Immunotherapy combinations with tyrosine-kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) had significantly improved outcomes of patients with mRCC. Predictive and prognostic factors are crucial to improve patients' counseling and management. The present study aimed to externally validate the prognostic value of a previously developed red cell-based score, including hemoglobin (Hb), mean corpuscular volume (MCV) and red cell distribution width (RDW), in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). We performed a sub-analysis of a multicentre retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. Uni- and multivariable Cox regression models were used to assess the correlation between the red cell-based score and progression-free survival (PFS), and overall survival (OS). Logistic regression were used to estimate the correlation between the score and the objective response rate (ORR). The prognostic impact of the red cell-based score on PFS and OS was confirmed in the whole population regardless of the immunotherapy combination used [median PFS (mPFS): 17.4 vs 8.2 months, HR 0.66, 95% CI 0.47-0.94; median OS (mOS): 42.0 vs 17.3 months, HR 0.60, 95% CI 0.39-0.92; p < 0.001 for both]. We validated the prognostic significance of the red cell-based score in patients with mRCC treated with first-line immunotherapy combinations. The score is easy to use in daily clinical practice and it might improve patient counselling.
Urachal carcinoma (UrC) is an exceedingly rare neoplasm that develops from the urachus, an embryologic remnant of the urogenital sinus and allantois. The most commonly encountered histologic subtype is adenocarcinoma. The aim of this study is to characterize a series of UrC by morphology, immunohistochemistry, and molecular analysis. We retrospectively investigated seven cases of UrCs and assessed patient symptoms, imaging, histologic features, immunohistochemical profile, molecular characteristics, pathologic stages, and type of treatment. Immunostaining for CK7, CK20, Muc-2, CDX2, GATA3, β-catenin, and CK34βE12 was carried out on each neoplasm and on seven non-neoplastic urachal remnants as the control group. Additionally, a mutational analysis was performed using the QIAact Actionable Insights Tumor Panel Kit, which analyzes KRAS, NRAS, KIT, BRAF, PDGFRA, ALK, EGFR, ERBB2, PIK3CA, ERBB3, ESR1, and RAF1. Our cohort comprised five females and two males with a mean age of 64 years. UrCs consisted of two mucinous cystadenocarcinomas and five invasive, non-cystic adenocarcinomas. Carcinoma antigen expression profile was positive for CK20 and negative for CK34βE12 and GATA3 in all cases. Five of seven cases stained positively for Muc-2 and CDX2. On the contrary, non-neoplastic urachal remnants were immunoreactive for CK34βE12, CK7, and GATA3. Mutational analysis gave a positive result in four out of seven (57.1%) cases. All four positive tumors showed RAS mutation and one an additional mutation in PIK3CA. Urachal tumors exhibit peculiar morphologic, immunohistochemical, and molecular features. Due to the advanced stage at presentation, individualized treatment should be undertaken.
- MeSH
- biopsie MeSH
- imunohistochemie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mucinózní cystadenokarcinom chemie diagnóza genetika patologie MeSH
- mutace * MeSH
- mutační analýza DNA * MeSH
- nádorové biomarkery * analýza genetika MeSH
- nádory močového měchýře chemie diagnóza genetika patologie MeSH
- prediktivní hodnota testů MeSH
- retrospektivní studie MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Renal cell carcinomas with t(6;11) chromosome translocation involving the TFEB gene are indolent neoplasms which often occur in young patients. In this study, we report seven cases of renal cell carcinoma with TFEB rearrangement, two of whom had histologically proven metastasis. Patients (4F, 3M) ranged in age from 19 to 55 years (mean 37). One patient developed paratracheal and pleural metastases 24 months after surgery and died of disease after 46 months; another one recurred with neoplastic nodules in the perinephric fat and pelvic soft tissue. Histologically, either cytological or architectural appearance was peculiar in each case whereas one tumor displayed the typical biphasic morphology. By immunohistochemistry, all tumors labelled for cathepsin K, Melan-A and CD68 (KP1 clone). HMB45 and PAX8 staining were detected in six of seven tumors. All tumors were negative for CD68 (PG-M1 clone), CKAE1-AE3, CK7, CAIX, and AMACR. Seven pure epithelioid PEComa/epithelioid angiomyolipomas, used as control, were positive for cathepsin K, melanocytic markers, and CD68 (PG-M1 and KP1) and negative for PAX8. Fluorescence in situ hybridization results showed the presence of TFEB gene translocation in all t(6;11) renal cell carcinomas with a high frequency of split TFEB fluorescent signals (mean 74%). In the primary and metastatic samples of the two aggressive tumors, increased gene copy number was observed (3-5 fluorescent signals per neoplastic nuclei) with a concomitant increased number of CEP6. Review of the literature revealed older age and larger tumor size as correlating with aggressive behavior in these neoplasms. In conclusion, we present the clinical, morphological and molecular features of seven t(6;11) renal cell carcinomas, two with histologically demonstrated metastasis. We report the high frequency of split signals by FISH in tumors with t(6;11) chromosomal rearrangement and the occurrence of TFEB gene copy number gains in the aggressive cases, analyzing either the primary or metastatic tumor. Finally, we demonstrate the usefulness of CD68 (PG-M1) immunohistochemical staining in distinguishing t(6;11) renal cell carcinoma from pure epithelioid PEComa/epithelioid angiomyolipoma.
