WITH INCREASING TUMOUR SIZE HISTOPATHOLOGICAL FEATURES ARE MORE AGGRESSIVE IN CLEAR CELL RCC, BUT NOT IN PAPILLARY RCC

AbstractTo investigate the detection of peritumoral pseudocapsule (PC) using multi-detector row computed tomography (MDCT) for tumors resected by robot-assisted laparoscopic partial nephrectomy (RAPN) for T1 renal cell carcinoma (RCC). Study participants included 206 patients with clinical T1 RCC who underwent RAPN between October 2017 and February 2018. Two radiologists who were blinded to the pathological findings evaluated the computed tomography (CT) images. Radiological diagnosis of a PC was defined by a combination of observations, including a low-attenuation rim between the tumor and renal cortex in the cortico-medullary phase and a high-attenuation rim at the edge of the tumor in the nephrogenic or excretory phase. A PC was detected on CT in 156/206 tumors (76%) and identified by pathology in 182/206 (88%) tumors including 153/166 (92%) clear cell RCC, 13/14 (93%) papillary RCC, and 7/16 (44%) chromophobe RCC. In the whole cohort, CT findings showed a sensitivity of 81.3% (148/182), specificity of 66.7% (16/24), and positive predictive value of 94.9% (148/156). When the data were stratified according to pathological subtypes, MDCT was observed to have a sensitivity of 86.9% (133/153) and specificity of 61.5% (8/13) in clear cell RCC, sensitivity of 38.5% (5/13) and specificity of 100% (1/1) in papillary RCC, and sensitivity of 44.4% (4/7) and specificity of 66.7% (6/9) in chromophobe RCC. A low or high-attenuation rim around the tumor in the cortico-medullary or nephrographic-to-excretory phase indicates a PC of RCC, though the accuracy is not satisfactory even with 64- or 320-detector MDCT.

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Ιστική μελέτη στην επιθήλιο-μεσεγχυματική μετατροπή σε νεφροκυτταρικό καρκίνωμα

10.12681/eadd/49844 ◽

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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Patients with metastatic papillary renal cell carcinoma (RCC) who may benefit from sunitinib therapy (tx): Results from an international metastatic RCC database.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.486 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 486-486 ◽

Cited By ~ 1

Author(s):

Daniel Kejzman ◽

Maya Gottfried ◽

Natalie Maimon ◽

Hans J. Hammers ◽

Mario A. Eisenberger ◽

...

Keyword(s):

Cox Regression ◽

Clear Cell ◽

Progression Free Survival ◽

Papillary Renal Cell Carcinoma ◽

Active Smoking ◽

Factors Associated ◽

Clinicopathologic Factors ◽

Papillary Rcc ◽

Clear Cell Rcc ◽

Pre Treatment

486 Background: The VEGFR inhibitor sunitinib is a standard tx for metastatic clear cell RCC. Data on the activity of sunitinib in metastatic non clear cell RCC, is limited by small or heterogeneous (mixed histology or targeted therapies) studies, that revealed a lower antitumor activity than in patients with clear cell histology. We aimed to analyze the activity of sunitinib in a large international cohort of patients with metastatic papillary RCC, and to characterize patients who may benefit for this therapy. Methods: Records from metastatic papillary RCC patients treated with sunitinib in 10 centers across 3 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and clinical outcome were performed using Cox regression. Results: Between 2004-2013, 74 patients (median age 60, 68% male) with metastatic papillary RCC were treated with sunitinib. 78% had a prior nephrectomy. HENG risk was good 11%, intermediate 56%, and poor 33%. 21% were active smokers, and 31% users of angiotensin system inhibitors. 24% and 41% had liver and bone metastases, respectively. 55% had a pre-treatment neutrophil to lymphocyte ratio (NLR) >3. 40% had dose reduction/treatment interruption. Sunitinib induced hypothyroidism and hypertension (HTN) occurred in 30% and 43%, respectively. 70% achieved a clinical benefit (partial response + stable disease), while 30% had disease progression within the first 3 months of therapy. Median progression free survival (PFS) and overall survival (OS) were 5 and 12 months, respectively. 27% had a PFS ≥ 1 year, and 26% survived ≥ 2 years. Factors associated with PFS were sunitinib induced HTN (HR 0.31, p=0.002), pre-treatment NLR >3 (HR 5.3, p=0.001), and active smoking (HR 2.5, p=0.01). Factors associated with OS were sunitinib induced hypothyroidism (HR 0.4, p=0.024), past nephrectomy (HR 0.41, p=0.02), pre-treatment NLR >3 (HR 2.25, p=0.036), and active smoking (HR 2.3, p=0.027). Conclusions: Clinicopathologic factors may be used to identify patients with metastatic papillary RCC who may benefit from sunitinib tx. A prolonged PFS and OS were noted in 26-27% of patients.

