Somatic ASXL1 p.R693X mutation identified by next generation sequencing in isolated myeloid sarcoma involving the mediastinum

Abstract

Introduction

Isolated myeloid sarcoma (MS) is characterized by extramedullary immature myeloid cell infiltration without bone marrow involvement. The diagnosis of isolated MS is sometimes difficult in cases without expression of typical immunohistochemical markers, such as CD64, MPO or lysozyme.

Clinical presentation

We report a case of isolated MS involving the mediastinum, with negative staining of MPO and lysozyme, which was misdiagnosed for 20 months. A comprehensive analysis in our institution showed MS with a characteristic staining pattern positive for CD34, CD117 and CD33, but negative for MPO, lysozyme, CD3 and CD79a. Next-generation sequencing (NGS) targeting 112 acute myeloid leukemia (AML)- and myelodysplastic syndromes (MDS)-associated genes confirmed the existence of an ASXL1 p.R693X mutation with a frequency of 13.17% of total cells. The patient acquired sustainable remission under the alternative treatment of intermediate-dose cytarabine and decitabine.

Discussion and conclusion

The ASXL1 p.R693X mutation, a truncated mutation, has been widely reported to be associated with poor prognosis in myeloid malignance. We report the role of this mutation and recommend the utilization of NGS to discover more profound pathobiological information with limited samples, facilitate the diagnosis, and further clarify the uncertainties of prognosis and treatment in more isolated MS patients.

Keywords:

• ASXL1 mutation
• next generation sequencing
• isolated myeloid sarcoma
• mediastinum
• decitabine

Transparency

Declaration of funding

This work was supported by the National Natural Science Foundation of China [grant number 81700125].

Declaration of financial/other relationships

No potential conflict of interest was reported by the authors. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

None reported.