Evaluation of PD-L1 expression in PBRM1-altered clear cell renal cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) often harbors Polybromo 1 (PBRM1) alterations. These alterations are associated with immune checkpoint blockade response in ccRCC, particularly antiprogrammed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1)-targeted therapy. However, the association between PBRM1 alterations and PD-L1 expression in ccRCC remains unclear. MATERIALS AND METHODS: We analyzed alterations in PBRM1 and PD-L1 expression using immunohistochemistry (IHC) targeting PBRM1 and PD-L1 (22C3) in tissues collected from patients with localized ccRCC (Cohort 1) and advanced ccRCC (Cohort 2). Additionally, next-generation sequencing (NGS) was conducted on Cohort 2 patients to analyze PBRM1 alterations. RESULTS: Cohort 1 comprised 526 patients, of whom 139 (26.4%) exhibited PD-L1 positivity and 205 (38.9%) exhibited loss of PBRM1 expression in IHC. PD-L1 expression was positively associated with the loss of PBRM1 expression (P < 0.001) in localized ccRCC. Kaplan-Meier analysis indicated that PBRM1 expression loss and PD-L1 expression positively correlated with tumor recurrence (P < 0.001 and P = 0.003, respectively). Cohort 2 comprised 59 patients with advanced ccRCC, of whom 33 (56.9%) exhibited PBRM1 genetic alterations. PBRM1 IHC exhibited a sensitivity of 84.48% and specificity of 87.5% compared to NGS results. We did not find a significant association between PBRM1 mutation and PD-L1 expression, in contrast to the findings in Cohort 1. However, we frequently observed that PBRM1 mutation and PD-L1 expression occur concurrently, with 60% of PBRM1-altered ccRCC cases being PD-L1 positive. CONCLUSION: Although our study did not establish a correlation between PBRM1 mutations and PD-L1 expression, it demonstrated that the occurrence of PBRM1-altered ccRCC with PD-L1 expression is not uncommon. Therefore, the presence of PBRM1 alterations may challenge the use of PD-L1 IHC as a predictive marker for PD-L1 blockade in ccRCC.

Exploring the potential of ex-vivo 7-T magnetic resonance imaging on patients with clinically significant prostate cancer: visibility and size perspective.

Background: Despite progress in multiparametric magnetic resonance imaging (MRI), issues of prostate cancer invisibility and underestimated tumor burden persist. This study investigates the potential of an ultra-high field MRI at 7-T in an ex-vivo setting to address these limitations. Methods: This prospective study included 54 tumors from 20 treatment-naïve clinically significant prostate cancer patients, confirmed by biopsy, despite negative findings on preoperative 3-T MRI. Ex-vivo 7-T MRI of resected prostates was performed, with assessment on tumor visibility and size. Factors influencing visibility were analyzed using logistic regression analyses. Results: Tumor visibility was confirmed in 80% of patients, and 48% of all tumors on ex-vivo imaging. Gleason pattern 4 percentage (odds ratio 1.09) and tumor size on pathology (odds ratio 1.36) were significantly associated with visibility (P < 0.05). Mean MRI-visible and invisible tumor sizes were 10.5 mm and 5.3 mm, respectively. The size discrepancy between MRI and pathology was 2.7 mm. Conclusion: Tumor visibility on ex-vivo 7-T MRI was influenced by tumor grade and size. The notable tumor visibility initially overlooked on 3-T MRI, along with small size discrepancy with pathology, suggests potential improvements in resolution.

Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression.

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

An artificial intelligence-powered PD-L1 combined positive score (CPS) analyser in urothelial carcinoma alleviating interobserver and intersite variability.

