Impact of implementing the first edition of the Paris system for reporting: A systematic review and meta-analysis.

Urine cytology is a noninvasive, widely used diagnostic tool for screening and surveillance of genitourinary tract neoplasms. However, the absence of unified terminology and clear objective morphological criteria limits the clinical benefit of urine cytology. The Paris System for Reporting Urine Cytology (TPS) was developed with the goal of standardizing reporting and improving urine cytology performance in detecting high-grade malignancy (HGM). We aimed to evaluate potential effects of TPS on improving urine cytology diagnostic performance and clinical utility by conducting a systematic review and meta-analysis. We searched six electronic databases to identify cross-sectional and cohort studies written in English assessing the accuracy of urine cytology in detecting genitourinary tract malignancies of patients under surveillance or with clinical suspicion of malignancy from January 2004 to December 2022. We extracted relevant data from eligible studies to calculate relative distribution of cytology diagnostic categories; ratio of atypical to HGM cytology diagnosis; and risk of HGM (ROHGM) and HGM likelihood ratio (HGM-LR) associated with cytology diagnostic categories. We used a generalized linear mixed model with logit transformation to combine proportions and multilevel mixed-effect logistic regression to pool diagnostic accuracy measurements. We performed meta-regression to evaluate any significant difference between TPS and non-TPS cohorts. We included 64 studies for 99,796 combined total cytology samples, across 31 TPS and 49 non-TPS cohorts. Pooled relative distribution [95% confidence interval (CI)] of negative for high-grade urothelial carcinoma (NHGUC)/negative for malignancy (NM); atypical urothelial cells (AUC); suspicious for high-grade urothelial carcinoma (SHGUC)/suspicious for malignancy (SM); low-grade urothelial neoplasm (LGUN); and HGM categories among satisfactory cytology cases were 83.8% (80.3%-86.9%), 8.0% (6.0%-10.6%), 2.2% (1.4%-3.3%), 0.01% (0.0%-0.1%), and 4.2% (3.2%-5.5%) in TPS versus 80.8% (76.8-2.7%), 11.3% (8.6%-14.7%), 1.8% (1.2%-2.7%), 0.01% (0.0%-0.1%), and 3.3% (2.5%-4.3%) in non-TPS cohorts. Adopting TPS classification resulted in a significant increase in the frequency of NHGUC and a reduction in AUC cytology diagnoses, respectively. The AUC/HGM ratio in TPS cohort was 2.0, which showed a statistically significant difference from the atypical/HGM ratio of 4.1 in non-TPS cohort (p-value: 0.01). Moreover, the summary rate (95% CI) of LGUN called AUC on cytology significantly decreased to 20.8% (14.9%-28.3%) in the TPS compared with 34.1% (26.4%-42.8%) in non-TPS cohorts. The pooled ROHGM (95% CI) was 20.4% (6.2%-50.0%) in nondiagnostic (NDX), 15.5% (9.6%-24.2%) in NHGUC, 40.2% (30.9%-50.2%) in AUC, 80.8% (72.9%-86.8%) in SHGUC, 15.1% (5.7%-34.3%) in LGUN, and 91.4% (87.3%-94.3%) in HGM categories in TPS studies. NHGUC, AUC, SHGUC, and HGM categories were associated with HGM-LR (95% CI) of 0.2 (0.1-0.3), 0.9 (0.6-1.3), 6.9 (2.4-19.9), and 16.8 (8.3-33.8). Our results suggest that TPS 1.0 has reduced the relative frequency of AUC diagnosis, AUC/HGM ratio, and the frequency of LGUNs diagnosed as AUC on cytology. Adopting this classification has improved the clinical utility of SHGUC and HGM cytology diagnoses in ruling in high-grade lesions. However, an NHGUC diagnosis does not reliably rule out the presence of a high-grade lesion.

Prostate tumors of native men from West Africa show biologically distinct pathways-A comparative genomic study.

BACKGROUND: Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS: To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS: Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling. CONCLUSIONS: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.

