Cases Of Papillary Renal Cell Carcinoma Research Articles

Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma: a clinicopathologic and molecular study of 17 renal cell carcinomas including 10 papillary adenomas.

Biphasic papillary renal cell carcinoma (synonymous with biphasic squamoid alveolar renal cell carcinoma) is considered within the spectrum of papillary renal cell carcinoma (PRCC). With < 70 reported cases of biphasic PRCC, there is limited data on the pathologic spectrum and clinical course. Seventeen biphasic PRCC cases and 10 papillary adenomas with similar biphasic morphology were assessed. The mean age of the biphasic PRCC patients was 62years (male to female ratio of 1.8:1), from 10 partial nephrectomies, 6 radical nephrectomies, and 1 biopsy. The mean tumor size was 3.6cm (range 1.6-8cm), with 24% showing multifocality. Fifteen out of 17 cases were limited to the kidney (one of which was staged as pT2a but had lung metastases at diagnosis) and 2/17 cases were staged as T3a. All tumors showed typical biphasic morphology with an extent of squamoid foci widely variable from 10 to 95%. Emperipolesis was identified in 88% of cases. All biphasic PRCC tested exhibited positivity for PAX8 (16/16), keratin 7 (17/17), EMA (15/15), AMACR (17/17), and vimentin (12/12) in both large and small cells; cyclin D1 was only expressed in the large cells (16/16). The 10 papillary adenomas showed a similar immunoprofile to biphasic PRCC. NGS testing performed on 13 biphasic PRCC revealed 4 (31%) harboring MET SNVs. In 1/5 (20%) papillary adenomas, a pathogenic MET SNV was identified. Biphasic PRCC is rare with a generally similar immunoprofile to "type 1" PRCC but with notable strong positivity for cyclin D1 in the large cell component. Although most of the biphasic PRCC cases were of small size, low stage, and with an indolent behavior, one patient had metastatic disease and one patient died of the disease.

SARS-CoV-2 replicates and displays oncolytic properties in clear cell and papillary renal cell carcinoma.

The SARS-CoV-2 virus is currently causing a global pandemic. Infection may result in a systemic disease called COVID-19, affecting primarily the respiratory tract. Often the gastrointestinal tract and kidneys also become involved. Angiotensin converting enzyme 2 (ACE2) serves as the receptor for SARS-CoV-2. The membrane proteins, Transmembrane serine protease 2 (TMPRSS2) and Neuropilin 1 (NRP1) are accessory proteins facilitating the virus entry. In this study we show that the human proximal kidney tubules, express these factors. We hypothesized that cancers derived from proximal tubules as clear cell (CCRCC) and papillary renal cell carcinoma (PRCC), retain the expression of the SARS-CoV-2 entry factors making these cancers susceptible to SARS-CoV-2 infection. We used bioinformatics, western blotting, and assessment of tissue micro arrays (TMA) including 263 cases of CCRCC, 139 cases of PRCC and 18 cases of chromophobe RCC to demonstrate that the majority of CCRCC and PRCC cases retained the RNA and protein expression of the entry factors for SARS-CoV-2. We furthermore show that SARS-CoV-2 virus propagated robustly in primary cultures of CCRCC and PRCC cells with a visible virus cytopathogenic effect correlating with viral RNA expression levels. We also noted that the delta-variant of SARS-CoV-2 causes cancer cells to form syncytia in-vitro. This phenomenon was also identified histologically in CCRCC tissue from a patient that had been hospitalized for COVID-19, twelve months prior to nephrectomy. Our data provide insights into SARS-CoV-2 infectivity in renal cell carcinoma and that the virus causes a distinct cytopathogenic effect.

High CENPA expression in papillary renal cell carcinoma tissues is associated with poor prognosis.

