scholarly journals Development of Pathological Diagnostics of Human Kidney Cancer by Multiple Staining Using New Fluorescent Fluolid Dyes

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dilibaier Wuxiuer ◽  
Yun Zhu ◽  
Takunori Ogaeri ◽  
Keiji Mizuki ◽  
Yuki Kashiwa ◽  
...  
Keyword(s):  
Room Temperature ◽  
Clear Cell ◽  
Human Kidney ◽  
Renal Tumors ◽  
Renal Angiomyolipoma ◽  
Renal Tubules ◽  
Cell Renal Cell Carcinoma ◽  
Fluorescent Markers ◽  
Chromophobe Rcc ◽  
Papillary Rcc

New fluorescent Fluolid dyes have advantages over others such as stability against heat, dryness, and excess light. Here, we performed simultaneous immunostaining of renal tumors, clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, acquired cystic disease-associated RCC (ACD-RCC), and renal angiomyolipoma (AML), with primary antibodies against Kank1, cytokeratin 7 (CK7), and CD10, which were detected with secondary antibodies labeled with Fluolid-Orange, Fluolid-Green, and Alexa Fluor 647, respectively. Kank1 was stained in normal renal tubules, papillary RCC, and ACD-RCC, and weakly or negatively in all other tumors. CK7 was positive in normal renal tubules, papillary RCC, and ACD-RCC. In contrast, CD10 was expressed in renal tubules and clear cell RCC, papillary RCC, AML, and AC-RCC, and weakly in chromophobe RCC. These results may contribute to differentiating renal tumors and subtypes of RCCs. We also examined the stability of fluorescence and found that fluorescent images of Fluolid dyes were identical between a tissue section and the same section after it was stored for almost three years at room temperature. This indicates that tissue sections can be stored at room temperature for a relatively long time after they are stained with multiple fluorescent markers, which could open a door for pathological diagnostics.

scholarly journals Magnetic resonance diffusion kurtosis imaging in differential diagnosis of benign and malignant renal tumors

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianxiong Fu ◽  
Jing Ye ◽  
Wenrong Zhu ◽  
Jingtao Wu ◽  
Wenxin Chen ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Mean Diffusivity ◽  
Threshold Value ◽  
Renal Tumors ◽  
Diffusion Kurtosis Imaging ◽  
Renal Oncocytoma ◽  
Renal Angiomyolipoma ◽  
Planar Imaging ◽  
Cell Renal Cell Carcinoma ◽  
Diffusion Kurtosis

Abstract Background Benign and malignant renal tumors share similar some imaging findings. Methods Sixty-six patients with clear cell renal cell carcinoma (CCRCC), 13 patients with renal angiomyolipoma with minimal fat (RAMF) and 7 patients with renal oncocytoma (RO) were examined. For diffusion kurtosis imaging (DKI), respiratory triggered echo-planar imaging sequences were acquired in axial plane (3 b-values: 0, 500, 1000s/mm2). Mean Diffusivity (MD), fractional Anisotropy (FA), mean kurtosis (MK), kurtosis anisotropy (KA) and radial kurtosis (RK) were performed. Results For MD, a significant higher value was shown in CCRCC (3.08 ± 0.23) than the rest renal tumors (2.93 ± 0.30 for RO, 1.52 ± 0.24 for AML, P < 0.05). The MD values were higher for RO than for AML (2.93 ± 0.30 vs.1.52 ± 0.24, P < 0.05), while comparable MD values were found between CCRCC and RO (3.08 ± 0.23 vs. 2.93 ± 0.30, P > 0.05). For MK, KA and RK, a significant higher value was shown in AML (1.32 ± 0.16, 1.42 ± 0.23, 1.41 ± 0.29) than CCRCC (0.43 ± 0.08, 0.57 ± 0.16, 0.37 ± 0.11) and RO (0.81 ± 0.08, 0.86 ± 0.16, 0.69 ± 0.08) (P < 0.05). The MK, KA and RK values were higher for RO than for CCRCC (0.81 ± 0.08 vs. 0.43 ± 0.08, 0.86 ± 0.16 vs. 0.57 ± 0.16, 0.69 ± 0.08 vs. 0.37 ± 0.11, P < 0.05). Using MD values of 2.86 as the threshold value for differentiating CCRCC from RO and AML, the best result obtained had a sensitivity of 76.1%, specificity of 72.6%. Using MK, KA and RK values of 1.19,1.13 and 1.11 as the threshold value for differentiating AML from CCRCC and RO, the best result obtained had a sensitivity of 91.2, 86.7, 82.1%, and specificity of 86.7, 83.2, 72.8%. Conclusion DKI can be used as another noninvasive biomarker for benign and malignant renal tumors’ differential diagnosis.