Lesions of Ligamentum Teres: Diagnostic Performance of MRI and MR Arthrography-A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study is to determine the diagnostic performance of MRI and MR arthrography for depicting ligamentum teres lesions. MATERIALS AND METHODS: A literature search was performed. Original studies reporting the diagnostic accuracy of MRI examinations for the depiction of ligamentum teres lesions were included. RESULTS: Eight studies entailing 1456 MRI examinations were included (frequency of median ligamentum teres injury, 25.9%; interquartile range, 14.1-45.3%). Two studies reported the results of unenhanced MRI examinations, and their diagnostic performance could not be estimated. Sensitivity, specificity, and diagnostic odds ratio (DOR) of all MRI examinations were 64.7%, 86.9%, and 12.2, respectively, whereas the sensitivity, specificity, and DOR of MR arthrography examinations were 82.2%, 88.6%, and 35.9, respectively. The heterogeneity (I2) for all MRI and MR arthrography examinations was 92.3% and 88.2%, respectively. Five blinded MR arthrography studies with 643 MR arthrography examinations found an appropriate threshold effect for summary ROC construction (AUC, 0.95). The summary estimate of these studies yielded a sensitivity of 87.8%, a specificity of 91%, and DOR of 73.1. The heterogeneity (I2) for this group was 64.3%. In patients with low pretest probability (25%), MR arthrography enabled the exclusion of ligamentum teres lesion (postprobability for a negative result, 4%; negative likelihood ratio, 0.13). CONCLUSION: MR arthrography can depict ligamentum teres lesions with high accuracy. However, its diagnostic performance for differentiating various types of ligamentum teres lesions (partial, complete ligamentum teres tears, and hypertrophic ligamentum teres), as well as the diagnostic performance of unenhanced MRI for the depiction of ligamentum teres lesions, is yet to be determined because of the paucity of reported data in the literature.

Whole-body MR neurography: Prospective feasibility study in polyneuropathy and Charcot-Marie-Tooth disease.

PURPOSE: To evaluate the feasibility of whole-body magnetic resonance neurography (WBMRN) in polyneuropathy for technical feasibility, distribution of nerve abnormalities, and differentiation. MATERIALS AND METHODS: Twenty WBMRN examinations were performed on a 3T scanner over 2 years. Patient demographics including history of hereditary and acquired neuropathy were recorded. The images were evaluated by two independent readers with nerve imaging experience for quality. The nerve signal and size alterations were measured in the brachial plexus, lumbosacral plexus, and femoral and sciatic nerves; diffusion tensor imaging parameters (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) were determined in plexuses, and tractography was performed. Nonparametric Wilcoxon rank sum test, receiver operating characteristic (ROC) analysis, and intraclass correlation coefficients (ICCs) were obtained. RESULTS: Excellent image quality was obtained for the majority of lumbosacral (LS) plexus (18/20) and 50% of brachial plexus (10/20) regions. Qualitatively among cases, the nerve hyperintensity and/or thickening involved the brachial plexus (11/11), LS plexus (7/11), and both plexuses (7/11), with most nerve thickenings observed in Charcot-Marie-Tooth disease type 1. The nerve signal intensity alterations were significantly different for both brachial (P < 0.05) and LS (P < 0.05) plexuses in cases versus controls. The femoral and sciatic nerve size alterations were different (P < 0.05), while signal intensity differences were not significant (P = 0.1-0.97). Transverse dimensions of C8 (4 mm), L5 (6.2 mm) and S1 (5.1 mm) nerve roots, and sciatic nerves (10.2 mm) were the most accurate diagnostic performance measures in distinguishing cases from controls. CONCLUSION: WBMRN is feasible for use in the clinical practice for the identification and potential characterization of polyneuropathy. J. Magn. Reson. Imaging 2016;44:1513-1521.

Impact of high resolution 3 tesla MR neurography (MRN) on diagnostic thinking and therapeutic patient management.

