Diffuse large B-cell non-Hodgkin's lymphoma in Gaucher disease

Abstract

Gaucher disease type 1 (GD1) is the most common lysosomal storage disease and affects nearly 1 in 40,000 live births. In addition, it is the most common genetic disorder in the Ashkenazi Jewish population with phenotypic variation presenting in early childhood to asymptomatic nonagenarians. There have been a number of studies showing an increased risk of certain malignancies in patients, especially non- Hodgkin's lymphoma (NHL) and multiple myeloma. We describe a 66-year-old Ashkenazi Jewish male with GD1 who was first started on enzyme replacement therapy (ERT) with imiglucerase for GD1 at age 57 years, followed a year later by the diagnosis of diffuse large b-cell non-Hodgkin's lymphoma (DLBCL). He was treated with R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone, plus the monoclonal antibody rituximab), however relapsed and developed myelodysplasia necessitating an allo-stem-cell transplantation but succumbed to severe graft vs. host disease. In addition, we also describe a 38-year-old Ashkenazi Jewish male with GD1 who was diagnosed with DLBCL at age 22 years with Gaucher disease diagnosed on pre-treatment bone marrow biopsy which was confirmed by enzyme assay and genotyping. At age 24 years, he was started on ERT with imiglucerase and at age 35 years, he switched to eliglustat. He has remained in remission from the lymphoma. A meta-analysis of the literature will be elaborated upon and we will discuss the relationship of GD1 to NHL and discuss more recent information regarding lyso-GL1 and the development of NHL and multiple myeloma.

Cancer risk and gammopathies in 2123 adults with Gaucher disease type 1 in the International Gaucher Group Gaucher Registry

“…32 Eliglustat is also highly effective in reducing plasma concentrations of lyso-GL1 in patients with GD, 35 a potential antigen for the development of monoclonal antibodies. 36 Worldwide, NHL is the most common hematologic malignancy (4.3% of all cancers in US). 37 The risk for NHL in patients with GD1 may not encompass the entire spectrum of subtypes that comprise the NHL super-family.…”

“…The effects of eliglustat on GD patients with existent MGUS are still unknown, although anecdotal reports exist of MGUS concentrations decreasing 32 . Eliglustat is also highly effective in reducing plasma concentrations of lyso‐GL1 in patients with GD, 35 a potential antigen for the development of monoclonal antibodies 36 …”

Genetics of enzymatic dysfunctions in metabolic disorders and cancer

“…According to the Gaucher Registry, GD1 is the most common accounting for 90% - 95% of all documented cases of GD in Europe and North America ( 123 ). Notably, several case reports have shown a link between patients with GD1 and different cancers, including bone ( 124 ), breast ( 125 ), colon ( 126 , 127 ), hematologic ( 125 , 128 ), kidney ( 125 , 129 ), liver ( 125 , 130 , 131 ), melanoma ( 125 ), multiple myeloma ( 125 , 132 ), and non‐Hodgkin lymphoma ( 125 , 133 ). The development of cancer in GD patients could be explained by the accumulation of glucocerebroside in macrophages, leading to lipid-engorged macrophage activation, which affects immune system regulation in several different ways.…”

Gaucheroma of Mesenteric Lymph Nodes and Their Ultrasound Appearance: A Case Report

“…This, to our knowledge, is the first description of the ultrasound appearance of lymph node Gaucheromas. Due to the propensity of Gaucher patients to develop B-Cell non-Hodgkin's as well as Hodgkin's lymphomas, it is important to be able to differentiate the two entities (see Table 1) [6,7]. Table 1 Juxtaposition of lymph node appearances in Gaucheromas and lymphomas [6].…”