scholarly journals Comprehensive Immunoprofiles of Renal Cell Carcinoma Subtypes

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 602 ◽  
Author(s):  
Moonsik Kim ◽  
Jin Woo Joo ◽  
Seok Joo Lee ◽  
Yoon Ah Cho ◽  
Cheol Keun Park ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Collecting Duct ◽  
Cathepsin K ◽  
Renal Tumors ◽  
Duct Carcinoma ◽  
Epithelial Tumors ◽  
Papillary Type

In recent years, renal epithelial tumors have been among the fastest reclassifying tumors, requiring updates to the tumor classification system. Nonetheless, immunohistochemistry (IHC) remains the most widely used tool for renal epithelial tumors. In this proposal, we aimed to create the most efficient IHC panel for categorizing the diverse subtypes of renal tumors, and to find out more specific immunohistochemical results in each subtype or each antibody. A total of 214 renal tumors were analyzed using 10 possible IHC markers to differentiate subtypes, including three major renal cell carcinoma (RCC) subtypes, clear-cell type (50 cases), papillary type (50 cases), and chromophobe type (20 cases), and minor subtypes (MiT RCC, 13 cases; collecting duct carcinoma, 5 cases; and oncocytoma, 10 cases). A triple immunomarker (cytokeratin 7 (CK7)-carbonic anhydrase IX (CAIX)- alpha-methylacyl-CoA racemase (AMACR)) panel is useful in particular high-grade clear-cell tumors. If IHC remains ambiguous, the use of an adjunctive panel can be suggested, including CD10, epithelial membrane antigen, cathepsin K, c-kit, hepatocyte nuclear factor 1-β, and E-cadherin. For an efficient immunohistochemical strategy for subtyping of RCC, we conclude that the CK7-CAIX-AMACR panel is the best primary choice for screening subtyping.

scholarly journals The Differential Diagnosis of Medullary-Based Renal Masses

2021 ◽  
Author(s):  
Nicholas Baniak ◽  
Harrison Tsai ◽  
Michelle S. Hirsch
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Collecting Duct ◽  
Fumarate Hydratase ◽  
Growth Patterns ◽  
Renal Tumors ◽  
Renal Masses ◽  
Duct Carcinoma

Context.— Renal malignancies can be divided into cortical- and medullary-based tumors, the latter of which classically infiltrate the renal parenchyma by extending between nonneoplastic structures. Although high-grade cortical tumors can rarely exhibit the same growth pattern, the infiltrative morphology should elicit a differential diagnosis to be considered in each case. However, these diagnoses can be challenging to distinguish, especially on small renal biopsy samples. Objective.— To provide an overview of the clinical, gross, and microscopic findings; genetic and molecular alterations; and immunohistochemical evaluation of medullary-based renal tumors and other tumor types with overlapping morphologies and growth patterns. Data Sources.— Literature review and personal observations were used to compile the information in this review. Conclusions.— Collecting duct carcinoma is a prototypical medullary-based tumor, and although diagnostic criteria exist, it remains a diagnosis of exclusion, especially with ancillary techniques aiding the recognition of established as well as more recently described neoplasms. Other medullary-based malignancies included in the differential diagnosis include renal medullary carcinoma/renal cell carcinoma unclassified with medullary phenotype, fumarate hydratase–deficient renal cell carcinoma, and upper tract urothelial carcinoma. Moreover, other rare entities should be excluded, including metastatic carcinoma, lymphoma, and melanoma. In addition to potential prognostic differences, accurate diagnoses can have important surgical and clinical management implications.

Renal Tumor With Overlapping Distal Nephron Morphology and Karyotype

2004 ◽  
Vol 128 (11) ◽  
pp. 1274-1278 ◽  
Author(s):  
Valerie Lindgren ◽  
Gladell P. Paner ◽  
Robert C. Flanigan ◽  
Joseph I. Clark ◽  
Steven C. Campbell ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Collecting Duct ◽  
Chromophobe Renal Cell Carcinoma ◽  
Renal Tumors ◽  
Distal Nephron ◽  
Duct Carcinoma ◽  
Collecting Duct Carcinoma ◽  
Not Otherwise Specified

Abstract Although most renal epithelial tumors are derived from the proximal nephron, approximately 10% are believed to originate in the distal nephron. This latter group encompasses oncocytoma, chromophobe renal cell carcinoma, and several rare types, including collecting duct carcinoma and renal medullary carcinoma. Despite progress in the classification of renal tumors, a small subset of renal carcinomas remains unclassified (ie, renal cell carcinoma, not otherwise specified). We describe a metastatic tumor consisting of cells with overlapping distal nephron morphologies, including foci of oncocytoma, chromophobe renal cell carcinoma, and collecting duct carcinoma, as well as sarcomatoid dedifferentiation. Special stains were inconclusive, and ultrastructural study demonstrated abundant mitochondria and no microvesicles. The karyotype was hypodiploid with 41 chromosomes and abnormalities reported in all 3 phenotypes present. Rearrangements of 1p and of 11q13 previously seen in divergent subsets of oncocytomas were concomitantly present in the current tumor. Thus, this malignancy has features consistent with distal nephron derivation and demonstrates the convergence of the varied tumor morphologies arising within this site. Furthermore, this case exemplifies the value of cytogenetic analysis in the characterization of renal cell carcinoma, not otherwise specified. In view of recent advances in treatment approach, especially for collecting duct carcinoma, further categorization of this nondescript and heterogeneous group of renal cell carcinomas, not otherwise specified, at least by its derivation in relationship to the renal nephron (distal vs proximal), may be of value in the choice of treatment modality.