OBJECTIVE: To evaluate the impact of magnetic resonance neurography (MRN) on diagnostic thinking and therapeutic choices in patients with suspected peripheral neuropathy. METHODS: IRB approval was obtained for this HIPAA-compliant study. Questionnaires were administered to six surgeons regarding the diagnosis and treatment in 85 patients suspected of having peripheral neuropathy, before (pretest) and after (posttest) MRN. Multiple outcome measures related to diagnostic confidence and surgical decision-making were assessed. RESULTS: The final cohort included 81 patients (30 men and 51 women, age 47 ± 17 years). The following changes were observed from pretest to posttest questionnaires: 23% in nerve involvement (P < 0.05), 48% in degree of confidence of nerve involvement (P < 0.01), 27% in grade of injury (P < 0.05), 33% in differential diagnosis (P < 0.05), 63% in degree of confidence in need for surgery (P < 0.001), 41% in timing of surgery (P < 0.01), 30% in approach to surgery (P < 0.05), 58% in degree of confidence in approach to surgery (P < 0.001), 30% in estimated length of surgery (P < 0.05) and 27% in length of incision (P < 0.05). The dichotomous decision regarding surgical or nonsurgical treatment changed from pro to con in 17%. CONCLUSION: MRN results significantly influenced the diagnostic thinking and therapeutic recommendations of peripheral nerve surgeons. KEY POINTS: • In patients with peripheral neuropathy, MRN significantly impacts diagnostic thinking. • In patients with peripheral neuropathy, MRN significantly impacts therapeutic choices. • 3-T MRN should be considered in presurgical planning of patients with peripheral neuropathy.

Can MR imaging be used to predict tumor grade in soft-tissue sarcoma?

PURPOSE: To identify the magnetic resonance (MR) imaging features that can be used to differentiate high-grade from low-grade soft-tissue sarcoma (STS). MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. Patients with STS who had undergone MR imaging with T1-weighted, T2-weighted, and contrast material-enhanced sequences prior to neoadjuvant therapy and surgery were included retrospectively. Tumor grade (grades 1-3) was recorded from the histologic specimen for each STS. Images were evaluated by two observers for tumor size and MR features (signal intensity, heterogeneity, margin, and perilesional characteristics) on images obtained with each sequence. Descriptive statistics for low-grade (grade 1) and high-grade (grades 2 and 3) STS were recorded, and the accuracy of individual features was determined. A multivariate logistic regression model was developed to identify features that were independently predictive of a high-grade tumor. RESULTS: Ninety-five patients (48 female [mean age, 55.8 years; age range, 7-96 years] and 47 male [mean age, 55.3 years; age range, 1-87 years]) with STS (16 patients with grade 1 STS, 34 patients with grade 2 STS, and 45 patients with grade 3 STS) were included. High-grade STS differed from low-grade STS in size (>5 cm, P = .004), tumor margin (partly or poorly defined margin on T1-weighted images, P = .002; with other sequences, P < .001), internal signal intensity composition (heterogeneous signal intensity on T2-weighted images, P = .009), and peritumoral characteristics (peritumoral high signal intensity on T2-weighted images, P = .025; peritumoral enhancement on contrast-enhanced T1-weighted images, P < .001). The logistic regression model showed that peritumoral contrast enhancement is the strongest independent indicator of high-grade status (odds ratio, 13.6; 95% confidence interval: 2.9, 64.6). CONCLUSION: Among several MR imaging features that aid in the discrimination of high-grade from low-grade sarcomas, the presence of peritumoral contrast enhancement is a feature that may be solely used to diagnose high-grade STS.

Detection and characterization of tendon abnormalities with multidetector computed tomography.

With recent advances in multidetector computed tomography (MDCT) acquisition and reconstruction options, MDCT can now be used successfully for evaluating tendon abnormalities. In this article, MDCT protocol optimization for the imaging of tendons is underscored, and applications of MDCT for assessing tendon pathology are highlighted. Although our retrospective experience of CT imaging with 2-dimensional multiplanar reconstructions and 3-dimensional postprocessing techniques is reviewed, potential applications for newer CT technologies, including dual-energy CT and 4-dimensional CT imaging of the peripheral tendons, are also discussed.

VEGF and p53 biomarkers in pediatric patients with Langerhans cell histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease with abnormal accumulation of the dendritic Langerhans cells. In the localized form (single system), the disease is self-limiting but in the cases of multisystem disease, one third of the patients develop organ dysfunction with poor prognosis. The aim of this study was to examine the role of p53 and vascular endothelial growth factor (VEGF) in the pathogenesis of LCH and look for association of them with the extent of the disease. MATERIALS AND METHODS: Biopsy specimens obtained from 26 patients with definitive diagnosis of LCH were stained immunohistochemically for p53 and VEGF. RESULTS: There were 13 male and 13 female cases. The mean age of patients at presentation was 41.9 months (range, 2 mo to 18 y). Multisystem disease was presented by 61% of the patients (8 boys and 8 girls). Patients with multisystem disease were on average older than those with single system disease. p53 protein could be detected in 92% of cases and 61.5% of patients expressed VEGF, mostly from multisystem group. CONCLUSIONS: These findings highlight the role of angiogenic factors in the clinical behavior of LCH and might be of prognostic or therapeutic importance. However, further studies, with larger sample sizes are warranted.

