Possible pathogenetic relationship between Fabry disease and renal cell carcinoma.

The occurrence of renal cell carcinoma (RCC) in Fabry disease (FD) is a rare event. We report a deep ultrastructural study of RCC in a patient with a previous histological diagnosis of FD. In order to highlight analogies and differences between the two histological samples, we used the nephrectomy specimen as a 'repeat biopsy', making a dynamic analysis of the evolution of the disease-related kidney damage. Secondly, a comparative ultrastructural analysis between non-neoplastic tissue and cancer demonstrated for the first time the presence of zebra bodies in the tumor cells. Finally, a hypothetical speculation about the relationship between the lysosomal accumulation, the oxidative damage and the genesis of the tumor was performed. The link connected the accumulation of glycosphingolipid globotriaosylceramide, characteristic of FD, with the expression of CD74 and macrophage migration inhibitory factor that may play an important role in tumorigenesis regulated by the Von Hippel-Lindau/hypoxia-inducible factor 1α pathway.

[Clinical and histological findings in Fabry nephropathy]. / Il danno renale nella malattia di Fabry: aspetti clinici ed istologici.

Fabry disease is a complex pathology, requiring a multidisciplinar approach both in the diagnostic workout and in the management of therapy. Clinical criteria able to predict its morbidity have not yet been found. The wide variability of clinical signs and symptoms requires an individual approach based on the single patient, in order to achieve an optimal management. Enzyme replacement therapy (ERT) has been introduced in the clinical setting for over ten years, but its ability to change the course of the disease has not yet been clearly proved. Recently the hypothesis that ERT may be ineffective in patients with severe organ involvement has emerged. The clinical course of Fabry disease is usually slower in eterozygous women than emizygous men, but can be frequently associated to severe organ failure and premature death in both cases. In this review we discuss the histological aspects of Fabry nephropathy in relation to diagnosis, prognosis, therapy and its effectiveness.