scholarly journals Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in the Era of Targeted Therapies and Personalized Medicine

2013 ◽  
Vol 137 (4) ◽  
pp. 467-480 ◽  
Author(s):  
Rajen Goyal ◽  
Elizabeth Gersbach ◽  
Ximing J. Yang ◽  
Stephen M. Rohan
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumor ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Immunohistochemical Stains

Context.—The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and—with the exception of some rare tumors—the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies. Objective.—To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management. Data Sources.—Published literature and personal experience. Conclusions.—In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.

Claudin-7 Immunohistochemistry in Renal Tumors: A Candidate Marker for Chromophobe Renal Cell Carcinoma Identified by Gene Expression Profiling

2007 ◽  
Vol 131 (10) ◽  
pp. 1541-1546 ◽  
Author(s):  
Christopher D. Hornsby ◽  
Cynthia Cohen ◽  
Mahul B. Amin ◽  
Maria M. Picken ◽  
Diane Lawson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Clear Cell ◽  
Renal Tumor ◽  
Renal Tumors ◽  
Tumor Subtypes ◽  
Chromophobe Rcc ◽  
Clear Cell Rccs ◽  
Expression Marker

Abstract Context.—The differential diagnosis of eosinophilic renal tumors can be difficult by light microscopy. In particular, chromophobe renal cell carcinoma (RCC) is difficult to distinguish from oncocytoma. This differential diagnosis is important because chromophobe RCC is malignant, whereas oncocytoma is benign. Furthermore, chromophobe RCC has distinct malignant potential and prognosis compared with eosinophilic variants of other RCC subtypes. Immunohistochemistry is useful for distinguishing chromophobe RCC from other subtypes of renal carcinoma, but no expression marker reliably separates chromophobe RCC from oncocytoma. Objective.—In a previous gene expression microarray analysis of renal tumor subtypes, we found the distal nephron markers claudin-7 and claudin-8 to be overexpressed in chromophobe RCC versus oncocytoma and other tumor subtypes. We have confirmed similar findings in independent microarray data and validated differential claudin-7 protein expression by immunohistochemistry. Design.—Immunohistochemical analysis of claudin-7 in 36 chromophobe RCCs, 43 oncocytomas, 42 clear cell RCCs, and 29 papillary RCCs. Results.—Membranous claudin-7 expression was detected in 67% chromophobe RCCs, compared with 0% clear cell RCCs, 28% papillary RCCs, and 26% oncocytomas (P &lt; .001). Conclusions.—Based on microarray and immunohistochemical data, we propose claudin-7 to be a candidate expression marker for distinguishing chromophobe RCC from other renal tumor subtypes, including the morphologically similar oncocytoma. The clinical utility of claudin-7 should be validated in independent studies of renal tumors, possibly in combination with additional targets in a multiplex immunohistochemical panel.

scholarly journals Differentiation of Clear Cell Renal Cell Carcinoma from other Renal Cell Carcinoma Subtypes and Benign Oncocytoma Using Quantitative MDCT Enhancement Parameters