ObjectiveThis work focused on investigating the relation of centromeric protein A (CENPA) gene expression with prognosis of papillary renal cell carcinoma (PRCC).MethodsWe obtained data from PRCC cases in TCGA. Thereafter, CENPA levels between the paired PRCC and matched non-carcinoma samples were analyzed by Wilcoxon rank-sum test, while the relations of clinicopathological characteristics with CENPA level were examined by logistic regression and Wilcoxon rank-sum test. The prognostic value of CENPA was assessed by plotting the receiver operating feature curve (ROC) and calculating the value of area under curve (AUC). In addition, relations between clinicopathological characteristics and PRCC survival were analyzed through Kaplan–Meier (KM) and Cox regression analyses. After dividing the total number of patients into the trial cohort and the validation cohort in a ratio of 7:3, we constructed a nomogram in trial cohort according to multivariate Cox regression results for predicting how CENPA affected patient survival and used the calibration curve to verify its accuracy in both cohorts. We also determined CENPA levels within cancer and matched non-carcinoma samples through immunohistochemistry (IHC). Finally, we utilized functional enrichment for identifying key pathways related to differentially expressed genes (DEGs) between PRCC cases with CENPA up-regulation and down-regulation.ResultsCENPA expression enhanced in PRCC tissues compared with healthy counterparts (P < 0.001). CENPA up-regulation was related to pathological TNM stage and clinical stage (P < 0.05). Meanwhile, the ROC curves indicated that CENPA had a remarkable diagnostic capacity for PRCC, and the expression of CENPA can significantly improve the predictive accuracy of pathological TNM stage and clinical stage for PRCC. As revealed by KM curves, PRCC cases with CENPA up-regulation were associated with poor survival compared with those with CENPA down-regulation (Risk ratio, RR = 3.07, 95% CI: 1.58–5.97, P = 0.001). In the meantime, univariate as well as multivariate analysis showed an independent association of CENPA with overall survival (OS, P < 0.05) and the nomogram demonstrated superior predictive ability in both cohorts. IHC analysis indicated that PRCC cases showed an increased CENPA positive rate compared with controls. As revealed by functional annotations, CENPA was enriched into pathways associated with neuroactive ligand receptor interactions, cytokine receptor interactions, extracellular matrix regulators, extracellular matrix glycoproteins and nuclear matrisome.ConclusionCENPA expression increases within PRCC samples, which predicts dismal PRCC survival. CENPA may become a molecular prognostic marker and therapeutic target for PRCC patients.

Metabolic Adaptation as Potential Target in Papillary Renal Cell Carcinomas Based on Their In Situ Metabolic Characteristics.

Metabolic characteristics of kidney cancers have mainly been obtained from the most frequent clear cell renal cell carcinoma (CCRCC) studies. Moreover, the bioenergetic perturbances that affect metabolic adaptation possibilities of papillary renal cell carcinoma (PRCC) have not yet been detailed. Therefore, our study aimed to analyze the in situ metabolic features of PRCC vs. CCRCC tissues and compared the metabolic characteristics of PRCC, CCRCC, and normal tubular epithelial cell lines. The protein and mRNA expressions of the molecular elements in mammalian target of rapamycin (mTOR) and additional metabolic pathways were analyzed in human PRCC cases compared to CCRCC. The metabolic protein expression pattern, metabolite content, mTOR, and metabolic inhibitor sensitivity of renal carcinoma cell lines were also studied and compared with tubular epithelial cells, as “normal” control. We observed higher protein expressions of the “alternative bioenergetic pathway” elements, in correlation with the possible higher glutamine and acetate consumption in PRCC cells instead of higher glycolytic and mTOR activity in CCRCCs. Increased expression of certain metabolic pathway markers correlates with the detected differences in metabolite ratios, as well. The lower lactate/pyruvate, lactate/malate, and higher pyruvate/citrate intracellular metabolite ratios in PRCC compared to CCRCC cell lines suggest that ACHN (PRCC) have lower Warburg glycolytic capacity, less pronounced pyruvate to lactate producing activity and shifted OXPHOS phenotype. However, both studied renal carcinoma cell lines showed higher mTOR activity than tubular epithelial cells cultured in vitro, the metabolite ratio, the enzyme expression profiles, and the higher mitochondrial content also suggest increased importance of mitochondrial functions, including mitochondrial OXPHOS in PRCCs. Additionally, PRCC cells showed significant mTOR inhibitor sensitivity and the used metabolic inhibitors increased the effect of rapamycin in combined treatments. Our study revealed in situ metabolic differences in mTOR and metabolic protein expression patterns of human PRCC and CCRCC tissues as well as in cell lines. These underline the importance in the development of specific new treatment strategies, new mTOR inhibitors, and other anti-metabolic drug combinations in PRCC therapy.

SAMETA: An open-label, three-arm, multicenter, phase III study of savolitinib + durvalumab versus sunitinib and durvalumab monotherapy in patients with MET-driven, unresectable, locally advanced/metastatic papillary renal cell carcinoma (PRCC).

