RESUMEN
a-Methylacyl coenzyme A racemase (AMACR) is traditionally considered to be a marker of papillary renal cell carcinoma. However, AMACR expression can be seen in other renal tumors. The aim of this study was to investigate AMACR immunoreactivity within the spectrum of clear cell renal cell neoplasms. Fifty-three clear cell renal epithelial tumors were used in assembling the following four cohorts: low grade (LG) clear cell renal cell carcinoma (CCRCC), high grade (HG) CCRCC, CCRCC with cystic changes, and multilocular cystic renal neoplasm of low malignant potential (MCRNLMP). Representative blocks were stained for AMACR, using two different clones (SP52 and OV-TL12/30). There were at least some AMACR immunoreactivity in 77.8 % and 68.9 % of CCRCCs (using SP52 and OV-TL12/30 clone, respectively). Moderate to strong positivity, or positivity in more than one third of the tumor (even weak in intensity) was detected in 46.7 % of CCRCCs using SP52 and in 48.9 % of CCRCC using OV-TL12/30 clone. The highest AMACR reactivity was observed in HG CCRCC (60 % by SP52 and 66.7 % by OV-TL12/30). Strong and diffuse AMACR positivity was detected in 8.9 % of all CCRCCs. AMACR immunoreactivity in MCRNLMP was 37.5 % (SP52 clone) and 25 % (OV-TL12/30 clone). We demonstrated relatively high expression rate of AMACR in CCRCC, while very variable in intensity and distribution. This finding may have diagnostic implications especially in limited samples (i.e., core biopsies), as AMACR positivity does not exclude the diagnosis of CCRCC.
Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Renales , Neoplasias Renales , Racemasas y Epimerasas , Racemasas y Epimerasas/metabolismo , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/diagnóstico , Biomarcadores de Tumor/metabolismo , Inmunohistoquímica/métodos , Masculino , Femenino , Persona de Mediana Edad , AncianoRESUMEN
Clear cell renal cell carcinoma (CCRCC) is well known for intratumor heterogeneity. An accurate mapping of the tumor is crucial for assessing prognosis, and perhaps this can be linked to potential success/failure of targeted therapies. We assembled a cohort of 7 CCRCCs with prominent vasculature and microvascular hyperplasia (ccRCCPV), resembling those seen in high grade gliomas. A control group of classic CCRCC with no variant morphologies was also included. Both groups were analyzed for clinicopathologic, morphologic, immunohistochemical, and molecular genetic features. No statistically significant differences in mRNA expression of studied genes between the two groups were found. Using NGS panel Trusight Oncology 500 (TSO500), only one clinically significant gene mutation, VHL c.263G > A, p. (Trp88Ter), was found. TMB (Tumor Mutation Burden) and MSI (MicroSatellite Instability) were low, and no copy number variations (CNVs) were detected in the study cohort. Prominent microvascular hyperplasia in CCRCC is a rare phenomenon. From molecular genetic point of view, these tumors do not appear to be different from classic CCRCC. Prognostically, they also demonstrated similar clinical behaviors.
Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Anciano , Biomarcadores de Tumor , Carcinoma de Células Renales/genética , Femenino , Humanos , Hiperplasia/genética , Hiperplasia/patología , Neoplasias Renales/genética , Masculino , Persona de Mediana Edad , Mutación , PronósticoRESUMEN
Predicting the clinical behavior and trajectory of chromophobe renal cell carcinoma (ChRCC) by histologic features has so far proven to be challenging. It is known that ChRCC represents a heterogeneous group of neoplasms demonstrating variable, yet distinctive morphologic and genetic profiles. In this international multi-institutional study, we aimed to assess the impact of histologic diversity in ChRCC (classic/eosinophilic versus rare subtypes) on survival outcome. This is an international multi-institutional matched case-control study including 14 institutions, examining the impact of histologic subtypes of ChRCC on survival outcome. The study group (cases) included 89 rare subtypes of ChRCC. The control group consisted of 70 cases of ChRCC including classic and eosinophilic features, age- and tumor size-matched. Most of the rare subtypes were adenomatoid cystic/pigmented ChRCC (66/89, 74.2%), followed by multicystic ChRCC (10/89, 11.2%), and papillary ChRCC (9/89, 10.1%). In the control group, there were 62 (88.6%) classic and 8 (11.4%) eosinophilic ChRCC. There were no statistically significant differences between the study and control groups for age at diagnosis, gender distribution, tumor size, presence of tumor necrosis, presence of sarcomatoid differentiation, and adverse outcomes. No statistically significant differences were found in clinical outcome between the rare subtypes and classic/eosinophilic groups by tumor size, necrosis, and sarcomatoid differentiation. Further, no statistically significant differences were found in clinical outcome between the two groups, stratified by tumor size, necrosis, and sarcomatoid differentiation. Our findings corroborated previous studies that both sarcomatoid differentiation and tumor necrosis were significantly associated with poor clinical outcome in classic/eosinophilic ChRCC, and this was proven to be true for ChRCC with rare histologic subtypes as well. This study suggests that rare morphologic patterns in ChRCC without other aggressive features play no role in determining the clinical behavior of the tumor.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Biomarcadores de Tumor , Carcinoma de Células Renales/patología , Estudios de Casos y Controles , Neoplasias Renales/patología , NecrosisRESUMEN
The 5th edition of WHO classification of the urinary tract tumors is only mildly edited version of the previous WHO classification (from year 2016). The most prominent changes are represented by modifications in the structure and concept of chapters and there are minor alterations in the nomenclature of some entities. Histological characteristics are still the gold standard for classification of urothelial tract neoplasms.
Asunto(s)
Neoplasias Urológicas , Humanos , Neoplasias Urológicas/diagnóstico , Organización Mundial de la SaludRESUMEN
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.
Asunto(s)
Adenoma Oxifílico/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Células Oxífilas/metabolismo , Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Biopsia con Aguja Gruesa/normas , Carcinoma de Células Renales/epidemiología , Aberraciones Cromosómicas , Variaciones en el Número de Copia de ADN/genética , Diagnóstico Diferencial , Errores Diagnósticos , Femenino , Genes Sobrepuestos/genética , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Células Oxífilas/patologíaRESUMEN
The diagnosis of primary adenocarcinoma of the urinary bladder may be challenging in routine practice. These tumors may morphologically and immunohistochemically overlap with urachal adenocarcinoma and colorectal adenocarcinoma. Further, their genetic background is poorly understood. We systematically searched the PubMed database for results of complex genetic evaluation of primary bladder adenocarcinoma subtypes. Subsequently, we designed our own series of bladder lesions. We evaluated 36 cases: 16 primary enteric-type adenocarcinomas, 7 urachal enteric adenocarcinomas, 3 primary mucinous/colloid adenocarcinomas, and 10 intestinal-type metaplasia/villous adenoma. Detailed clinical data were collected, and all cases were examined using targeted next-generation sequencing. On the basis of the literature, the first mutated gene in these tumors was reported to be KRAS in 11.3% of cases, followed by TERT promoter mutations in 28.5%. In addition to KRAS and TERT, other genes were also found to be frequently mutated in primary bladder adenocarcinoma, including TP53, PIK3CA, CTNNB1, APC, FBXW7, IDH2, and RB1. In our series, the most frequent gene mutations in primary enteric-type adenocarcinomas were as follows: TP53 (56%); BRCA2, KMT2B (both 33%); NOTCH2, KDR, ARID1B, POLE, PTEN, KRAS (all 28%); in urachal enteric adenocarcinoma they were as follows: TP53 (86%); PTEN, NOTCH (both 43%); in primary mucinous/colloid adenocarcinomas they were as follows: KRAS, GRIN2A, AURKB (all 67%); and, in intestinal-type metaplasia/villous adenoma, they were as follows: APC, PRKDC (both 60%); ROS1, ATM, KMT2D (all 50%). No specific mutational pattern was identified using cluster analysis for any of the groups. Herein, we describe the pathologic features and immunohistochemical staining patterns traditionally used in the differential diagnoses of glandular lesions of the bladder in routine surgical pathology. We outline the mutational landscape of these lesions as an aggregate of published data with additional data from our cohort. Although diagnostically not discriminatory, we document that the most common genetic alterations shared between these glandular neoplasms include TP53, APC (in the Wnt pathway), and KRAS (in the MAPK pathway) mutations.
