Development and Validation of a Preoperative Nomogram for Endoscopic Management Decision Making in Upper Urinary Tract Urothelial Carcinoma.

OBJECTIVE: We aimed to develop and validate a preoperative nomogram that predicts low-grade, non-muscle invasive upper urinary tract urothelial carcinoma (LG-NMI UTUC), thereby aiding in the accurate selection of endoscopic management (EM) candidates. METHODS: This was a retrospective study that included 454 patients who underwent radical surgery (Cohort 1 and Cohort 2), and 26 patients who received EM (Cohort 3). Utilizing a multivariate logistic regression model, a nomogram predicting LG-NMI UTUC was developed based on data from Cohort 1. The nomogram's accuracy was compared with conventional European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) models. External validation was performed using Cohort 2 data, and the nomogram's prognostic value was evaluated via disease progression metrics in Cohort 3. RESULTS: In Cohort 1, multivariate analyses highlighted the absence of invasive disease on imaging (odds ratio [OR] 7.04; p = 0.011), absence of hydronephrosis (OR 2.06; p = 0.027), papillary architecture (OR 24.9; p < 0.001), and lack of high-grade urine cytology (OR 0.22; p < 0.001) as independent predictive factors for LG-NMI disease. The nomogram outperformed the two conventional models in predictive accuracy (0.869 vs. 0.759-0.821) and exhibited a higher net benefit in decision curve analysis. The model's clinical efficacy was corroborated in Cohort 2. Moreover, the nomogram stratified disease progression-free survival rates in Cohort 3. CONCLUSION: Our nomogram ( https://kmur.shinyapps.io/UTUC_URS/ ) accurately predicts LG-NMI UTUC, thereby identifying suitable candidates for EM. Additionally, the model serves as a useful tool for prognostic stratification in patients undergoing EM.

Diagnostic performance of photodynamic diagnosis with oral 5-aminolevulinic acid for upper tract- and bladder urothelial carcinoma: a single-centre, retrospective analysis.

PURPOSE: To compare the diagnostic performance of photodynamic diagnosis (PDD) enhanced with oral 5-aminolaevulinic acid between the suspected upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) cases. METHODS: This retrospective study included 18 patients with suspected UTUC who underwent ureteroscopy (URS) with oral 5-ALA in the PDD-URS cohort between June 2018 and January 2019; and 110 patients with suspected BUC who underwent transurethral resection of bladder tumour (TURBT) in the PDD-TURBT cohort between January 2019 and March 2023. Sixty-three and 708 biopsy samples were collected during diagnostic URS and TURBT, respectively. The diagnostic accuracy of white light (WL) and PDD in the two cohorts was evaluated, and false PDD-positive samples were pathologically re-evaluated. RESULTS: The area under the receiver operating characteristic curve (AUC) of PDD was significantly superior to that of WL in both cohorts. The per biopsy sensitivity, specificity, and positive and negative predictive values of PDD in patients in the PDD-URS and PDD-TURBT cohorts were 91.2 vs. 71.4, 75.9 vs. 75.3, 81.6 vs. 66.3, and 88.0 vs. 79.4%, respectively. The PDD-URS cohort exhibited a higher AUC than did the PDD-TURBT cohort (0.84 vs. 0.73). Seven of four false PDD-positive samples (57.1%) in the PDD-URS cohort showed potential precancerous findings compared with eight of 101 (7.9%) in the PDD-TURBT cohort. CONCLUSION: The diagnostic performance of PDD in the PDD-URS cohort was at least equivalent to that in the PDD-TURBT cohort.

Prognostic impact of combination therapy with gemcitabine and cisplatin plus S-1 and subsequent conversion surgery for initially unresectable upper biliary tract cancers.