An umbrella review of systematic reviews on the impact of the COVID-19 pandemic on cancer prevention and management, and patient needs.

The relocation and reconstruction of health care resources and systems during the coronavirus disease 2019 (COVID-19) pandemic may have affected cancer care. An umbrella review was undertaken to summarize the findings from systematic reviews on impact of the COVID-19 pandemic on cancer treatment modification, delays, and cancellations; delays or cancellations in screening and diagnosis; psychosocial well-being, financial distress, and use of telemedicine as well as on other aspects of cancer care. Bibliographic databases were searched for relevant systematic reviews with or without meta-analysis published before November 29th, 2022. Abstract, full- text screening, and data extraction were performed by two independent reviewers. AMSTAR-2 was used for critical appraisal of included systematic reviews. Fifty-one systematic reviews were included in our analysis. Most reviews were based on observational studies judged to be at medium and high risk of bias. Only two reviews had high or moderate scores based on AMSTAR-2. Findings suggest treatment modifications in cancer care during the pandemic versus the pre-pandemic period were based on low level of evidence. Different degrees of delays and cancellations in cancer treatment, screening, and diagnosis were observed, with low- and- middle- income countries and countries that implemented lockdowns being disproportionally affected. A shift from in-person appointments to telemedicine use was observed, but utility of telemedicine, challenges in implementation and cost-effectiveness in cancer care were little explored. Evidence was consistent in suggesting psychosocial well-being of patients with cancer deteriorated, and cancer patients experienced financial distress, albeit results were in general not compared to pre-pandemic levels. Impact of cancer care disruption during the pandemic on cancer prognosis was little explored. In conclusion, substantial but heterogenous impact of COVID-19 pandemic on cancer care has been observed.

The onset of the COVID-19 pandemic disrupted many aspects of human life, not least healthcare. As resources were redistributed towards the crisis, social isolation rules also limited access to medical professionals. In particular, these measures may have affected many aspects of cancer care, such as early detection or treatment. Many studies have aimed to capture the impact of these changes, but most have been observational, with researchers recording events without trying to impose a controlled design. These investigations also often faced limitations such as small sample sizes, or only focusing on one aspect of cancer care. Systemic reviews, which synthetize and assess existing research on a topic, have helped to bypass these constraints. However, they are themselves not devoid of biases. Overall, a clear, unified picture of the impact of COVID-19 on cancer care is yet to emerge. In response, Muka et al. carried an umbrella analysis of 51 systematic reviews on this topic. They used a well-known critical appraisal tool to assess the methodological rigor of each of these studies, while also summarising their findings. This work aimed to capture many aspects of the patients' experience, from diagnosis to treatment and the financial, psychological, physical and social impact of the disease. The results confirmed that the pandemic had a substantial impact on cancer care, including delays in screening, diagnosis and treatment. Throughout this period cancer patients experienced increased rates of depression, post-traumatic stress and fear of their cancer progressing. The long-term consequences of these disruptions remain to be uncovered. However, Muka et al. also showed that, overall, these conclusions rely on low-quality studies which may have introduced unaccountable biases. In addition, their review highlights that most of the data currently available has been collected in high- and middle-income countries, with evidence lacking from regions of the world with more limited resources. In the short-term, these results indicate that interventions may be needed to mitigate the negative impact of the pandemic on cancer care; in the long-term, they also demonstrate the importance of rigorous systematic reviews in guiding decision making. By shining a light on the ripple effects of certain decisions about healthcare resources, this work could also help to shape the response to future pandemics.

Subcategorization of T1 Bladder Cancer on Biopsy and Transurethral Resection Specimens for Predicting Progression.