TPS4601 Background: Papillary renal cell carcinoma (PRCC) is the most common subtype of non-clear cell RCC and accounts for 10–15% of RCCs. Approximately 80% of PRCC cases are MET-driven, characterized by genomic abnormalities resulting in dysregulation of the MET signaling pathway, making these abnormalities a potential therapeutic target for treatment. Savolitinib is an oral, potent and highly selective MET tyrosine-kinase inhibitor (TKI) demonstrating preliminary clinical activity in advanced solid tumors, including in MET-driven PRCC, defined as presence of any of the following molecular alterations, in the absence of co-occurring fumarate hydratase mutations: chromosome 7 gain, MET amplification, MET kinase domain variations, or hepatocyte growth factor amplification. In the Phase III SAVOIR study, in PRCC, savolitinib monotherapy showed encouraging efficacy vs the multi-targeted TKI, sunitinib. In addition, non-clinical studies suggest a possible synergistic anti-tumor effect of MET-inhibitors and programmed cell death-ligand (PD-L1) inhibitors, such as durvalumab; emerging data from the Phase I/II CALYPSO study investigating savolitinib plus durvalumab shows a notable efficacy signal in patients with MET-driven PRCC. Following these findings, the SAMETA study (NCT05043090) is designed to evaluate the efficacy and safety of savolitinib in combination with durvalumab vs sunitinib and durvalumab monotherapy in PRCC. Methods: In this open-label, three-arm, multi-center, Phase III study, adult patients with unresectable, MET-driven and locally advanced/metastatic PRCC are eligible. An estimated 200 patients (25 countries, 165 centers) will be randomized in a 2:1:1 ratio into three treatment arms (A–C) with stratification by International metastatic RCC database consortium risk group &amp; PD-L1 expression tumor status. Arm A: oral savolitinib 600 mg once daily (QD) plus intravenous (IV) durvalumab 1500 mg every 4 weeks (Q4W); Arm B: oral sunitinib 50 mg QD for 4 consecutive weeks, followed by a sunitinib-free interval of 2 weeks Q6W; Arm C: IV durvalumab 1500 mg Q4W. Study treatment continues until RECIST 1.1 disease progression or another discontinuation criterion is met. The primary endpoint is progression-free survival (by BICR; RECIST v1.1). Secondary endpoints include overall survival, objective response rate and duration of response. Safety (adverse events, vital signs, ECG, hematology and biochemistry parameters) will also be reported. The first patient was enrolled onto the study on 28 October 2021. Clinical trial information: NCT05043090.

Papillary renal cell carcinoma: a single institutional study of 199 cases addressing classification, clinicopathologic and molecular features, and treatment outcome

AbstractThe morphologic spectrum of type 1 papillary renal cell carcinoma (PRCC) is not well-defined, since a significant proportion of cases have mixed type 1 and 2 histology. We analyzed 199 cases of PRCC with any (even if focal) type 1 features, with a median follow-up of 12 years, to identify clinicopathological features associated with outcome. Ninety-five tumors (48%) of the cohort contained some type 2 component (median amount: 25%; IQR: 10%, 70%). As a group they showed high rates of progression-free (PFS) and cancer-specific survival (CSS). Tumor size, mitotic rate, lymphovascular invasion, sarcomatoid differentiation, sheet-like architecture, and lack of tumor circumscription were significantly associated with CSS (p ≤ 0.015) on univariate analysis. While predominant WHO/ISUP nucleolar grade was associated with PFS (p = 0.013) and CSS (p = 0.030), the presence of non-predominant (<50%) nucleolar grade did not show association with outcome (p = 0.7). PFS and CSS showed no significant association with the presence or the amount of type 2 morphology. We compared the molecular alterations in paired type 1 and type 2 areas in a subset of 22 cases with mixed type 1 and 2 features and identified 12 recurrently mutated genes including TERT, ARID1A, KDM6A, KMT2D, NFE2L2, MET, APC, and TP53. Among 78 detected somatic mutations, 61 (78%) were shared between the paired type 1 and type 2 areas. Copy number alterations, including chromosome 7 and 17 gains, were similar between type 1 and 2 areas. These findings support that type 2 features in a PRCC with mixed histology represent either morphologic variance or clonal evolution. Our study underscores the notion that PRCC with any classic type 1 regions is best considered as type 1 PRCC and assigned the appropriate WHO/ISUP nucleolar grade. It provides additional evidence that type 2 PRCC as a separate category should be re-assessed and likely needs to be abandoned.

Papillary Renal Cell Carcinomas Demonstrating Micropapillary Features: An Investigation Into the Diagnostic and Prognostic Implications.

Aims: Papillary renal cell carcinoma (PRCC) with micropapillary carcinoma (MC) has been rarely described. We conducted a retrospective descriptive evaluation of the association of MC with PRCC and the possible prognostic implications.Methods: A database search was made at the University of Southern California (USC) and Lenox Hill Hospital (LHH; New York City) in June 2016-June 2019 of PRCC cases with MC. Diagnosis of MC was made using routine histology, based on the presence of small clusters of cells without a vascular core. Features evaluated included: percent of MC, gross appearance, PRCC typing, nuclear grade, lymphovascular invasion, and lymph node metastasis.Results: 848 RCC cases (690 from USC and 157 from LHH); 70 cases PRCC (54 from USC, 16 from LHH) of these cases, 13 had an MC, 12 were from radical nephrectomy, and 12 cases were male. Mean age was 68.3 years; seven were located in the right kidney. Average tumor size was 8.6 cm. MC ranged from 10% to 80% (average 37.5%), nine cases were PRCC type 2 and four type 1. Nuclear grade: three cases (grade 2), nine cases (grade 3), and one case (grade 4); 11 out of 13 tumors presented with extrarenal extension; nine cases that had lymph nodes submitted had metastatic carcinoma.Conclusions: The presence of a micropapillary component in PRCC was found to be 18.5%, and it was predominantly associated with high pathologic stage and lymph node metastases. The clinical course of these tumors seems similar to MC in other tissues/organ systems. We advocate reporting this pattern when identified.

