Tomáš Pitra

Morphological Characterization of Papillary Renal Cell Carcinoma Type 1, the Efficiency of Its Surgical Treatment.

Aim: Papillary renal cell carcinoma type 1 (pRCC1) represents the second most common type of malignant renal epithelial tumour. The origin of its characteristic appearance, its growth mechanism, and the long-term efficiency of its surgical treatment remain uncertain. Our aim was to determine typical characteristics of surgically treated pRCC1. Methods: pRCC1 was verified in 83 of 1,629 (5.1%) kidney tumours surgically treated in the period of January 2007-January 2016. The clinical and radiological characteristics, type of surgery, histopathology results and follow up data were recorded. Spearman correlation, Kruskal-Wallis analysis of variance, Fishers exact, and chi-square test were used to analyse appropriate variables. The overall survival rate was evaluated using the Gehan-Wilcoxon test and the Cox proportional hazards model. Results: The mean tumour size was 52.0 mm (15-180); 98.8% of the tumours showed a spherical shape and in 82.1%, exophytic growth was observed. Partial nephrectomy was performed in 80.7%. A majority (81.9%) were classified as pT1. Tumours, 89.2% of them, belonged to Fuhrman grade 1 or 2. The mean follow-up was 46.8 months. The overall survival was associated with pT category (p ≤ 0.0001). Conclusions: Typical signs of pRCC1 are a spherical shape, exophytic growth and low Fuhrmans grade. More than three-fourths of pRCC1 could be treated by the nephron-sparing surgery.

A practical guide and decision-making protocol for the management of complex renal cystic masses

Abstract Objectives: To analyse the management, pathology and outcomes of complex renal cystic masses (CRCM) and to develop a decision-making tool for daily clinical care using the Bosniak classification system for CRCM. Patients and methods: A comprehensive dataset of 185 patients with 188 CRCM and a minimum follow-up of 3 years were analysed for management, pathology and outcomes. Results: We analysed 35 Bosniak II, 34 Bosniak IIF, 58 Bosniak III, and 61 Bosniak IV lesions. The overall incidence of renal cell carcinoma was 8.6%, 29.4%, 62.1%, and 78.7% for each category. Based on our surveillance strategy of Bosniak IIF masses, we recommend computed tomography (CT)/magnetic resonance imaging (MRI) every 2 years after the initial examination. We also recommend performing one MRI (as an adjunct to CT) during the early follow-up period (<4 years). The use of MRI correlation for differential diagnostic purposes has proven useful for marginal Bosniak II, IIF and III cases. Conclusions: From our data, we have created a decision-making protocol to guide urologists in planning a safe and effective diagnostic and treatment strategy for CRCM. The Bosniak classification is a useful tool for clinical decision-making. Uncertainties still remain for Bosniak IIF and III lesions. Our protocol shows that individualised decision-making is necessary in a significant proportion of CRCM.

Mixed Epithelial and Stromal Tumor of the Kidney: Mutation Analysis of the DICER 1 Gene in 29 Cases.

Cystic nephroma (CN) and mixed epithelial stromal tumor (MEST) of the kidney have been considered as synonymous terms describing a single nosologic entity in adult patients. Cystic nephroma in pediatric patients (PCN) is, apparently, a completely different nosologic entity. Although the presence of DICER 1 mutations is well established in PCN, nothing is currently known about the DICER 1 gene status in adult MEST/CN. About 33 cases of MEST/CN were selected from the Plzen Tumor Registry; 4 cases were later excluded from the study due to low DNA quality. About 28 of the studied tumors displayed a benign morphology, whereas 1 was diagnosed as a malignant MEST/CN with sarcomatoid differentiation of the stromal component. All 29 samples analyzed using polymerase chain reaction and direct sequencing, including the case with the malignant morphology, were negative for mutation in DICER 1 hot-spot codons 1705, 1709, 1809, 1810, 1813, and 1814. Our results show that MEST/CN has no relation to PCN on a molecular genetic level. On the basis of our findings and the established morphologic differences between PCN and MEST/CN, we conclude that the term CN should be used for pediatric cases only and should be avoided in adult cases of MEST.