CONTEXT.­: Despite continued surveillance and intravesical therapy, a significant subset of patients with lamina propria-invasive bladder cancer (T1) will progress to muscle-invasive disease or metastases. OBJECTIVE.­: To analyze the value of pathologic subcategorization of T1 disease in predicting progression. DESIGN.­: Six substaging methods were applied to a retrospective cohort of 73 patients, with pT1 urothelial carcinoma diagnosed on biopsy/transurethral resection. Additionally, the immunohistochemistry for GATA3 and cytokeratin 5/6 (CK5/6) was performed to study the prognostic value of stratifying T1 cancers into luminal or basal phenotypes. RESULTS.­: On follow-up (mean, 46 months), 21 patients (29%) experienced at least 1 recurrence without progression, and 16 (22%) had progression to muscle-invasive disease and/or distant metastasis. No differences were noted between progressors and nonprogressors with regard to sex, age, treatment status, medical history, tumor grade, and presence of carcinoma in situ. Substaging using depth of invasion (cutoff ≥1.4 mm), largest invasive focus (≥3.6 mm), aggregate linear length of invasion (≥8.9 mm), and number of invasive foci (≥3 foci) correlated significantly with progression and reduced progression-free survival, whereas invasion into muscularis mucosa or vascular plexus, or focal versus extensive invasion (focal when ≤2 foci, each <1 mm) failed. Patients with luminal tumors had higher incidence of progression than those with nonluminal tumors (27% versus 11%), although the difference was statistically insignificant (P = .14). CONCLUSIONS.­: Substaging of T1 bladder cancers should be attempted in pathology reports. Quantifying the number of invasive foci (≥3) and/or measuring the largest contiguous focus of invasive carcinoma (≥3.6 mm) are practical tools for prognostic substaging of T1 cancers.

The Milan system for reporting salivary gland cytopathology: A comprehensive review of the literature.

BACKGROUND: The Milan system for Reporting Salivary Gland Cytopathology (MSRSGC) was published in 2018. Since then, many authors have published their institutional experience by retrospectively assigning salivary gland fine-needle aspiration cases to each of the MSRSGC categories and calculated their risk of malignancy (ROM) accordingly. METHODS: We reviewed all published articles available online in English that used the MSRSGC since or near its publication. We calculated the risk of neoplasm and ROM for each diagnostic category. In addition, the false-negative and false-positive rates from all studies were examined. RESULTS: Thirty-seven articles were identified in the English literature; 2 were published in 2017, 14 in 2018, 18 in 2019, and 3 in 2020. The total number of cases was 16 394, and 8 468 had surgical follow-up. The mean ROM was 16.9% for category I, 10.5% for category II, 39.3% for category III, 2.9% for category IVa, 39.4% for category IVb, 84.2% for category V, and 97.5% for category VI. The mean false-negative rate for MSRSGC categories II and IVa was 4.5%. Similarly, the mean false-positive rate for MSRSGC categories V and VI was 5.1%. CONCLUSION: A tiered classification scheme of MSRSGC is helpful in effectively guiding clinical management of patients with salivary gland lesions. The reported mean ROM for each category in most studies is within the recommended range published by the MSRSGC.

PD-L1 Positivity Associated With Presence of Tertiary Lymphoid Structures and High-Stage Disease in Upper Tract Urothelial Carcinoma.

OBJECTIVES: Persistent antigen exposure leads to the accumulation of lymphocytes and subsequent tertiary lymphoid structures (TLS). We investigated the relationship of tumor microenvironment (TME) with respect to programmed death ligand 1 (PD-L1), its receptor programmed death 1 (PD-1), and TLS in upper tract urothelial carcinoma (UTUC) cases and compared them with UTUC associated with urothelial bladder carcinoma (UTUC-BCa). METHODS: We retrospectively identified 72 patients with UTUC. Representative slides were reviewed, and TLS were counted. Immunohistochemical stains for PD-1 and PD-L1 were performed. PD-1-positive lymphocytes were counted and H-score for PD-L1-positive membranous staining was determined. RESULTS: PD-L1 expression in the tumor was present in 55.1% of the UTUC cases. Higher stage was associated with increased PD-L1 expression (P = .035). TLS were present in 33.3% and their presence was significantly associated with PD-L1 positivity (P = .024). This association remained significant after adjustment for UTUC-BCa. TLS were also associated with a greater number of infiltrating PD-1-positive lymphocytes (P = .013). CONCLUSIONS: This study is one of the first comparative studies of the TME in UTUC and UTUC-BCa. PD-L1 is expressed in a subset of UTUC and is associated with TLS. The presence of TLS is an inherent characteristic of UTUC and not secondary to the presence of BCa.

