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1.
Histopathology ; 83(3): 465-476, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37317674

RESUMEN

AIMS: Yolk sac tumour postpubertal-type (YSTpt) shows a wide range of histological patterns and is challenging to diagnose. Recently, forkhead box transcription factor A2 (FoxA2) emerged as a driver of YSTpt formation and a promising marker for diagnosing YSTpt. However, FoxA2 has not been tested in the different patterns of YSTpt. This study aimed to assess the staining pattern of FoxA2 in te different patterns of YSTpt and other germ cell tumours of the testis (GCTT), comparing it with glypican-3 (GPC3) and α-fetoprotein (AFP). METHODS AND RESULTS: FOXA2, GPC3 and AFP immunohistochemistry was performed on 24 YSTpt (24 microcystic/reticular, 10 myxoid, two macrocystic, five glandular/alveolar, two endodermal sinus/perivascular, four solid, two polyembryoma/embryoid body and two polyvesicular vitelline) and 81 other GCTT. The percentage of positive cells (0, 1+, 2+, 3+) and the intensity (0, 1, 2, 3) were evaluated regardless of and within each YSTpt pattern. FoxA2 was positive in all YSTpt (24 of 24) and all but one (23 of 24) exhibited 2+/3+ stain, with higher intensity [median value (mv): 2.6] than AFP (1.8) and GPC3 (2.5). Both FoxA2 and GPC3 were positive in all microcystic/reticular (24 of 24), myxoid (10 of 10), macrocystic (two of two), endodermal sinus/perivascular (four of four) and polyembryoma/embryoid body (two of two) patterns. Nevertheless, only FoxA2 was positive in all glandular/alveolar (five of five), solid (four of four) and polyvesicular vitelline (two of two) patterns. The intensity of FoxA2 was higher than AFP and GPC3 in almost all YST patterns. In the other GCTT, FoxA2 was positive only in teratoma postpubertal-type (Tpt) [13 of 20 (65%)], with staining almost exclusively confined to the mature gastrointestinal/respiratory tract epithelium. CONCLUSIONS: FoxA2 is a highly sensitive and specific biomarker that supports the diagnosis of YSTpt. FoxA2 is superior to GPC3 and AFP, especially in rare and difficult-to-diagnose histological patterns of YSTpt, but mature glands of Tpt could represent a potential diagnostic pitfall.


Asunto(s)
Quistes , Tumor del Seno Endodérmico , Neoplasias Ováricas , Neoplasias Testiculares , Masculino , Humanos , Femenino , alfa-Fetoproteínas , Biomarcadores de Tumor , Tumor del Seno Endodérmico/diagnóstico , Tumor del Seno Endodérmico/patología , Neoplasias Testiculares/patología , Neoplasias Ováricas/patología , Glipicanos
2.
World J Urol ; 39(5): 1473-1479, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32621027

RESUMEN

PURPOSE: Diagnosis of anterior prostate cancer (PCa) can be quite challenging, often leading to delay in treatment. mpMRI-guided biopsy (GB) has been introduced aiming to increase the number of diagnoses of clinically significant PCa with fewer cores. The aim of our study is to compare pathological findings of prostate biopsy, In-bore or Fusion technique, with histopathological evaluation of radical prostatectomy. METHODS: We prospectively collected data from 90 consecutive patients who underwent either In-bore or Fusion biopsy following the detection of an index suspicious lesion at mpMRI in the anterior part of the prostatic gland. Bioptical pathological findings were compared with pathological findings reported after robot-assisted radical prostatectomy. RESULTS: Patients who underwent In-bore GB had a higher rate of previous negative prostate biopsies (19% vs 44%, p = 0.02). Median number of bioptic cores taken (13 vs 2) and number of positive cores (3 vs 2) were significantly superior in the Fusion group compared to the In-bore group (p < 0.001 and p = 0.002, respectively), whilst clinical International Society of Urological Pathology (ISUP) grade was homogeneous within groups. The concordance between anterior lesions detected at biopsy and those reported in the histopathological finding of radical prostatectomy was very high, without statistically significant difference between groups. CONCLUSION: Both Fusion and In-bore GB are accurate in detecting anterior PCa, with enhanced precision detecting clinically significant tumours, as evidenced by pathologic examinations which confirmed the presence of index anterior PCa in > 50% of patients overall. Additional sextant biopsy is still required, especially among biopsy-näive patients, to avoid missing clinically significant PCa.