- MeSH
- angiomyolipom chemie patologie MeSH
- antigeny diferenciační myelomonocytární analýza MeSH
- CD antigeny analýza MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- karcinom z renálních buněk chemie genetika sekundární MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 11 genetika MeSH
- lidské chromozomy, pár 6 genetika MeSH
- nádorové biomarkery analýza MeSH
- nádory ledvin chemie genetika patologie MeSH
- nádory z perivaskulárních epiteloidních buněk chemie patologie MeSH
- transkripční faktory BHLH-Zip genetika MeSH
- translokace genetická MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The new WHO 2016 classification of renal neoplasia encounters the new entity called "clear cell papillary renal cell carcinoma" (ccpRCC). The ccpRCC has been long included as a subtype of clear cell RCC histotype and it actually ranges from 2 to 9% in different routinely available cohort of renal carcinomas. Of important note, ccpRCC does not show any recurrences or metastases or lymph-node invasion and the outcome is always good. We reviewed twenty-four publications with available follow-up for patients (no. 362) affected by clear cell papillary RCCs/renal adenomatoid tumours and notably ccpRCC harbors an indolent clinical behavior after a mean of 38 months (3,5 years) of follow-up. This paper reviews the histological, molecular and clinical features characterizing ccpRCC, with the goal of focusing the knowledge of the benign fashion of this new tumour entity, supporting the idea of a new renal cell adenoma recruited morphologically from ex conventional clear cell RCC tumours.
- MeSH
- adenom patologie MeSH
- karcinom z renálních buněk klasifikace patologie MeSH
- lidé MeSH
- nádory ledvin klasifikace patologie MeSH
- papilární karcinom patologie MeSH
- staging nádorů normy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BRAF mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of BRAF-mutated metanephric adenoma and to correlate BRAF mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of BRAF mutation (BRAF V600E/V600E complex, BRAF V600D, BRAF V600K and BRAF V600R) using the BRAF RGQ PCR kit (Qiagen). Immunohistochemistry was performed using monoclonal mouse antibodies against p16(INK4) and VE1 (Spring Bioscience), recognizing the BRAF V600E mutant protein. Forty-one of 48 cases (85%) showed BRAF V600E mutation; none of the other BRAF variants was detected. Of 41 BRAF-mutated metanephric adenomas, 33 showed positive VE1 immunostaining (sensitivity 80%, specificity 100%); in all cases we detected p16(INK4) expression regardless of BRAF mutation status. All epithelial-predominant nephroblastomas were BRAF-wild-type and none expressed VE1. The following features were associated with BRAF V600E mutation: older patients (p=0.01), female predominance (p=0.005) and the presence of a predominantly acinar architecture (p=0.003). In summary, BRAF-mutated metanephric adenomas were associated with older age, female predominance, and the presence of a predominant acinar component. A subset (20%) of BRAF-mutated metanephric adenomas was not detected by VE1 immunostaining.
- Publikační typ
- časopisecké články MeSH
Metanephric adenoma is a benign renal neoplasm that overlaps in morphology with the solid variant of papillary renal cell carcinoma and epithelial-predominant nephroblastoma. To aid in resolving this differential diagnosis, we investigated the utility of immunohistochemical and molecular analyses in distinguishing between these entities; the first study, to our knowledge, to use a combined approach in analyzing all three tumors. We analyzed 37 tumors originally diagnosed as metanephric adenomas (2 of which we reclassified as papillary renal cell carcinomas), 13 solid variant papillary renal cell carcinomas, and 20 epithelial-predominant nephroblastomas using a combination of immunohistochemistry and fluorescence in situ hybridization (FISH) assessing for trisomy of chromosomes 7 and 17 and loss of Y. Immunohistochemical staining was performed for CK7, AMACR, WT1, and CD57. The combination of CK7-, AMACR-, WT1+, and CD57+ was considered characteristic of metanephric adenoma. Most of the tumors originally diagnosed as metanephric adenomas (31/37) showed the expected staining pattern of metanephric adenoma (CK7-, AMACR-, WT1+, and CD57+). Of the six tumors with discordant immunophenotype, two tumors were reclassified as papillary renal cell carcinoma after cytogenetic workup. It is recommended that all adult cases histologically resembling metanephric adenoma have WT1, CD57, CK7, and AMACR immunohistochemical staining performed. If the staining pattern is characteristic for metanephric adenoma (CK7-, AMACR-, WT1+, and CD57+, including membranous staining), then no other diagnostic tests are indicated. However, if there is a different immunostaining pattern, then we recommend FISH analysis.