Differences in PD-L1-Expressing Macrophages and Immune Microenvironment in Testicular Germ Cell Tumors.

OBJECTIVES: To characterize the tumor microenvironment of testicular germ cell tumors (GCTs) using immunohistochemical markers. METHODS: Seventy-seven orchiectomies, including 36 nonmetastatic (NM) seminomas, 15 metastatic (M) seminomas, 13 nonmetastatic nonseminomatous germ cell tumors (NSGCTs), and 13 metastatic NSGCTs, were studied with PD-1, PD-L1, FOXP3, CD68, CD163, and mismatch repair (MMR) immunohistochemistry. FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) expressing CD68 and CD163 were enumerated. PDL-1 expression was evaluated on tumor cells and macrophages. RESULTS: GCTs primarily express PD-L1 on TAMs, except choriocarcinoma, where true tumor cell positivity was noted. Seminomas reveal increased intratumoral PD-L1+ TAMs compared with NSGCTs (P < .05). Activated TILs are increased in NM-seminomas compared with M-seminomas (P < .05). All GCTs retained MMR expression. CONCLUSIONS: Robust PD-L1+ TAMs are significantly expanded in seminomas compared with NSGCTs. Among all GCTs, only choriocarcinoma cells reveal true positivity for PD-L1. These findings expand the realm of potentially targeted treatments for GCTs.

Are we ready to develop a tiered scheme for the effusion cytology? A comprehensive review and analysis of the literature.

BACKGROUND: Cytology is widely utilized in the initial evaluation of fluid accumulation in the body cavities. The aim of this study was to determine the accuracy of cytology in distinguishing between benign and malignant (MAL) effusions. METHODS: A comprehensive and systematic review of the literature was conducted to evaluate the accuracy of serous effusion cytology (SEC) against tissue biopsy/resection histology, imaging, or clinical follow-up as the reference test. Risk of publication bias and level of heterogeneity in the included studies was assessed. Meta-regression was performed to assess the effect of various variables on the accuracy of SEC. RESULTS: Eighty studies met the inclusion criteria for meta-analysis comprising of 34 941 samples; of which 52 (0.2%), 22 202 (72.7%), 194 (0.6%), 711 (2.3%), and 6507 (21.3%) could be reclassified as nondiagnostic (ND), negative for malignancy (NFM), atypical (atypia of uncertain significance-AUS), suspicious for malignancy (SFM), and malignant (MAL), respectively. On follow-up, the mean risk of malignancy for ND, NFM, AUS, SFM, MAL was 17.4%, 20.7%, 65.9%, 81.8%, and 98.9%, respectively. A total of 73 studies were included in estimating the diagnostic accuracy of SEC. The bivariate mixed-effect model estimated the SEC sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio as 73.1%, 99.9%, 7850.6%, 2112.2%, and 0.27%, respectively. CONCLUSION: Serous effusion cytology shows high specificity and moderate sensitivity in the evaluation of serous effusions. A tiered classification scheme can improve the consistency of terminology for reporting SEC results, thus improving communication between the pathologists and clinical team, and quality of patient care.

Retrospective assessment of the effectiveness of the Milan system for reporting salivary gland cytology: A systematic review and meta-analysis of published literature.

INTRODUCTION: Fine needle aspiration (FNA) has been widely utilized in establishing the nature of salivary gland lesions and guiding the clinical management. This study aimed to determine the accuracy of FNA in detecting salivary gland neoplasms and malignancies, employing the "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC). METHOD: A systematic search was conducted. The data on FNA and histologic diagnosis were extracted and categorized based on the MSRSGC and risk of malignancy (ROM) was calculated. The risk of publication bias and level of heterogeneity were evaluated. A mixed-effects model was used to estimate FNA accuracy. Meta-regression was conducted to assess the potential effect of different variables on FNA accuracy. RESULTS: Ninety-two studies with a total of 16 456 FNA with surgical follow-up were included. ROM was estimated as 17%, 8%, 34%, 4%, 42%, 58%, and 91%, in nondiagnostic, nonneoplastic, atypia of undetermined significance, benign neoplasm, salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, and malignant groups, respectively. High level of heterogeneity was detected (P-value <.001). Including cases with definite FNA diagnosis of neoplasm or malignancy, summary estimates of FNA sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratio in detecting neoplasms and malignancies were 96.9%, 95.3%, 636.8, 20.5, and 0.03, and 80.5%, 97.9%, 189.5, 37.8, and 0.2, respectively. Meta-regression showed several variables significantly impacting FNA accuracy; however, subgroup analysis did not reduce the level of heterogeneity. CONCLUSION: FNA can be used as a reliable diagnostic tool in the preoperative evaluation and management of salivary glands lesions. Concise of abstract is using Milan system for reporting salivary gland FNA could increase FNA reliability, facilitate communication, and improve patient care.