Papillary Renal Cell Carcinoma With Microcystic Architecture Is Strongly Associated With Extrarenal Invasion and Metastatic Disease.

Papillary renal cell carcinoma (PRCC) is well-recognized as a morphologically and molecularly heterogenous group of kidney tumors with variable clinical behavior. Our goal was to analyze a unique histologic pattern of PRCC we have observed in routine practice to evaluate for potential clinical significance or distinct molecular signature. We identified 42 cases of PRCC showing a morphologically distinct architecture characterized by numerous epithelial-lined cysts containing the papillary tumor (herein called "microcysts"), which are typically separated by fibrous stroma. Of the initial 42 case test set with microcystic features, 23 (55%) were stage pT3a or higher. Most tumors had strong and diffuse cytoplasmic immunoreactivity for CK7 (93%, 37/40) and AMACR (100%, 40/40). Fumarate hydratase staining was retained in all cases tested (39/39). We performed next-generation sequencing on 15 of these cases with available tissue and identified chromosomal alterations commonly reported in historically "type 1" PRCC, notably multiple chromosomal gains, particularly of chromosomes 7 and 17, and MET alterations. However, alterations in pathways associated with more aggressive behavior (including SETD2, CDKN2A, and members of the NRF pathway) were also identified in 6 of 15 cases tested (40%). Given this molecular and immunophenotypic data, we subsequently reviewed an additional group of 60 consecutive pT2b-pT3 PRCCs to allow for comparisons between cases with and without microcysts, to assess for potential associations with other recently described histologic patterns (ie, "unfavorable architecture": micropapillary, solid, and hobnail), and to assess interobserver reproducibility for diagnosing architectural patterns and grade. Of the total combined 102 PRCCs, 67 (66%) had microcystic architecture within the intrarenal component but were commonly admixed with other patterns (39% had micropapillary, 31% solid, and 31% hobnail). Twenty-seven cases (26%) had metastatic disease, and 24 of these 27 (89%) had microcystic architecture in the intrarenal tumor. Within the pT3 subset, 21 of 22 cases with metastases (95%) had extrarenal invasion as either individual microcysts in renal sinus fat or aggregates of microcysts bulging beyond the confines of the capsule. Backward elimination and stepwise regression methods to detect features significantly associated with adverse outcome identified solid architecture (hazard ratio [HR]: 6.3; confidence interval [CI]: 2.1-18.8; P=0.001), hobnail architecture (HR: 5.3; CI: 1.7-16.7; P=0.004), and microcystic architecture at the tumor-stromal interface (HR: 4.2; CI: 1.1-16.7; P=0.036) as strongest. Of architectural patterns and grade, the microcystic pattern had a substantial interobserver agreement (κ score=0.795) that was highest among the 6 observers. In summary, PRCCs with microcystic architecture represents a subset of historically "type 1" PRCC with a predilection for morphologically distinctive extrarenal involvement and metastatic disease. Microcysts co-vary with other "unfavorable" architectural patterns also associated with higher risk for aggressive disease (ie, micropapillary, hobnail, and solid), but microcysts were more common and have superior interobserver reproducibility. These findings suggest that microcystic PRCC should be recognized as a potentially aggressive histologic pattern of growth in PRCC.

Adverse Histopathologic Characteristics in Small Papillary Renal Cell Carcinomas Have Minimal Impact on Prognosis.

Tumor size has long been used in the management decision-making of patients with renal masses. Active surveillance had recently gained traction in selected patients with tumor size of 4 cm or less. Adverse histopathologic characteristics in papillary renal cell carcinoma (PRCC) have been shown to correlate with worse prognosis. We aimed to study whether such features in small PRCCs provide additional prognostic information. Nephrectomies from our institution were collected and reviewed to evaluate for adverse histopathologic features. Clinical follow-up information was collected for all cases. Relationships between the variables were examined by Wilcoxon test and logistic regression. We identified 291 consecutive cases of PRCC. Adverse tumor histopathologic characteristics were significantly related to size. In PRCCs with size greater than 4 cm, there were more cases with high World Health Organization/International Society of Urological Pathology grade and necrosis. Adverse histologic features are less commonly seen in small PRCC and are not associated with lower disease-free survival or disease-specific survival. Identification of these features in small PRCCs (≤4 cm) through needle core biopsy examination would not provide additional prognostic information in patients for whom active surveillance is considered. Clinical and radiologic follow-up in patients with small renal masses that have a known histologic diagnosis of PRCC should be sufficient.

