Acute subdural hematoma caused by hemorrhagic falx meningioma: A case report and review of the literature.

We herein report a case of acute subdural hematoma caused by hemorrhagic falx meningioma. The patient was a 64-year-old woman with no significant medical history or prior history of trauma. She experienced a sudden onset of headache and weakness in her extremities. Computed tomography (CT) scan and magnetic resonance imaging (MRI) showed a mass lesion with intratumoral hemorrhage or faint calcification along the left side of the fronto-parietal cerebral falx. There was also a linear lesion at the left side of the falx, suggesting acute subdural hematoma. MRI was performed again on the eleventh day. On precontrast T1-weighted images, intratumoral hemorrhage and widespread left subdural hematoma were shown as high intensity. On postcontrast T1-weighted images, the tumor showed heterogeneous enhancement with a dural tail sign on the falx, indicative of a falx meningioma. She underwent surgical resection, and the histological subtype was transitional meningioma. Nine cases of hemorrhagic falx meningioma associated with acute subdural hematoma have been reported. If not limited to the site of occurrence, there have been 59 reported cases overall. In our investigation, the incidence of hemorrhage is higher in the convexity and lower in the skull base. It is higher for fibrous, angiomatous, and metaplastic subtypes and lower for meningothelial subtype. The location and histological subtype might be risk factors for meningioma associated with subdural hematoma. Further accumulation of cases will be necessary to establish the cause of bleeding.

Carcinoma showing thymus-like elements (CASTLE) with amyloid deposition in the parotid gland.

Carcinoma showing thymus-like elements (CASTLE) is a rare tumor that commonly occurs in the thyroid gland. Extrathyroidal CASTLE is rarer, and only 11 cases of CASTLE of major salivary glands have been reported to date. We report the first case of amyloid deposition in parotid CASTLE. A 63-year-old man presented with a slowly growing mass in the left parotid region. Computed tomography revealed an approximately 28 × 23 mm mass lesion in the left parotid gland, and squamous cell carcinoma was suspected on biopsy. The patient underwent a parotidectomy with neck dissection. Morphologically, the tumor cells were squamoid and formed nests with lymphoid infiltration. Immunohistochemically, the tumor cells exhibited immunoreactivity for CD5, CD117/c-kit and Bcl-2, p40, and CK5 but not for p16. We diagnosed the tumor as parotid CASTLE. Amyloid deposition was also observed in the primary tumor and metastatic lymph node lesions, which were immunoreactive for cytokeratin 5. Tumor cytokeratin-derived amyloid deposition may be one of characteristics of parotid CASTLE.

Concordance Between Biopsy and Resection Diagnoses of Uterine Cervical Adenocarcinoma According to the Updated World Health Organization 2020 Classification: A Multi-Institutional Study Elucidating Real-World Practice in Japan.

CONTEXT.­: Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5h edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphological criteria used for biopsy specimens in real-world practice remains undetermined. OBJECTIVE.­: To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies. DESIGN.­: We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis. RESULTS.­: The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; κ = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization. CONCLUSIONS.­: The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied.

Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases.