AIMS: Immune checkpoint inhibitors targeting programmed death-ligand 1 (PD-L1) have shown promising clinical outcomes in urothelial carcinoma (UC). The combined positive score (CPS) quantifies PD-L1 22C3 expression in UC, but it can vary between pathologists due to the consideration of both immune and tumour cell positivity. METHODS AND RESULTS: An artificial intelligence (AI)-powered PD-L1 CPS analyser was developed using 1,275,907 cells and 6175.42 mm2 of tissue annotated by pathologists, extracted from 400 PD-L1 22C3-stained whole slide images of UC. We validated the AI model on 543 UC PD-L1 22C3 cases collected from three institutions. There were 446 cases (82.1%) where the CPS results (CPS ≥10 or <10) were in complete agreement between three pathologists, and 486 cases (89.5%) where the AI-powered CPS results matched the consensus of two or more pathologists. In the pathologist's assessment of the CPS, statistically significant differences were noted depending on the source hospital (P = 0.003). Three pathologists reevaluated discrepancy cases with AI-powered CPS results. After using the AI as a guide and revising, the complete agreement increased to 93.9%. The AI model contributed to improving the concordance between pathologists across various factors including hospital, specimen type, pathologic T stage, histologic subtypes, and dominant PD-L1-positive cell type. In the revised results, the evaluation discordance among slides from different hospitals was mitigated. CONCLUSION: This study suggests that AI models can help pathologists to reduce discrepancies between pathologists in quantifying immunohistochemistry including PD-L1 22C3 CPS, especially when evaluating data from different institutions, such as in a telepathology setting.

Primary Intracranial Ewing Sarcoma With EWSR1-FLI1 Gene Translocation Mimicking a Meningioma and a Multidisciplinary Therapeutic Approach: A Case Report and Systematic Review of Literatures.

Ewing sarcoma and peripheral primitive neuroectodermal tumor (ES/pPNET) is an undifferentiated malignant tumor that is most prevalent in children and young adults and often radiologically mimics a meningioma. A 38-year-old female patient visited our hospital with complaints of right-sided tinnitus, right hemiparesis, and imbalance. She underwent preoperative imaging and was subsequently diagnosed as having a meningioma on the petrous ridge. After partial resection, EWSR1-FLI1 gene fusion was confirmed, and she was diagnosed with ES/pPNET. The tumor was successfully treated using a multidisciplinary approach of adjuvant chemo- and radiotherapy. This case is noteworthy because it is an extremely rare case of an intracranial ES/pPNET, and it is worth sharing our clinical experience that the tumor was successfully treated through a multidisciplinary therapeutic approach even though complete resection was not achieved.

Diffuse Leptomeningeal Glioneuronal Tumor with FGFR1 Mutation in a 29-Year-Old Male.

This study reports on diffuse leptomeningeal glioneuronal tumor (DL-GNT) in a 29-year-old male. DL-GNT is a rare central nervous system (CNS) tumor mostly seen in children and only few cases have been reported in adult patients. Our patient presented with a chronic headache that lasted for five months. MR imaging showed mild hydrocephalus, multiple rim-enhancing nodular lesions in the suprasellar cistern, diffuse leptomeningeal enhancement in the lumbosacral area, and multiple small non-enhancing cyst-appearing lesions not suppressed on fluid attenuated inversion recovery (FLAIR) images in the bilateral basal ganglia, thalami, and cerebral hemispheres. Under the impression of germ cell tumor with leptomeningeal seeding, the patient underwent trans-sphenoidal tumor removal. DL-GNT was pathologically confirmed and FGFR1 mutation was detected through a next-generation sequencing test. In conclusion, a combination of leptomeningeal enhancement and multiple parenchymal non-enhancing cyst-appearing lesions not suppressed on FLAIR images may be helpful for differential diagnosis despite overlapping imaging features with many other CNS diseases that have leptomeningeal enhancement.

Tumor contact length with bladder wall provides effective risk stratification for lesions with a VIRADS score of 2-3.

OBJECTIVES: To evaluate the diagnostic performance of the tumor contact length (TCL) in the prediction of MIBC (muscle-invasive bladder cancer) in lesions corresponding to the vesical imaging-reporting and data system (VIRADS) score 2-3. METHODS: This is a single institution, retrospective study targeting 191 consecutive patients assigned of VIRADS score 2-3, who had pre-transurethral resection MRI from July 2019 to September 2021. Logistic regression analyses were performed to determine meaningful predictors of MIBC for this score group, and a nomogram was plotted with those variables. The diagnostic performance of each predictor was compared at predefined thresholds (VIRADS score 3 and TCL 3 cm) using the generalized linear model and ROC analysis. RESULTS: Both VIRADS score and TCL remained independent predictors of MIBC for this score group (odds ratio 7.3 for VIRADS score, and 1.3 for TCL, p < 0.01 for both). The contribution of TCL to the probability of MIBC in the nomogram was greater than that of the VIRADS score. VIRADS score had a sensitivity of 0.54 (14/26), specificity of 0.92 (203/221), and diagnostic accuracy of 0.88 (217/247), and TCL showed a sensitivity of 0.89 (23/26), specificity of 0.95 (209/221), and diagnostic accuracy of 0.94 (232/247). The difference in sensitivity (p = 0.03) and accuracy (p = 0.04) was statistically significant. The AUC was also significantly wider for TCL than for VIRADS (0.97 vs. 0.73, p < 0.01). CONCLUSION: A simple index, TCL, may be helpful in further risk stratification for MIBC in patients with a score of VIRADS 2-3. CLINICAL RELEVANCE STATEMENT: For bladder cancer patients with insufficient qualitative evidence of muscle layer invasion using VIRADS categorization, TCL, a simple quantitative indicator defined as the curvilinear contact length between the bladder wall and the tumor, may be helpful in risk stratification. KEY POINTS: • Even when only lesions with score 2-3 were targeted, VIRADS was still a meaningful indicator of MIBC. • With a predefined threshold of 3 cm applied, TCL outperformed VIRADS in the score 2-3 group, in predicting MIBC. • A longer TCL for a lesion with a VIRADS score 2 may warrant an additional warning for MIBC, whereas a shorter TCL for a lesion with a score 3 may indicate a lower risk of MIBC.