PURPOSE AND BACKGROUND: For the past decade, there have been few chemotherapy options for unresectable biliary tract cancer (BTC). Recently, however, combination therapy with gemcitabine and cisplatin plus S-1 (GCS) has been identified as a promising strategy. This retrospective study analyzes the clinical results of GCS therapy and subsequent conversion surgery (CS). METHOD: We analyzed the clinical data of 60 consecutive patients who received GCS therapy for unresectable upper BTC at our university hospital during the 5 years between September, 2018 and December, 2022. RESULTS: All patients received GCS therapy as first-line chemotherapy. The response rate was 33.9% and subsequent CS was performed in 35.0%. Of the patients who underwent CS, 81% required more than bisectionectomy of the liver with extrahepatic bile duct resection. The median overall survival of the patients who received GCS therapy and underwent subsequent CS was significantly longer than that of the patients who received GCS therapy alone (28.0 months vs. 12.4 months, respectively; p < 0.001). A decrease in the CA19-9 level 1 month after chemotherapy and RECIST PR were independent positive predictors of CS, whereas unresectable gallbladder cancer and pretreatment ALBI grade 3 were negative predictors of CS. CONCLUSION: GCS therapy and subsequent CS may contribute to the longer term survival of patients with unresectable upper BTC.

Prognostic value of PD-L1 expression in recurrent renal cell carcinoma after nephrectomy: a secondary analysis of the ARCHERY study.

BACKGROUND: Nephrectomy is a curative treatment for localized renal cell carcinoma (RCC), but patients with poor prognostic features may experience relapse. Understanding the prognostic impact of programmed death-ligand 1 (PD-L1) expression in patients who underwent nephrectomy for RCC may aid in future development of adjuvant therapy. METHODS: Of 770 surgical specimens collected from Japanese patients enrolled in the ARCHERY study, only samples obtained from patients with recurrent RCC after nephrectomy were examined for this secondary analysis. Patients were categorized into low- and high-risk groups based on clinical stage and Fuhrman grade. Time to recurrence (TTR) and overall survival (OS) were analyzed. RESULTS: Both TTR and OS were shorter in patients with PD-L1-positive than -negative tumors (median TTR 12.1 vs. 21.9 months [HR 1.46, 95% CI 1.17, 1.81]; median OS, 75.8 vs. 97.7 months [HR 1.32, 95% CI 1.00, 1.75]). TTR and OS were shorter in high-risk patients with PD-L1-positive than -negative tumors (median TTR 7.6 vs. 15.3 months [HR 1.49, 95% CI 1.11, 2.00]; median OS, 55.2 vs. 83.5 months [HR 1.53, 95% CI 1.06, 2.21]) but not in low-risk patients. CONCLUSIONS: This ARCHERY secondary analysis suggests that PD-L1 expression may play a role in predicting OS and risk of recurrence in high-risk patients with localized RCC. CLINICAL TRIAL REGISTRATION: UMIN000034131.

The academic impact and value of an international online surgery lecture series.

Due to the worldwide travel restrictions caused by the 2019 coronavirus disease pandemic, many universities and students lost opportunities to engage in international exchange over the past 2 years. Teleconferencing systems have thus been developed to compensate for severe travel restrictions. Kansai Medical University in Japan and Vilnius University in Lithuania have a collaborative research and academic relationship. The two universities have been conducting an online joint international surgery lecture series for the medical students of both universities. Fifteen lectures were given from October 2021 to May 2022. The lectures focused on gastrointestinal surgery, gastroenterology, radiology, pathology, genetics, laboratory medicine, and organ transplantation. A survey of the attendees indicated that they were generally interested in the content and satisfied with attending this lecture series. Our efforts were successful in providing Japanese and Lithuanian medical students with the opportunity to engage in international exchange through lectures held in each other's countries.

Learning from the past and present to change the future: Endoscopic management of upper urinary tract urothelial carcinoma.