scholarly journals Collecting Duct Carcinoma: A Rare Entity

2020 ◽  
Vol 4 (1) ◽  
pp. 129
Author(s):  
Ferdinant Martinus Djawa ◽  
Anny Setijo Rahaju
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Histopathological Examination ◽  
Collecting Duct ◽  
Abdominal Mass ◽  
Left Kidney ◽  
Renal Tumors ◽  
Duct Carcinoma ◽  
Collecting Duct Carcinoma

ABSTRACTCollecting duct carcinoma is a rare and highly aggressive subtype of renal cell carcinoma. The incidence rate is less than 1-2% of all renal tumors and usually, affect middle-aged adult, commonly in men. We reported a 76-year-old man complains of an intermittent painless gross hematuria, abdominal mass and left flank pain for approximately three months. The CT abdomen showed a slightly enhancing solid mass in the left kidney and para-aorta lymphadenopathy. Cut surfaces of the kidney showed a solid-cystic and ill-defined greyish-white tumor. Microscopically, tumor formed solid sheets and tubulopapillary structures lined by neoplastic cells, hobnailing nuclei, abnormal mitotic, and a desmoplastic stroma with lymphoplasmacytic infiltration, and the immunochemical profile were PAX8 (+) /p63 (-). Based on these findings, the diagnosis was a collecting duct carcinoma. This tumor arising from the collecting duct of Bellini in the renal medulla, accounts for less than 1-2% of all renal masses and important to be distinguished from other tumors due to differences in prognosis and therapeutic. Histopathological examination is needed to establish the diagnosis. A case of collecting duct carcinoma that occurred in a 76-year-old man has been reported. A definitive diagnosis can only be done with a detailed histopathological examination for patient management benefits.Keywords          : renal cell carcinoma, collecting duct carcinoma, urothelial carcinoma, PAX8, p63

scholarly journals Cathepsin K: A Novel Diagnostic and Predictive Biomarker for Renal Tumors

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2441
Author(s):  
Anna Caliò ◽  
Matteo Brunelli ◽  
Stefano Gobbo ◽  
Pedram Argani ◽  
Enrico Munari ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Therapy Response ◽  
Cathepsin K ◽  
Mtor Inhibitors ◽  
Predictive Marker ◽  
Predictive Biomarker ◽  
Renal Tumors ◽  
Epithelioid Angiomyolipoma

Cathepsin K is a papain-like cysteine protease with high matrix-degrading activity. Among several cathepsins, cathepsin K is the most potent mammalian collagenase, mainly expressed by osteoclasts. This review summarizes most of the recent findings of cathepsin K expression, highlighting its role in renal tumors for diagnostic purposes and as a potential molecular target. Indeed, cathepsin K is a recognized diagnostic tool for the identification of TFE3/TFEB-rearranged renal cell carcinoma, TFEB-amplified renal cell carcinoma, and pure epithelioid PEComa/epithelioid angiomyolipoma. More recently, its expression has been observed in a subgroup of eosinophilic renal neoplasms molecularly characterized by TSC/mTOR gene mutations. Interestingly, both TSC mutations or TFE3 rearrangement have been reported in pure epithelioid PEComa/epithelioid angiomyolipoma. Therefore, cathepsin K seems to be a downstream marker of TFE3/TFEB rearrangement, TFEB amplification, and mTOR pathway activation. Given the established role of mTOR inhibitors as a pharmacological option in renal cancers, cathepsin K could be of use as a predictive marker of therapy response and as a potential target. In the future, uropathologists may implement the use of cathepsin K to establish a diagnosis among renal tumors with clear cells, papillary architecture, and oncocytic features.

scholarly journals Implications of Programmed Death Ligand-1 Positivity in Non-Clear Cell Renal Cell Carcinoma

2018 ◽  
Vol 5 (4) ◽  
pp. 6-13 ◽  
Author(s):  
Juan Chipollini ◽  
Mounsif Azizi ◽  
Charles C Peyton ◽  
Dominic H Tang ◽  
Jasreman Dhillon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Type I ◽  
Cell Renal Cell Carcinoma ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Papillary Type