Medicina ◽  
2020 ◽  
Vol 56 (11) ◽  
pp. 569
Author(s):  
Claudia-Gabriela Moldovanu ◽  
Bianca Petresc ◽  
Andrei Lebovici ◽  
Attila Tamas-Szora ◽  
Mihai Suciu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumors ◽  
3D Analysis ◽  
Imaging Features ◽  
Enhancement Ratio ◽  
Cell Renal Cell Carcinoma ◽  
Renal Masses

Background and objectives: The use of non-invasive techniques to predict the histological type of renal masses can avoid a renal mass biopsy, thus being of great clinical interest. The aim of our study was to assess if quantitative multiphasic multidetector computed tomography (MDCT) enhancement patterns of renal masses (malignant and benign) may be useful to enable lesion differentiation by their enhancement characteristics. Materials and Methods: A total of 154 renal tumors were retrospectively analyzed with a four-phase MDCT protocol. We studied attenuation values using the values within the most avidly enhancing portion of the tumor (2D analysis) and within the whole tumor volume (3D analysis). A region of interest (ROI) was also placed in the adjacent uninvolved renal cortex to calculate the relative tumor enhancement ratio. Results: Significant differences were noted in enhancement and de-enhancement (diminution of attenuation measurements between the postcontrast phases) values by histology. The highest areas under the receiver operating characteristic curves (AUCs) of 0.976 (95% CI: 0.924–0.995) and 0.827 (95% CI: 0.752–0.887), respectively, were demonstrated between clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC)/oncocytoma. The 3D analysis allowed the differentiation of ccRCC from chromophobe RCC (chrRCC) with a AUC of 0.643 (95% CI: 0.555–0.724). Wash-out values proved useful only for discrimination between ccRCC and oncocytoma (43.34 vs 64.10, p < 0.001). However, the relative tumor enhancement ratio (corticomedullary (CM) and nephrographic phases) proved useful for discrimination between ccRCC, pRCC, and chrRCC, with the values from the CM phase having higher AUCs of 0.973 (95% CI: 0.929–0.993) and 0.799 (95% CI: 0.721–0.864), respectively. Conclusions: Our observations point out that imaging features may contribute to providing prognostic information helpful in the management strategy of renal masses.

Decreased prolyl hydroxylase 3 mRNA expression in oncocytomas compared with clear cell renal cell carcinoma

2020 ◽  
Vol 35 (4) ◽  
pp. 80-86
Author(s):  
Spyridon Kampantais ◽  
Ilias Kounatidis ◽  
Vasiliki Kotoula ◽  
Ioannis Vakalopoulos ◽  
Konstantinos Gkagkalidis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Prolyl Hydroxylase ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Fresh Frozen

Introduction: Hypoxia inducible factors (HIF) and prolyl hydroxylase domain (PHD) enzymes play a central role in tumor progression in clear cell renal cell carcinoma (ccRCC). However, there are currently no data regarding the behavior of this pathway (HIF/PHD) in a large number of benign renal tumors, the oncocytomas. The aim of the present study was to compare the expression levels of these factors between ccRCC and oncocytoma tumors. Material and methods: A total of 56 fresh frozen specimens from patients with ccRCC and 14 oncocytoma specimens were analyzed via reverse transcription-quantitative polymerase chain reaction in order to assess the expression levels of HIF-1α, HIF-2α, PHD1, PHD2, and PHD3. The analysis involved both fresh frozen tumor samples as well as adjacent normal kidney tissues. Results: In ccRCC, HIF-1α and HIF-2α levels were upregulated in 65.5% and 71.4% of cases, respectively. PHD3 was downregulated only in 15.4% of the ccRCC cases, in contrast with oncocytoma cases, which exhibited low expression levels in the majority. The upregulation of PHD3 messenger RNA (mRNA) levels in ccRCC when compared with oncocytoma was statistically significant ( P<0.001). No other comparisons (HIF-1α, HIF-2α, PHD1, and PHD2) were significantly different. HIF-2α and PHD3 mRNA expression levels were negatively correlated with Fuhrman Grade ( P=0.029 and P=0.026, respectively) in ccRCC. Conclusion: To the best of our knowledge, this is the first time that the HIF/PHD pathway was compared between ccRCC and a common benign tumor, identifying the upregulation of PHD3 as the possible underlying factor guiding the difference in the behavior of ccRCC.