Current guidelines recommend endoscopic management (EM) for patients with low-risk upper urinary tract urothelial carcinoma, as well as those with an imperative indication. However, regardless of the tumor risk, radical nephroureterectomy is still mainly performed worldwide despite the benefits of EM, such as renal function maintenance, no hemodialysis requirement, and treatment cost reduction. This might be explained by the association of EM with a high risk of local recurrence and progression. Furthermore, the need for rigorous patient selection and close surveillance following EM may be relevant. Nevertheless, recent developments in diagnostic modalities, pathological evaluation, surgical devices and techniques, and intracavitary regimens have been reported, which may contribute to improved risk stratification and treatments with superior oncological outcomes. In this review, considering recent advances in endourology and oncology, we propose novel treatment strategies for optimal EM.

[Radiofrequency Ablation for Pulmonary Metastasis of Ovarian Cancer Caused Iatrogenic Pneumothorax, Leading to Empyema].

A female patient in her 40s who underwent surgery for recurrent right lung metastasis from resected ovarian cancer was referred to our department because of the right pneumothorax due to radiofrequency ablation for multiple lung metastases. Methicillin-resistant Staphylococcus epidermidis( MRSE) was detected from the tip of the drainage catheter indicated persistent pulmonary fistula with right empyema, and surgical treatment was performed. A white coat of the whole lung surface and air leakage were observed at radiofrequency ablation (RFA) treated lesion and partial resection of the right lung, debridement, and irrigation were performed. A pathological examination revealed residual viable ovarian cancer cells and pleural fistula.

Sulfatide with ceramide composed of phytosphingosine (t18:0) and 2-hydroxy FAs in renal intercalated cells.

Diverse molecular species of sulfatide with differences in FA lengths, unsaturation degrees, and hydroxylation statuses are expressed in the kidneys. However, the physiological functions of specific sulfatide species in the kidneys are unclear. Here, we evaluated the distribution of specific sulfatide species in the kidneys and their physiological functions. Electron microscopic analysis of kidneys of Cst-deficient mice lacking sulfatide showed vacuolar accumulation in the cytoplasm of intercalated cells in the collecting duct, whereas the proximal and distal tubules were unchanged. Immunohistochemical analysis revealed that vacuolar H+-ATPase-positive vesicles were accumulated in intercalated cells in sulfatide-deficient kidneys. Seventeen sulfatide species were detected in the murine kidney by iMScope MALDI-MS analysis. The distribution of the specific sulfatide species was classified into four patterns. Although most sulfatide species were highly expressed in the outer medullary layer, two unique sulfatide species of m/z 896.6 (predicted ceramide structure: t18:0-C22:0h) and m/z 924.6 (predicted ceramide structure: t18:0-C24:0h) were dispersed along the collecting duct, implying expression in intercalated cells. In addition, the intercalated cell-enriched fraction was purified by fluorescence-activated cell sorting using the anti-vacuolar H+-ATPase subunit 6V0A4, which predominantly contained sulfatide species (m/z 896.6 and 924.6). The Degs2 and Fa2h genes, which are responsible for ceramide hydroxylation, were expressed in the purified intercalated cells. These results suggested that sulfatide molecular species with ceramide composed of phytosphingosine (t18:0) and 2-hydroxy FAs, which were characteristically expressed in intercalated cells, were involved in the excretion of NH3 and protons into the urine.

Clinical and molecular correlates of response to immune checkpoint blockade in urothelial carcinoma with liver metastasis.

Despite recent advancements in immunotherapy, urothelial carcinoma patients with liver metastasis have a poor response to immune checkpoint inhibitors (ICIs) and short survival durations. Here, we investigated the clinical activity and molecular correlates of resistance to ICI in patients with metastatic urothelial carcinoma (mUC), focusing on liver metastasis. In this study, 755 patients with mUC who received pembrolizumab (JUOG cohort), 144 mUC patients who were treated with atezolizumab (IMvigor210 cohort), and 59 mUC patients who had metastatic samples available were enrolled. The presence of liver metastasis was associated with increased peripheral monocytes and a reduction in lymphocytes when compared with other metastatic sites, and a poor prognosis for ICI therapy. The peripheral monocyte-to-lymphocyte ratio was significantly correlated with the CD163+M2-like tumor-associated macrophage (TAM)/CD8+ tumor-infiltrative lymphocyte (TIL) ratio in the primary and metastatic UC lesions. Exploratory molecular analyses indicated that ICI-resistant status, such as decreased tumor mutation burden, low CD8+ TILs and immune checkpoint signatures, and increased M2-like TAM markers, in primary tumors was correlated with the presence of liver metastasis. In metastatic lesions, the CD163+M2-like TAM/CD8+TIL ratio and expression of cancer-associated fibroblasts induced by the TGFß signaling pathway were higher in the liver versus the lung metastatic tumors. This study indicated that tumor-infiltrating lymphocyte and macrophage status in primary and metastatic lesions, which correlate with peripheral monocyte and lymphocyte status, may predict immunotherapy outcomes in UC patients with liver metastasis.

