Correlation of PET-MRI, Pathology, LOH, and Surgical Success in a Case of CHI With Atypical Large Pancreatic Focus

Abstract

Congenital hyperinsulinism (CHI) is a rare cause of severe hypoglycemia in newborns. In focal CHI, usually one activity peak in 18F-DOPA PET-MRI indicates one focal lesion and its resection results in cure of the child. We present the case of a 5-month-old girl with CHI. Mutational screening of genes involved in CHI revealed a heterozygous pathogenic variant in the ABCC8 gene, which was not detectable in the parents. 18F-DOPA PET-MRI revealed two distinct activity peaks nearby in the pancreatic body and neck. Surgical resection of the tissue areas representing both activity peaks resulted in long-lasting normoglycemia which was proven by a fasting test. Molecular analysis of tissue samples from various sites provided evidence that a single second genetic hit in a pancreatic precursor cell was responsible for the atypical extended pancreatic lesion. There was a close correlation in the resected areas of PET-MRI activity with focal histopathology and frequency of the mutant allele (loss of heterozygosity) in the tissue. Focal lesions can be very heterogenous. The resection of the most affected areas as indicated by imaging, histopathology and genetics could result in complete cure.

Syndromic forms of congenital hyperinsulinism

“…Pancreatic histology showed areas of irregular proliferation of endocrine tissue forming coalescing nodules and trabeculae with a more widespread pattern compared to typical focal pancreatic lesions (14,15), a pattern that probably reflects the distribution of mosaicism for the patUPD11p in the pancreas. Therefore, the spectrum of disorders caused by the combination of a paternally inherited K ATP channel mutation and a secondary somatic patUPD11p can be regarded as a continuum where the timing and distribution of the second event is critical: BWS symptoms represent the clinical correlate of an early embryonic occurrence leading to systemic involvement with patUPD11p, while late emergence of patUPD11p that is restricted to the pancreas causes non-syndromic focal CHI (19). However, the majority of cases with CHI and BWS due to patUPD11p reported by Kalish et al were not associated with a K ATP variant, suggesting that the UPD11p per se can also initiate CHI with a K ATP -independent mechanism (14) (Figure 1C).…”