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Various Histological Types of Renal Cell Carcinoma Associated With Hereditary Papillary Renal Cell Carcinoma (HPRCC): a Case Report

10.21203/rs.3.rs-736943/v1 ◽

2021 ◽

Author(s):

Sophie FERLICOT ◽

Pierre-Alexandre Just ◽

Eva Compérat ◽

Etienne Rouleau ◽

Frédérique Tissier ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Papillary Renal Cell Carcinoma ◽

Type I ◽

Renal Cell Carcinomas ◽

Genomic Study ◽

Papillary Rcc ◽

Clear Cell Rcc

Abstract Background: Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, distinctive histological features of RCC are described according to the familial renal cell carcinoma syndrome. To date, no clear cell RCC has been reported in HPRCC syndrome. Case presentation: We describe the case of a 51-year-old man with a germline MET mutation, who developed numerous papillary tumors but also unexpectedly clear cell renal cell carcinomas. During the follow-up, an adrenal metastasis was observed seven years after the initial diagnosis corresponding to a clear cell RCC metastasis. Using FISH, the metastatic tumor presented a trisomy of chromosomes 7 and 17. These genomic alterations are usually detected in papillary RCC, highlighting the potential link between both histological subtypes of tumors and the HPRCC syndrome.Conclusions: The pathologist must be aware that the presence of a non-papillary RCC associated with numerous papillary tumors should not exclude the diagnostic suspicion of HPRCC and thus to perform a thorough genomic study.

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FLUORESCENT IN SITU HYBRIDIZATION AND IMMUNOHISTOCHEMISTRY FOR SUBTYPING “NON-CLASSIFIABLE” RENAL CELL CARCINOMAS

Knowledge International Journal ◽

10.35120/kij3104921i ◽

2019 ◽

Vol 31 (4) ◽

pp. 921-924

Author(s):

Atanas Ivanov ◽

Vili Stoyanova

Keyword(s):

In Situ Hybridization ◽

Genetic Analysis ◽

Renal Cell ◽

Clear Cell ◽

Renal Tumors ◽

Renal Cell Carcinomas ◽

Trisomy 7 ◽

Papillary Rcc ◽

Clear Cell Rcc

Renal tumors account for about 3% of the malignancies in adults. Clear cell subtype renal cell carcinoma (RCC) and papillary RCC are the most common renal tubular epithelial carcinomas and their differentiation is important because they have a different prognosis and are associated with different treatment protocols. In most cases, histological features allow accurate diagnosis of renal cell carcinomas. There are also overlapping morphological findings between certain kidney neoplasms that make their subtyping extremely difficult. Some of them display papillary architecture but also have a clear cell component and it is not clear whether they should be classified as clear cell RCC or papillary RCC. In our study we performed an immunohistochemical and genetic analysis of 24 cases of RCC classified as non-classifiable with mixed papillary and clear cell components treated at Clinic of Urology in University Hospital "St. George "-Plovdiv. The mean age of patients was 54.5 years, and gender distribution: 60% male and 40% female. Based on the results of immunohistochemistry and fluorescence in situ hybridization (FISH), patients were stratified in 2 groups. The first group included 16 of the cases where strong immunoreactivity was found for alfa-methyl coenzyme A racemase (AMACR), with cytokeratin 7 (CK7) being present in 15 of these. In all cases in this group, FISH proved trisomy 7 and 17, in 4-9p deletion, and in 2- 3p deletion. The remaining 8 cases were stratified in the second group - all negative for CK7 and only one positive for AMACR. Genetic analysis showed a lack of trisomy 7 and 17 in all cases, as well as a deletion of 3p and 9p in 7 of them. The combination of immunohistochemical and genetic analyzes allows with a high accuracy to differentiate cases of papillary RCC from those with clear cell RCC.

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Characteristics and Treatment Challenges of Non-Clear Cell Renal Cell Carcinoma

Cancers ◽

10.3390/cancers13153807 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3807

Author(s):

Pierangela Sepe ◽

Arianna Ottini ◽

Chiara Carlotta Pircher ◽

Andrea Franza ◽

Melanie Claps ◽

...

Keyword(s):

Renal Cell ◽

Kinase Inhibitors ◽

Clear Cell ◽

Case Reports ◽

Treatment Options ◽

Single Agent ◽

Growth Factor Receptor ◽

Mtor Inhibitors ◽

Cell Renal Cell Carcinoma ◽

Clear Cell Rcc

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options.