Needle tract seeding in renal tumor biopsies: experience from a single institution

BackgroundPercutaneous needle biopsy of renal masses has been increasingly utilized to aid the diagnosis and guide management. It is generally considered as a safe procedure. However, tumor seeding along the needle tract, one of the complications, theoretically poses potential risk of tumor spread by seeded malignant cells. Prior studies on the frequency of needle tract seeding in renal tumor biopsies are limited and clinical significance of biopsy-associated tumor seeding remains largely controversial.MethodsHere we investigated the frequencies of biopsy needle tract tumor seeding at our institution by reviewing the histology of renal cell carcinoma nephrectomy specimens with a prior biopsy within the last seventeen years. Biopsy site changes were recognized as a combination of foreign body reaction, hemosiderin deposition, fibrosis and fat necrosis. The histologic evidence of needle tract tumor seeding was identified as clusters of tumor cells embedded in perinephric tissue spatially associated with the biopsy site. In addition, association between parameters of biopsy techniques and tumor seeding were investigated.ResultsWe observed needle tract tumor seeding to perinephric tissue in six out of ninety-eight (6 %) renal cell carcinoma cases including clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe, and clear cell papillary renal cell carcinoma. The needle tract tumor seeding was exclusively observed in papillary renal cell carcinomas (6/28, 21 %) that were unifocal, small-sized (≤ 4 cm), confined to the kidney and had type 1 features. No recurrence or metastasis was observed in the papillary renal cell carcinoma cases with tumor seeding or the stage-matched cases without tumor seeding.ConclusionsOur study demonstrated a higher than reported frequency of needle tract tumor seeding. Effective communication between pathologists and clinicians as well as documentation of tumor seeding is recommended. Further studies with a larger patient cohort and longer follow up to evaluate the impact of needle tract tumor seeding on long term prognosis are needed. This may also help reach a consensus on appropriate pathologic staging of renal cell carcinoma when the only site of perinephric fat invasion is within a biopsy needle tract.

Morphological, immunohistochemical, and genomic analyses of papillary renal neoplasm with reverse polarity

Papillary renal neoplasm with reverse polarity (PRNRP) is a recently proposed entity of renal tumor. It shows a far better prognosis than papillary renal cell carcinoma (PRCC) and frequently has KRAS missense mutation. In this study, we compared 14 cases of PRNRP and 10 cases of PRCC type 1 (PRCC1) and type 2 (PRCC2) from clinical, morphological, immunohistochemical, and molecular biological perspectives. We subjected all PRNRP and PRCC cases to immunohistochemical analysis. Whole-exome sequencing using next-generation sequencing (NGS) was performed for six cases of PRNRP, three cases of PRCC1, and four cases of PRCC2. A search for KRAS gene mutation in the remaining eight cases of PRNRP was performed by polymerase chain reaction (PCR) sequencing. The results showed that all cases of PRNRP were pT1N0M0, none of which followed a course of recurrence or tumor-related death. Immunohistochemical analysis revealed diffuse staining of CK7, EMA, PAX8, and GATA3 but weak or negative staining of CD10, CD15, and AMACR in PRNRP. By NGS and PCR, KRAS missense mutation was detected in 11 of 14 PRNRP cases, although pathogenic KRAS mutation was not observed in PRCC1 and PRCC2. NGS analysis revealed less tumor mutation burden in PRNRP than in PRCC. PRNRP also showed no specific chromosomal copy number abnormalities, including gains of 7 and 17. In conclusion, we propose that PRNRP is a distinct condition from PRCC.

Comparing World Health Organization/International Society of Urological Pathology Grading and Fuhrman Grading with the Prognostic Value of Nuclear Area in Patients with Renal Cell Carcinoma

This study was undertaken to compare Fuhrman grading with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading and stereologically measured nuclear area in patients with Clear Cell Renal Cell Carcinoma (ccRCC) or Papillary Renal Cell Carcinoma (PRCC) and to evaluate the independent predictive value of Fuhrman, WHO/ISUP and stereologically measured nuclear area combined with necrosis in a series of patients with ccRCC in relation to cancer-specific survival. In all, 124 cases of ccRCC and PRCC were included. All slides were blindly scored by two trained pathologists according to the Fuhrman and WHO/ISUP grading systems. Nuclear measurements were performed on digitally scanned slides in Visiopharm® and correlated to survival. Analysis of ccRCC and PRCC cases showed that application of WHO/ISUP grading resulted in a significant downgrading of cases from G2 to G1, when comparing with Fuhrman grading. Neither of these patients experienced progression. Cancer specific survival estimates in 101 ccRCC patients showed that WHO/ISUP grading was slightly superior in predicting cancer-specific survival. Novel models included WHO/ISUP grading and mean nuclear area (MNA) each of which combined with necrosis. Both demonstrated an increased ability to predict cancer-specific survival. The study demonstrates that WHO/ISUP grading provides superior prognostic information compared to Fuhrman grading and stereologically measured nuclear area. Necrosis in combination with either WHO/ISUP grading or MNA adds additional prognostic information.

