Case series and literature review of skeletal tumors and their incidence in the Gaucher disease population

Abstract

An Ashkenazi Jewish male first presented at age 40 with persistent bone pain and a tender mass on his right leg. This patient was the subject of a prior case report in 1995 [1]. He had onset of persistent bone pain and splenomegaly at age 5 years and at age 10 suffered from avascular osteonecrosis of the right femur. At age 15 years, he suffered from recurrent avascular necrosis of right femur and right humerus. Diagnosis of Gaucher Disease (GD) Type 1 was made on bone marrow biopsy, later confirmed by low leucocyte acid b-glucosidase activity and the finding of homozygosity for N370S mutation in GBA gene. He underwent osteotomy of his right hip at age 18. At age 25 years, the patient suffered from infectious mononucleosis resulting in massive splenomegaly and splenic rupture that necessitated emergency splenectomy. Subsequently, he underwent right hip replacement. At his presentation with right leg mass, the mass and bone pain had been present for the previous 6 months and had worsened until the patient could no longer continue his daily activities. At this time in 1992, enzyme replacement therapy had not yet become the standard of care for GD.Gaucher disease, an autosomal recessive disorder, is a prototype inborn error of metabolism due to biallelic mutations in GBA1 that results in deficiency of lysosomal acid b-glucocerebrosidase, a key enzyme in the degradation pathway of membrane glycosphingolipids [2]. GD displays a heterogeneous clinical presentation affecting multiple organs with major skeletal involvement based on the accumulation of glucocerebroside-laden macrophages, eponymously known as Gaucher cells [3]. The accumulation of primary substrate leads to generation of bioactive lipids that cause immune activation and chronic metabolic inflammation [4,5]. Bone disease was more common and more severe in asplenic patients with GD [2]. In fact, asplenia is a major independent risk factor for avascular osteonecrosis [6].Plain radiographs of tibia showed typical bony lesions of Gaucher disease including osteopenia, extensive bone marrow infarcts, and lytic lesions. In addition, there was a focal mass concerning for a malignant tumor. The tibia was resected and replaced with intercalary allograft, soleus muscle flap, and split thickness skin graft. Subsequently, infectious complications necessitated an above knee amputation.On gross examination, the tumor measured 4 3 4 3 3 cm and was focally friable and hemorrhagic. The tumor was dispersed in sheets and cords within a hyalinized basophilic background. Intensely eosinophilic nucleoli, abundant cytoplasm, and cytoplasmic vacuoles with red blood cells were present. The extraosseous segment showed increasing atypia with primitive anastomosing split like vascular spaces. The bone marrow was extensively necrotic and demonstrated infiltration by Gaucher cells. By immunohistochemistry, the cells stained positive for keratin, factor VIII antigen, Ulex europaeus agglutinin, and vimentin [1]. The cells demonstrated a high nuclear cytoplasmic ratio with striking euchrom...

Are Glucosylceramide-Related Sphingolipids Involved in the Increased Risk for Cancer in Gaucher Disease Patients? Review and Hypotheses

“…This study also pointed the high prevalence of MGUS (up to 16% in the Dutch GD patients) and underlined the absence of differences in GD activity, spleen status or GBA1 genotype in patients with or without cancer. Besides hematologic malignancies (non-Hodgkin's lymphoma, Hodgkin's disease, acute myeloid leukemia, acute leukemia lymphoid, myelodysplastic syndrome), numerous types of solid tumors have been described in GD patients (see for instance [34,[37][38][39]). Interestingly (see Section 4), GD patients display an increased risk of melanoma (relative risk from 2.26 to 3.07) [38,40].…”

Imaging of non-neuronopathic Gaucher disease: recent advances in quantitative imaging and comprehensive assessment of disease involvement

“…Bone-related malignancies may be slightly more common in Gaucher disease, perhaps related to osteonecrosis as a predisposing factor. MRI may often be warranted for evaluation of discrete lytic lesions given the incidence of malignant bone lesions such as multiple myeloma, osseous lymphoma, sarcomas, and malignant epithelioid hemangioendothelioma [118–120]. Particular attention should be paid to enlarging lesions and those with morphology dissimilar to more common Gaucher disease-related osteopenia, marrow infiltration, and osteonecrosis.…”