Development and validation of a vascularity-based architectural classification for clear cell renal cell carcinoma: correlation with conventional pathological prognostic factors, gene expression patterns, and clinical outcomes.

The prognostic significance of an architectural grading system for clear cell renal cell carcinoma (ccRCC) has recently been demonstrated. The present study aimed to establish a vascularity-based architectural classification using the cohort of 436 patients with localized ccRCC who underwent extirpative surgery and correlated the findings with conventional pathologic factors, gene expression, and prognosis. First, we assessed architectural patterns in the highest-grade area on hematoxylin and eosin-stained slides, then separately evaluated our surrogate score for vascularity. We grouped nine architectural patterns into three categories based on the vascular network score. "Vascularity-based architectural classification" was defined: category 1: characterized by enrichment of the vascular network, including compact/small nested, macrocyst/microcystic, and tubular/acinar patterns; category 2: characterized by a widely spaced-out vascular network, including alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary patterns; category 3: characterized by scattered vascularity without a vascular network, including solid sheets, rhabdoid and sarcomatoid patterns. Adverse pathological prognostic factors such as TNM stage, WHO/ISUP grade, and necrosis were significantly associated with category 3, followed by category 2 (all p < 0.001). We successfully validated the classification using The Cancer Genome Atlas (TCGA) cohort (n = 162), and RNA-sequencing data available from TCGA showed that the angiogenesis gene signature was significantly enriched in category 1 compared to categories 2 and 3, whereas the immune gene signature was significantly enriched in category 3 compared to categories 1 and 2. In univariate analysis, vascularity-based architectural classification showed the best accuracy in pathological prognostic factors for predicting recurrence-free survival (c-index = 0.786). The predictive accuracy of our model which integrated WHO/ISUP grade, necrosis, TNM stage, and vascularity-based architectural classification was greater than conventional risk models (c-index = 0.871 vs. 0.755-0.843). Our findings suggest that the vascularity-based architectural classification is prognostically useful and may help stratify patients appropriately for management based on their likelihood of post-surgical recurrence.

Useful diagnostic histogenetic features of ectopic odontogenic ghost cell tumours.

BACKGROUND: Ectopic odontogenic tumours are rare and difficult to diagnose. Consequently, they are occasionally misdiagnosed as other tumours and overtreated. Dentinogenic ghost cell tumours (DGCTs) are odontogenic neoplasms characterised by a CTNNB1 mutation, ghost cell appearance, and dentinoid-like calcification. Herein, we present a case of ectopic DGCT on the floor of a patient's mouth, providing reliable clinicopathological and genetic evidence of its odontogenicity for the first time. CASE PRESENTATION: A 72-year-old man presented with painless sublingual swelling. Imaging revealed a multi-lobulated, solid-cystic mass on the floor of his mouth. Cytological evaluation showed folded epithelial clusters composed of basaloid cells, keratinised material, and calcification. Histological analysis revealed a multi-cystic, cribriform to solid nest, with an odontogenic satellate reticulum-like epithelium, including ghost cells and dentinoid matrix deposition. Immunohistochemical analysis found that CK19, CK5/6, bcl-2, and p63 were diffuse positive, ß-catenin was focal positive in the nuclei, and the cells in the dentinoid matrix were positive for DMP1. The CTNTTB1 mutation was detected, leading to the final diagnosis of ectopic DGCT. There was no recurrence during the 6-month follow-up. CONCLUSIONS: Overall, we have presented a comprehensive clinical overview of DGCT and identified its pathological and genetic features. This report will aid in the recognition of this rare disease in the future and help to avoid misdiagnosis and overtreatment.