PAIP 2020: Microsatellite instability prediction in colorectal cancer.

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics.

IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma: a case report.

Primary glioblastoma develops de novo without clinical or histological evidence of a low-grade precursor lesion, whereas secondary glioblastoma develops from a low-grade glioma. The present report describes an extraordinary case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma. A 31-year-old female had a surgical history of IDH-mutant diffuse astrocytoma on the left frontal lobe six years before. Magnetic resonance imaging revealed new infiltrative lesions in the left frontal lobe adjacent to the previous lesion. The patient underwent tumourectomy, and the new infiltrative lesion was diagnosed as glioblastoma. Interestingly, the IDH-1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing. ATRX (p.Gln1670Ter) and TP53 (p.His193Arg) mutations were found in both lesions. Additionally, the PTEN (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the IDH mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the IDH mutation to develop from low grade glioma with IDH mutation. However, this case showed that the other genetic mutations can be initiated before the IDH mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma.

Diagnostic value of multiparametric MRI in detecting residual or recurrent prostate cancer after high-intensity focused ultrasound.

PURPOSE: To evaluate the diagnostic performance of follow-up multiparametric MRI for prediction of recurrent prostate cancer after high-intensity focused ultrasound (HIFU), and to find other, if any, clinical or radiological predictors. MATERIALS AND METHODS: Post-HIFU MRIs of 110 consecutive patients who underwent follow-up biopsies between August 2019 and April 2021 were retrospectively analyzed and the likelihood of recurrence was assessed on a five-point Likert scale by two board-certified uroradiologists. Diagnostic performance of the Likert scale assigned to the post-HIFU MRI was assessed using the follow-up biopsy results as a reference standard. Among the clinical and radiological variables, predictors of the recurrence were examined through logistic regression. RESULTS: In per-patient and per-sector analyses, Likert scale on post-HIFU MRI showed a sensitivity and specificity of 0.37 and 0.97, and 0.42 and 0.87, respectively, in predicting recurrence. Two patients with high suspicion on MRI required additional treatment to regain biochemical control despite negative biopsies. High suspicion on post-HIFU MRI (odds ratio = 1.74; p < 0.01), and more cancer-positive cores on initial biopsy (odds ratio = 1.25; p = 0.03) were independent predictors of recurrence. CONCLUSION: Albeit with low sensitivity, high suspicion on post-HIFU MRI may be clinically important because of its high specificity, especially when considering the possibility of sampling error in biopsies. Patients with a high number of cancer-positive cores at diagnosis should avoid HIFU as they have an increased risk of recurrence.

Volumetric changes in gray matter after radiotherapy detected with longitudinal magnetic resonance imaging in glioma patients.