Asunto(s)
Biopsia Guiada por Imagen , Imagen por Resonancia Magnética , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Prostatectomía , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos
3.
Eur J Nucl Med Mol Imaging ; 47(9): 2100-2105, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32006061

RESUMEN

PURPOSE: To perform an external validation of a recently published nomogram aimed to predict positive 68Ga-PSMA-11 PET/CT in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) by Rauscher et al. (Eur Urol 73(5):656-661, 2018). METHODS: Overall, 413 PCa patients with BCR after RP (two consecutive PSA ≥ 0.2 ng/ml) and PSA value between 0.2 and 1 ng/ml were included. A multivariable logistic regression model was produced to assess the predictors of positive 68Ga-PSMA-11 PET/CT results. The performance characteristics of the model were assessed by quantifying the predictive accuracy, according to model calibration. Yuden's index was used to find the best nomogram's cut-off. Finally, decision curve analysis (DCA) was implemented to quantify the nomogram's clinical value. RESULTS: In the external cohort, the overall detection rate of 68Ga-PSMA-11 PET/CT was 44% vs. 64.7% in the original population. At multivariate analysis, PSA at 68Ga-PSMA-11 PET/CT (OR: 7.06, p < 0.001) and ongoing ADT at time of 68Ga-PSMA-11 PET/CT (OR: 2.07, p = 0.03) were the only independent predictors of PET/CT positivity. The predictive accuracy of nomogram was suboptimal and comparable to that reported in the original model (64% vs. 67%, respectively). The calibration plot indicated suboptimal concordance. The best nomogram's cut-off to predict positive 68Ga-PSMA-11 PET/CT was 35% (AUC = 0.61). In DCA, the nomogram revealed clinical net benefit when the threshold probabilities of positive 68Ga-PSMA-11 PET/CT is > 35%. CONCLUSION: We assessed similar suboptimal predictive accuracies in the external cohort compared to the original one. PSA and ongoing ADT were confirmed as positive predictors, and the most informative nomogram cut-off resulted 35%.


Asunto(s)
Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Ácido Edético/análogos & derivados , Isótopos de Galio , Radioisótopos de Galio , Humanos , Masculino , Recurrencia Local de Neoplasia , Nomogramas , Oligopéptidos , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía
4.
Surg Technol Int ; 34: 296-301, 2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-31034578

RESUMEN

OBJECTIVES: To compare the perioperative and short-term outcomes of robotic pyelolithotomy (RP) and laparoscopic pyelolithotomy (LP) for the treatment of renal stones. MATERIALS AND METHODS: We retrospectively evaluated 39 patients who underwent robotic or laparoscopic pyelolithotomy from January 2015 to December 2018. RESULTS: The preoperative characteristics of the two groups were comparable. The mean operative time was 173 ± 51 and 182 ± 62 min in the RP and LP groups, respectively (p=0.6). Blood loss and length of hospital stay with the robotic approach were lower than those with the laparoscopic approach (210 ± 180 ml vs. 639 ± 412 ml, p<0.001, and 3.8 ± 3 days vs. 7.3 ± 2.8 days, p=0.001). A complete stone-free status was achieved in 17 (85%) patients in the RP group and 8 (42%) in the LP group (p=0.01). Post-operative complications with the two approaches were also similar. CONCLUSIONS: In some selected cases, laparoscopic and robotic pyelolithotomy are alternative procedures for large, multiple and complex kidney stones. The robotic approach was associated with less intraoperative blood loss and fewer days of hospitalization compared to the laparoscopic method, and also gives a better stone-free rate.


