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Aims: Very early‐onset inflammatory bowel disease (VEO‐IBD) is a clinical umbrella term referring to IBD‐like symptoms arising in children before the age of 6 years, encompassing both 'pure' IBD, such as ulcerative colitis (UC) and Crohn's disease (CD) and monogenic diseases (MDs), the latter often involving genes associated with primary immunodeficiencies. Moreover, histological features in gastrointestinal (GI) biopsies in MD can also have IBD‐like morphology, making differential diagnosis difficult. Correct diagnosis is fundamental, as MDs show a more severe clinical course and their inadequate/untimely recognition leads to inappropriate therapy. Methods and results: Biopsy samples from the lower and upper GI tract of 93 clinically diagnosed VEO‐IBD children were retrospectively selected in a multicentre cohort and histologically re‐evaluated by 10 pathologists blinded to clinical information. Each case was classified according to morphological patterns, including UC‐like; CD‐like; enterocolitis‐like; apoptotic; eosinophil‐rich; and IBD‐unclassified (IBD‐U). Nine (69%) MD children showed IBD‐like morphology; only the IBD‐U pattern correlated with MD diagnosis (P = 0.02) (available in 64 cases: 51 non‐MD, true early‐onset IBD/other; 13 MD cases). MD patients showed earlier GI symptom onset (18.7 versus 26.9 months) and were sent to endoscopy earlier (22 versus 37 months), these differences were statistically significant (P < 0.05). Upper GI histology was informative in 37 biopsies. Conclusions: The diagnosis of the underlying cause of VEO‐IBD requires a multidisciplinary setting, and pathology, while being one of the fundamental puzzle pieces, is often difficult to interpret. A pattern‐based histological approach is therefore suggested, thus aiding the pathologist in VEO‐IBD reporting and multidisciplinary discussion. [ABSTRACT FROM AUTHOR]

Serrated adenomas are genetically heterogeneous, and the histological classification into sessile serrated (SSA) adenoma and traditional serrated adenoma (TSA) does not reflect the molecular landscape. The objective of this study was to assess clinical or pathological factors associated with BRAF‐V600E mutation in serrated adenomas. Systematic review and meta‐analysis was performed by searching electronic databases from January 2011 to January 2019 for studies assessing the association of BRAF‐V600E mutation with clinical or pathological features of serrated adenomas. Odds ratio (OR) was calculated for each factor; a P‐value <0.05 was considered significant. Forty studies assessing 3511 serrated adenomas (2375 SSAs and 1136 TSAs) were included. BRAF‐V600E mutation was significantly associated with proximal localisation (OR = 2.71; P < 0.00001) and CIMP‐H status (OR = 4.81; P < 0.0001) in both SSA and TSA, with polyp size <10 mm (OR = 0.41; P = 0.02) in TSA, and with endoscopic pit pattern II‐O (OR = 13.11; P < 0.00001) and expression of MUC5A5 (OR = 4.43; P = 0.003) and MUC6 (OR = 2.28; P < 0.05) in SSA. Conversely, BRAF mutation was not associated with age <70 years (OR = 1.63; P = 0.34), age <60 years (OR = 0.86; P = 0.79), female sex (OR = 0.77; P = 0.12), flat morphology (OR = 1.52; P = 0.16), presence of any dysplasia (OR = 1.01; P = 0.59), serrated dysplasia (OR = 1.23; P = 0.72) and invasive cancer (OR = 0.67; P = 0.32), nuclear β‐catenin expression (OR = 0.73; P = 0.21) and p53 overexpression (OR = 1.24; P = 0.82). In conclusion, BRAF‐V600E mutation is associated with proximal localisation and CIMP‐H status in both SSA and TSA, with size <10 mm only in TSA, and with expression of MUC5A5 and MUC6 and endoscopic pit pattern II‐O at least in SSA. In serrated adenomas, BRAF‐V600E mutation does not seem to be associated with age and sex, with the prevalence of dysplasia and cancer and with the morphology of the dysplastic component. [ABSTRACT FROM AUTHOR]