English

BACKGROUND Renal tumours encompass a wide spectrum as distinct entities both in adults and in children. Renal cell carcinomas constitute majority of all renal neoplasms. Proper typing of renal tumours is not possible before surgery and histopathological examination. Accurate histopathological diagnosis and proper tumour typing is very important for early and proper surgical treatment. We wanted to study the various histomorphological patterns of renal tumours. METHODS We studied nephrectomy specimens with renal tumours received in the department of pathology from January 2018 to June 2020 (2 years 6 months, retrospective study). A total of 29 cases with renal tumours were included. Relevant Clinical details along with gross findings were recorded from the histopathology forms. Nephrectomy specimens were fixed overnight in 10 % formalin. Gross examination was done, representative tissue bits taken, routinely tissue processed, embedded and the sections were cut (4 – 5 microns). Haematoxylin and Eosin staining was done. Pathological diagnosis was done by two pathologists and arrived at a common consensus. RESULTS A total of 29 cases were included in our study. Of these 16 patients were male and 13 were female, with a male to female ratio of 1.2: 1. Most common age group affected was 5th decade. Mean age was 48 years. Out of 29 cases, 24 cases were malignant (82.75 %) and 5 cases were benign (17.24 %). Renal cell carcinoma (RCC) accounted for 18 cases out of 24 malignant tumours. Clear cell RCC was common subtype with 13 cases followed by 3 cases of chromophobe RCC and 2 cases of papillary RCC. In benign tumours, we had 4 cases of angiomyolipoma and 1 case of oncocytoma. Right sided kidney was affected with 17 cases (58.62 %) and left sided kidney 12 cases (41.7 %). Common tumour location was in upper pole. Pathological stage pT1 was seen in 9 cases followed pT2-5 cases, pT3-4 and pT4-2 cases. WHO / ISUP nuclear grading was noted. Grade II was seen in 11 cases followed by grade III seen in 4 cases. CONCLUSIONS Malignant renal tumours were most common than the benign tumours. Renal cell carcinoma was most common of the malignant tumours. Clear cell RCC was the most common subtype. Pathological stage pT1 was most common. Grade II was the most common grade. Proper histological typing, staging and grading are important for appropriate surgical treatment of renal tumours. KEYWORDS Renal Tumours, Renal Cell Carcinoma, Nephrectomy

Is hypervascular papillary renal cell carcinoma present?

We aimed to investigate atypical papillary renal cell carcinoma (PRCC) presenting with early contrast enhancement and late washout and to investigate the correlation between the CT attenuation value of the corticomedullary phase (CMP) of contrast-enhanced CT in PRCCs and the endothelial cell counts of these tumors. Twenty-two patients with pathologically confirmed PRCC were enrolled in this study. PRCCs were categorized into 18 typical PRCCs and 4 atypical PRCCs. The CT attenuation value of the lesion in the CMP was measured in the maximal section of the tumor using the region of interest. Microvessel density (MVD) was evaluated as a histopathologic parameter using tissue specimens immunohistochemically stained with an anti-ERG antibody. The CT attenuation value and MVD were compared between atypical and typical PRCCs using the Mann-Whitney U test, where p < 0.05 was considered significant. The correlations between CT attenuation value and MVD were evaluated in all PRCCs using single linear regression analysis. The mean CT attenuation value and the MVD were significantly higher in atypical than in typical PRCCs. Correlation analyses revealed a weak positive correlation between the CT attenuation value and MVD. We confirmed several cases of atypical PRCC that present with early contrast enhancement, such as clear cell renal cell carcinoma. In addition, a positive correlation was found between the CT attenuation value in the CMP of PRCCs and the vascular endothelial cell count.