BACKGROUND: We encountered a cervical lymphoepithelial carcinoma (LEC) possessing a predominantly solid architecture with deficient mismatch repair (dMMR) and loss of expression of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex subunit. This is the first case report of LEC with dMMR and loss of SWI/SNF complex subunit. CASE PRESENTATION: A 34-year-old woman presented at our hospital with menstrual irregularities and abnormal vaginal bleeding. Magnetic resonance imaging revealed an exophytic mass in the posterior uterine cervix. Biopsy specimens confirmed squamous cell carcinoma with a 2018 International Federation of Gynecology and Obstetrics (FIGO) uterine cervical cancer stage of IB2. In a subsequent conization specimen, the tumor appeared exophytic. Microscopically, the tumor cells formed a predominant solid architecture. Abundant lymphocytic infiltration was observed. The pathological diagnosis indicated human papillomavirus (HPV)-associated squamous cell carcinoma with LEC pattern and pT1b2. Immunohistochemically, high programmed death-ligand 1 (PD-L1) expression, dMMR, and loss of the switch/sucrose non-fermentable family-related, matrix-associated, actin-dependent regulator of chromatin subfamily member 4 (SMARCA4)/BRG1, an SWI/SNF complex subunit, were observed. The patient underwent a radical hysterectomy and is alive without disease one year and five months later. Our analysis of five additional LEC cases revealed a consistent association with high-risk HPV and elevated PD-L1 expression. In addition to the present case, another patient exhibited dMMR. The SWI/SNF complex was retained except in the present case. The prognosis was favorable in all cases. CONCLUSIONS: This unique case of LEC with dMMR suggests a distinct clinical entity with potential immunotherapy implications. Analysis of the other five LEC cases revealed that LEC was immune hot, and immune checkpoint inhibitors may be effective. The two dMMR cases showed loss of MLH1 and PMS2 expressions, and prominently high tumor PD-L1 expression. In those cases, dMMR might have contributed to the morphological characteristics of LEC.

Inter- and intra-tumor heterogeneity of genetic and immune profiles in inherited renal cell carcinoma.

Patients with von Hippel-Lindau disease (vHL) are at risk of developing spatially and temporally multiple clear cell renal cell carcinomas (ccRCCs), which offers a valuable opportunity to analyze inter- and intra-tumor heterogeneity of genetic and immune profiles within the same patient. Here, we perform whole-exome and RNA sequencing, digital gene expression, and immunohistochemical analyses for 81 samples from 51 ccRCCs of 10 patients with vHL. Inherited ccRCCs are clonally independent and have less genomic alterations than sporadic ccRCCs. Hierarchical clustering of transcriptome profiles shows two clusters with distinct immune signatures: immune hot and cold clusters. Interestingly, not only samples from the same tumors but also different tumors from the same patients tend to show a similar immune signature, whereas samples from different patients frequently exhibit different signatures. Our findings reveal the genetic and immune landscape of inherited ccRCCs, demonstrating the relevance of host factors in shaping anti-tumor immunity.

Complete response to pembrolizumab in a patient with recurrent and metastatic urothelial bladder carcinoma reflecting coexisting sarcomatoid subtype and glandular differentiation: a case report.

In advanced urothelial carcinoma (UC), approximately 20% of patients respond to pembrolizumab, an anti-programmed cell death-1 (PD-1) antibody. Herein, we reported a single case of UC showing coexistence of sarcomatoid subtype and glandular differentiation. Notably, only glandular differentiation was recurrent, probably progressive, and metastatic, which showed complete response to pembrolizumab. An 80-year-old woman presented with hematuria and dysuria, and an intra-vesical tumor was detected on ultrasound. Transurethral resections (TUR) were performed three times. In the first TUR, a sub-pedunculated tumor and a flat lesion were closely but independently located. Pathologically, the sub-pedunculated tumor was an invasive UC, sarcomatoid subtype. Meanwhile, the flat lesion was invasive UC with glandular differentiation. Despite the second and the additional TUR, the tumor was growing and a lymph node metastasis was detected. The third TUR specimen showed UC with glandular differentiation, and a positive PD-L1 expression as well as high density CD8-positive lymphocytic cells infiltration were observed. Pembrolizumab was administered for four courses after terminating the chemotherapy. The CT scan revealed shrinkage of both primary tumor and metastases. Cystectomy and lymph nodes dissection were performed, and no residual carcinoma was detected. The therapeutic effect was regarded as pathological complete response. Pembrolizumab could be effective for special subtype or divergent differentiation of UC, particularly in an event of an 'immune hot' tumor. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-022-00568-5.

