Objectives: 
We present three cases of a myeloid neoplasm in combination with a KIT mutation. A 46y old male was diagnosed with de novo AML: peripheral blood showed 89% blasts expressing myeloid markers. A secondary AML (sAML from MDS) was diagnosed in a woman (68y): bone marrow (BM) showed 23% blasts. In both cases no core binding factor (CBF) fusion genes were detected. A man (82y), asymptomatic, presented with thrombocytopenia and leukocytosis. After BM examination, CMML diagnosis was established. All diagnoses were made according to the WHO 2016 criteria.

Methods: 
All cases were analysed with next generation sequencing with in-house panels.

Results: 
KIT mutations with co-existing myeloid neoplasms are frequently associated with SM-AHN. Moreover, Jawhar et al. (Leukemia, 2019) recently described a CBF-negative AML subgroup with KIT D816 mutations (KITmut/CBFneg) and histologically proven SM (SM-AML). SM-AHN, including SM-AML, are challenging to diagnose because neoplastic cells may obscure the presence of mast cell infiltrates and vice versa. However, reclassification to SM-AHN may be important considering prognostic evaluation and treatment options, especially in KITmut/CBFneg AML. A KIT D816X mutation was detected in all three patients, in addition to multiple other mutations. Both AML cases showed low variant allele frequencies of 4% while it was 47% for the CMML patient. Histopathologic BM examination of the CMML patient showed clustered mast cell infiltrates with positive tryptase and CD117 immunochemical staining. Together with clinical features, diagnosis was reclassified to indolent SM-CMML. Unfortunately, histopathologic examination and/or immunophenotyping for the presence of co-existing SM could not be performed for both AML cases.

Conclusion: 
Presenting these cases, we want to raise awareness for the importance of re-evaluating patients with diverse myeloid neoplasms with a KIT mutation, for the presence of SM. Reclassification to SM-AHN, especially SM-AML, allows better risk stratification and optimal therapy selection (e.g. use of KIT inhibitors).

KIT D816 mutation in myeloid neoplasms: look out for systemic mastocytosis associated hematologic neoplasms (SM-AHN)