope surgery with a CO2-laser (removal of the formation of the root of the tongue) with a preliminary imposition of a tracheostomy, without complications. According to the results of the morphological study, the structures of a clear cell malignant tumor were revealed.

Rare variant of renal cell carcinoma: A case report from rural tertiary care centre

Rare variant of renal cell carcinoma: A case report from rural tertiary care centre

Kidney tumors associated with germline mutations of FH and SDHB show a CpG island methylator phenotype (CIMP).

Germline mutations within the Krebs cycle enzyme genes fumarate hydratase (FH) or succinate dehydrogenase (SDHB, SDHC, SDHD) are associated with an increased risk of aggressive and early metastasizing variants of renal cell carcinoma (RCC). These RCCs express significantly increased levels of intracellular fumarate or succinate that inhibit 2-oxoglutarate-dependent dioxygenases, such as the TET enzymes that regulate DNA methylation. This study evaluated the genome-wide methylation profiles of 34 RCCs from patients with RCC susceptibility syndromes and 11 associated normal samples using the Illumina HumanMethylation450 BeadChip. All the HLRCC (FH mutated) and SDHB-RCC (SDHB mutated) tumors demonstrated a distinct CpG island methylator phenotype (CIMP). HLRCC tumors demonstrated an extensive and relatively uniform level of hypermethylation that showed some correlation with tumor size. SDHB-RCC demonstrated a lesser and more varied pattern of hypermethylation that overlapped in part with the HLRCC hypermethylation. Combined methylation and mRNA expression analysis of the HLRCC tumors demonstrated hypermethylation and transcription downregulation of genes associated with the HIF pathway, HIF3A and CITED4, the WNT pathway, SFRP1, and epithelial-to-mesenchymal transition and MYC expression, OVOL1. These observations were confirmed in the TCGA CIMP-RCC tumors. A selected panel of probes could identify the CIMP tumors and differentiate between HLRCC and SDHB-RCC tumors. This panel accurately detected all CIMP-RCC tumors within the TCGA RCC cohort, identifying them as HLRCC -like, and could potentially be used to create a liquid biopsy-based screening tool. The CIMP signature in these aggressive tumors could provide both a useful biomarker for diagnosis and a target for novel therapies.

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

A Rare and Unusual Renal Tumour: A Case Report

Introduction: Multilocular cystic renal cell neoplasm of low malignant potential is a rare histologically identified form of clear cell renal cell carcinoma included in 2016 Renal tumour classification of WHO. It is a low risk neoplasm with clear cells that have less expansile proliferation than other clear cell variants of renal cell carcinoma with no recurrence and metastasis with few exceptional cases. The incidence of multilocular cystic renal cell carcinoma is estimated to be 1-2 percent.6,12 Although the WHO classification of multilocular cystic renal cell carcinoma with low malignant potential was reported in 2004. The WHO 2016 categorization of renal cell tumour has been assessed as a special entity with no documented cases of metastasizing and recurrent tumour development.4 We present a rare clinical case of multilocular cystic renal cell neoplasm with low malignant potential, which should not be mistaken with other differential diagnoses such as cystic necrosis in conventional renal cell carcinoma, tubulo cystic renal cell carcinoma, multilocular cystic nephroma, clear cell variant of renal cell carcinoma and other benign multilocular renal tumors.

INCIDENTAL CUTANEOUS METASTASIS OF RENAL CELL CARCINOMA – REPORT OF AN INTERESTING CASE.

Background : Clear cell variant of renal cell carcinoma has highest risk of metastasizing. Cutaneous metastasis is however unusually rare. We report a case of an elderly male with a lesion on the chin, clinically suspected to be haemangioma, on histopathology diagnosed as cutaneous deposits of renal cell carcinoma, an incidental nding. A 75 year oldCase Report : male presented to the surgical OPD with a swelling on the chin, noticed after trauma whilst shaving. The painless lesion rapidly progressed over a period of one and half month with no associated pain. Swelling was surgically excised with clinical suspicion of haemangioma. With histopathological and immunohistochemical examination, a diagnosis of metastasis of clear cell carcinoma originating from the kidney was made. In the present case, the patient was an old male presenting with metastasis to the skin of chin, rapidly growing, an incidentalDiscussion : nding, search for the primary lesion revealed a renal mass diagnosed as renal cell carcinoma. Although cutaneous metastasis ofConclusion : Renal cell carcinoma to skin is rare specially in chin region, proper clinical evaluation with the help of radiological correlation must be done to nd out the primary lesion

Современные молекулярно-генетические аспекты гистологических вариантов почечно-клеточной карциномы

The article presents the main molecular mechanisms of the pathogenesis of renal cell carcinoma. The molecular pathways that determine the development of histological variants of renal cell carcinoma and the role of stem cells markers in the carcinogenesis of these tumors are considered.

