Liver pathology in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: vasculopathic disease beyond nodular regenerative hyperplasia

• Published in: Human pathology Vol. 135; pp. 22 - 34
• Main Authors: Khonde, Pooja, Chatterjee, Deyali, Bogacki, Madonna, Liszewski, M. Kathryn, Ford, Andria L., Miner, Jonathan J., Atkinson, John P., Brunt, Elizabeth M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2023
• Subjects: Female; Fibrosis; Humans; Hyperplasia - pathology; Leukoencephalopathies - genetics; Leukoencephalopathies - pathology; Liver - pathology; Liver Diseases - genetics; Liver Diseases - pathology; Male; Microvasculopathy; Nodular regenerative hyperplasia; RVCL-S; TREX1 mutations; Vascular Diseases - genetics; Vascular Diseases - pathology; H and E; ALP; NRH; IHC; K7; GS; Nodular regenerative hyperplasia; α-SMA; TREX1 mutations; Fibrosis; RVCL-S; Liver pathology; Microvasculopathy; PAS-D
• ISSN: 0046-8177; 1532-8392; 1532-8392
• DOI: 10.1016/j.humpath.2023.02.013

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare autosomal dominant disease resulting from a frame-shift mutation in TREX1, an intracellular 3′–5′ exonuclease 1. Hepatic findings include an elevated alkaline phosphatase (ALP) and nodular regenerative hyperplasia (NRH). Affected individuals typically succumb to brain lesions before clinically apparent hepatic manifestations; thus, little else is known about the hepatic pathology. Autopsy reports and a liver section from each (n = 11) of three unrelated kindreds with the most common mutation in TREX1 (V235Gfs∗6) were studied with standard and immunohistochemical stains. Cases were compared with “normal liver” controls from similar autopsy years. Cases consisted of six men and five women who died at a median age of 50 yr (range, 41–60 yr.). Seven had elevated ALP. Two had liver atrophy. Foci of NRH were variably detected in all. Inhomogeneous distribution of other findings included patternless parenchymal fibrous bands, approximation of vascular structures, and commonly, architectural changes of vascular structures. Only bile duct epithelia were unaffected. In addition, small trichrome-positive nodules were found along vein walls or isolated in the parenchyma. Rare foci of non-NRH hepatocytic nodules were noted in 3. Increased CD34 and altered α-SMA IHC expression were variably noted. Periportal ductules and perivenular K7 IHC expression were increased to unpredictable degrees. The extensive but inhomogeneous histopathologic findings in livers of autopsied patients with RVCL-S appear to involve hepatic vascular structures. These findings validate inclusion of vascular liver involvement beyond NRH in this complex hereditary disorder. •Nodular regenerative hyperplasia (NRH) is a recognized hepatic feature of individuals affected by RCVL-S.•Our autopsy-based study confirmed NRH to varying degrees in all 11 subjects; 63% also had elevated alkaline phosphatase.•Inhomogenous patternless fibrosis, but no cirrhosis, irregular vascular spacing and parenchymal atrophy were also seen.•Vascular changes were common and involved all vascular structures with thickened arteries or veins and ruptured sinusoids.•Two demarcated fatty nodules were uncommon; one was in diffuse macrosteatosis, the other resembled a dysplastic nodule.