[A Case of Retroperitoneal Bronchogenic Cyst Diagnosed by Fluorescence in situ Hybridization].

A 50-year-old woman was referred to our hospital for consultation for a suspected left adrenal tumor detected by ultrasonography during a health check. Computed tomography and magnetic resonance imaging revealed a 4.7×3.4 cm tumor in the retroperitoneal space near the adrenal gland. The patient subsequently underwent laparoscopic tumor resection. Using fluorescence in situ hybridization (FISH), the resected tumor was diagnosed as a retroperitoneal bronchial cyst. Here we present a case of a definitive diagnosis of a retroperitoneal bronchial cyst using FISH, and review the cases of retroperitoneal bronchial cyst in the literature.

Familial Hyperaldosteronism Type 3 with a Rapidly Growing Adrenal Tumor: An In Situ Aldosterone Imaging Study.

Primary aldosteronism is most often caused by aldosterone-producing adenoma (APA) and bi-lateral adrenal hyperplasia. Most APAs are caused by somatic mutations of various ion channels and pumps, the most common being the inward-rectifying potassium channel KCNJ5. Germ line mutations of KCNJ5 cause familial hyperaldosteronism type 3 (FH3), which is associated with severe hyperaldosteronism and hypertension. We present an unusual case of FH3 in a young woman, first diagnosed with primary aldosteronism at the age of 6 years, with bilateral adrenal hyperplasia, who underwent unilateral adrenalectomy (left adrenal) to alleviate hyperaldosteronism. However, her hyperaldosteronism persisted. At the age of 26 years, tomography of the remaining adrenal revealed two different adrenal tumors, one of which grew substantially in 4 months; therefore, the adrenal gland was removed. A comprehensive histological, immunohistochemical, and molecular evaluation of various sections of the adrenal gland and in situ visualization of aldosterone, using matrix-assisted laser desorption/ionization imaging mass spectrometry, was performed. Aldosterone synthase (CYP11B2) immunoreactivity was observed in the tumors and adrenal gland. The larger tumor also harbored a somatic ß-catenin activating mutation. Aldosterone visualized in situ was only found in the subcapsular regions of the adrenal and not in the tumors. Collectively, this case of FH3 presented unusual tumor development and histological/molecular findings.

The SSPN Score, a Novel Scoring System Incorporating PBRM1 Expression, Predicts Postoperative Recurrence for Patients with Non-metastatic Clear Cell Renal Cell Carcinoma.

BACKGROUND: The loss of PBRM1 expression (as identified by immunohistochemistry) is associated with a high risk of postoperative recurrence for patients with clear cell renal cell carcinoma (ccRCC). The authors developed a scoring system to predict recurrence based on clinicopathologic factors incorporating PBRM1 expression. METHODS: This study retrospectively reviewed 479 ccRCC patients who underwent radical surgery between 2006 and 2017. The study extracted a subset of 389 non-metastatic ccRCC patients for whom relevant clinicopathologic factors were available. The primary end point was recurrence-free survival (RFS). The Kaplan-Meier method and the Cox proportional hazards model were used for statistical analysis. Leibovich score, SSIGN score, and University of California, Los Angeles (UCLA) Integrated Staging System were included as conventional prediction models. RESULTS: Of the 389 patients, 53 (13.6%) experienced recurrence during a median period of 61 months. Multivariable analyses showed that that the independent factors for RFS were ≥ pT3 (hazard ratio [HR] 3.64; P < 0.001), sarcomatoid or rhabdoid component (HR 3.29; P = 0.005), PBRM1 negativity (HR 3.39; P = 0.001), and necrosis (HR 3.60; P < 0.001). A scoring system calculated with these factors, named the SSPN (stage, sarcomatoid, PBRM1 expression, and necrosis) score, showed significant differences in RFS among the following four groups; low-risk group (0 factors), intermediate-risk group (1 factor), high-risk group (2 to 3 factors), and very high-risk group (4 factors) (P < 0.001). The authors' model also showed a greater predictive accuracy for 5-year RFS than the conventional models (0.841 vs 0.747-0.792). CONCLUSIONS: The SSPN score, which integrates clinicopathologic findings and PBRM1 expression, can accurately predict postoperative recurrence for patients with non-metastatic ccRCC after radical surgery.

