The classification of systemic mastocytosis should include mast cell leukemia (MCL) and systemic mastocytosis with a clonal hematologic non–mast cell lineage disease (SM-AHNMD)

To the editor:

We have read with interest the letter of Drs Pardanani and Tefferi, suggesting that the current World Health Organization (WHO) classification of systemic mastocytosis (SM) should be revised.¹  They suggest eliminating mast cell leukemia (MCL) and SM with associated clonal hematologic non–mast cell lineage disorder (SM-AHNMD) as variants, and to regard smoldering SM (SSM) as a separate category. We first note that the EU/US Consensus-Group defined criteria for SSM in 2001²  and proposed in 2007 that SSM should be a separate category of SM.³  In 2001, SSM was defined as a provisional subcategory of indolent SM (ISM),²  a concept adopted by the WHO in 2001⁴  and preserved in 2008.⁵ 

Regarding MCL, we believe this category of SM is best defined by SM criteria set by the Consensus Group,^2,,–5  not by an increase in myeloblasts or other criteria of acute myeloid leukemia (AML). Clinically, MCL closely resembles ASM: in both neoplasms, major sites involved are the liver (typically with ascites, usually not seen in AML), spleen (splenomegaly, infrequent in AML), bone marrow (also in AML), and skeletal system (often with osteolysis, not seen in AML).^2,,–5  Moreover, ASM and MCL are histologically indistinguishable neoplasms; only the percentage of mast cells in bone marrow and blood smears reveals the final diagnosis by definition.^2,,–5  Furthermore, the KIT D816V mutation is found with almost the same high frequency in MCL as in ASM or other variants of SM.^2,,–5  Lastly, ASM and MCL share aberrant phenotypes including CD30.^6,7  Hence, we believe it would be a conceptual flaw to lump MCL together with AML.

We also believe there is no justification for removing SM-MDS or SM-CMML from other categories of SM-AHNMD. Removal of these patients from SM does not take into account the shared molecular and clinical aspects of SM variants.^2,–4  Likewise, the KIT mutation D816V is found in almost all of these patients, and may even be expressed in the AHNMD component of the disease.^2,–4,8  Therefore, we recommend to adhere to the WHO classification and to the algorithm provided by the Consensus Group^2,–4 : (1) define SM by SM criteria, (2) explore whether an AHNMD is also present, and (3) define the nature of AHNMD and the type of SM by WHO criteria. We believe that no type of AHNMD should be excluded by this algorithm, and that any shift of SM variants into a completely different category of hematopoietic neoplasms would produce confusion rather than clarification.

Finally, we would like to point out that bone marrow mastocytosis (BMM) is a provisional subcategory of ISM as defined by the Consensus Group.^2,–4  We agree with Drs Pardanani and Tefferi that BMM is indistinguishable from typical ISM with skin lesions. However, it is also important to be aware of this condition, as patients with typical findings (eg, anaphylaxis after bee/wasp stings, unexplained osteoporosis) should have a serum tryptase test, even if skin lesions are absent, and should undergo a bone marrow biopsy to clarify whether SM/BMM is an underlying disease, which may have clinical (therapeutic) implications.^9,10 

In conclusion, we welcome a formal discussion with the aim of refining the current classification of mastocytosis, and some of the suggestions by Drs Pardanani and Tefferi are helpful in this regard. However, we do not support reallocation of MCL and SM-AHNMD to other unrelated categories of hematopoietic neoplasms.