Browsing by Author "Pivovarcikova, Kristyna"

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Lynch syndrome-associated upper tract urothelial carcinoma frequently occurs in patients older than 60 years: an opportunity to revisit urology clinical guidelines.
(Virchows Archiv, 2023-08-23) Slisarenko, Maryna; Pivovarcikova, Kristyna; Pitra, Tomas; Alaghehbandan, Reza
Upper tract urothelial carcinoma (UTUC) is the third most common malignancy associated with Lynch syndrome (LS). The current European urology guidelines recommend screening for LS in patients with UTUC up to the age of 60 years. In this study, we examined a cohort of patients with UTUC for potential association with LS in order to establish the sensitivity of current guidelines in detecting LS. A total of 180 patients with confirmed diagnosis of UTUC were enrolled in the study during a 12-year period (2010-2022). Loss of DNA-mismatch repair proteins (MMRp) expression was identified in 15/180 patients (8.3%). Germline analysis was eventually performed in 8 patients confirming LS in 5 patients (2.8%), including 4 germline mutations in MSH6 and 1 germline mutation in MSH2. LS-related UTUC included 3 females and 2 males, with a mean age of 66.2 years (median 71 years, range 46-75 years). Four of five LS patients (all with MSH6 mutation) were older than 65 years (mean age 71.3, median 72 years). Our findings indicate that LS-associated UTUCs can occur in patients with LS older than 60 years. In contrast to previous studies which used mainly highly pre-selected populations with already diagnosed LS, the most frequent mutation in our cohort involved MSH6 gene. All MSH6 mutation carriers were > 65 years, and UTUC was the first LS manifestation in 2/4 patients. Using current screening guidelines, a significant proportion of patients with LS-associated UTUC may be missed. We suggest universal immunohistochemical MMRp screening for all UTUCs, regardless of age and clinical history.
Renal cell carcinomas with tubulopapillary architecture and oncocytic cells: Molecular analysis of 39 difficult tumors to classify.
(Annals of Diagnostic Pathology, 2021-06) Slisarenko, Maryna; Pivovarcikova, Kristyna; Grossmann, Petr; Hajkova, Veronika
So-called oncocytic papillary renal cell carcinoma (OPRCC) is a poorly defined variant of papillary renal cell carcinoma. Since its first description, several studies were published with conflicting results, and thus precise definition is lacking. A cohort of 39 PRCCs composed of oncocytic cells were analyzed. Cases were divided into 3 groups based on copy number variation (CNV) pattern. The first group consisted of 23 cases with CNV equal to renal oncocytoma. The second group consisted of 7 cases with polysomy of chromosomes 7 and 17 and the last group of 9 cases included those with variable CNV. Epidemiologic, morphologic and immunohistochemical features varied among the groups. There were not any particular histomorphologic features correlating with any of the genetic subgroups. Further, a combination of morphologic, immunohistochemical, and molecular-genetic features did not allow to precisely predict biologic behavior. Owing to variable CNV pattern in OPRCC, strict adherence to morphology and immunohistochemical profile is recommended, particularly in limited samples (i.e., core biopsy). Applying CNV pattern as a part of a diagnostic algorithm can be potentially misleading. OPRCC is a highly variable group of tumors, which might be misdiagnosed as renal oncocytoma. Using the term OPRCC as a distinct diagnostic entity is, thanks to its high heterogeneity, questionable.
Utility of NKX3.1 immunohistochemistry in the differential diagnosis of seminal vesicles versus prostatic tissue in needle biopsy.
(Annals of Diagnostic Pathology, 2020-12) Slisarenko, Maryna; Pitra, Tomas; Pivovarcikova, Kristyna; Alaghehbandan, Reza
NKX3.1 is considered a reliable immunohistochemical marker of prostatic origin with high specificity and sensitivity. However, NKX3.1 positivity has been described in other neoplastic and non-neoplastic tissues, such as mesenchymal chondrosarcoma, sex-cord stromal tumors, rete testis adenocarcinoma, lobular and ductal carcinoma of the breast, salivary glands, peribronchial submucosal glands, and Sertoli cells. We analyzed expression of two antibodies (mono and polyclonal) of NKX3.1 in a total of 63 non-neoplastic seminal vesicles. We used 52 resection materials (12 seminal vesicles without prostatic adenocarcinoma, 26 seminal vesicles with prostatic adenocarcinoma infiltration, and 14 cases of seminal vesicles infiltrated by urothelial carcinoma) and 11 prostatic core needle biopsies with incidentally sampled fragment of seminal vesicles. In all cases, tissues from seminal vesicles were completely negative for NKX3.1, despite using polyclonal and monoclonal NKX3.1 antibodies, and regardless of the detection system utilized (diaminobenzidine (DAB) versus alkaline phosphatase (AF)). However, prostatic adenocarcinoma was negative in several cases (n = 6), when AF detection system was used. Reaction with DAB was strong and robust in all cases. Based on our data, we can recommend NKX3.1 as a negative immunohistochemical marker of seminal vesicles.