Asunto(s)
Adenocarcinoma Mucinoso/genética , Adenocarcinoma/genética , Adenoma/genética , Neoplasias Intestinales/genética , Neoplasias de la Vejiga Urinaria/genética , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/patología , Adenoma/patología , Biomarcadores de Tumor/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Intestinales/patología , Metaplasia/genética , Metaplasia/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
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.
Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/análisis , Proteínas de Homeodominio/metabolismo , Neoplasias de la Próstata/diagnóstico , Vesículas Seminales/patología , Factores de Transcripción/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Biopsia con Aguja , Diagnóstico Diferencial , Proteínas de Homeodominio/análisis , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Próstata/metabolismo , Vesículas Seminales/metabolismo , Factores de Transcripción/análisisRESUMEN
Although typically arranged in solid alveolar fashion, chromophobe renal cell carcinoma (RCC) may also show several other architectural growth patterns. We include in this series 8 chromophobe RCC cases with prominent papillary growth, a pattern very rarely reported or only mentioned as a feature of chromophobe RCC, which is lacking wider recognition The differential diagnosis of such cases significantly varies from the typical chromophobe RCC with its usual morphology, particularly its distinction from papillary RCC and other relevant and clinically important entities. Of 972 chromophobe RCCs in our files, we identified 8 chromophobe RCCs with papillary growth. We performed immunohistochemistry and array Comparative Genomic Hybridisation (aCGH) to investigate for possible chromosomal aberrations. Patients were 3 males and 5 females with age ranging from 30 to 84 years (mean 57.5, median 60 years). Tumor size was variable and ranged from 2 to 14 cm (mean 7.5, median 6.6 cm). Follow-up was available for 7 of 8 patients, ranging from 1 to 61 months (mean 20.1, median 12 months). Six patients were alive with no signs of aggressive behavior, and one died of the disease. Histologically, all cases were composed of dual cell population consisting of variable proportions of leaf-like cells with pale cytoplasm and eosinophilic cells. The extent of papillary component ranged from 15 to 100% of the tumor volume (mean 51%, median 50%). Sarcomatoid differentiation was identified only in the case with fatal outcome. Immunohistochemically, all tumors were positive for CK7, CD117 and Hale's Colloidal Iron. PAX8 was positive in 5 of 8 cases, TFE3 was focally positive 3 of 8 tumors, and Cathepsin K was focally positive in 2 of 8 tumors. All cases were negative for vimentin, AMACR and HMB45. Fumarate hydratase staining was retained in all tested cases. The proliferative activity was low (up to 1% in 7, up to 5% in one case). Three cases were successfully analyzed by aCGH and all showed a variable copy number variation profile with multiple chromosomal gains and losses. CONCLUSIONS: Chromophobe RCC demonstrating papillary architecture is an exceptionally rare carcinoma. The diagnosis can be challenging, although the cytologic features are consistent with the classic chromophobe RCC. Given the prognostic and therapeutic implications of accurately diagnosis other RCCs with papillary architecture (i.e., Xp11.2 translocation RCC, FH-deficient RCC), it is crucial to differentiate these cases from chromophobe RCC with papillary architecture. Based on this limited series, the presence of papillary architecture does not appear to have negative prognostic impact. However, its wider recognition may allow in depth studies on additional examples of this rare morphologic variant.