Clinicopathologic spectrum of adult nephrectomy specimens – A two year study

Nephrectomy is indicated in patients with a wide range of conditions such as irreversibly damaged kidney resulting from symptomatic chronic infections, obstruction, calculi, severe traumatic injury, treatment of renovascular hypertension from non correctable renal artery disease or renal cell carcinoma. To review the clinicopathological spectrum of renal lesions in total or partial nephrectomy specimens in a tertiary care hospital in Mangalore and to study the non neoplastic renal parenchyma in tumor nephrectomy specimens. Materials and MethodsThe present study was done on 52 nephrectomy specimens received at the Department of Pathology, A.J Institute of Medical Sciences &amp; Research Centre, Mangalore during a period of 2 years (May 2014 - May 2016). A total of 52 cases over a period of 2 years were studied out of which 35(67.3%) were neoplastic.34/35 were malignant out of which, 29 were Clear cell Renal Cell Carcinoma (RCC) followed by 2 cases of papillary RCC, 2 cases of sarcomatoid RCC and 1 case of chromophobe RCC. A single case of angiomyolipoma were found. The most common finding in nonneoplastic renal parenchyma immediately adjacent to the tumor was chronic pyelonephritis 57.1% and one case showed caseating tuberculous nephritis. Out of 17 non-neoplastic conditions, 52.9% were hydronephrosis in association with chronic pyelonephritis. Two cases each of adult polycystic kidney disease and caseating tuberculous pyelonephritis were found. Malignant renal tumors are the major indication for nephrectomy and adequate examination of the adjacent non-neoplastic renal parenchyma is an important tool in recognising patients at risk for early patient care. A detailed histological study of benign nephrectomies could be a clinical predictor for further clinical course, as well as a management strategy for slowing down the progression or decline of renal function.

Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma

Papillary renal cell carcinoma (PRCC) is the most common type of non-clear cell RCC. Because some cases of PRCC are MET-driven, MET inhibition could be a targeted treatment approach. In previous studies, savolitinib (AZD6094, HMPL-504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in this patient group. To determine whether savolitinib is a better treatment option for this patient population, vs standard of care, sunitinib. The SAVOIR phase 3, open-label, randomized clinical trial was a multicenter study carried out in 32 centers in 7 countries between July 2017 and the data cutoff in August 2019. Overall, 360 to 450 patients were to be screened to randomize approximately 180 patients. Patients were adults with MET-driven (centrally confirmed), metastatic PRCC, with 1 or more measurable lesions. Exclusion criteria included prior receipt of sunitinib or MET inhibitor treatment. Overall, 254 patients were screened. Patients received 600 mg of savolitinib orally once daily (qd), or 50 mg of sunitinib orally qd for 4 weeks, followed by 2 weeks without treatment. The primary end point was progression-free survival (PFS, assessed by investigator and confirmed by blinded independent central review). Secondary end points included overall survival (OS), objective response rate (ORR), duration of response, and safety/tolerability. At data cutoff, 60 patients were randomized (savolitinib n = 33; sunitinib n = 27); most patients had chromosome 7 gain (savolitinib, 30 [91%]; sunitinib, 26 [96%]) and no prior therapy (savolitinib, 28 [85%]; sunitinib, 25 [93%]). For savolitinib and sunitinib, 4 (12%) and 10 (37%) patients were women, and the median (range) age was 60 (23-78) and 65 (31-77) years, respectively. Following availability of external data on PFS with sunitinib in patients with MET-driven disease, study enrollment was closed. Progression-free survival, OS, and ORR were numerically greater with savolitinib vs sunitinib. Median PFS was not statistically different between the 2 groups: 7.0 months (95% CI, 2.8-not calculated) for savolitinib and 5.6 months (95% CI, 4.1-6.9) for sunitinib (hazard ratio [HR], 0.71; 95% CI, 0.37-1.36; P = .31). For savolitinib and sunitinib respectively, grade 3 or higher adverse events (AEs) were reported in 14 (42%) and 22 (81%) of patients and AE-related dose modifications in 10 (30%) and 20 (74%). After discontinuation, 12 (36%) and 5 (19%) of patients on savolitinib and sunitinib respectively, received subsequent anticancer therapy. Although patient numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy vs sunitinib, with fewer grade 3 or higher AEs and dose modifications. Further investigation of savolitinib as a treatment option for MET-driven PRCC is warranted. ClinicalTrials.gov Identifier: NCT03091192.

SAVOIR: A phase III study of savolitinib versus sunitinib in pts with MET-driven papillary renal cell carcinoma (PRCC).

5002 Background: PRCC is the most common type of non-clear cell RCC, accounting for 10–15% of renal malignancies. As a subset of PRCC cases are MET-driven, MET inhibition may be an appropriate targeted treatment approach. In a single-arm Phase II study, savolitinib (AZD6094, HMPL‐504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in pts with MET-driven PRCC (Choueiri et al. JCO 2017). The Phase III SAVOIR study (NCT03091192) further assessed savolitinib vs standard of care sunitinib in pts with MET-driven PRCC. Methods: In this open-label (sponsor blinded), randomized study, pts with centrally confirmed MET-driven ( MET and/or HGF amplification, chromosome 7 gain and/or MET kinase domain mutations), metastatic PRCC were randomized to savolitinib 600 mg once daily (QD), or sunitinib 50 mg QD 4 weeks on / 2 weeks off. Primary objective was progression-free survival (PFS; RECIST 1.1 by blinded independent central review). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety and tolerability. Results: After external data on predicted PFS with sunitinib in pts with MET-driven disease became available, study enrollment was closed. At data cutoff (Aug 2019), only 60 of the planned 180 pts were randomized (savolitinib n = 33; sunitinib n = 27). Most had chromosome 7 gain (savolitinib 91%; sunitinib 96%) and no prior therapy (savolitinib 85%; sunitinib 93%). PFS, OS, and ORR were numerically improved with savolitinib vs sunitinib (Table). CTCAE grade ≥3 adverse events (AEs) were reported in 42% and 81% of pts; dose modifications were related to AEs in 30% and 74% of pts with savolitinib and sunitinib respectively. After discontinuation, 36% of all savolitinib and 19% of all sunitinib pts received subsequent anticancer therapy. Conclusions: Although pt numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy and an improved safety profile vs sunitinib, with fewer grade ≥3 AEs and fewer dose modifications required. Sunitinib performance was poorer than expected based on external retrospective data. Further investigation of savolitinib as a treatment option for MET-driven PRCC is warranted. Clinical trial information: NCT03091192 . [Table: see text]