- MeSH
- adenom diagnóza MeSH
- cytogenetické vyšetření MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- dospělí MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- karcinom z renálních buněk diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádorové biomarkery analýza MeSH
- nádory ledvin diagnóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Wilmsův nádor diagnóza MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
UNLABELLED: t(6;11) renal cell carcinoma (RCC) has been recognized as a rare and mostly nonaggressive tumor (NAT). The criteria for distinguishing aggressive tumors (AT) from NATs are not well established. A total of 6 cases were selected for the study. Five cases of t(6;11) RCCs behaved nonaggressively, and 1 was carcinoma with aggressive behavior. The tumors were analyzed morphologically using immunohistochemistry and by molecular-genetic methods. The specimen of aggressive t(6;11) RCC was from a 77-year-old woman who died of the disease 2.5 months after diagnosis. The specimens of nonaggressive t(6;11) RCCs were from 3 women and 2 men whose ages range between 15 and 54 years. Follow-up was available in all cases (2.5 months-8 years). The tumor size ranged from 3 to 14 cm in nonaggressive t(6;11) RCC. In the aggressive carcinoma, the tumor size was 12 cm. All tumors (6/6) were well circumscribed. Aggressive t(6;11) RCC was widely necrotic. Six (100%) of 6 all tumors displayed a solid/alveolar architecture with occasional tubules and pseudorosettes. Pseudopapillary formations lined by bizarre polymorphic cells were found focally in the aggressive t(6;11) RCC case. Mitoses, though rare, were found as well. All cases (AT and NAT) were positive for HMB-45, Melan-A, Cathepsin K, and cytokeratins. CD117 positivity was seen in 4 of 5 NATs, as well as in the primary and metastatic lesions of the AT. mTOR was positive in 2 of 5 NATs and vimentin in 4 of 5 NATs. Vimentin was negative in the primary lesion of the AT, as well as in the metastasis found in the adrenal gland. Translocation t(6;11)(Alpha-TFEB) or TFEB break was detected in 4 of 5 NATs and in the AT case. Aggressive tumor showed amplification of TFEB locus. Losses of part of chromosome 1 and chromosome 22 were found in 1 of 5 NATs and in the AT. CONCLUSIONS: (1) Aggressive t(6;11) RCCs generally occur in the older population in comparison with their indolent counterparts. (2) In regard to the histologic findings in ATs, 3 of 5 so far published cases were morphologically not typical for t(6;11) RCC. Of the 3 cases, 2 cases lacked a small cell component and 1 closely mimicked clear cell-type RCC. (3) Necroses were only present in aggressive t(6;11) RCC. (4) Amplification of TFEB locus was also found only in the aggressive t(6;11) RCC.
- MeSH
- dospělí MeSH
- karcinom z renálních buněk genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 11 genetika MeSH
- lidské chromozomy, pár 6 genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory ledvin genetika patologie MeSH
- senioři MeSH
- transkripční faktory BHLH-Zip genetika MeSH
- translokace genetická * MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- srovnávací studie MeSH
To date, only a few cases of "rosette forming t(6;11), HMB45-positive renal carcinoma" have been published. In this article, we contribute further data on 4 cases of this rare entity. Patients were 3 women and 1 man with an age range of 20 to 54 years (median, 23 years). Follow-up (range, 3-5 years; median, 4 years) did not reveal any metastatic events or recurrences. All tumors were well circumscribed and mostly encapsulated with homogeneous gray to tan cut surfaces. No necrosis was seen. All tumors displayed a solid or solid/alveolar architecture and contained occasionally long and branching tubular structures composed of discohesive neoplastic cells and pseudorosettes. The presence of pseudorosettes was a constant finding, but the number of pseudorosettes varied significantly among cases. All cases displayed focal immunoreactivity for the melanocytic marker HMB45, cathepsin K, and vimentin. Melan A, tyrosinase, cytokeratins, CD10, and microphthalmia transcription factor were each positive in 3 of 4 cases. On ultrastructural examination, numerous electron-dense secretory cytoplasmic granules with some resemblance to melanosomes were identified. The pseudorosettes were composed of reduplicated basement membrane material surrounded by small lymphocyte-like neoplastic cells. Using reverse transcription polymerase chain reaction, 2 tumors were positive for the Alpha-TFEB fusion transcript. The presence of the translocation t(6;11)(Alpha-TFEB) was confirmed in 2 analyzed cases. No von Hippel-Lindau tumor suppressor gene mutation, promotor methylation or loss of heterozygosity of 3p was found. Losses of part of chromosome 1 and chromosome 22 were found in one case.