Asunto(s)
Cálculos Renales/cirugía , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Procedimientos Quirúrgicos Urológicos/métodos , Humanos , Laparoscopía/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del Tratamiento
5.
Surg Technol Int ; 34: 302-309, 2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-31037718

RESUMEN

AIM: To compare surgical, functional and early survival outcomes for robot-assisted radical cystectomy (RARC) with intracorporeal orthotopic neobladder (ONB) reconstruction in patients age = 75 y to those in patients age < 75 y using Propensity Score Matching. METHODS: We collected data from 15 patients age = 75 y from among 60 consecutive RARC with ONB reconstruction performed at our institution from January 2015 to July 2018. All procedures were performed by a single surgeon after modular training under the supervision of a skilled surgeon. Demographic, surgical, functional and survival data were prospectively collected and compared to the corresponding data from 15 patients from the same series age < 75 y, matched according to the ASA score, body mass index, clinical stage and associated carcinoma in situ using Propensity Score Matching. RESULTS: There were no significant differences between the two groups with regard to preoperative parameters, such as ASA score, BMI and preoperative stage. The same homogeneity was found for intraoperative parameters, such as operation time, number of nodes retrieved and ONB time. The only statistically significant difference noted was in the percentage of nerve-sparing procedures, which was higher in the younger patient group (p < 0.001). The percentages of early and late postoperative complications were higher in the older patients, but the differences were not statistically significant. Moreover, there were no differences among the two populations in terms of functional outcomes (daytime and nighttime continence, potency), or in either cancer-specific or overall mortality. CONCLUSIONS: RARC with totally intracorporeal ONB diversion can be offered to older patients with an expectation of good surgical, functional and early survival outcomes, although further studies with a larger sample size will be needed to confirm these results.


Asunto(s)
Cistectomía/métodos , Íleon/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Derivación Urinaria/métodos , Anciano , Cistectomía/estadística & datos numéricos , Humanos , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Resultado del Tratamiento , Derivación Urinaria/estadística & datos numéricos
6.
Int J Urol ; 25(6): 574-581, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29633372

RESUMEN

OBJECTIVES: To assess the predictive accuracy and the clinical value of a recent nomogram predicting cancer-specific mortality-free survival after surgery in pN1 prostate cancer patients through an external validation. METHODS: We evaluated 518 prostate cancer patients treated with radical prostatectomy and pelvic lymph node dissection with evidence of nodal metastases at final pathology, at 10 tertiary centers. External validation was carried out using regression coefficients of the previously published nomogram. The performance characteristics of the model were assessed by quantifying predictive accuracy, according to the area under the curve in the receiver operating characteristic curve and model calibration. Furthermore, we systematically analyzed the specificity, sensitivity, positive predictive value and negative predictive value for each nomogram-derived probability cut-off. Finally, we implemented decision curve analysis, in order to quantify the nomogram's clinical value in routine practice. RESULTS: External validation showed inferior predictive accuracy as referred to in the internal validation (65.8% vs 83.3%, respectively). The discrimination (area under the curve) of the multivariable model was 66.7% (95% CI 60.1-73.0%) by testing with receiver operating characteristic curve analysis. The calibration plot showed an overestimation throughout the range of predicted cancer-specific mortality-free survival rates probabilities. However, in decision curve analysis, the nomogram's use showed a net benefit when compared with the scenarios of treating all patients or none. CONCLUSIONS: In an external setting, the nomogram showed inferior predictive accuracy and suboptimal calibration characteristics as compared to that reported in the original population. However, decision curve analysis showed a clinical net benefit, suggesting a clinical implication to correctly manage pN1 prostate cancer patients after surgery.


Asunto(s)
Técnicas de Apoyo para la Decisión , Nomogramas , Prostatectomía , Neoplasias de la Próstata/mortalidad , Anciano , Toma de Decisiones Clínicas , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Curva ROC , Tasa de Supervivencia , Resultado del Tratamiento
7.
Virchows Arch ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259293