Lower neutrophil-to-lymphocyte ratio and positive programmed cell death ligand-1 expression are favorable prognostic markers in patients treated with pembrolizumab for urothelial carcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective in some cancer patients; however, they may show no efficacy in others. Predictive biomarkers are crucial for appropriately selecting the patients who receive ICI therapy. This study aimed to clarify the predictors of disease progression in urothelial carcinoma (UC) patients treated with an ICI, pembrolizumab. METHODS: We analyzed the response patterns of 50 UC patients who were treated with pembrolizumab, as well as the association between survival and clinicopathological factors. Clinical factors included age, sex, body mass index, clinical courses, laboratory data, metastases, and adverse events. Pathological factors included special variant, squamous differentiation, programmed cell death ligand-1 (PD-L1) expression, CD8-positive lymphocytes density, and CDKN2A/p16 homozygous deletion. RESULTS: During pembrolizumab treatment, four (8%), 11 (22%), and eight (16%) patients achieved the best-case scenarios of complete response, partial response, and stable disease, respectively. Twenty-seven patients (54%) showed progressive disease. In this study, younger age, lower preoperative neutrophil-to-lymphocyte ratio (NLR), and positive PD-L1 expression were significantly correlated with longer progression-free survival and overall survival. Moreover, lower NLR and positive PD-L1 expression were independently associated with longer OS in multivariate analysis. CONCLUSIONS: Based on our observations, lower NLR and positive PD-L1 expression may be independent favorable prognostic markers in UC patients treated with pembrolizumab. These results suggest that both host and tumor status can reflect the effectiveness of pembrolizumab among patients with UC.

Case Study: A Japanese patient with metastatic renal cell carcinoma who achieved long-term treatment-free survival with pembrolizumab and axitinib in the KEYNOTE-426 phase III trial of pembrolizumab and axitinib versus sunitinib.

Introduction: Our patient treated with pembrolizumab and axitinib is one of the longest survivors in Japan on KEYNOTE 426, despite adverse events, including delayed-onset hepatitis. We herein present a detailed clinical course and short discussion on the case. Case presentation: This was a 49-year-old male with clear cell renal cell carcinoma and lung metastases. After cytoreductive nephrectomy, treatment with pembrolizumab plus axitinib was initiated and the patient demonstrated a radiographic partial response as best response. The main adverse event was pembrolizumab-induced delayed-onset hepatitis, which was successfully treated with prednisolone. Pembrolizumab was re-initiated and completed. Conclusion: The survival benefit in the present case may be due to the initial potent anti-cancer effects of axitinib and durable immune effects of pembrolizumab, leading to long-term treatment-free survival.

An Autopsy Case of Late-onset Fulminant Myocarditis Induced by Nivolumab in Gastric Cancer.

Nivolumab is an immune-checkpoint inhibitor (ICI) that can induce unique treatment-related toxicities, such as immune-related adverse events (irAEs). Myocarditis is a serious irAE with an incidence between 0.06% and 1.14%. Although the peak onset of irAE is generally within three months from the start of treatment, we experienced an autopsy case of late-onset fulminant myocarditis caused by nivolumab in Epstein Barr virus-associated gastric cancer. Pathological complete remission of the primary lesion was confirmed by the autopsy. We should consider possible complications of cardiac irAEs, especially fulminant myocarditis, even beyond three months after starting ICI therapy.

Squamous differentiation is a potential biomarker predicting tumor progression in patients treated with pembrolizumab for urothelial carcinoma.