Возможности второй линии терапии метастатического почечноклеточного рака. Клинический случай

In 2020, there were about 19,3 million new cancers and 10,0 million cancer deaths worldwide, according to GLOBOCAN. Renal cell carcinoma is one of the ten most commonly diagnosed cancers in the world. Anti-angiogenic drugs targeting VEGF (bevacizumab) and its receptors (sunitinib, sorafenib, pazopanib, and axitinib) are standard therapies. Cabosantinib is an oral small molecule tyrosine kinase inhibitor including MET, VEGF receptors (VEGFR) and AXL. A randomized phase III study METEOR evaluated the efficacy of cabozantinib versus everolimus in patients with renal cell carcinoma that progressed after anti-VEGFR therapy with targeted drugs. A clinical case of a 32-year-old patient with metastatic renal cell carcinoma is presented. The patient underwent cytoreductive nephrectomy. Renal cell carcinoma, sarcomatoid subtype, was morphologically established. Against the background of the first line of targeted therapy with sunitinib, the progression of the disease was registered after three months ― multiple metastases to the lungs, peritoneal carcinomatosis, ascites, hydrothorax. The patient is undergoing the second line of therapy ― cabozantinib, after three courses a partial response was recorded. The given clinical observation demonstrates a patient with one of the most unfavorable variants of renal cell carcinoma ― sarcomatoid subtype. The three courses of the second line of targeted therapy with cabozantinib provided a partial response and, which is important, improved the patient’s quality of life.

Renal Cell Carcinoma Clear Cell Variant with Chromophobe Differentiation -A Rare Case Presentation

Renal Cell Carcinoma (RCC) is a diverse growth of various histological cell forms, as well as genetic, biological, and behavioral variations, accounting for around 2%-4% of all genitourinary cancers worldwide and having the highest mortality rate. RCC is a rare symptom that occurs from the lower pole of the left kidney. Histopathological testing is critical for diagnosis, staging, and treatment evaluation. As a consequence, proper surgical and pathological correlation is critical for the diagnosis of such an unusually presented RCC. As a result, various RCC variants should be considered for proper diagnosis. We are here presenting a case of a woman aged44-year-old, complaining for two months about a lump in her abdomen. Pain in the left lumbar area was noticed, which was progressive and accompanied by hematuria. The post-nephrectomy specimen was sent for histopathological analysis, and RCC was found (Clear Cell variant with chromophobe differentiation). RCC (a Clear cell variant with Chromophobe differentiation) is an unusual manifestation that arises from the left kidney's lower pole. In terms of diagnosis, staging, and treatment assessment, histopathological testing is crucial. As a result, for the diagnosis of such an unusually presented RCC, proper surgical and pathological correlation is essential. It's critical to acknowledge the presence of this clinical entity, which, though uncommon, may offer yet another reason to pursue surgical or immunological treatment for metastatic renal cancer. The finding will inspire &amp; motivate researchers to pursue immunologic and other disease-related research.

Sarcomatoid renal cell carcinoma mimicking a non-functioning kidney with stone: A rare case report

Background: Sarcomatoid differentiation is a rare variant of renal cell carcinoma (RCC) and is associated with a worse prognosis. To date, there is still no reliable method to diagnose sarcomatoid renal cell carcinoma (sRCC) preoperatively. This malignancy is sometimes hidden in the minority cases of the non-neoplastic disease, making it difficult to diagnose and leading to diagnostic pitfalls particularly in limited diagnostic tool settings.Case presentation: A 72-year-old male presented with mild, dull pain in the left flank for one year. The initial assessment revealed a non-functioning left kidney with severe hydronephrosis and a stone. However, after a simple nephrectomy was done, the pathological examination showed a sarcomatoid variant of RCC. In the following weeks, a recurrent inhomogeneous tumor aggressively raised in the left kidney bed infiltrating the adjacent structures to the abdominal wall. An embolization procedure of the tumor feeding artery was carried out followed by administration of tyrosine kinase inhibitor. However, the patient’s condition quickly deteriorated and survived for about one month.Conclusion: In the non-functional kidney associated with stone, a consideration of potentially malignant lesions as a differential diagnosis is suggested. A rare sRCC with the worst prognosis may also exist in this condition. A thorough preoperative examination must be done carefully to avoid a diagnostic pitfall.

Mit family translocation renal cell carcinoma: a rare variant of renal cell carcinoma showing unusual aggressive pathological features

Mit family translocation renal cell carcinoma: a rare variant of renal cell carcinoma showing unusual aggressive pathological features

Immunoexpression of SDHB, FH, and CK20 among eosinophilic renal tumors: A tissue microarray study

BackgroundDifferential diagnosis can be a challenge for eosinophilic subtypes of renal cell tumors due to their overlapping histomorphological and immunohistochemical features. We aimed to investigate the frequency of rare variants of renal cell carcinomas (RCCs) such as succinate dehydrogenase-deficient RCC (SDDRCC), hereditary leiomyomatosis and RCC (HLRCC)-associated RCC, and eosinophilic, solid, and cystic RCC (ESCRCC) in our population. Materials and methodsRenal tumors which could be considered in the eosinophilic tumor category were included: 91 conventional clear cell RCCs with eosinophilic cytoplasm, 72 papillary RCCs, 74 chromophobe RCCs, 88 oncocytomas, and 37 other rare subtypes. Using the tissue microarray method, succinate dehydrogenase B (SDHB), fumarate hydratase (FH), and cytokeratin 20 (CK20) antibodies were performed by immunohistochemistry. Immunohistochemistry was repeated on whole block sections for selected cases. The utility of these antibodies in the differential diagnosis was also investigated. ResultsLoss of SDHB expression was detected in three tumors, two of which showed typical morphology for SDDRCC. In additional two tumors, SDHB showed weak cytoplasmic expression without a mitochondrial pattern (possible-SDHB deficient). None of the tumors showed loss of FH expression. Heterogeneous reactions were observed with SDHB and FH antibodies. Only one ESCRCC was detected with diffuse CK20 positivity. ConclusionSDDRCCs, HLRCC-associated RCCs, and ESCRCCs are very rare tumors depending on the population. Possible weak staining and focal loss of SDHB and FH expression should be kept in mind and genetic testing must be included for equivocal results.