RESUMEN

Embryonic-type neuroectodermal tumor (ENT) is a somatic-type malignancy characterized by overgrowth of embryonic-type neuroectodermal tissue (EtNT). In germ cell tumors, EtNT is frequently intermingled with other components that may exhibit significant morphologic overlap [mature neuro-glial tissue (MNGT), nephroblastomatous tissues, and primitive endodermal-type glands]. Therefore, the quantification of EtNT (crucial for the diagnosis of ENT) can be challenging. In this study, we investigated the immunohistochemical profile of ENT, EtNT, and MNGT using a broad immunohistochemical panel. We found that SOX2 was the most sensitive marker for EtNT (100%), but it also stained MNGT (28.6%). GFAP and S100 were relatively sensitive (71.4%) and highly specific (GFAP 100%, S100 85.8%) for MNGT, whereas synaptophysin stained both. Combining our results with those of previous studies, we propose that a combination of SOX11, SOX2, GFAP, S100, AFP, villin, CDX2, PAX8, and nuclear WT1 may help to identify and quantify EtNT in germ cell tumors.

8.
Pathol Res Pract ; 241: 154269, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36502737

RESUMEN

The recently described SWI/SNF complex-deficient sinonasal carcinoma (SMARCB1 & SMARCA4) may exhibit a yolk sac-like morphology. Tumors with similar features (yolk sac-like histology combined with the immunohistochemical loss of SMARCB1/INI1 and/or SMARCA4/BRG1) have also been described in other sites, such as the female genital tract. In this study, we immunohistochemically assessed SMARCB1/INI1 and SMARCA4/BRG1 expression to evaluate if these proteins could be involved in the pathogenesis of testicular yolk sac tumors of postpubertal type (YSTpt). Specifically, we analyzed a retrospective case series comprising pure YSTpt and mixed germ cell tumors of the testis (GCTT) with YSTpt components. In the present study, no testicular YSTpt showed loss of SMARCB1/INI1 (0/24, 0%) or SMARCA4/BRG1 (0/24, 0%). However, testicular choriocarcinoma (CHC) and isolated syncytiotrophoblast cells (iSTCs) demonstrated abnormal staining patterns for SMARCA4/BRG1 [CHC: 4/4 (100%); iSTCs: 12/12 (100%), respectively], including focal or diffuse loss of expression in a subset of cases. The results of our study suggest that functional loss of SMARCA4/BRG1 represents a recurrent event that may be relevant for the pathogenesis of a subset of testicular CHC.


Asunto(s)
Carcinoma , Coriocarcinoma , Tumor del Seno Endodérmico , Masculino , Femenino , Humanos , Estudios Retrospectivos , Biomarcadores de Tumor , Proteína SMARCB1/metabolismo , Carcinoma/patología , ADN Helicasas , Proteínas Nucleares , Factores de Transcripción
9.
Pathol Res Pract ; 242: 154337, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36706585

RESUMEN

BACKGROUND: Lymphovascular invasion (LVI) is a relevant prognostic factor in germ cell tumors of the testis (GCTT), and it is included in the pT stage. However, its detection on hematoxylin and eosin (H&E) slides is very challenging, and previous studies reported fair to moderate inter-observer agreement among dedicated uropathologists. In the present study, we tested H&E and a recently developed in-house double staining for OCT4/CD34 to detect LVI in GCTT. METHODS: Nine authors [5 non-uropathologists and 4 uropathologists] independently evaluated 34 consecutive and retrospectively enrolled cases of GCTT. We assessed the inter-observer agreement (Fleiss's Kappa) with both H&E and OCT4/CD34. Besides, we compared the consensus diagnosis on both H&E and OCT4/CD34-stained sections with the original diagnosis to evaluate the pT re-staging (McNemar test) and identify the sources of disagreement. RESULTS: The inter-observer agreement among uropathologists plus non-uropathologists was fair with both H&E (KF=0.398; p < 0.001) and OCT4/CD34 (KF=0.312; p < 0.001). OCT4/CD34 (KF=0.290; p < 0.001) slightly reduces the inter-observer agreement compared to H&E (KF=0.321; p < 0.001) for non-uropathologists; in contrast, OCT4/CD34 (KF=0.293; p < 0.001) significantly reduces the inter-observer agreement compared to H&E (KF=0.529; p < 0.001) for uropathologists, changing it from moderate to fair. Consensus diagnosis with H&E modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.070), with pT re-staging in 2/34 (5.9 %) cases (p: 0.500). Consensus diagnosis with OCT4/CD34 modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.289), with pT re-staging in 3/34 (8.8 %) cases (p: 0.250). The consensus diagnosis with OCT4/CD34 modified the consensus diagnosis with H&E in 8/34 (23.5 %) cases (p: 0.727), and these findings resulted in pT-restaging in 3/34 (8.8 %) cases (p: 0.500). The sources of disagreement among uropathologists were: H&E [artefactual clefts misinterpreted as LVI in 4/6 (66.7 %) cases and true foci of LVI misinterpreted as clusters of histiocytes within the vessels in 2/6 (33.3 %) cases], OCT4/CD34 [artefactual clefts misinterpreted as LVI in 2/8 (25 %) cases, true LVI misinterpreted as artefactual clefts in 2/8 (25 %) cases or floaters in 4/8 (50 %) cases]. CONCLUSIONS: OCT4/CD34 does not improve the inter-observer agreement for the assessment of LVI in OCT4(+) GCTT. Consensus diagnosis with H&E modifies the LVI status in a significant number of cases, resulting in changes of the pT stage in a relatively small subgroup. Consensus diagnosis with OCT4/CD34 provides little additional benefit since it cannot exclude mimickers of LVI such as floaters and artefactual clefts. These results argue against the adoption of this diagnostic tool for the routine assessment of OCT4(+) GCTT.


