Ma, Changqing

The WHO 2019 classification of digestive tract tumors introduced a high-grade (G3) category for well-differentiated neuroendocrine tumors (NETs). These neoplasms appear to have a better prognosis than poorly differentiated neuroendocrine carcinomas (NECs) and may not respond to platinum-based chemotherapy, which is the treatment of choice for NECs, justifying the creation of this new category. Most existing data on G3 NETs are derived from pancreatic neuroendocrine neoplasms, as the majority of G3 neuroendocrine neoplasms (NENs) arise there. G3 NETs are rare at extrapancreatic sites, and their prognosis and behavior are not well studied. We collected and analyzed a multi-institutional cohort of 24 extrapancreatic primary gastrointestinal G3 NETs based on mitotic rate and/or Ki67 index (5 gastric, 13 small bowel, 6 colorectal/anal). Mean Ki67 index was 29.3% (range: 10.5% to 50.2%). Cases generally showed typical well-differentiated NET morphology. Nodal metastases were present in 17/17 (100%) patients; 13/24 (45%) had distant metastases at initial presentation, and 7 patients developed them on follow-up. With a median of 29 months of follow-up, only 2 patients (8%) were alive without disease. Outcomes of G3 NETs were compared with a separate cohort of 125 extrapancreatic G1/G2 gastrointestinal NETs. G3 tumors presented at a higher pT-category stage ( P <0.001) and overall stage ( P =0.002), and patients with G3 disease were more likely to die than those with G1/G2 disease ( P <0.001). Our data show that, like pancreatic G3 NETs, rare extrapancreatic gastrointestinal G3 NETs exhibit aggressive behavior compared with their G1/G2 counterparts (although small bowel NETs tend to recur irrespective of grade). In most cases, the G3 designation is driven by Ki67 index, though exceptions exist, emphasizing the need for reviewing mitotic count in every case.

AimsWe compiled two cohorts of colorectal adenosquamous carcinoma (ASC) to describe its histologic and molecular aspects using modern parameters to compare them with literature reports using meta‐analysis of cohorts and individual case series.Methods and ResultsWe identified 53 colorectal ASC from 19 North American academic medical centres, in addition to national database reports on 94 Dutch cases. We analysed available clinical, histologic, and immunohistochemical features and patient outcome. ASC comprised 0.02% of colorectal cancers in the Dutch database. The median cohort patient ages at resection were 65 and 69 years (North American and Dutch cohorts, respectively), with a roughly equal male:female ratio. The squamous component represented between 5% and 95% of each tumour, with a median of 50%. Tumour‐infiltrating lymphocytes (TILs) were generally low (66%), and tumour budding was often Bd1 (64%). Most cases were pT3 (55%) or pT4 (40%), with nodal metastases in more than half (58%). Twenty‐three cases (43%) metastasized distantly, most commonly to the liver. Mismatch repair (MMR) deficiency was identified in 34% of the cases. Follow‐up was available for 48 patients; 13 (27%) had recurrent disease and 29 (60%) died. A total of 31 patients progressed, with median time to progression of 18 months. Available data for the Dutch cohort revealed largely similar findings, as did review of cases in the literature.ConclusionColorectal ASC usually presents at an advanced stage. Despite high rates of MMR deficiency and low tumour budding, TILs were generally low, and there is a high recurrence rate and poor prognosis.

INTRODUCTION: Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. METHODS: Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. RESULTS: Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. DISCUSSION: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.