Increased incidence of HCC in Gaucher disease: A multicentric long-term analysis from 4 German centers

Introduction Gaucher disease (GD) is a rare monogenic autosomal-recessive disease caused by deficient β-glucocerebrosidase. Intralysosomal accumulation of glucocerebroside leads to ballooning and inflammatory transformation of macrophages. As shown in previous own work [1]–[3], total cancer incidence among GD patients is increased 2.5-fold and 12.7-fold for hematological tumors as compared to the general population with splenectomized patients being at highest risk [1]. The exact incidence of HCC in Gaucher patients and its relationship to pre-existing cirrhosis is unknown.

Methods In a cohort of 249 patients from 4 German centers observed for an average of approx. 12 years (manifestation age 28-68 years), the incidence of HCC and the role of cirrhosis was investigated.

Results In a cohort of 249 patients, 4 new cases of HCC were observed for an average observation time of 11.9 years/patient (mean age at Dx 54 yrs., 2963 pt. years total, m/w=3/1). Out of 4 patients, two had been splenectomized. In 3/4 cases, cirrhosis had not been present prior to advent of HCC. A lethal course within 1-3 years after Dx despite multimodal therapy was observed in 3/4 HCC cases, and one patient developed recurrence of HCC after CT-guided brachytherapy and is currently treated by BSC.

Conclusion Whereas normal incidence of HCC is about 7/100.000 [4], the data from the German Gaucher cohort suggest an increase of HCC incidence to 135/100.000. As incidence of HCC without cirrhosis is significantly increased in Gaucher disease and a deleterious course is frequent, the role of sphingolipids and immune dysregulation related to tumorigenesis in GD remains to be elucidated. Glucosylceramide-laden, chronically activated macrophages are known to release immunologic factors, e.g. interleukins, and accumulation of sphingolipids might contribute to tumorigenesis under these conditions. The results extend studies from previous work [1]-[3] and as most patients had not been cirrhotic, all GD patients should undergo regular HCC surveillance.

Publikationsverlauf

Artikel online veröffentlicht:
04. Januar 2021

• 1 de Fost. et al. Blood Cells Mol Dis. 2006; 36: 53-8.
• 2 Mistry. et al. Crit Rev Oncog. 2013; 18: 235-46.
• 3 Regenboog. et al. J Inherit Metab Dis. 2018; 41: 819-827.
• 4 Robert-Koch-Institut. , Zentrum für Krebsregisterdaten (ZfKD), http://www.krebsdaten.de.