Asunto(s)
Carcinoma Embrionario , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Eosina Amarillenta-(YS) , Hematoxilina , Seminoma/diagnóstico , Seminoma/patología , Estudios Retrospectivos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patología , Procesos Neoplásicos , Invasividad Neoplásica , Pronóstico
10.
Pathol Res Pract ; 247: 154540, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37209574

RESUMEN

BACKGROUND: In recent years, several studies focused on the process of reprogramming of seminoma (S) cells, which regulates the transition from pure S (P-S) to S component (S-C) of mixed germ cell tumors of the testis (GCTT) and finally to embryonal carcinoma (EC) and other nonseminomatous GCTT (NS-GCTT). The accepted pathogenetic model is driven and regulated by cells (macrophages, B- and T-lymphocytes) and molecules of the tumor microenvironment (TME). Herein, we tested a series of GCTT with double staining (DS) for CD68-PD-L1 to evaluate tumor-associated macrophages (TAMs) expressing programmed death-ligand 1 (PD-L1) [TAMs PD-L1(+)] and clarify if these cells may be involved in establishing the fate of GCTT. METHODS: We collected 45 GCTT (comprising a total of 62 different components of GCTT). TAMs PD-L1(+) were evaluated with three different scoring systems [TAMs PD-L1(+)/mm2, TAMs PD-L1(+)/mm2H-score, TAMs PD-L1(+) %], and compared using pertinent statistic tests (Student's t-test and Mann-Whitney U test). RESULTS: We found that TAMs PD-L1(+) values were higher in S rather than EC (p = 0.001, p = 0.015, p = 0.022) and NS-GCTT (p < 0.001). P-S showed statistically significant differences in TAMs PD-L1(+) values compared to S-C (p < 0.001, p = 0.006, p = 0.015), but there were no differences between S-C and EC (p = 0.107, p = 0.408, p = 0.800). Finally, we found statistically significant differences also in TAMs PD-L1(+) values between EC and other NS-GCTT (p < 0.001). CONCLUSIONS: TAMs PD-L1(+) levels gradually decrease during the reprogramming of S cells {P-S [(high values of TAMs PD-L1(+)] → S-C and EC [(intermediate values of TAMs PD-L1(+)] → other NS-GCTT [(low values of TAMs PD-L1(+)], supporting a complex pathogenetic model where the interactions between tumor cells and TME components [and specifically TAMs PD-L1(+)] play a key role in determining the fate of GCTT.