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Two Cases of Sporadic Eosinophilic Solid and Cystic Renal Cell Carcinoma in Manitoba Population

International Journal of Surgical Pathology ◽

10.1177/1066896921993229 ◽

2021 ◽

pp. 106689692199322

Author(s):

Seyed Mohammad Mohaghegh Poor ◽

Shivani Mathur ◽

Karl Kassier ◽

Janetta Rossouw ◽

Robert Wightman ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Preoperative Imaging ◽

Renal Neoplasm ◽

Renal Masses ◽

Cystic Renal Cell Carcinoma ◽

Eosinophilic Cytoplasm ◽

Clear Cell Rcc

Two sporadic cases of eosinophilic solid and cystic renal cell carcinoma (ESC RCC), at our institution, are presented in this study to contribute to the growing literature on this novel renal neoplasm. The first patient was a 38-year-old female with two synchronous renal masses measuring 3.5 and 1.9 cm on preoperative imaging. The second patient was a 44-year-old female with an incidental renal mass measuring 4 cm. Both patients underwent uncomplicated radical nephrectomies. The 1.9 cm mass in the first patient was consistent with clear cell RCC. The dominant mass in the first patient and the tumor in the second patient had microscopic and macroscopic findings in keeping with ESC RCC including a tan appearance, abundant eosinophilic cytoplasm, and CK20+ and CK7− staining. Both patients had an uncomplicated course following surgery with no evidence of local recurrence or distant metastatic disease for 1 and 2 years for the first and second patient accordingly. These cases contribute to a growing body of literature regarding ESC RCC including, to our knowledge, the first reported case of synchronous ESC RCC and clear cell RCC. Further research about this novel renal neoplasm is needed.

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Nivolumab plus cabozantinib in patients with non-clear cell renal cell carcinoma: Results of a phase 2 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4509 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4509-4509

Author(s):

Chung-Han Lee ◽

Martin H Voss ◽

Maria Isabel Carlo ◽

Ying-Bei Chen ◽

Eduard Reznik ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Clear Cell ◽

Phase 2 ◽

Phase 3 ◽

Cell Renal Cell Carcinoma ◽

Stage Design ◽

Phase 2 Trial ◽

Clear Cell Rcc ◽

Grade 3

4509 Background: Cabozantinib plus nivolumab (CaboNivo) improved objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) over sunitinib in a phase 3 trial for metastatic clear cell renal cell carcinoma (RCC). (Choueiri, abstract 6960, ESMO 2020) We report the results of a phase 2 trial of CaboNivo in patients (pts) with non-clear cell RCC. Methods: Pts had advanced non-clear cell RCC, 0 or 1 prior systemic therapies excluding prior immune checkpoint inhibitors, and measurable disease by RECIST. Cabo 40 mg/day plus Nivo 240 mg every 2 weeks or 480 mg every 4 weeks was given across two cohorts. Cohort 1: papillary, unclassified, or translocation associated RCC; Cohort 2: chromophobe RCC. The primary endpoint was ORR by RECIST; secondary endpoints included PFS, OS, and safety. Cohort 1 was a single stage design that met its primary endpoint and was expanded to produce more precise estimates of ORR. Cohort 2 was a Simon two-stage design that closed early for lack of efficacy. Correlative analyses by next generation sequencing were performed and to be presented. Results: A total of 40 pts were treated in Cohort 1, and 7 pts were treated in Cohort 2 (data cutoff: Jan 20, 2021). Median follow up time was 13.1 months (range 2.2 – 28.6). In Cohort 1, 26 (65%) pts were previously untreated, and 14 (35%) pts had 1 prior line: 10 (25%) received prior VEGF-targeted therapy and 8 (20%) received prior mTOR-targeted therapy. ORR for Cohort 1 was 48% (95% CI 31.5–63.9; Table). Median PFS was 12.5 months (95% CI 6.3–16.4) and median OS was 28 months (95% CI 16.3–NE). No responses were seen among 7 patients in Cohort 2 with chromophobe histology (Table). Grade 3/4 treatment emergent adverse events were consistent with that reported in the phase 3 trial; Grade 3/4 AST and ALT were 9% and 15%, respectively. Cabozantinib and nivolumab were discontinued due to toxicity in 17% and 19% of pts, respectively. Conclusions: CaboNivo had an acceptable safety profile and showed promising efficacy in metastatic non-clear cell RCC pts with papillary, unclassified, or translocation associated histologies whereas activity in patients with chromophobe RCC was limited. Clinical trial information: NCT03635892. [Table: see text]

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Outcomes with novel combinations in non-clear cell renal cell carcinoma(nccRCC): ORACLE study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4580 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4580-4580

Author(s):

Deepak Kilari ◽

Aniko Szabo ◽

Pooja Ghatalia ◽

Tracy L Rose ◽

Nicole Weise ◽

...