BACKGROUND AND PURPOSE: We evaluated volumetric changes in the gray matter (GM) after radiotherapy (RT) and identified factors that were strongly associated with GM volume reduction. MATERIALS AND METHODS: A total of 461 magnetic resonance imagings (MRI) from 105 glioma patients treated with postoperative RT was retrospectively analyzed. Study patients' MRIs were collected at five time points: before RT and 1 month, 6 months, 1 year, and 2 years after RT. Using the 'FastSurfer' platform, a deep learning-based neuroimaging pipeline, 73 regions were automatically segmented from longitudinal MRIs and their volumetric changes were calculated. Regions were grouped into 10 functional fields. A multivariable linear mixed-effects model was established to identify the potential predictors of significant volume reduction. RESULTS: The median age was 50 years (range, 16-86 years). Forty-seven (44.8 %) patients were female and 68 (64.8 %) had glioblastoma. Postoperative RT was delivered at 54-60 Gy with or without concurrent chemotherapy. At 2 years after RT, the median volumetric changes in the overall, ipsilateral, and contralateral GM were -3.5%, -4.5%, and -2.4%, respectively. The functional fields of cognition and execution of movement showed the greatest volume reductions. In the multivariable linear mixed model, female sex (normalized coefficient = -0.14, P < 0.001) and the interaction between age at RT and days after RT (normalized coefficient = -6.48e-6, P < 0.001) were significantly associated with GM reduction. The older patients received RT, the greater volume reduction was seen over time. However, in patients with relatively younger age (e.g., 45, 50, and 60 years for hippocampus, Broca area, and Wernicke area, respectively), the volume was not significantly reduced. CONCLUSIONS: GM volume reduction was identified after RT that could lead to long-term treatment sequelae. Particularly for susceptible patients, individualized treatment and prevention strategies are needed.

Clinicopathologic Characteristics of Grade 2/3 Meningiomas: A Perspective on the Role of Next-Generation Sequencing.

Background: Grade 2/3 meningiomas have locally aggressive behaviors often requiring additional treatment plans after surgical resection. Herein, we explored the clinical significance of next-generation sequencing (NGS) in characterizing the molecular profiles of high-grade meningiomas. Methods: Patients with intracranial meningioma who underwent surgical resection in a single institution were retrospectively reviewed. Clinicopathologic relevance was evaluated using recurrence-free survival (RFS) as an outcome measure. NGS for the targeted gene regions was performed in 40 participants. Results: Among the 713 individuals in the study population, 143 cases (20.1%) were identified as having grade 2 or 3 meningiomas with a significantly lower female predominance. While the difference in RFS between grade 2 and 3 meningiomas was insignificant, a few conventional grade 2 cases, but with TERT promoter hotspot mutation, were highly progressive and refractory to the treatment. From the NGS study, recurrent mutations in TRAF and AKT1 were identified with a higher prevalence (17.5% and 12.5%, respectively) compared with grade 2/3 meningiomas reported in previous literature. However, their relations to other histopathologic properties or clinical factors were rarely observed. Conclusions: Grade 2/3 meningiomas show a broad spectrum of molecular profiles, as they have heterogeneous histologic characteristics.

Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study).

PURPOSE: The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). MATERIALS AND METHODS: In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). RESULTS: Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). CONCLUSION: The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.

Clinical strategy of repeat biopsy in patients with atypical small acinar proliferation (ASAP).

Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30-40% of patients with ASAP have biopsy detectable prostate cancer (PCa) within 5 years. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis. The aim of the present study was to examine the association between ASAP and subsequent diagnosis of clinically significant PCa (csPCa). The need for immediate repeat biopsy was also evaluated. We identified 212 patients with an ASAP diagnosis on their first biopsy at our institution between February 2006 and March 2018. Of these patients, 102 (48.1%) had at least one follow-up biopsy. Clinicopathologic features including rates of subsequent PCa and csPCa were assessed. Thirty-five patients subsequently underwent radical prostatectomy (RP). Their pathologic results were reviewed. csPCa was defined as the presence of Gleason score (GS) ≥ 3 + 4 in ≥ 1 biopsy core. Adverse pathology (AP) was defined as high-grade (primary Gleason pattern ≥ 4) or non-organ-confined disease (pT3/N1) after RP. Of 102 patients, 87 (85.3%), 13 (12.7%), and 2 (2.0%) had one, two, and three follow-up biopsies, respectively. Median time from the initial ASAP diagnosis to the 2nd follow-up biopsy and the last follow-up biopsy were 21.9 months (range 1-129 months) and 27.7 months (range 1-129 months), respectively. Of these patients, 46 (45.1%) were subsequently diagnosed with PCa, including 20 (19.6%) with csPCa. Only 2 (2.0%) patients had GS ≥ 8 disease. Five (4.9%) patients had number of positive cores > 3. Of 35 patients who subsequently underwent RP, seven (20%) had AP after RP and 17 (48.6%) showed GS upgrading. Of these 17 patients, the vast majority (16/17, 94.1%) had GS upgrading from 3 + 3 to 3 + 4. 45.1% of patients with an initial diagnosis of ASAP who had repeat prostate biopsy were subsequently diagnosed with PCa and 19.6% were found to have csPCa. Our findings add further evidence that after a diagnosis of ASAP, a repeat biopsy is warranted and that the repeat biopsy should not be postponed.