Asunto(s)
Neoplasias Testiculares , Macrófagos Asociados a Tumores , Masculino , Humanos , Antígeno B7-H1 , Células Germinativas , Microambiente Tumoral
11.
Virchows Arch ; 483(5): 687-698, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37845471

RESUMEN

The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43-79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9-3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without "canonical" mutations.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Masculino , Anciano , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Riñón/patología , Mutación , Carcinoma de Células Renales/patología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo
12.
Pathol Res Pract ; 234: 153937, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35561522

RESUMEN

BACKGROUND: The differential diagnosis between flat urothelial lesions [reactive urothelial atypia (RUA), atypia of unknown significance (AUS), urothelial dysplasia (UD) and carcinoma in situ (CIS)] has relevant prognostic and therapeutic implications. This crucial distinction could be very challenging but it is currently performed on hematoxylin and eosin (H&E) slides, with a great amount of partially discordant and/or not conclusive findings of the potential adjunctive role of immunohistochemistry. Herein, we tested double staining (DS) for p53/CK20 to verify if p53(+) cells, CK20(+) cells and double-positive cells (DPCs) are differentially expressed among these lesions and if p53/CK20 could be a useful tool in this diagnostic setting. METHODS: We tested 50, 9, 36 and 29 consecutive and retrospectively enrolled cases of RUA, AUS, UD and CIS, respectively. p53(+) cells, CK20(+) cells and DPCs were evaluated and compared by adopting the appropriate statistic tests (Mann-Whitney U and Kruskal-Wallis tests). RESULTS: We found that p53(+) cells (p = 0.000), CK20(+) cells (p = 0.000) and DPCs (p = 0.000) showed statistically significant differences among the different flat urothelial lesions. Besides, when dichotomized, both CIS and RUA are easily differentiable from their histological mimickers adopting all these markers; by contrast, AUS and UD did not reach statistically significant differences able to differentiate them from each other [p53(+) cells, p = 0.123; CK20(+) cells, p = 0.567; DPCs, p = 0.409], except if compared to CIS [AUS VS CIS: p53(+) cells, p = 0.013; CK20(+) cells, p = 0.000; DPCs, p = 0.000; UD vs CIS: p53(+) cells, p = 0.000; CK20(+) cells, p = 0.000; DPCs, p = 0.000]. CONCLUSIONS: p53(+) cells, CK20(+) cells and DPCs are differently expressed by flat urothelial lesions and p53/CK20 could be a time- and money-saving tool for the appropriate management of these lesions if applied to a routine scenario.


Asunto(s)
Carcinoma in Situ , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patología , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Colorantes , Humanos , Queratina-20/análisis , Queratina-20/metabolismo , Estudios Retrospectivos , Coloración y Etiquetado , Proteína p53 Supresora de Tumor/análisis , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología
13.
Pathol Res Pract ; 237: 154044, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35930824

RESUMEN

BACKGROUND: In recent years, several studies investigated the complex process called "reprogramming" of seminoma (S) cells. The accepted pathogenetic model is a complex network including SOX2, SOX17, OCT3/4 and PRAME, which modulates the epigenetic transcription of numerous downstream genes and drives a divergent gene expression profile resulting in the transition from pure S (P-S) to S component (S-C) of mixed germ cell tumors of the testis (M-GCTT), and finally to embryonal carcinoma (EC). Herein, we tested a large cohort of GCTT with SOX2 and PRAME to evaluate their expression in the evolutionary steps of GCTT and verify if the modulation in the expression of these two molecules could be relevant for the fate of GCTT. METHODS: We tested 43, 19 and 17 consecutive and retrospectively enrolled cases of GCTT, germ cell neoplasia in situ (GCNIS) and uninvolved background testes (UBT), respectively. SOX2 and PRAME expressions have been evaluated with H-score and compared by adopting the appropriate statistic tests (Student's t-test and Mann-Whitney U test). RESULTS: We found that SOX2 was more expressed by nonseminomatous-GCTT (NS-GCTT) (p < 0.001) and EC (p < 0.001) rather than S; by contrast, PRAME showed an opposite expression profile being expressed by S but not by NS-GCTT (p < 0.001) and EC (p < 0.001). S-C showed different expressions of SOX2 and PRAME compared to both P-S (p = 0.002 and <0.001, respectively) and EC (p < 0.001 and 0.042, respectively), with intermediate values between these latter two categories. GCNIS and UBT showed no expression of SOX2 (scattered positive Leydig cells) but high H-score levels of PRAME. CONCLUSIONS: SOX2 and PRAME are differentially expressed and specularly modulated during the "reprogramming" of S cells [P-S (high levels of PRAME, no expression/low levels of SOX2) → S-C (intermediate levels of PRAME, intermediate levels of SOX2) → EC (no expression/low levels of PRAME, high levels of SOX2)], therefore supporting a complex pathogenetic model where the interactions between these two molecules are crucial in determining the fate of GCTT.