Keyword(s):

Clear Cell ◽

Objective Response ◽

Mammalian Target Of Rapamycin ◽

Progression Free Survival ◽

Mtor Inhibitors ◽

New Combination ◽

Clinical Activity ◽

Cell Renal Cell Carcinoma ◽

Clear Cell Rcc ◽

Rhabdoid Differentiation

4580 Background: Despite advances in the treatment of clear cell RCC, there is a paucity of data to guide management of nccRCC due to the heterogeneity and rarity of these tumors. The clinical activity of new combination therapies (including immunotherapy (IO), anti-vascular endothelial growth factor inhibitors (VEGF), and mammalian target of rapamycin (mTOR) inhibitors) in metastatic nccRCC is not known. Methods: In this multicenter retrospective analysis, we explored the efficacy of combination systemic therapies in patients with nccRCC. Baseline and follow-up demographic, clinical, treatment, and radiographic data were collected. The primary endpoint was objective response rate (ORR) assessed by investigator review. Secondary endpoints include progression- free survival (PFS), disease control rate (DCR), median duration of response (DOR), overall survival (OS), and biomarker correlates. Results: Among 66 included patients, median age was 59 yr; 60% were male and 62% white. Histologies included papillary (38%), chromophobe (17%), unclassified (24%), translocation (12%), and other (9 %). Sarcomatoid and/or rhabdoid differentiation was present in 18%, 70% had prior nephrectomy, 86% were IMDC intermediate/poor risk, 29% and 32% had liver and bone metastasis respectively. 67% received combination treatment in the first line. Comparison of outcomes based on treatment regimen is shown in the table. Conclusions: Antitumor activity was observed with novel combinations in nccRCC which warrants further prospective studies. Response rates and survival with combination therapy in this dataset remain inferior to rates seen in clear cell RCC.[Table: see text]

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Chromophobe Renal Cell Carcinoma With Retrograde Venous Invasion and Gain of Chromosome 21: Potential Harbingers of Aggressive Clinical Behavior

International Journal of Surgical Pathology ◽

10.1177/1066896918763948 ◽

2018 ◽

Vol 26 (6) ◽

pp. 536-541 ◽

Cited By ~ 2

Author(s):

Mohsin Jamal ◽

Kanika Taneja ◽

Sohrab Arora ◽

Ravi Barod ◽

Craig G. Rogers ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Aggressive Behavior ◽

Cell Carcinoma ◽

Renal Cell ◽

Renal Vein ◽

Clear Cell ◽

Venous Invasion ◽

Chromosome 21 ◽

Chromophobe Rcc ◽

Clear Cell Rcc

Occasionally, renal cell carcinoma (RCC) with renal vein extension spreads against the flow of blood within vein branches into the kidney, forming multifocal nodules throughout the renal parenchyma. These foci are not regarded as multiple tumors but rather reverse spread of tumor along the venous system. This intravascular spread has previously been reported in clear cell RCC and RCC unclassified. However, to our knowledge, this has never been reported in chromophobe RCC. Chromophobe RCC is a unique histologic subtype of renal cancer, generally thought to have less aggressive behavior. However, it nonetheless has the potential to undergo sarcomatoid dedifferentiation, which is associated with poor prognosis. We report a unique case of a 65-year-old man with chromophobe RCC (pT3a) showing classic morphology (nonsarcomatoid), yet presenting with retrograde venous invasion and hilar lymph node metastasis at the time of right radical nephrectomy. Fluorescence in situ hybridization revealed gain of chromosome 21 with loss of multiple other chromosomes. Partial hepatectomy was performed to resect metastatic RCC 7 months after nephrectomy, revealing chromophobe RCC with classic morphology. Bone biopsy confirmed skeletal metastases 38 months after initial diagnosis. Although invasion of the renal vein and retrograde venous invasion are characteristically seen in clear cell RCC, this unusual phenomenon may also occur in chromophobe RCC, despite its unique tumor biology. This and gain of chromosome 21, which was postulated to be associated with aggressive behavior in a previous report, were associated with adverse behavior in our patient, who had short-term progression to multi-organ metastatic disease.

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