PD-L1 Expression Reveals Significant Association With Squamous Differentiation in Upper Tract Urothelial Carcinoma.

OBJECTIVES: Limited literature is available on the tumor microenvironment (TM) of upper tract urothelial carcinoma (UTUC). This study comprehensively reviews programmed death 1 receptor (PD-1)-positive and CD8+ tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on tumor epithelium (TE). METHODS: Seventy-two nephroureterectomy specimens were analyzed for PD-L1, PD-1, and CD8. One percent or more tumor and lymphohistiocyte PD-L1 expression was considered positive. TIL density by H&E was scored semiquantitatively from 0 to 3, and CD8+ and PD-1+ TILs were quantified in hotspots. RESULTS: Of the cases, 37.5% demonstrated PD-L1+ on TE. PD-L1+ TE showed an association with pathologic stage (P = .01), squamous differentiation (SqD) (P < .001), TILs by H&E (P = .02), PD-1+ peritumoral TILs (P = .01), and PD-L1+ peritumoral lymphohistiocytes (P = .002). Finally, there was a significant difference in PD-1+ peritumoral TILs in cases with SqD vs no SqD (P = .03). CONCLUSIONS: Aggressive UTUC is associated with a distinct TM. Furthermore, TM of UTUC-SqD was distinctly different from those with no SqD, warranting study in a larger cohort.

Incremental value of magnetic resonance neurography of Lumbosacral plexus over non-contributory lumbar spine magnetic resonance imaging in radiculopathy: A prospective study.

AIM: To test the incremental value of 3T magnetic resonance neurography (MRN) in a series of unilateral radiculopathy patients with non-contributory magnetic resonance imaging (MRI). METHODS: Ten subjects (3 men, 7 women; mean age 54 year and range 22-74 year) with unilateral lumbar radiculopathy and with previous non-contributory lumbar spine MRI underwent lumbosacral (LS) plexus MRN over a period of one year. Lumbar spine MRI performed as part of the MRN LS protocol as well as bilateral L4-S1 nerves, sciatic, femoral and lateral femoral cutaneous nerves were evaluated in each subject for neuropathy findings on both anatomic (nerve signal, course and caliber alterations) and diffusion tensor imaging (DTI) tensor maps (nerve signal and caliber alterations). Minimum fractional anisotropy (FA) and mean apparent diffusion coeffcient (ADC) of L4-S2 nerve roots, sciatic and femoral nerves were recorded. RESULTS: All anatomic studies and 80% of DTI imaging received a good-excellent imaging quality grading. In a blinded evaluation, all 10 examinations demonstrated neural and/or neuromuscular abnormality corresponding to the site of radiculopathy. A number of contributory neuropathy findings including double crush syndrome were observed. On DTI tensor maps, nerve signal and caliber alterations were more conspicuous. Although individual differences were observed among neuropathic appearing nerve (lower FA and increased ADC) as compared to its contralateral counterpart, there were no significant mean differences on statistical comparison of LS plexus nerves, femoral and sciatic nerves (P > 0.05). CONCLUSION: MRN of LS plexus is useful modality for the evaluation of patients with non-contributory MRI of lumbar spine as it can incrementally delineate the etiology and provide direct objective and non-invasive evidence of neuromuscular pathology.

Bone marrow lesions: A systematic diagnostic approach.

Bone marrow lesions on magnetic resonance (MR) imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion-weighted imaging (DWI), to achieve accurate final diagnosis has been highlighted.