Comparison of Accuracies between Real-Time Nonrigid and Rigid Registration in the MRI-US Fusion Biopsy of the Prostate.

Magnetic resonance imaging (MRI) is increasingly important in the detection and localization of prostate cancer. Regarding suspicious lesions on MRI, a targeted biopsy using MRI fused with ultrasound (US) is widely used. To achieve a successful targeted biopsy, a precise registration between MRI and US is essential. The purpose of our study was to show any decrease in errors using a real-time nonrigid registration technique for prostate biopsy. Nineteen patients with suspected prostate cancer were prospectively enrolled in this study. Registration accuracy was calculated by the measuring distance of corresponding points by rigid and nonrigid registration between MRI and US, and compared for rigid and nonrigid registration methods. Overall cancer detection rates were also evaluated by patient and by core. Prostate volume was measured automatically from MRI and manually from US, and compared to each other. Mean distances between the corresponding points in MRI and US were 5.32 ± 2.61 mm for rigid registration and 2.11 ± 1.37 mm for nonrigid registration (p < 0.05). Cancer was diagnosed in 11 of 19 patients (57.9%), and in 67 of 266 biopsy cores (25.2%). There was no significant difference in prostate-volume measurement between the automatic and manual methods (p = 0.89). In conclusion, nonrigid registration reduces targeting errors.

Favorable intermediate risk prostate cancer with biopsy Gleason score of 6.

BACKGROUND: To identify potential prognostic factors among patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6. METHODS: From 2003 to 2019, favorable intermediate risk patients who underwent radical prostatectomy were included in this study. All patients were evaluated preoperatively with MRI. Using PI-RADS scores, patients were divided into two groups, and clinic-pathological outcomes were compared. The impact of preoperative factors on significant pathologic Gleason score upgrading (≥ 4 + 3) and biochemical recurrence were assessed via multivariate analysis. Subgroup analysis was performed in patients with PI-RADS ≤ 2. RESULTS: Among the 239 patients, 116 (48.5%) were MRI-negative (PI-RADS ≤ 3) and 123 (51.5%) were MRI-positive (PI-RADS > 3). Six patients in the MRI-negative group (5.2%) were characterized as requiring significant pathologic Gleason score upgrading compared with 34 patients (27.6%) in the MRI-positive group (p < 0.001). PI-RADS score was shown to be a significant predictor of significant pathologic Gleason score upgrading (OR = 6.246, p < 0.001) and biochemical recurrence (HR = 2.595, p = 0.043). 10-years biochemical recurrence-free survival was estimated to be 84.4% and 72.6% in the MRI-negative and MRI-positive groups (p = 0.035). In the 79 patients with PI-RADS ≤ 2, tumor length in biopsy cores was identified as a significant predictor of pathologic Gleason score (OR = 11.336, p = 0.014). CONCLUSIONS: Among the patients with favorable intermediate risk prostate cancer with a biopsy Gleason score 6, preoperative MRI was capable of predicting significant pathologic Gleason score upgrading and biochemical recurrence. Especially, the patients with PI-RADS ≤ 2 and low biopsy tumor length could be a potential candidate to active surveillance.

Programmed cell death-ligand 1 assessment in urothelial carcinoma: prospect and limitation.

Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.

Development and operation of a digital platform for sharing pathology image data.

BACKGROUND: Artificial intelligence (AI) research is highly dependent on the nature of the data available. With the steady increase of AI applications in the medical field, the demand for quality medical data is increasing significantly. We here describe the development of a platform for providing and sharing digital pathology data to AI researchers, and highlight challenges to overcome in operating a sustainable platform in conjunction with pathologists. METHODS: Over 3000 pathological slides from five organs (liver, colon, prostate, pancreas and biliary tract, and kidney) in histologically confirmed tumor cases by pathology departments at three hospitals were selected for the dataset. After digitalizing the slides, tumor areas were annotated and overlaid onto the images by pathologists as the ground truth for AI training. To reduce the pathologists' workload, AI-assisted annotation was established in collaboration with university AI teams. RESULTS: A web-based data sharing platform was developed to share massive pathological image data in 2019. This platform includes 3100 images, and 5 pre-processing algorithms for AI researchers to easily load images into their learning models. DISCUSSION: Due to different regulations among countries for privacy protection, when releasing internationally shared learning platforms, it is considered to be most prudent to obtain consent from patients during data acquisition. CONCLUSIONS: Despite limitations encountered during platform development and model training, the present medical image sharing platform can steadily fulfill the high demand of AI developers for quality data. This study is expected to help other researchers intending to generate similar platforms that are more effective and accessible in the future.