Differential diagnosis of chromophobe renal cell carcinoma and papillary renal cell carcinoma with dual-energy spectral computed tomography

Computed tomography (CT) image features of chromophobe renal cell carcinoma (ChRCC) and papillary renal cell carcinoma (PRCC) are, occasionally, sometimes difficult to identify. However, spectral CT might provide quantitative parameters to differentiate them. To differentiate between ChRCC and PRCC with quantitative parameters using spectral CT. Forty cases of RCC confirmed with pathological tests were analyzed retrospectively (27 cases of PRCC and 13 cases of ChRCC). All patients underwent non-enhanced CT and dual-phase contrast-enhanced CT scans. For each lesion, the CT value of monochromatic images as well as iodine and water concentrations were measured, and the slope of spectrum curve was calculated. Data were analyzed using Student's t-test. Sensitivity and specificity of the quantitative parameters were analyzed using the receiver operating characteristic (ROC) curve. During the cortex phase (CP) and parenchyma phase (PP), the CT value and slope of spectrum curve of ChRCC were higher than those of PRCC, and significant differences were observed at low energy levels (40-70 keV). Normalized iodine concentration of ChRCC and that of PRCC was significantly different during CP and PP (P < 0.05). The water (iodine) concentrations of ChRCC and PRCC in CP and PP were not statistically different (P > 0.05). All the ROCs for parameters were above the reference line. Spectral CT may help increase the diagnostic accuracy of differentiating PRCC from ChRCC using a quantitative analysis.

Histopathological Study and Expression of CD 117 in Renal Cell Carcinoma

Background: Hypernephroma or Renal Cell Carcinoma (RCC) accounts for over 90% of all malignancies of the kidney occurring in adults. Of all renal cell carcinomas, Clear cell carcinoma accounts for around two-thirds to three-quarters and Chromophobe RCC accounts for around 5%. The present study highlights the diagnostic usefulness of CD117 as a phenotypic marker in Renal Cell Carcinoma. Methods: Current study include 48 cases of histopathology proven renal cell carcinoma. Each case was reviewed and classified according to the WHO classification criteria. The expression of CD117 was assessed using immunohistochemistry. Result: Of the 48 cases studied, 6cases, that is 2 case of Papillary RCC and 3 case of Chromophobe RCC showed moderate intensity and diffuse positivity for CD 117 and 1case of clear cell RCC with sarcomatoid areas showed mild and focal positivity. Papillary RCC showed both cytoplasmic and membrane positivity, while Chromophobe RCC showed mainly membranous positivity. Sarcomatoid areas showed weak cytoplasmic positivity. Conclusion: Histopathology supported by immunohistochemistry is a helpful tool in subtyping the various RCC. Treatment options in advanced disease is minimal. CD 117 positivity may favour the use of targeted therapy in renal cell carcinomas.

Incidence and significance of psammoma bodies in Xp11.2 translocation renal cell carcinoma and papillary renal cell carcinoma.

The aim of the present study was to investigate the incidence and significance of psammoma bodies (PBs) in Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) and papillary renal cell carcinoma (PRCC). The presence of PBs, irregular calcifications, hyaline globules and nested architecture in RCC tissues, which included 47 cases of Xp11.2 tRCC and 95 cases of PRCC, was examined by two pathologists. Compared with PRCC, patients with Xp11.2 tRCC exhibited a higher frequency of PBs, hyaline globules and nested architecture. The presence of PBs in combination with the occurrence of a nested architecture achieved a specificity of 93.7% when diagnosing Xp11.2 tRCC. However, there were no significant differences in the overall survival between patients with and without PBs in both types of RCC. Therefore, the presence of PBs combined with nested architecture may provide guidance for the diagnosis of Xp11.2 tRCC; however, PBs cannot predict tumor behavior in Xp11.2 tRCC or PRCC.