1558 Histologic Characterization of Gallbladder Pathology in Metachromatic Leukodystrophy

Amy Huang; Jonathan Davick; Dustin Bosch; Andrew Bellizzi; Matthew Gosse

doi:10.1016/j.labinv.2025.105858

Background Metachromatic leukodystrophy (MLD) is an inherited demyelinating disorder due to excess accumulation of incorrectly processed sulfatides in the central nervous system and peripheral nervous system. This accumulation causes a progressive neurodegenerative disease with a poor prognosis. Current treatment best serves patients who are pre-symptomatic for the neurologic effects of MLD. Interestingly, these same sulfatides accumulate in the gallbladder, and increase risks for gallbladder (GB) disease. We sought to describe the GB pathology of these patients and to better describe the histologic presentation. Design We searched our electronic health record system for patients coded with a diagnosis of MLD. Clinical factors such as subtype of MLD (late-infantile, LI; juvenile, J; and adult-onset, A), GB symptoms, GB imagining, and if cholecystectomy was performed. The histopathology of resected GB cases was reviewed and characterized by a variety of factors found in the Table. Results 12 patient with MLD were identified. 8 had GB symptoms, 8 had cholecystectomy and 5 cases were available for review. Grossly the gallbladders showed thicken and irregular mucosa (Fig 1A), 2 had polyps. Histopathology showed papillary hyperplasia (Fig 1B) with mucinous, pyloric, and intestinal metaplasia in 4 (80%). Debris-laden histiocytes were observed, 2 (40%) with typical cholesterolsis foamy change, 2 (40%) with flocculant cytoplasm (Fig 1C) and 1 (20%) with a blue hue to the cytoplasm (Fig 1D). Rochitansky Aschoff sinuses were seen in 4 (80%) cases with an average of 1.1/per cm and gallstones were found in 2 (40%). 2 had inflammatory-type polyps and 3 had epithelial atypia with serrated type changes (Figure 2). One case was interpreted as indefinite for dysplasia had molecular sequencing performed (as part of the clinical work up), which did not reveal any pathologic variants. One case had cholecystectomy preceeding onset of neurologic symptoms. Conclusions The histopathology of the GB in patients with MLD has papillary hyperplasia, frequent mucinous, intestinal, and pyloric metaplasia, and is associated with inflammatory-type polyps. The epithelial atypia with serrated changes that is sometimes encountered appears to be reactive and non-neoplastic. A better understanding of gallbladder histology in patients with MLD is useful in this patient type and may even allow for earlier identification of MLD in patients with GB pathology who are pre-symptomatic for neurologic disease.

1558 Histologic Characterization of Gallbladder Pathology in Metachromatic Leukodystrophy

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