Histopathology. 2024 Feb;84(3):440-450. doi: 10.1111/his.15084. Epub 2023 Oct 30.

Paola Parente ¹, Maria C Macciomei ², Anna M Buccoliero ³, Luisa Santoro ⁴, Barbara Cafferata ⁵, Delfina Bifano ⁶, Jacopo Ferro ⁵, Alessandro Vanoli ⁷, Matteo Fassan ^8 9, Valentina Angerilli ⁸, Rita Alaggio ¹⁰, Luca Mastracci ^11 12, Maria D'Armiento ¹³, Federica Grillo ^11 12, Paola Francalanci ¹⁰

Author information

¹Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

²Pathology Unit, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy.

³Pathology Unit, Meyer Children's Hospital IRCCS, Firenze, Italy.

⁴Pathology Unit, Azienda Ospedaliera Padova, Padova, Italy.

⁵Pathology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy.

⁶Department of Pathology, 'AORN Santobono Pausilipon', Pediatric Hospital, Naples, Italy.

⁷Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, IRCCS San Matteo Hospital, Pavia, Italy.

⁸Department of Medicine (DIMED), Surgical Pathology Unit, Via Gabelli 61, University Hospital of Padua, Padua, Italy.

⁹Istituto Oncologico Veneto IOV-IRCCS, Viale Gattamelata, Padua, Italy.

¹⁰Pathology Unit, Department of Laboratories, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.

¹¹Pathology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

¹²Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genoa, Italy.

¹³Pathology Unit, Department of Public Health, University of Naples Federico II, Napoli, Italy.

Abstract

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.