The purpose of this study was to assess the prognostic value of programmed death ligand-1 (PD-L1) positivity in a non-clear cell renal cell carcinoma (non-ccRCC) cohort. PD-L1 expression was evaluated by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded (FFPE) specimens from 45 non-ccRCC patients with available tissue. PD-L1 positivity was defined as ?1% of staining. Histopathological characteristics and oncological outcomes were correlated to PD-L1 expression. Cancer-specific survival (CSS) and recurrence-free survival (RFS) stratified by PD-L1 status were estimated using the Kaplan–Meier method. Median age was 58 years and median follow-up was 40 months. Non-ccRCC subtypes included sarcomatoid (n = 9), rhabdoid (n = 6), medullary (n = 2), Xp11.2 translocation (n = 2), collecting duct (n = 1), papillary type I (n = 11), and papillary type II (n = 14). PD-L1 positivity was noted in nine (20%) patients. PD-L1 positivity was significantly associated with higher Fuhrman nuclear grade (P = 0.048) and perineural invasion (P = 0.043). Five-year CSS was 73.2 and 83% for PD-L1 positive and negative tumors, respectively (P = 0.47). Five-year RFS was 55.6 and 61.5% for PD-L1 positive and negative tumors, respectively (P = 0.58). PD-L1 was expressed in a fifth of non-ccRCC cases and was associated with adverse histopathologic features. Expression of biomarkers such PD-L1 may help better risk-stratify non-ccRCC patients to guide treatment decisions and follow-up strategies.

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.

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.

scholarly journals Renal Tumors in Young Adults: Is Preoperative Computer Tomography Imaging Suggestive for the Nature of the Tumors?

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 380
Author(s):  
Andreea Zaharie ◽  
Sorana D. Bolboacă ◽  
Tudor Moisoiu ◽  
Dan Burghelea ◽  
Gheorghita Iacob ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Young Adults ◽  
Cell Carcinoma ◽  
Computer Tomography ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumors ◽  
Tomography Imaging ◽  
Computer Tomography Imaging

Renal cell carcinoma (RCC) accounts for 2–3% of all adult malignant neoplasms and is even rarer in patients under 45 years old. Clear-cell carcinoma represents most of the pathological subtypes. Our study aimed to investigate the association between preoperative computer tomography imagistic evaluation and histopathological diagnosis of renal tumors in young adults. Patients younger than 45 years old with renal tumors who were referred for medical treatment at the Clinical Institute of Urology and Renal Transplantation Cluj-Napoca from 2012 to 2019 were considered eligible for the study. Medical charts were retrospectively reviewed, and patients with complete data regarding preoperative diagnostic, histopathological evaluation, and follow-up data, regardless of gender, were included in the study. Sixteen patients younger than 45 years fulfilled all the inclusion criteria and were evaluated. With two exceptions, the evaluated patients were in a T1 and T2 stage, with no vascular invasion or of the adjacent organs. Two-thirds of our patients had a clear-cell renal cell carcinoma. None of our patients fitted in the low complexity surgery category of the R.E.N.A.L. Nephrometry Score and 37.5% of them benefited from partial nephrectomy. Half of the suppositions made based on imaging were concordant with the histopathology report. Fifteen of the patients showed no recurrence during the respective follow-up interval. Computer tomography imaging reports showed on our sample a higher concordance with the histopathological report in the more common subtypes (namely Renal Clear Cell RCC), with typical appearances.

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.

Histopathology in surgically treated renal cell carcinoma: Is there a survival difference when stratified by stage?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5089-5089
Author(s):  
K. A. Keegan ◽  
N. J. Hellenthal ◽  
K. Chamie ◽  
T. M. Koppie
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Collecting Duct ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Cancer Specific Survival ◽  
Stage Disease ◽  
The Impact

5089 Background: The impact of renal cell carcinoma histopathology (RCC) on survival has been conflicting and limited to retrospective institutional studies. Therefore, we sought to determine the role of RCC histopathology on stage-specific survival rates in a population-based cohort. Methods: We utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results database and identified 21,258 patients who underwent partial or radical nephrectomy for RCC between 1996 and 2004. Patients were stratified based on histopathologic diagnosis (clear cell, papillary, chromophobe, sarcomatoid, and collecting duct) and pathologic stage. We performed Cox-proportional hazard modeling and Kaplan-Meier survival analyses to determine overall- and cancer-specific survival. Results: Using univariate analysis, histopathology significantly impacted overall- and cancer-specific survival (p< 0.001). Specifically, patients with papillary and chromophobe variants had lower stage disease at the time of surgery and had improved survival compared to clear cell subtypes, (HR: 0.50; 95% CI, 0.42–0.60 and HR: 0.31; 95% CI, 0.22–0.44, respectively). When controlled for stage, improved outcomes for chromophobe and papillary histologies persisted, although it did not achieve statistical significance at all stages. On the other hand, patients with sarcomatoid disease were more likely to present with high stage disease and invariably had worse survival compared to clear cell carcinoma (HR: 8.74; 95%, CI 7.70–9.91). When controlled for stage, this difference achieved statistical significance across all stages (p< 0.001). Conclusions: Histopathologic subtype in patients with RCC does predict overall- and cancer-specific survival. Patients with sarcomatoid RCC, even those presenting with low-stage disease, have poor survival. These findings may give further value to recent data suggesting the increased utility of percutaneous renal biopsy and its potential impact on management. [Table: see text] No significant financial relationships to disclose.

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