- MeSH
- dospělí MeSH
- karcinom z renálních buněk genetika metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 11 MeSH
- lidské chromozomy, pár 6 MeSH
- melanomové antigeny genetika metabolismus MeSH
- metylace MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádorový supresorový protein VHL genetika metabolismus MeSH
- nádory ledvin genetika metabolismus patologie MeSH
- promotorové oblasti (genetika) MeSH
- translokace genetická MeSH
- ztráta heterozygozity MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
We attempted to investigate the clinicopathological correlation of renal oncocytoma (RO) with renal vein extension. We identified seven ROs with extension into the branches of renal vein. The age of seven patients ranged from 61 to 82 years. Five cases were identified; incidentally, two patients had gross hematuria. After surgery, all patients were alive and free of tumors with follow-up of 1 to 5 years (mean=3.6). Oncocytomas measured from 2.2 to 7.5 cm. Renal vein extension was grossly suspected in 5/7 cases and histologically confirmed in all seven cases. Tumor cells were positive for cytokeratins, mitochondrial antigen, epithelial membrane antigen, and parvalbumin; 5/7 tumors were focally positive for cluster of differentiation 117. Ultrastructurally, the cytoplasm was packed by mitochondria. Molecular genetic analysis did not detect abnormal numbers of chromosomes 1, 2, 6, 7, 10, 17, and XY by fluorescence in situ hybridization, loss of heterozygosity on 3p, and mutation of Von Hippel-Lindau gene in all cases. Array comparative genomic hybridization analysis of two cases did not show any major genetic changes. Conclusions are: (1) renal oncocytomas may have intravascular extension to the branches of the renal vein; (2) renal oncocytomas with intravascular extension to the branches of the renal vein have the same morphological, immunohistochemical, and cytogenetic findings as have their counterparts without evidence of intravascular invasion; (3) the absence of metastases suggests an overall benign behavior of this tumor, but this has to be substantiated by further studies with a long-term follow-up; (4) in a renal tumor with granular cytoplasm showing renal vein extension, it is necessary to carefully exclude renal cell carcinomas (RCC) such as chromophobe RCC, oncocytic variant of papillary RCC, and granular variant of clear cell RCC.
- MeSH
- biologické markery analýza MeSH
- diferenciální diagnóza MeSH
- genom lidský MeSH
- hybridizace in situ fluorescenční MeSH
- hybridizace nukleových kyselin MeSH
- imunohistochemie MeSH
- keratiny analýza MeSH
- ledviny krevní zásobení metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mucin 1 analýza MeSH
- mutace MeSH
- nádorový supresorový protein VHL genetika MeSH
- nádory ledvin genetika metabolismus patologie MeSH
- oxyfilní adenom genetika metabolismus patologie MeSH
- parvalbuminy analýza MeSH
- proteiny Caenorhabditis elegans MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vakuolární protonové ATPasy analýza MeSH
- ztráta heterozygozity MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
CONTEXT: The expression of vimentin in benign renal oncocytomas has been controversial. However, this is of clinical significance because immunostains may be used in differential diagnosis of renal tumors on limited biopsy specimens. Using different staining and analysis methods, we studied vimentin immunoreactivity in a large series of renal oncocytomas with a special emphasis on the immunoreactivity patterns. OBJECTIVE: Immunohistochemical expression of vimentin has been used in the differential diagnosis of renal epithelial neoplasms. Although typically expressed in most renal cell carcinomas, the immunoreactivity of this intermediate filament in renal oncocytomas has been controversial. DESIGN: We studied vimentin immunoreactivity in a large series of 234 renal oncocytomas using 2 staining methods as well as manual and automated imaging analyses. RESULTS: We found that the focal vimentin immunoreactivity can be seen in most (72.6%) renal oncocytomas with vimentin-positive tumor cells usually found in the edge of a central scar or in small clusters scattered throughout the tumor. Computer-aided imaging analysis using ChromaVision Automatic Cellular Imaging System II confirmed the difference in vimentin immunoreactivity between oncocytoma and other renal neoplasms. CONCLUSIONS: Our study of vimentin immunohistochemistry in a series of renal oncocytomas, which to our knowledge is the largest ever published, showed focal vimentin positivity detected in most oncocytomas. Because the vimentin staining patterns in renal oncocytomas are different from those seen in clear cell or papillary renal cell carcinomas, we consider vimentin staining to be helpful in the differential diagnosis of oncocytoma from other renal tumor mimics. Furthermore, strong vimentin positivity in a renal cell neoplasm does not exclude the diagnosis of renal oncocytoma, particularly in a limited biopsy specimen.