Management challenges associated with a pineal region chordoma: illustrative case.

BACKGROUND: Chordomas, which are rare malignant neoplasms arising from notochordal remnants, often cause gradually progressive clinical symptoms. Intradural cranial chordomas (ICCs) are extremely rare and generally have a favorable prognosis. However, the authors reported the case of a primary ICC originating in the pineal gland presenting with recurrent thalamic hemorrhage and displaying an aggressive postoperative clinical course. OBSERVATIONS: A 41-year-old man arrived at the emergency department with morning headaches and recurrent syncope that had lasted several months. Computed tomography and magnetic resonance imaging (MRI) revealed a pineal gland mass causing obstructive hydrocephalus and a subacute hematoma in the right thalamus. Three weeks after an endoscopic third ventriculostomy was performed, recurrent hemorrhage was observed in the right thalamus. The tumor was promptly removed surgically. The yellowish-white tumor did not exhibit abundant bleeding. No evidence of intratumoral hemorrhage around the hematoma pocket was found. Histopathological examination revealed the characteristics of a chordoma with minimal vascularity. MRI performed 10 weeks postoperatively for worsening headaches revealed abnormal enhancement of multiple cranial nerves, suggesting leptomeningeal seeding (LMS) of the tumor. LESSONS: Despite radiotherapy and intrathecal chemotherapy, the patient's neurological status worsened; he died 2 years postoperatively. A pineal ICC may cause recurrent thalamic hemorrhage and potentially fatal LMS, even in the early postoperative period.

Quantitation of bladder cancer for the prediction of muscle layer invasion as a complement to the vesical imaging-reporting and data system.

OBJECTIVES: To examine the diagnostic performance of Vesical Imaging-Reporting and Data System (VIRADS) and to find a quantitative indicator for predicting muscle layer invasion of bladder cancer. METHODS: 3-T MRI of 82 patients performed before transurethral resection of bladder tumors or radical cystectomy between July 2018 and June 2019 were retrospectively analyzed. For one index lesion of each patient, two radiologists independently assigned VIRADS score and measured tumor-wall interface (contact length between tumor and bladder wall) on T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. Inter-reader agreement was assessed, and logistic regression analysis was performed to find indicators of muscle layer invasion. Comparison of indicators' diagnostic performance was done with receiver operating characteristic (ROC) curve and generalized linear model analyses. Optimal cutoff point was determined by the Youden index J. RESULTS: Inter-reader agreement was at least substantial for VIRADS categorization (κ 0.77-0.81), and almost perfect for tumor-wall interface (intraclass correlation coefficient 0.88-0.90). Tumor-wall interface (odds ratio [OR] 1.90-2.00) and VIRADS score (OR 8.59-8.89) were independently associated with muscle layer invasion (p ≤ 0.02). For VIRADS, area under the ROC curve (AUROC) was 0.94, and the accuracy was 0.93 at score 3, the optimal threshold for predicting muscle layer invasion. Depending on the MRI sequence, tumor-wall interface showed AUROCs of 0.90-0.92 and accuracy of 0.84-0.90 at suggested thresholds (3 ± 0.3 cm). Tumor-wall interface showed insignificant differences in accuracy compared with VIRADS (p > 0.10), except as measured on diffusion-weighted images (p = 0.01). CONCLUSIONS: VIRADS is a good predictor of muscle layer invasion. As an independent quantitative indicator, tumor-wall interface may complement VIRADS to enhance prediction. KEY POINTS: • Vesical Imaging-Reporting and Data System (VIRADS) is a promising predictor of muscle invasion of bladder cancer with good reproducibility, as suggested by previous studies. • VIRADS score and the tumor-wall interface (curvilinear contact length between the tumor and the bladder wall) are independent predictors of muscle layer invasion. • As an easy-to-use quantitative indicator, tumor-wall interface is expected to be used as an indicator complementary to VIRADS, a qualitative indicator.