scholarly journals Unilateral synchronous papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma: a case report with KRAS and PIK3CA mutations

2020 ◽  
Author(s):  
Hyun Jung Lee ◽  
Dong Hoon Shin ◽  
Joon Young Park ◽  
So Young Kim ◽  
Chung Su Hwang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Mutation ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumors ◽  
Renal Neoplasm ◽  
Reverse Polarity ◽  
Cell Renal Cell Carcinoma ◽  
Exon 2

Abstract Background: The presence of histologically different neoplasms in the same organ is rare in pathologic practice. We report the first case of synchronous clear cell renal cell carcinoma (clear cell RCC) and papillary renal neoplasm with reverse polarity (PRNRP) with comprehensive immunohistochemical and molecular characterization using next-generation sequencing (NGS). Case presentation: A 61-year-old man was incidentally found to have a left renal mass on imaging studies performed for workup of left back pain and urine color change for one week. A laparoscopic left radical nephrectomy was performed. Gross examination showed lobulated masses measuring 5.6 × 4.0 × 3.3 cm in the upper to mid pole and 1.1 × 1.0 × 1.0 cm in the lower pole. Microscopic findings revealed these to be two different separate masses of clear cell renal cell carcinoma and papillary renal neoplasm with reverse polarity. NGS analyses revealed KRAS gene mutation (c.35G>T/p.G12V in exon 2) in the papillary renal neoplasm with reverse polarity, with PIK3CA gene mutation restricted to the clear cell renal cell carcinoma (c.1624G>A/p.E542K in exon 10).Conclusions: We report here an extraordinarily rare case of synchronous renal tumors of papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma. We identified simultaneous KRAS and PIK3CA mutations in two different renal masses in the same kidney for the first time. New pathologic assessment with comparative molecular analysis of mutational profiles may be helpful for tumor studies.

scholarly journals Single cell derived mRNA signals across human kidney tumors

2020 ◽  
Author(s):  
Matthew D Young ◽  
Thomas J Mitchell ◽  
Lars Custers ◽  
Thanasis Margaritis ◽  
Francisco Morales ◽  
...  
Keyword(s):  
Single Cell ◽  
Human Cancer ◽  
Human Kidney ◽  
Cell Types ◽  
Renal Tumors ◽  
Tumor Type ◽  
Kidney Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Cellular Origin ◽  
Normal Tissues

AbstractThe cellular transcriptome may provide clues into the differentiation state and origin of human cancer, as tumor cells may retain patterns of gene expression similar to the cell they derive from. Here, we studied the differentiation state and cellular origin of human kidney tumors, by assessing mRNA signals in 1,300 childhood and adult renal tumors, spanning seven different tumor types. Using single cell mRNA reference maps of normal tissues generated by the Human Cell Atlas project, we measured the abundance of reference “cellular signals” in each tumor. Quantifying global differentiation states, we found that, irrespective of tumor type, childhood tumors exhibited fetal cellular signals, thus replacing the long-held presumption of “fetalness” with a precise, quantitative readout of immaturity. By contrast, in adult cancers our assessment refuted the suggestion of dedifferentiation towards a fetal state in the overwhelming majority of cases, with the exception of lethal variants of clear cell renal cell carcinoma. Examining the specific cellular phenotype of each tumor type revealed an intimate connection between the different mesenchymal populations of the developing kidney and childhood renal tumors, whereas adult tumors mostly represented specific mature tubular cell types. RNA signals of each tumor type were remarkably uniform and specific, indicating a possible therapeutic and diagnostic utility. We demonstrated this utility with a case study of a cryptic renal tumor. Whilst not classifiable by clinical pathological work-up, mRNA signals revealed the diagnosis. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.