Immune checkpoint inhibitor (ICI) is widely used and highly effective for some cancer patients but may result in disease progression in others. Hyperprogressive disease in particular is characterized by an acceleration of tumor growth during ICI therapy and has been reported in patients including those with urothelial carcinoma. Biomarkers predicting treatment efficacy are crucial to avoid tumor progression and unnecessary adverse effects. This study aims to clarify the predictors of disease progression for ICI treatment in patients with urothelial carcinoma. We analyzed the response pattern of 23 urothelial carcinomas treated with pembrolizumab and its association with pathological features and potential immunohistochemical markers including EGFR, MDM2, p53, p16, and programmed cell death ligand-1 (PD-L1) expression and CD8- and CD204-positive cell infiltration. During ICI therapy, 13 (57 %) patients showed progressive disease including 6 (26 %) with hyperprogressive disease. Notably, squamous differentiation combined with MAC387 expression was observed exclusively in cases with progressive disease (6 of 13, 46 %); it was not present in cases with stable disease or partial/complete response (0 of 10, p = 0.0019). All tumors with squamous differentiation showed positive staining for EGFR. Additionally, the loss of p16 expression occurred more frequently in cases with progressive disease (8 of 13, 62 %) than in other cases (3 of 10, 30 %), but this finding did not reach statistical significance. Squamous differentiation was also significantly associated with shorter overall survival. Based on our observations, squamous differentiation may be a novel biomarker for predicting disease progression in patients with urothelial carcinoma who receive pembrolizumab.

Intracytoplasmic dot-like inclusions as cytopathologically useful findings of ependymoma: Case report of adolescent supratentorial anaplastic ependymoma with clear cell morphology.

Pediatric supratentorial ependymomas often have a clear cell morphology and reveal a RELA fusion. When a clear cell neoplasm is intraoperatively diagnosed, intracytoplasmic dot-like inclusions by cytology are a useful cytopathological feature of ependymoma.

An autopsy case of prostatic rhabdomyosarcoma with DICER1 hotspot mutation.

Somatic hotspot DICER1 mutations, which frequently coexist with germline inactivating mutation (i.e., DICER1 syndrome), have been identified in various types of benign and malignant conditions. Herein, we report an autopsy case of prostatic rhabdomyosarcoma (RMS) with a hotspot DICER1 c.5125G>A (p.D1709N) mutation. A 26 year-old man presented with a prostatic mass, hematuria, and urinary retention. He underwent total pelvic exenteration, colostomy, ileal conduit construction and partial urethrectomy. Five months postoperatively, he developed multiple metastases to the lungs, brain, iliopsoas muscles and bones. He died of respiratory failure, and autopsy was performed. Microscopically, the tumor was primarily composed of uniform primitive mesenchymal cells infiltrating to the prostate with cambium layer. Rhabdomyoblasts and anaplastic cells were focally observed. Immunohistochemically, tumor cells were positive for desmin, myogenin, PAX7, HMGA2. Multinodular goiter was detected at autopsy. Because the morphology is similar to pleuropulmonary blastoma and DICER1-mutant RMS of the female genital tract, we tested and identified a hotspot DICER1 mutation with Sanger sequencing. Recognizing DICER1-mutant tumor is important because of its frequent association with germline DICER1 inactivation and potential therapeutic implication. Further research is needed to clarify whether this case can be classified as embryonal RMS with anaplasia or 'DICER1-associated sarcoma'.

Hepatoid adenocarcinoma of the lung mimicking metastatic hepatocellular carcinoma.

Hepatoid adenocarcinoma of the lung is a rare subtype of lung cancer. We report a case of a metastatic hepatoid adenocarcinoma of the lung with aggressive behavior, including biopsy and autopsy findings. The pulmonary tumors showed features indistinguishable from hepatocellular carcinoma and were diffusely positive for Hepatocyte Paraffin 1.

B7-H3 expression in upper tract urothelial carcinoma associates with adverse clinicopathological features and poor survival.

