Pseudo-Gaucher cells
in monoclonal gammopathies

Article written and reviewed by Dr Luca Moretti

Pseudo-Gaucher cells, also called Gaucher-like cells, are macrophages with abundant fibrillary cytoplasm that morphologically resemble the cells seen in Gaucher disease. They do not define a “monoclonal Gaucher-like syndrome” and do not represent an independent disease. They are a histological or cytological finding that may occur in the bone marrow in conditions characterized by high cellular turnover, including chronic myeloid leukemia, thalassemias, lymphomas, infections and, more rarely, monoclonal gammopathies and plasma cell neoplasms.

Etiology, pathogenesis and pathophysiology

In inherited Gaucher disease, glucosylceramide accumulation results from lysosomal beta-glucocerebrosidase deficiency caused by pathogenic variants in GBA1. In pseudo-Gaucher cells, by contrast, enzyme activity is generally preserved and the cellular appearance is attributed to an excessive lipid load derived from the degradation of cell membranes. The finding therefore primarily reflects the activity and turnover of the underlying disease.

Isolated cases of pseudo-Gaucher cells have been described in monoclonal gammopathies. In most settings these cells are macrophages, although rare plasma cells with pseudo-Gaucher morphology have been reported; the finding does not necessarily result from accumulation of monoclonal immunoglobulins. Crystalline immunoglobulin deposits in macrophages belong instead to the spectrum of crystal-storing histiocytosis, which is a distinct diagnosis.

Clinical manifestations

Pseudo-Gaucher cells do not produce a specific clinical syndrome. Anemia, thrombocytopenia, splenomegaly, bone pain or systemic symptoms, when present, should be attributed to the underlying hematologic or infectious disease rather than to the morphological finding itself. Their identification must therefore be interpreted in the context of the complete blood count, overall bone marrow morphology, immunophenotype and other clinical data.

Investigations and Diagnosis

The finding is identified in a bone marrow aspirate or biopsy. The cells show abundant, pale, fibrillary cytoplasm, but morphology alone cannot exclude true Gaucher disease. When compatible clinical features are present, such as marked splenomegaly, unexplained cytopenias, bone involvement or a relevant family history, measurement of beta-glucocerebrosidase activity and analysis of GBA1 are indicated. Investigation for a gammopathy includes electrophoresis, immunofixation, serum free light chains and bone marrow assessment of the clone.

The diagnostic evaluation must distinguish:

• inherited Gaucher disease, documented by enzyme deficiency and genetic confirmation;
• reactive pseudo-Gaucher cells associated with high cellular turnover;
• crystal-storing histiocytosis related to monoclonal immunoglobulins;
• other histiocytoses and storage diseases.

Treatment and Prognosis

There is no specific treatment for pseudo-Gaucher cells. Treatment is directed at the underlying disease, for example a myeloid neoplasm, lymphoma, clinically significant monoclonal gammopathy or infection. In MGUS without organ damage, standard monitoring is indicated, whereas multiple myeloma and other neoplasms require their respective treatment protocols. Enzyme replacement therapy is not indicated in the absence of documented Gaucher disease.

Complications

The main concern is the risk of diagnostic error. Interpreting the finding as proof of Gaucher disease may lead to inappropriate investigations or treatments; considering it specific for a gammopathy may instead delay the diagnosis of other high-turnover disorders. Its clinical and prognostic significance depends entirely on the associated disease.

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