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Papilar/diagnóstico , Carcinoma de Células Renales/diagnóstico , Variaciones en el Número de Copia de ADN , Neoplasias Renales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Aberraciones Cromosómicas , Hibridación Genómica Comparativa , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Papillary renal cell carcinoma (PRCC) is currently a well-studied type of RCC. In addition to PRCC type 1, there are a number of other subtypes and variants of PRCCs which have been reported. We describe a series of 6 PRCCs with papillary, micropapillary and/or tubulopapillary architecture and prominent spindle cell stroma, resembling stroma in mixed epithelial and stromal tumor of the kidney (MESTK) or sarcomatoid RCC. Clinicopathologic, morphologic, immunohistochemical and molecular features were analyzed. All patients were males with an age range of 44-98 years (mean 65.3, median 65.5 years). Tumor size ranged from 2.4-11.4 cm (mean 5.8, median 4.5 cm). Follow-up data were available for 4 patients, ranging from 3 to 96 months (mean 42.75, median 36 months). Epithelial cells were mostly cylindrical with eosinophilic cytoplasm, showing nuclear grade 2 and 3 (ISUP/WHO). In all cases, loose to compact prominent stroma composed of spindle cells, without malignant mesenchymal heterologous elements was detected. No atypical mitoses were found, while typical mitoses were rare in both epithelial and stromal components. Epithelial cells were positive for CK7, AMACR, and vimentin in all cases, while negative for TFE3, HMB45, desmin, CD34, and actin. The stroma was positive for vimentin, actin and focally for CD34, while negative for CK7, AMACR, TFE3, HMB45, and desmin. Estrogen and progesterone receptors were completely negative. FH and SDHB expression was retained in all analyzable cases. Proliferative index was barely detectable in stromal component and low in epithelial component, ranging 0 to 5% positive stained cells/high power field. Copy number variation was variable with no distinct pattern. No mutations in CDKN2A, BAP1, MET were detected. PRCC with MESTK-like features is a distinct variant of PRCC mimicking MESTK. Our findings add to the body of literature on ever expanding variants of PRCCs. Both epithelial and stromal components lacked true Müllerian features, which was also proven by immunohistochemistry.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/patología , Carcinoma de Células Renales/patología , Variaciones en el Número de Copia de ADN , Neoplasias Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Papilar/metabolismo , Carcinoma de Células Renales/metabolismo , Células Epiteliales/patología , Humanos , Inmunohistoquímica , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , Células del Estroma/patologíaRESUMEN
AIMS: Primary renal well-differentiated neuroendocrine tumour (NET) (hereafter referred to as renal NET) is rare, with ~100 cases having been reported in the literature. There are also limited data on the molecular-genetic background of primary renal NETs. METHODS AND RESULTS: We analysed 11 renal NETs by using next-generation sequencing (NGS) to identify characteristic genetic aberrations. All tumours were positive for synaptophysin, and also expressed insulinoma-associated protein 1 (10/11), chromogranin-A (8/11), and CD56 (3/11). Cytoplasmic positivity of CD99 was present in eight of 11 cases, and strong nuclear expression of α-thalassaemia/mental retardation syndrome X-linked (ATRX) was retained in all 11 cases. Molecular-genetic analysis of aberration of VHL gave negative results in all cases. Loss of heterozygosity on chromosome 3p21 was found in three of nine analysable cases. NGS was successful in nine cases, showing a total of 56 variants being left after the updated filtering process, representing an average of five variants per sample. All analysable cases were negative for ATRX and DAXX (death-domain associated protein X) mutations. The most frequently mutated genes were CDH1 and TET2, with three mutations in two cases. Mutations in AKT3, ROS1, PIK3R2, BCR and MYC were found in two cases. The remaining 41 genes were found to be mutated only in individual cases. In four cases, the mutations affected a subset of genes related to angiogenesis. CONCLUSIONS: Overall, the mutation profile of primary renal NETs is variable, and none of the studied genes or affected pathways seems to be specific for renal NET.
