Wang, Dongliang

AimsThere are no standardized histologic criteria for diagnosing serrated epithelial change (SEC) in inflammatory bowel disease (IBD), but two commonly used definitions are currently in use. The first definition (DEF1) is a simpler definition but requires endoscopic correlation. It encompasses all endoscopically invisible or non‐targeted serrated lesions without morphologic evidence of dysplasia that do not meet the diagnostic criteria of sessile serrated lesion (SSL) or traditional serrated adenoma (TSA). In contrast, the second definition (DEF2) incorporates more complex morphologic criteria (i.e., disorganized crypt architecture with some crypts no longer perpendicular or extending down to the muscularis mucosae, irregular serration spanning the entire thickness of the mucosa, and goblet cell‐rich epithelium), but does not necessitate endoscopic correlation. The reproducibility of SEC diagnoses using these definitions among gastrointestinal (GI) pathologists has not yet been evaluated.Methods and resultsSeven GI pathologists independently evaluated 38 GI cases, including 21 digitally scanned biopsy slides and 17 previously published images, demonstrating various types of serrated changes and their morphologic mimics. The diagnostic categories included: (1) SEC, (2) hyperplastic polyp (HP), (3) SSL, (4) TSA, (5) hypermucinous dysplasia (HMD), and (6) no serrated change or dysplasia (NSD). All cases were selected by a single pathologist (WTC) who did not participate in the interobserver study. The pathologists initially assessed each case as if it were endoscopically normal and provided a diagnosis using DEF1. Next, they re‐evaluated each case, this time considering it as a nodular or polypoid lesion, and again made a diagnosis using DEF1. The same process was then repeated for each case but using DEF2. A total of 532 diagnoses were made for each definition (7 pathologists × 38 cases × 2 endoscopic appearances). Fleiss' kappa statistics were used to assess the level of agreement among the seven pathologists. The total number of SEC diagnoses using DEF1 (n = 110 of 532) was more than twice that of DEF2 (n = 50 of 532). Also, the number of SEC diagnoses per pathologist was higher using DEF1 (mean: 16, range: 12–18) compared to DEF2 (mean: 7, range: 0–14). Furthermore, the instances where four or more pathologists agreed on the diagnosis of SEC were more frequent with DEF1 (16 of 38 cases) than with DEF2 (1 of 38 cases). The overall agreement in diagnosing SEC (vs. no SEC) using DEF1 was substantial (k = 0.69, P < 0.001), whereas the agreement using DEF2 was only slight (k = 0.18, P < 0.001). Among potential SEC mimics, there was substantial agreement in diagnosing HP (k = 0.69 using DEF1), SSL (k = 0.68), TSA (k = 1.00), HMD (k = 0.79), and NSD (k = 0.61) (P < 0.001).ConclusionsThe diagnosis of SEC using DEF1 is significantly more reproducible than using DEF2. Utilizing DEF1 is also less likely to miss potentially important cases of SEC. Therefore, DEF1 could be adopted to separate SEC from other serrated lesions and morphologic mimics in IBD.

Abstract Purpose: Embryonal tumor with multilayered rosettes (ETMR) is a rare pediatric CNS embryonal tumor with poor survival. The Pediatric Proton/Photon Consortium Registry (PPCR) was queried for outcomes data from prospectively consenting pediatric patients with ETMR treated with proton radiation therapy (RT). Methods: 20 patients (2013-2021) at 9 institutions had ETMR; 2 with prior RT were excluded from statistical analyses (PPCR ETMR, N=18). Overall Survival (OS) and Event Free Survival (EFS) analyses were performed using the Kaplan-Meier method and log-rank values. Median follow-up was calculated using the reverse Kaplan-Meier method. Results: Median age at RT was 3.0 years (1.7-12.2); median follow-up was 55.5 months (2.6-119.4). 8 patients (44%) expired and 6 patients (33%) are surviving ≥55 months. 11 (61%) patients received systemic therapy with stem cell support. The majority (89%) had focal RT, while 2 patients received craniospinal irradiation (CSI). 4-year OS and EFS were 59.6% and 54.2%, respectively. Local control (LC) at 4 years was 81%. No differences in OS or EFS were observed for receipt of systemic therapy with stem cell support (p=0.361, p=0.57), progression prior to RT (p=0.127, p=0.18), or surgery to RT ≥200 days (p=0.35, p=0.254). Symptomatic radionecrosis was not reported. Conclusion: Focal proton RT provided effective local control as part of multimodality therapy for ETMR, with encouraging survival for this rare and often infant age tumor. Outcomes for CSI were limited to 2 patients treated upfront, and 1 patient receiving salvage CSI for disseminated relapse after focal RT who is surviving >1 year. Trial: DFCI protocol 12-103, clinicaltrials.gov NCT01696721, date of registration 9/27/2012

AbstractPurposeRadiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta‐analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI).MethodsAfter abstract screening, 25 studies (1995–2020) contained necessary patient, disease, and radiation treatment information (N = 96). All abstract, full text, and data capture were independently double‐reviewed. The corresponding author was contacted for cases of insufficient information. Response to pre‐radiation chemotherapy (N = 57) was categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Univariate and multivariate statistics were performed to investigate survival correlation. Patients with M4 disease were excluded.ResultsThe 2‐ and 4‐year overall survival (OS) was 63.8% and 45.7%, respectively, with a median follow‐up of 2 years (range 0.3–13.5). The median age was 2 years (range 0.2–19.5), and 96% received chemotherapy. On univariate analysis, gross total resection (GTR, p = .0007), pre‐radiation chemotherapy response (p < .001), and high‐dose chemotherapy with stem cell recuse (HDSCT, p = .002) correlated with survival. On multivariate analysis, pre‐radiation chemotherapy response (p = .02) and GTR (p = .012) retained survival significance as compared to a trend for HDSCT (p = .072). Comparisons of focal RT (vs. CSI) and greater than or equal to 5400 cGy primary dose were nonsignificant. Following CR or PR, a statistical trend favored focal radiation (p = .089) over CSI.ConclusionChemotherapy response prior to RT and GTR correlated with improved survival on multivariate analysis for ATRT M+ receiving RT. No benefit was observed for CSI compared to focal RT among all patients and following favorable chemotherapy response, inviting further study of focal RT for ATRT M+.