Signet-ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next-generation sequencing.

Signet-ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85-year-old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet-ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E-cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next-generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.

Association of intraductal carcinoma of the prostate detected by initial histological specimen and neuroendocrine prostate cancer: A report of three cases.

We present three cases of neuroendocrine prostate cancer (NEPC) and histologically investigate the association of intraductal carcinoma of the prostate (IDC-P) and NEPC. Case 1 was a 76-year-old man who had NEPC identified by repeated biopsy specimens when his prostate-specific antigen (PSA) level became elevated 8 years after the initiation of androgen deprivation therapy (ADT). Case 2 was a 70-year-old man who had NEPC detected when multiple bone metastases were found 3 years after the initiation of ADT. Case 3 was a 70-year-old man who was diagnosed with NEPC based on histological examination of transurethral resected specimens. The histological findings in these three cases showed mixed neuroendocrine carcinoma-acinar adenocarcinoma with various proportions of both components. In all three cases, the neuroendocrine carcinoma components were positive for synaptophysin and chromogranin A, whereas the adenocarcinoma components were positive for PSA and NKX3.1. When we retrospectively reviewed the initial hematoxylin and eosin-stained slides, IDC-P was detected in all three cases. Furthermore, we collected nine additional cases of NEPC and found that all six cases with initial biopsy specimens available had an IDC-P component. Detecting IDC-P on initial histological specimens of the prostate may predict transformation to NEPC.

Comprehensive pathological assessment of histological subtypes, molecular subtypes based on immunohistochemistry, and tumor-associated immune cell status in muscle-invasive bladder cancer.

Molecular assessments of muscle-invasive bladder cancer (MIBC) have yielded several molecular categorizations associated with basal and luminal subtypes or tumor-associated immune cell status (TAICs). However, the histological relationships among histological subtypes, molecular subtypes, and TAICs and their clinical implications remain unclear. Thus, we aimed to evaluate the histological associations among these factors and their clinicopathological outcomes. We retrospectively analyzed 106 patients with MIBC who underwent radical cystectomy. The histological subtypes and TAICs were evaluated with hematoxylin and eosin staining, while the basal and luminal molecular subtypes were determined by immunohistochemical expression of cytokeratin (CK) 5/6, CK14, CK20, GATA3 and uroplakin II. Urothelial carcinoma with squamous differentiation and the sarcomatoid variant were highly associated with the basal subtype (P < 0.001 and P = 0.04, respectively). Additionally, high TAICs were significantly correlated with the basal subtype (P < 0.001). Although there was no significant difference in the cancer-specific survival (CSS) rate between molecular subtypes (P = 0.295), TAICs significantly discriminated CSS rates (P < 0.001). Furthermore, the combination of molecular subtypes and TAICs significantly stratified cancer-specific mortality rates. In conclusion, a comprehensive pathological evaluation of histological subtypes, molecular subtypes, and TAICs is feasible and can influence the oncological outcome.

SWI/SNF-deficient neoplasms of the genitourinary tract.