scholarly journals Ιστική μελέτη στην επιθήλιο-μεσεγχυματική μετατροπή σε νεφροκυτταρικό καρκίνωμα

2021 ◽  
Author(s):  
Γρηγόριος Θεοδωρόπουλος
Keyword(s):  
Clear Cell ◽  
Chromophobe Rcc ◽  
Grade Classification ◽  
Papillary Rcc ◽  
Clear Cell Rcc

Το φαινόμενο της επιθηλιομεσεγχυματικής μετατροπής είναι η διεργασία κατά την οποία ένα επιθηλιακό κύτταρο αποκτά φαινότυπο μεσεγχυματικού κυττάρου. Η μετατροπή αυτή στον φαινότυπο του επιθηλιακού κυττάρου απαιτεί την δημιουργία ενός νέου μοριακού προγράμματος του επιθηλιακού ιστού με νέες βιοχημικές οδηγίες. Η ΕΜΤ συμμετέχει σε φυσιολογικές καθώς και σε παθολογικές διεργασίες του οργανισμού. Σκοπό της παρούσας ερευνητικής δραστηριότητας αποτέλεσε η διερεύνηση της ανοσοιστοχημικής πρωτεινικής συνέκφρασης των μορίων ε-καντχερίνης και βιμεντίνης σε σειρά καρκινωμάτων νεφρού διάφορης ιστολογικής τυποποίησης και η συσχέτισή τους με τα κλινικοεργαστηριακά χαρακτηριστικά τους γνωρίσματα. Το υλικό αναδύθηκε από την αρχειακή ιστική βάση του Παθολογο-ανατομικού Τμήματος του Γενικού Νοσοκομείου Αθηνών ‘’ΕΛΠΙΣ’’ και αφορούσε σε - εμπεδωμένα σε κύβους παραφίνης – εκατό (n=100) σποραδικά πρωτοπαθή καρκινώματα νεφρού (RCC), προιόντα νεφρεκτομής. Παθολογοανατομικά ταξινομημένα σύμφωνα με τα ιστολογικά κριτήρια της WHO και όσον αφορά τη διαφοροποίηση βαθμονομημένα με το σύστημα κατά Furhman. Τα εξετασθέντα καρκινώματα αφορούσαν σε 75 διαυγοκυτταρικού τύπου (clear cell RCC), 13 θηλώδους τύπου (papillary RCC) και 12 χρωμόφοβου τύπου (chromophobe RCC). Σύμφωνα με τη συνδυασμένη συμβατική και ψηφιακή ανάλυση, υποέκφραση ή απώλεια της έκφρασης της ε-καντχερίνης παρατηρήθηκε σε 52 περιπτώσεις (52%), ενώ οι υπόλοιπες 48 (48%) χαρακτηρίστηκαν από μετρίου εώς ισχυρού βαθμού ανοσοέκφραση. Όσον αφορά τον ιστολογικό τύπο των εξετασθέντων περιστατικών, απώλεια της έκφρασης της ε-καντχερίνης συσχετίσθηκε περισσότερο με τα διαυγοκυτταρικά και θηλώδους τύπου (p=0.001). Ενδιαφέρουσα παρατήρηση αποτελεί ακόμη η προοδευτική απώλεια της έκφραση του μορίου σε σχέση με το βαθμό διαφοροποίησης του νεοπλάσματος κατά ταξινόμηση Fuhrman’s grade classification (p=0.002). Yποέκφραση ή απώλεια της έκφρασης της βιμεντίνης παρατηρήθηκε σε 19 περιπτώσεις (19%), ενώ οι υπόλοιπες 81 (81%) χαρακτηρίστηκαν από μετρίου εώς ισχυρού βαθμού ανοσοέκφραση. Όσον αφορά τον ιστολογικό τύπο των εξετασθέντων περιστατικών, απώλεια της έκφρασης της βιμεντίνης συσχετίσθηκε περισσότερο με τα διαυγοκυτταρικά και θηλώδους τύπου (p=0.001).

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