Chromosomal numerical aberration pattern in papillary renal cell carcinoma: Review article

Traditionally, papillary renal cell carcinomas (PRCCs) have been divided in two subgroups - type 1 and type 2. Based on recent molecular and genetic developments in the understanding of RCCs, it seems that this traditional classification may not be adequate and that the spectrum of PRCCs is much wider than initially proposed. Small series of distinct types of PRCC which do not fit into the above mentioned categories have been described in the literature. Published studies investigating molecular genetic changes in various types of PRCCs have shown that the molecular genetic features are remarkably heterogeneous across the whole spectrum of PRCCs. Of all PRCC subtypes/variants, PRCC type 1 seems to be a genetically uniform group, while other types showed different degrees of heterogeneity. Among different molecular-genetic features, chromosomal numerical aberration status is one of the most frequently studied features so far. It is becoming more evident that tumor type-specific chromosomal numerical aberration status in PRCCs may not exist. In this review, we present the most current knowledge concerning chromosomal numerical aberration status in PRCCs.

Comparative study of TERT gene mutation analysis on voided liquid-based urine cytology and paraffin-embedded tumorous tissue ☆,☆☆

Abstract Noninvasive reliable urine-based screening method for detection of urothelial carcinoma (UC) is still highly elusive. Recently, studies have shown the presence of telomerase reverse transcriptase ( TERT ) gene mutation in a high number of UCs. This finding can be used as a marker in screening voided urine samples. The aim of this study was to assess sensitivity of TERT mutation in detecting UC between liquid-based cytology (LBC) voided urine and formalin-fixed, paraffin-embedded neoplastic tissue (FFPE). Voided urine of 29 patients was collected before surgery via LBC. Subsequently, neoplastic tissue from transurethrally resected tumors of the same patients was analyzed. Both LBC and paraffin-embedded tissues were analyzed independently for the TERT gene mutation using Sanger sequencing and next-generation sequencing. Using Sanger sequencing, TERT mutation was detected in 17 of 29 samples of voided urine, whereas 4 cases showed weak positivity. Of 17 patients with TERT mutation, 6 had mutation in C250T and 11 in C228T. Using next-generation sequencing, 19 of 28 LBC (1 case was not suitable for analysis) were positive for TERT mutation, of which 5 contained C250T mutation and 14 had C228T mutation. Sanger sequencing was performed in all 29 resected UC cases. TERT gene mutation was found in 21 cases in FFPE, for which 6 tumors had mutation in C250T, and C228T mutation was found in the remaining 15 tumors. TERT promoter mutation is not positive in all UCs, and that negative result in LBC samples does not exclude the possibility of UC. It is evident from our results that there is 100% agreement of results between the material from FFPE and the corresponding LBC material in cases of high-grade UC. In contrary, the agreement rate between results of FFPE and LBC material (analyzed by Sanger sequencing or next-generation sequencing) varied in low-grade lesions. The use of such a test is more clinically relevant for detecting recurrence in the surveillance setting such as known UC patients with associated TERT promoter mutation (from routine-processed histologic samples).

Cystic Appearance on Imaging Methods (Bosniak III-IV) in Histologically Confirmed Papillary Renal Cell Carcinoma is Mainly Characteristic of Papillary Renal Cell Carcinoma Type 1 and Might Predict a Relatively Indolent Behavior of Papillary Renal Cell Carcinoma

Aim: The aim of this study was to determine the proportion of cystic tumors according to preoperative CT (Bosniak III, IV) among surgically treated patients with histologically confirmed papillary renal cell carcinoma (pRCC) and to assess progression rates among patients with and without cystic appearance on imaging. Methods: A total of 138 patients with pRCC histology surgically treated in the period of January 2007–March 2017 were included. Clinical and radiological characteristics, type of surgery, histopathology results, and follow-up data were recorded and statistically evaluated. Results: Forty-one cases (29.7%) of cystic lesions (10× BIIF, 14× BIII, 17× BIV) were detected by CT. Patients with pRCC1 significantly more frequently presented with cystic appearance on CT (33/78; 42.3%) in comparison to other papillary types (8/60; 13.3%; p = 0.0002). During a median follow-up time of 49.4 months, only 2 patients with cystic lesions progressed after surgery. Conclusions: Cystic appearance on imaging methods is mainly a characteristic of pRCC1 (42.3%). Cystic morphology on imaging might predict a relatively indolent behavior of all pRCC types. Preoperative scoring systems including tumor growth patterns (cystic vs. solid) are needed for further classification.