Triple-negative breast cancer (TNBC) is an aggressive disease that disproportionately affects African American (AA) women. Limited targeted therapeutic options exist for patients with TNBC. Here, we employ spatial transcriptomics to interrogate tissue from a racially diverse TNBC cohort to comprehensively annotate the transcriptional states of spatially resolved cellular populations. A total of 38,706 spatial features from a cohort of 28 sections from 14 patients were analyzed. Intratumoral analysis of spatial features from individual sections revealed heterogeneous transcriptional substructures. However, integrated analysis of all samples resulted in nine transcriptionally distinct clusters that mapped across all individual sections. Furthermore, novel use of join count analysis demonstrated nonrandom directional spatial dependencies of the transcriptionally defined shared clusters, supporting a conserved spatio-transcriptional architecture in TNBC. These findings were substantiated in an independent validation cohort comprising 17,861 spatial features representing 15 samples from 8 patients. Stratification of samples by race revealed race-associated differences in hypoxic tumor content and regions of immune-rich infiltrate. Overall, this study combined spatial and functional molecular analyses to define the tumor architecture of TNBC, with potential implications in understanding TNBC disparities. Significance: Spatial transcriptomics profiling of a diverse cohort of triple-negative breast cancers and innovative informatics approaches reveal a conserved cellular architecture across cancers and identify proportional differences in tumor cell composition by race.

Several new renal tumor types with distinctive pathologic, epidemiologic, and genetic signatures have recently been adopted in the fourth edition of the World Health Organization classification. In succeeding years, the cytologic features of most of these new types have been described, adding to the trend of increasing diagnostic accuracy for most common renal cell carcinoma subtypes and the important diagnostic role of cytologic sampling in the management and personalization of therapy. The current article reviews the cytologic findings from these recently established renal cell carcinoma subtypes. Emphasis is placed on cytologic diagnostic clues, confirmatory ancillary testing, salient differential diagnoses, and challenges that can be encountered in an attempt to render accurate interpretations in small samples.

Background: Avascular necrosis is a delayed complication of proximal humerus fractures that increases the likelihood of poor clinical outcomes. CT scans are routinely performed to guide proximal humerus fracture management. We hypothesized iodine concentration on post-contrast dual energy CT scans identifies subjects who develop avascular necrosis and ischemia due to compromised blood flow. Materials and methods: 55 patients with proximal humerus fractures enrolled between 2014 and 2017 underwent clinical, radiographic and contrast enhanced dual energy CT assessment. Iodine densities of the humeral head and the glenoid (control) were measured on CT. Subjects managed with open reduction internal fixation or conservatively (non-surgical) were followed for up to two years for radiographic evidence of avascular necrosis. Arthroplasty subjects underwent histopathologic evaluation for ischemia of the resected humeral head. Results: 17 of 55 subjects (30.9%) were treated conservatively, 21 (38.2%) underwent open reduction internal fixation and 17 of 55 (30.9%) underwent arthroplasty. Of the 38 subjects treated conservatively or with ORIF, 20 (52.6%) completed 12 months of follow up and 14 (36.8%) 24 months of follow up. At 12 months follow up, two of 20 subjects (10%) and at 24 months 3 of 14 subjects (21.4%) developed avascular necrosis. At 12 months, the mean humerus/glenoid iodine ratio was 1.05 (standard deviation 0.24) in subjects with AVN compared to 0.91 (0.24) in those who did not. At 24 months, subjects with avascular necrosis had a mean humerus/glenoid iodine concentration ratio of 1.06 (0.17) compared to 0.924 (0.21) in those who did not. Of 17 arthroplasty subjects, 2 had severe ischemia and an iodine ratio of 1.08 (0.30); 5 had focal ischemia and a ratio of 1.00 (0.36); and 8 no ischemia and a ratio of 0.83 (0.08). Conclusions: Quantifying iodine using dual energy CT in subjects with proximal humerus fractures is technically feasible. Preliminary data suggest higher humeral head iodine concentration may increase risk of avascular necrosis; however, future studies must enroll and follow enough subjects managed with open reduction internal fixation or conservatively for two or more years to provide statistically significant results. Trial Registrations NCT02170545 registered June 23, 2014, ClinicalTrials.gov.

BACKGROUND: With the development of new technologies and the changing patient profiles, cytopathology departments receive increasing numbers of adrenal gland cytology specimens. In this study, the authors analyzed archival adrenal gland cytology cases and attempted to implement a diagnostic reporting system.DESIGN: Retrospective electronic medical record search was performed for adrenal gland cytology specimens in seven tertiary care centers. The cytology diagnoses were grouped in 7 categories: nondiagnostic, nonneoplastic, benign adrenal cortical elements (BACE), primary neoplasm of noncortical origin (NONC), atypia of undetermined significance (AUS), suspicious for malignancy (SM), and malignant (MAL). If available, histopathology results of concurrent and/or follow‐up biopsies and/or resections were documented.RESULTS: A total of 473 adrenal gland cytology cases were included. BACE cases comprised 21.8%, whereas MAL cases were 57.5% of all cases. For BACE and MAL categories, there were 100% and 98.9% correlation, respectively, in the cases with histopathology follow‐up. Six of 10 NONC cases had histopathology diagnoses and there were 3 pheochromocytomas and 3 schwannomas. Twenty‐one AUS cases had histology follow‐up and 10 (47.6%) of them were malignant. Six cases of SM had histopathology follow‐up, and all of them were malignant on the follow‐up.CONCLUSIONS: The authors propose a 7‐tier diagnostic scheme for adrenal gland cytology. The risk of malignancy was 98.9% in MAL cases (87/88) in the cohort. The only case with discordance was reported as “adrenal cortical adenoma with marked atypia”' on resection. There was no difference between endoscopic ultrasound‐guided and percutaneous methods. Further studies are needed to validate and make this approach universal.;