Asunto(s)
Carcinoma Embrionario , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Seminoma/genética , Seminoma/metabolismo , Seminoma/patología , Neoplasias Testiculares/patología , Estudios Retrospectivos , Factores de Transcripción SOXB1/metabolismo , Carcinoma Embrionario/genética , Carcinoma Embrionario/metabolismo , Carcinoma Embrionario/patología , Antígenos de Neoplasias/metabolismo
14.
Curr Urol ; 14(1): 22-31, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32398993

RESUMEN

OBJECTIVES: Transrectal ultrasound-guided biopsy (TRUS-GB) is the current reference standard procedure for diagnosis of prostate cancer (PCa) but this procedure has limitations related to the low detection rate (DR) described in the literature. The aim of the study was to evaluate the DR efficiency, and complication rate in a pure "in-bore" magnetic resonance imaging-guided biopsy (MRI-GB) series according to the Prostate Imaging Reporting and Data System, version 2 (PI-RADS v2). MATERIALS AND METHODS: From July 2015 to April 2018, a series of 142 consecutive patients undergoing MRI-GB were prospectively enrolled. According to the European Society of Urogenital Radiology guidelines, the presence of clinically significant PCa (csPCa) on multiparametric magnetic resonance imaging was defined as equivocal, likely, or highly likely according to a PI-RADS v2, score of 3, 4, or 5, respectively. RESULTS: Of 142 patients, 76 (53.5%) were biopsy naive and 66 (46.5%) had ≤ 1 previous negative set of random TRUS-GB findings. The MRI-GB findings were positive in 75 of 142 patients with a DR of 52.8%. Of the 76 patients with ≤ 1 previous set of TRUS-GB, 43 had PCa found by MRI-GB, with a DR of 57.3%. The DR in the 66 biopsy-naive patients was 48% (32/66). Of the 75 patients with positive biopsy findings, 54 (80.5%) were found to have csPCa on histological examination. Of these 54 patients, 28 had an International Society of Urological Pathology grade 2; 5 had grade 3, 19 had grade 4, and 2 had grade 5. Considering the anatomic distribution of the index lesions using the PI-RADS v2 scheme, the probability of PCa was greater for lesions located in the peripheral zone (55 of 75, 73.3%) than for those in the central zone (20 of 75, 26.7%). CONCLUSIONS: Our study conducted on 142 patients confirmed the greater DR of csPCa by MRI-GB, with a very low number of cores needed and a negligible incidence of complications, especially in patients with a previous negative biopsy. MRI-GB is optimal for the diagnosis of anterior and central lesions.

15.
Clin Genitourin Cancer ; 18(6): e669-e678, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32354617

RESUMEN

INTRODUCTION: The purpose of this study was to evaluate the impact of 3-dimensional (3D) digital reconstructions of renal models on the arterial clamping approach during partial nephrectomy (PN). PATIENTS AND METHODS: Fifty-seven patients with T1 renal mass, referred for PN, were prospectively enrolled in 2 groups: Group 1 (n = 32) with revision of both 2-dimensional (2D) computed tomography (CT) imaging and 3D virtual model before surgery; Group 2 (n = 25) with revision of 2D CT imaging. Segmentation of the 3D models from preoperative high-quality CT scan was achieved using D2P software. In a sub-analysis of patients treated with PN with the on-clamp approach (n = 36), the effective intraoperative level of arterial clamping was compared with the preoperative planning. RESULTS: In the sub-group of patients referred to PN with the on-clamp approach, the intraoperative selective clamping was performed in 12 (57.1%) patients of Group 1 and in 2 (13.3%) cases of Group 2 (P = .01). The intraoperative management of the renal pedicle was done as preoperatively planned in 61.9% of patients in Group 1 and in 86.6% of cases in Group 2 (P = .1). CONCLUSION: The 3D-guided plan of PN allows to perform selective clamping in higher proportion of patients compared with the standard 2D-guided approach without increasing intraoperative and postoperative complications.