Since the discovery of association of SMARCB1 mutations with malignant rhabdoid tumors and renal medullary carcinoma, mutations in genes of the SWI/SNF chromatin remodeling complex have been increasingly identified across a diverse spectrum of neoplasms. As a group, SWI/SNF complex subunit mutations are now recognized to be the second most frequent type of mutations across tumors. SMARCB1 mutations were originally reported in malignant rhabdoid tumors of the kidney and thought to be pathognomonic for this tumor. However, more broadly, recognition of typical rhabdoid cytomorphology and SMARCB1 mutations beyond rhabdoid tumors has changed our understanding of the pathobiology of these tumors. While mutations of SWI/SNF complex are diagnostic of rhabdoid tumors and renal medullary carcinoma, their clinical relevance extends to potential prognostic and predictive utility in other tumors as well. Beyond SMARCB1, the PBRM1 and ARID1A genes are the most frequently altered members of the SWI/SNF complex in genitourinary neoplasms, especially in clear cell renal cell carcinoma and urothelial carcinoma. In this review, we provide an overview of alterations in the SWI/SNF complex encountered in genitourinary neoplasms and discuss their increasing clinical importance.

Predictors of postoperative recurrence in patients with non-metastatic pT3a renal cell carcinoma.

OBJECTIVE: To analyze the effect of patterns of extrarenal tumor extension with other pathological factors on postoperative recurrence in patients with non-metastatic pT3a renal cell carcinoma. METHODS: We retrospectively reviewed 587 non-metastatic renal cell carcinoma patients who underwent radical surgery between 2006 and 2017 at Kansai Medical University Hospital, Hirakata, Osaka, Japan. We extracted a subset of 114 patients with pT3a of predominant histological types: 93 with clear cell renal cell carcinoma (81.6%), 13 with unclassified renal cell carcinoma (11.4%), six with chromophobe renal cell carcinoma (5.3%) and two with papillary renal cell carcinoma. The primary end-point was recurrence-free survival. The Kaplan-Meier method and Cox proportional hazards model were used for statistical analysis. RESULTS: Of the 114 patients with pT3a renal cell carcinoma, 42 patients (36.8%) experienced recurrence. Multivariate analysis showed that perinephric fat invasion (hazard ratio 2.36, P = 0.009), sarcomatoid or rhabdoid component (hazard ratio 2.88, P = 0.022) and necrosis (hazard ratio 2.34, P = 0.030) were independent factors for recurrence-free survival. The high-risk pT3a group, which had more than two independent predictors, had poor prognosis. Recurrence-free survival of the high-risk pT3a group and the pT3b or greater group were similar (median recurrence-free survival 23.0 and 10.8 months, respectively). CONCLUSIONS: Perinephric fat invasion, sarcomatoid or rhabdoid component and necrosis are independent predictors of recurrence-free survival in patients with pT3a-predominant renal cell carcinoma. Patients with more than two of these predictors have poor oncological outcomes. These findings will aid in risk stratification for predicting recurrence and provide prognostic information for patient counseling.

Review of TFEB-amplified renal cell carcinoma with focus on clinical and pathobiological aspects.

The disease entity of TFEB-amplified renal cell carcinoma (RCC) has been recently established. In this article, we review such cases. Clinically, the age of patients ranged from 28 to 83 years with a mean age of 62.8 years. The size of the tumor ranged from 1.9 to 19.5 cm with a mean size of 8.7 cm. The tumor demonstrated a variety of architectural patterns such as solid, alveolar, papillary, pseudopapillary, nested or tubular. The International Society of Urological Pathology (ISUP) grade usually corresponds to grade 3 or 4. Cytomorphology shows eosinophilic, clear, amphophilic or even oncocytic cytoplasm. Necrosis can be frequently observed. Neoplastic cells with TFEB-amplified RCC show diffuse or patchy positivity for TFEB. Fluorescence in situ hybridization frequently show the amplification of more than 10 or 20 copies of the TFEB gene. Most TFEB-amplified RCCs behave in an aggressive fashion. Metastasis frequently occurs. In conclusion, this tumor seems to be characterized by occurrence in older patients, frequent necrosis, papillary/pseudopapillary growth pattern, high-grade nuclear grade, TFEB gene amplification, and aggressive clinical behavior. In order to clarify whether this tumor is a distinct entity from previously described renal tumors or not, a further examination in a large scale study will be required in the future.