B7-H3, a member of the B7 superfamily, is an immune checkpoint molecule. An association between B7-H3 expression and poor survival has been reported in many types of cancer. However, its prognostic value in patients with upper tract urothelial carcinoma (UTUC) has not yet been reported. The aim of this study was to examine the clinical significance of tumor B7-H3 expression in UTUC. B7-H3 positivity was observed in 36 of 271 cases (13 %) by immunohistochemistry and was significantly associated with several adverse clinicopathological features such as tumor grade, tumor stage, and lymph node metastasis. In addition, B7-H3 positivity was significantly associated with shorter metastasis-free survival and cancer-specific survival. We also found that B7-H3/programmed cell death ligand-1 (PD-L1) co-positivity was significantly associated with worse prognosis. These results suggest the utility of B7-H3 positivity and B7-H3/PD-L1 co-positivity as novel prognostic biomarkers in UTUC, and the potential usefulness of B7-H3 targeted therapy for patients with UTUC, the effect of which may be enhanced by combination with programmed cell death-1 /PD-L1 blockade.

Hepatoid adenocarcinoma of the lung mimicking metastatic hepatocellular carcinoma

Hepatoid adenocarcinoma of the lung is a rare subtype of lung cancer. We report a case of a metastatic hepatoid adenocarcinoma of the lung with aggressive behavior, including biopsy and autopsy findings. The pulmonary tumors showed features indistinguishable from hepatocellular carcinoma and were diffusely positive for Hepatocyte Paraffin 1.

Inverted papilloma of the urinary bladder shows fluorescence on photodynamic diagnosis using 5-aminolevulinic acid.

Photodynamic diagnosis (PDD) of non-muscle invasive bladder cancer using 5-aminolevulinic acid (5-ALA) has recently attracted attention as a diagnostic method for observing cancer lesions based on fluorescence emission using a fluorescent endoscope. However, there are few reports of false positives associated with benign bladder neoplasms. Here, we provide report of two cases of inverted papillomas of the bladder that were fluorescent on PDD using 5-ALA. In each case, a surface-smooth, pedunculated bladder tumor was observed, which fluoresced red on PDD after oral administration of 5-ALA. Histopathological findings demonstrated inverted papilloma of the bladder. Although inverted papilloma of the bladder is usually regarded as a benign neoplasm, some recent studies have revealed that it could be a risk factor for urothelial carcinoma. Our present report may support the hypothesis that inverted papilloma of the bladder has malignant potential.

A case of Birt-Hogg-Dubé syndrome implying reduced or no wild-type folliculin without mutated protein is pathogenic.

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant cancer syndrome caused by a germline mutation of the folliculin (FLCN) gene. Previous studies have suggested that truncated mutant folliculin proteins generated by disease causing FLCN mutations may retain partial functionality and contribute to disease phenotype. A 38-year-old Russian man presented with a left renal tumor. He underwent a left radical nephrectomy and histological examination confirmed the diagnosis of chromophobe renal cell carcinoma. He had papulae on his face suggestive of fibrofolliculomas, and pulmonary cysts on his computed tomography of the chest. He had a family history of skin manifestations. Genetic analysis identified a genomic deletion including the putative promoter region of FLCN exon 1 in the germline, and the second hit on the remaining wild-type FLCN in the renal carcinoma cells, which is expected to cause the complete lack of folliculin protein. Immunohistochemistry with the use of anti-folliculin antibody showed no antibody-binding on chromophobe renal carcinoma cells. These findings suggest that the decreased FLCN expression itself without producing mutated folliculin proteins can be at risk for developing clinical manifestations of BHDS: fibrofolliculomas, lung cysts, and tumorigenesis in the kidneys. This sheds light on the pathogenesis of BHDS and the role of FLCN as a tumor suppressor gene.

Fluorescence Detection of Prostate Cancer by an Activatable Fluorescence Probe for PSMA Carboxypeptidase Activity.

