Myelomastocytic leukemia: histopathological features, diagnostic criteria and differential diagnosis

Abstract

Myelomastocytic leukemia (MML) is an extremely rare myeloid overlap-neoplasm that belongs to the group of tryptase-positive (T+) myeloid neoplasms. Main differential diagnoses include aggressive systemic mastocytosis (ASM), in particular ASM in transformation; mast cell leukemia; T+ acute myeloid leukemia (T+ AML); acute basophilic leukemia and chronic basophilic leukemia. MML exhibits both proliferative and dysplastic features and is characterized by prominent differentiation into the mast cell lineage in an advanced myeloid neoplasm, usually primary or secondary AML. While the histological key feature of MML is a diffuse increase in neoplastic cells expressing mast cell-related antigens like tryptase and CD117 (KIT), the most important cytomorphological finding in bone marrow (BM) and peripheral blood (PB) is the metachromatically granulated blast cell (= metachromatic blast). In contrast to systemic mastocytosis (SM), MML neither shows activating point mutations at codon 816 of KIT nor the aberrant expression of CD25 by mast cells is seen. MML can only be diagnosed when tryptase-staining is performed on BM biopsy specimens, PB and BM smears are investigated for presence of metachromatic blasts and other T+ leukemias have been excluded.

Keywords::

• acute myeloid leukemia
• basophilic leukemia
• mast cell leukemia
• mast cells
• myelomastocytic leukemia
• systemic mastocytosis
• tryptase

Financial & competing interests disclosure

The authors were supported by the Austrian Science Fund (FWF) project grant #SFB F4704-B20. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Myelomastocytic leukemia (MML) is a rare and underrecognized myeloid neoplasm.

• The diagnosis of MML is based on histomorphological findings showing a significant increase in atypical immature metachromatic cells (identified as mast cell precursors by phenotyping) in the bone marrow and peripheral blood.

• Antibodies against mast cell-related antigens are pivotal to document the presence of atypical/immature mast cells in these patients.

• MML is defined as partial or predominant differentiation toward the mast cell lineage in an advanced underlying myeloid neoplasm, usually MDS-RAEB or acute myeloid leukemia.

• MML should be separated from other T+ leukemias, including acute basophilic leukemia, chronic basophilic leukemia, mast cell leukemia and T+ acute myeloid leukemia.

• MML is neither a part of the WHO nor of the FAB classification systems of myeloid and lymphoid neoplasms.

• MML carries no specific (recurrent) molecular or cytogenetic markers; specifically, systemic mastocytosis-related activating point mutations at codon 816 of KIT are not detectable in MML.

• Systemic mastocytosis must be excluded.

Notes