Asunto(s)
Tumor Carcinoide/genética , Tumor Carcinoide/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Cadherinas/genética , Tumor Carcinoide/metabolismo , Diferenciación Celular , Proteínas de Unión al ADN/genética , Dioxigenasas , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Neoplasias Renales/metabolismo , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Mutación , Tumores Neuroendocrinos/metabolismo , Proteínas Proto-Oncogénicas/genéticaRESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Papilar/genética , Carcinoma de Células Renales/genética , Aberraciones Cromosómicas , Neoplasias Renales/genética , Aneuploidia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patología , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Humanos , Riñón/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , MasculinoRESUMEN
Hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma (HLRCC)/fumarate hydratase deficient renal cell carcinoma (FHRCC) is defined by molecular genetic changes (mutation/LOH in fumarate hydratase (FH) gene). We investigated chromosomal numerical aberration pattern (CNV) in FHRCC/HLRCC using array comparative genomic hybridization analysis and low pass whole genome sequencing. Genetic analysis was successfully completed in 12 tumors. Most common chromosomal aberrations detected were a complete or partial loss of chromosome 4 (5/12 cases), chromosome 15 (4/12 cases), and chromosomes 9, 13, and 14 (each in 3/12 cases), as well as a complete or partial gain of chromosome 17 (in 4/12 cases). No chromosomal losses or gains were detected in 4 cases. Copy number variation pattern in FHRCC/HLRCC appears to be highly variable and does not provide a useful diagnostic tool in identifying these cases. Immunohistochemical staining and especially molecular genetic evaluation of FH gene mutations/LOH remain the gold standard in identifying FHRCC/HLRCC.
Asunto(s)
Carcinoma de Células Renales/genética , Aberraciones Cromosómicas , Fumarato Hidratasa/deficiencia , Neoplasias Renales/genética , Adulto , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Secuenciación Completa del GenomaRESUMEN
Urine cytology is used for detection of neoplastic cells in urine. It has high sensitivity and specificity in detection high-grade urothelial carcinoma, but it is low sensitive in detection of low-grade carcinoma. Different classification systems were published in the past, need for a more standardized terminology results in Paris System for Reporting Urine cytology. This classification was published in 2016, and it is based on clear diagnostic criteria. Implementation of The Paris System will lead to global standardization and uniformity of urine cytology reports.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Carcinoma de Células Transicionales/diagnóstico , Citodiagnóstico , Humanos , Urinálisis , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias Urológicas/diagnósticoRESUMEN
Hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma (HLRCC)/ fumarate hydratase deficient renal cell carcinoma (FHRCC) is an aggressive tumor defined by molecular genetic changes - alteration in fumarate hydratase (FH) gene. The morphologic spectrum of HLRCC/FHDRCC is remarkably variable. The presence of large nuclei and prominent dark red inclusion-like nucleoli and perinucleolar clearing are considered as helpful morphologic clue. We selected 23 renal neoplasms primarily based on their morphologic features suspicious for HLRCC/FHDRCC. Morphological, basic immunohistochemical, and genetic analysis was performed. The tumors were divided in two groups according to the molecular genetic findings. The first group included 13 tumors with detected FH mutation/LOH (compatible with diagnosis FHRCC), and the second group included 10 tumors without FH mutation/LOH (FH-like RCCs). In the FHRCC group, the vast majority of cases (9/13) had mixed morphology with different architectural growth patterns. All cases showed prominent macronucleoli, and perinucleolar clearing was found in 10/13 cases. Immunohistochemically, 6/7 FHRCC cases were negative for FH antibody, while one case showed strong diffuse FH reactivity. The FH-like RCC group showed more uniform architectural growth pattern. All 10 tumors had prominent macronucleoli, and perinucleolar clearing was present in 8/10 cases. Eight FH-like RCC cases showed diffuse strong positivity for FH, although 2 cases were completely negative for FH. It is evident that neither morphologic feature nor immunohistochemical analysis can be reliably used in routine practice for the diagnosis of HLRCC/FHRCC. In suspected cases, the diagnosis of HLRCC/FHRCC can be confirmed by molecular-genetic testing for FH mutation. It should be noted that the traditionally described morphologic features of HLRCC/FHRCC (prominent eosinophilic macronuclei with perinucleolar halos) can frequently be seen in other renal neoplasms.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Leiomiomatosis , Síndromes Neoplásicos Hereditarios , Neoplasias Cutáneas , Neoplasias Uterinas , Femenino , Fumarato Hidratasa , HumanosRESUMEN
