BSPED2016 Poster Presentations Miscellaneous/other (14 abstracts)
New histological characterisation of focal lesions and clinical implications
Maria Salomon Estebanez 1, , Ross Craigie 2 , Bing Han 3 , Walaa Mal 3 , Zainab Mohammed 1 , Melanie Newbould 4 , Edmund Cheeseman 4 , Stefania Bitetti 4 , Lindsey Rigby 1 , Indi Banerjee 1 & Mark Dunne 3
1Paediatric Endocrinology Department, Royal Manchester Children’s Hospital, Manchester, UK; 2Paediatric Surgery Department, Royal Manchester Children’s Hospital, Manchester, UK; 3Faculty of Life Sciences, University of Manchester, Manchester, UK; 4Paediatric Histopathology Department, Royal Manchester Children’s Hospital, Manchester, UK.
Introduction: Congenital Hyperinsulinism (CHI) is a heterogeneous condition caused by dysregulation of insulin secretion. Paternally inherited mutations in ABCC8 or KCNJ11 are associated with loss of the maternal 11p15 allele in focal CHI (CHI-F). CHI-F can be curative after selective lesionectomy. However, histological heterogeneity within the CHI-F lesions has not been previously reported. We aimed to examine the diversity in focal lesions and correlate with clinical phenotypes and outcomes.
Methods: About 20 subjects with CHI-F were included over a 12-year period. About 18F-DOPA PET-CT was used to localise lesions in patients with CHI-F, following mutation testing for ABCC8/KCNJ11. Immunohistochemistry, transmission electron microscopy and serial block face-scanning electron microscopy were used to further characterise the structural organisation within the lesions.
Results: In our group, 85% had paternal heterozygous mutations in ABCC8, and 15% in KCNJ11; one child had a de novo ABCC8 mutation. About 18F-DOPA PET-CT confirmed and localised the focus before surgical lesionectomy. Sixty five percent of patients (13/20) were found to have a clearly demarcated and identifiable mass of insulin-expressing cells in the focal lesion, identified as Type 1 disease. Type 1 CHI-F lesions were encapsulated in a basement membrane that was composed of collagen fibre bundles organized into a loose orthogonal structure. In these patients, lesions were palpable at surgery and a focal lesionectomy was successful and resulted in curative outcomes. By contrast, in 35% of patients islet cell hyperplasia was not tightly encapsulated and not clearly demarcated from healthy tissue, identified as Type 2 disease. Type 2 CHI-F patients presented with symptoms earlier than Type 1 CHI-F (23±20 days vs. 55±17 days), the surgical procedure was more complex and not completely curative in 50% of the patients. It was not possible to distinguish Type 2 CHI-F from Type 1 by 18F-DOPA uptake profiles, and there were no correlation between the subtypes of CHI-F and the genetic basis of disease.
Conclusions: CHI-F has an underlying heterogeneity in the organisation of focal lesions, unrelated to the genotype and not identifiable with 18F-DOPA-PET-CT. Classification into Types 1 and 2 has implications for surgical margin of resection and predicting disease outcomes.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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