Asunto(s)
Neoplasias Renales , Estudios de Casos y Controles , Humanos , Imagenología Tridimensional , Riñón/diagnóstico por imagen , Riñón/cirugía , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Nefrectomía
16.
Cent European J Urol ; 72(2): 106-112, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31482016

RESUMEN

INTRODUCTION: Purpose of the study was to investigate the correlation of a preoperative multiparametric magnetic resonance imaging of the prostate (mpMRI) in patients with a suspicion of prostate cancer and eligible for Holmium Laser Enucleation of the Prostate (HoLEP). MATERIAL AND METHODS: Data of 228 patients who had undergone HoLEP was selected and retrospectively analyzed from a multicentric database. All patients presented with a raised serum PSA and/or an abnormal digital rectal examination (DRE). Prostate cancer (PCa) was excluded either with a negative mpMRI (group 'NEGATIVE MRI' n = 113) or a standard biopsy (group 'NO MRI' n = 115). Preoperative characteristic surgical and histological outcomes were confronted. A univariate and multivariate logistic regression model was performed to investigate independent predictors of incidental Prostate Cancer (iPCa). RESULTS: Both groups presented with no statistical differences in preoperative characteristics besides previous acute urinary retention rates and post-voided residual volume, found to be higher (27.8% vs. 14.2% and median 120cc vs. 80cc) in NO MRI and NEGATIVE MRI respectively.No differences were registered in surgical time, removed tissue, catheterization time, hospital stay and complications rate.Statistically lower rate of iPCa (p = 0.03) was detected in the NEGATIVE MRI group (6.2%) in comparison with NO MRI group (14.8%). In multivariate logistic regression only presence of a preoperative negative mpMRI correlated (p = 0.04) as an independent predictive factor (OR 2.63; 95% CI: 1.02-6.75). CONCLUSIONS: A negative mpMRI might be a useful tool to be included in a novel preoperative assessment to patients eligible for HoLEP with a suspicion of PCa in order to avoid an incidental PCa.

17.
Cent European J Urol ; 72(2): 113-120, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31482017

RESUMEN

INTRODUCTION: The aim of this study was to assess surgical and functional outcomes of 17 consecutive patients undergoing robot- assisted radical cystectomy (RARC) with palliative intent in a monocentric single surgeon series. MATERIAL AND METHODS: We collected data from 17 consecutive patients who underwent RARC with palliative intent performed by a single surgeon at our institution. Patients undergoing palliative RARC were those with advanced bladder cancer (BC) or advanced comorbidities. Clinical, surgical and functional outcomes were prospectively collected. Patients completed a specific questionnaire (Functional Assessment of Cancer Therapy-Bladder Cancer, FACT-BL) before and after surgery to assess the role of palliative RARC in terms of quality of life improvement. RESULTS: Median age at surgery was 78 years, with median Charlson Comorbidity Index (CCI) and age-adjusted CCI of 3 and 7, respectively. Clinical stage was T2, T3 or T4 in 7, 8 and 2 patients respectively, with 52.9% and 29.4% with cN+ and cM+ disease. Median estimated blood loss was 200 ml, with 1 patient requiring intra-operative blood transfusion. Median hospital stay was 7 days. A total of 3 and 2 patients were re-hospitalized during the first 30 and 30-90 post-operative days, respectively. One major Clavien grade complication was recorded.At median follow-up of 8 months, 9 and 2 patients succumbed due to tumor progression and other causes. Pre-operative and post-operative FACT-BL scores improved significantly in each domain. CONCLUSIONS: A RARC is a safe and feasible technique which could be offered as part of palliative care in patients with advanced BC or comorbidities. Precise guidelines for palliating BC patients should be better.

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