INTRODUCTION: CT imaging is the standard examination for renal cystic lesions and defines the Bosniak category, which dictates further management. Given that Bosniak II/IIF/III renal cystic lesions can potentially harbor renal cell carcinoma (RCC), additional diagnostic modalities may be required in management decision making. AIM: To determine the value of additional magnetic resonance imaging in CT-defined Bosniak IIF-III renal cystic lesions. MATERIALS AND METHODS: This a multicenter retrospective study of 46 consecutive patients, diagnosed with cystic renal lesions between 2009 and 2016. The inclusion criteria were: (1) cystic renal lesion classified as Bosniak IIF-III on CT, (2) a subsequent MRI examination, and (3) documented outcome via surgery for cystic renal mass or follow-up. RESULTS: 46 patients (35 males, 11 females) were included. The mean size of the cystic lesion was 3.92 cm (0.7-10 cm). According to the CT findings, Bosniak IIF and III were found in 12 (26.1%) and 34 (73.9%) cases. Reclassification of Bosniak category was done after MRI examination in 31 cases (67.4%). An upgrade rate of 58.7% (27 cases) to a higher category was made, while the downgrade rate to a lower category was achieved in 4 cases (8.7%). As a result, significant therapeutic management change was made in 12/31 patients (38.7%), of whom 8 underwent subsequent surgery. CONCLUSION: MRI study may reduce the use of Bosniak IIF category (in comparison with CT), which has a direct impact on therapeutic management (surgery vs. surveillance) in a significant proportion of patients.
Asunto(s)
Enfermedades Renales Quísticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Austria , Quistes , República Checa , Femenino , Humanos , Enfermedades Renales Quísticas/patología , Neoplasias Renales , Masculino , Polonia , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
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.
Asunto(s)
Carcinoma de Células Renales/diagnóstico por imagen , Enfermedades Renales Quísticas/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Medios de Contraste , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Enfermedades Renales Quísticas/patología , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Periodo Preoperatorio , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
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, Fisher's 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 Fuhrman's grade. More than three-fourths of pRCC1 could be treated by the nephron-sparing surgery.
Asunto(s)
Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Riñón/patología , Nefrectomía , Nefronas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
A syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in patients with hereditary leiomyomatosis and renal cell carcinoma syndrome or that some seminomas may occur in Lynch syndrome patients. Additionally, an association between testicular sex cord stromal tumors and paratesticular sarcomas with Familial adenomatous polyposis syndrome and DICER1 syndrome, respectively, has been proposed as well. This review provides a comprehensive overview of the intricate relationship between familial syndromes and associated testicular and paratesticular tumors, shedding light on their clinicopathological and molecular characteristics.
Asunto(s)
Síndromes Neoplásicos Hereditarios , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/genética , Neoplasias Testiculares/patología , Síndromes Neoplásicos Hereditarios/patología , Síndromes Neoplásicos Hereditarios/genética , Predisposición Genética a la Enfermedad , Neoplasias de los Genitales Masculinos/patología , Neoplasias de los Genitales Masculinos/genéticaRESUMEN
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.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias de la Vejiga Urinaria , Urología , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Carcinoma de Células Transicionales/genética , Homólogo 1 de la Proteína MutL/genética , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Mutación de Línea Germinal , Reparación de la Incompatibilidad de ADNRESUMEN
A number of recently described renal tumor entities share an eosinophilic/oncocytic morphology, somewhat solid architectural growth pattern, and tendency to present as low-stage tumors. The vast majority of such tumors follow a non-aggressive clinical behavior. In this review, we discuss the morphological, immunohistochemical, and molecular genetic profiles of the three most recent novel/emerging renal entities associated with TSC/mTOR pathway mutations. These are eosinophilic solid and cystic renal cell carcinoma, eosinophilic vacuolated tumors, and low-grade oncocytic tumors, which belong to a heterogeneous group of renal tumors, demonstrating mostly solid architecture, eosinophilic/oncocytic cytoplasm, and overlapping morphological and immunohistochemical features between renal oncocytoma and chromophobe renal cell carcinoma. All three tumors also share a molecular genetic background with mutations in the mTORC1 pathway (TSC1/TSC2/mTOR/RHEB). Despite the common genetic background, it appears that the tumors with TSC/mTOR mutations represent a diverse group of distinct renal neoplasms.