Prostate cancer (PCa) is a common malignant tumor among adult males, and convenient intraoperative detection of PCa would reduce the risk of leaving positive surgical margins, especially during nerve-sparing procedures. To achieve rapid, fluorescence-based visualization of PCa, we focused on the glutamate carboxypeptidase (CP) activity of prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein that is attracting attention as a PCa biomarker. Based on our finding that aryl glutamate conjugates with an azoformyl linker are recognized by PSMA and have a sufficiently low LUMO (lowest unoccupied molecular orbital) energy level to quench the fluorophore through photoinduced electron transfer, we designed and synthesized a first-in-class activatable fluorescence probe for CP activity of PSMA. The developed probe allowed us to visualize the CP activity of PSMA in living cells and in clinical specimens from PCa patients and is expected to be useful for rapid intraoperative detection and diagnosis of PCa.

The prognostic value of PD-L1 expression in upper tract urothelial carcinoma varies according to platelet count.

Programmed cell death ligand-1 (PD-L1) is a ligand for programmed cell death-1 (PD-1) that negatively regulates T-cell activation and plays a crucial role in suppressing anti-tumor host immunity. Although PD-L1 is a promising immunotherapy target in various cancers, including urothelial carcinoma (UC), the prognostic significance of PD-L1 in UC is unclear. As platelets help protect tumor cells from immune elimination in the circulatory system, we hypothesized that tumor PD-L1 and circulating platelets might synergistically promote tumor metastasis, and that the prognostic significance of PD-L1 might vary according to platelet count. We immunohistochemically examined tumor PD-L1 expression in 271 patients with upper tract UC, which revealed PD-L1 positivity in 31 of 271 cases (11%). The associations of tumor PD-L1 expression with outcomes varied among patients with high or low platelet counts (Pinteraction  < 0.004). Among patients with high platelet counts (N = 136), PD-L1 positivity (N = 15) was significantly associated with shorter metastasis-free survival (univariate hazard ratio [HR]: 6.23, 95% confidence interval [CI]: 2.95-13.1; multivariate HR: 2.68, 95% CI: 1.27-5.64) and shorter overall survival (univariate HR: 4.92, 95% CI: 2.14-11.3, multivariate HR: 2.78, 95% CI: 1.19-6.51). In contrast, among patients with low platelet counts (N = 135), PD-L1 positivity (N = 16) was not significantly associated with these outcomes. Our results suggest that tumor PD-L1 expression and platelet count might interact and help regulate tumor progression. Although a larger prospective study is needed to validate our findings, this relationship is important to consider, as immunotherapies targeting the PD-1/PD-L1 axis have gained significant attention as promising therapies for UC.

The loss of BAP1 protein expression predicts poor prognosis in patients with nonmetastatic clear cell renal cell carcinoma with inferior vena cava tumor thrombosis.

OBJECTIVES: Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT). MATERIAL AND METHODS: Thirty-five patients with nonmetastatic ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical (IHC) analyses were performed for the expression of BAP1 protein, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate analyses of the associations between disease-free survival (DFS) and clinical variables including BAP1 protein expression, tumor size, Karnofsky performance status (KPS) score, and the extension level of the tumor thrombus were performed using a Cox proportional hazard model. RESULTS: The median follow-up time was 58.8 months (range: 2-130 months). The median age was 68 years (range: 37-80 years). The median size of the primary tumor was 9.6cm (range: 3.0-15.0cm). The IVCTT extended above and below the diaphragm in 10 (28.6%) and 25 (71.4%) patients, respectively. The KPS score was>80 in 23 patients (65.7%). BAP1 protein expression on IHC was positive in 24 cases (68.8%) and negative in 11 cases (31.2%). The median overall survival in cases with BAP1-negative and -positive tumor on IHC staining were 44.7 and 81.5 months, respectively (P = 0.052). BAP1-negative tumor on IHC staining was associated with a significantly shorter DFS than BAP1-positive tumor (median DFS = 10.0 vs. 26.0 months, respectively; P = 0.011). Multivariate analysis showed that only BAP1-negative tumor on IHC staining was significantly associated with shorter DFS (P = 0.004). CONCLUSIONS: Patients whose tumors had loss of BAP1 protein expression were significantly associated with poor prognosis in patients with ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy.