Systemic mastocytosis with associated clonal hematological non‐mast‐cell lineage disease: Analysis of clinicopathologic features and activating c‐kit mutations

Abstract

The majority of patients with systemic mastocytosis with associated clonal, hematological non-mast cell lineage disease (SM-AHNMD) have a myeloid stem cell malignancy including myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative disorders, acute myeloid leukemia (AML), or chronic myeloproliferative disease. The clinicopathologic features of SM-AHNMD have not been fully characterized. We describe seven cases of this entity: 3 with MDS, 3 with AML, and 1 with chronic myelomonocytic leukemia. In the majority of cases, SM was diagnosed concurrently with the myeloid malignancy and aberrant mast cell morphology was observed. The commonly described c-kit enzymatic site mutation Asp816Val was detected only in 2 cases, while 3 patients carried the Asp816His mutation. Among the 3 cases with AML, 2 patients carried the translocation t(8;21). On the basis of our results and other reported cases, there appears to be a specific association between SM and AML with t(8;21). Concurrent occurrence of SM may define a subset of patients with de novo AML and other myeloid malignancies who have an adverse prognosis. As clinically effective tyrosine kinase inhibitors that inhibit enzymatic-type c-kit mutations are being developed, detection of mast cell proliferation associated with myeloid malignancy may have important therapeutic implications. Am. J. Hematol. 73:12-17, 2003.

Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow

“…Mutations other than D816V are not uncommon in systemic mastocytosis with associated clonal hematologic non-mast-cell disease; however, these mutations were not tested in our study group. 19 In addition to testing for the KIT mutation, we also screened for the presence of FIP1L1-PDGFRa either by FISH or RT-PCR, as these mutations are associated with eosinophilia and often sensitive to treatment with imatinib. [20][21][22] The FIP1L1-PDGFRa was not identified in any case.…”

Systemic mastocytosis with acute myelomonocytic leukemia: a case report

“…The clinical relevance of coexistence of mastocytosis with AML is not very well characterized. According to a previous study, concurrent occurrence of SM may defi ne a subset of patients with de novo AML and other myeloid malignancies who have an adverse prognosis [2]. In patients with SM-AHNMD, separate treatment plans for the SM-component and the AHNMD should be established [14].…”

“…Neoplastic mast cells have activating c-kit mutations which is a receptor tyrosine kinase required for their development, proliferation, and survival. Apart from the commonly described c-kit enzymatic site mutation Asp816Val detected in neoplastic mast cell disease, another mutation described is Asp816His mutation [2,10]. Some studies show evidence of clonal origin of the mast cells from the same neoplastic clone as the blasts by demonstration of the same fusion transcript such as t (8; 21) in the tryptase positive mast cells and tryptase negative blasts by fl uorescence in situ hybridization (FISH) [4,6] and also by the demonstration of tryptase positivity by immunocytochemistry in some blasts (mast cell blasts) and mature mast cells [7].…”

“…Bone marrow mastocytosis may be associated with many clonal nonmast cell hematological neoplasms including myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia [2]. Mastocytosis in association with acute myeloid leukemia especially with t (8;21) has been described in earlier studies [2][3][4][5][6] and there is evidence of origin of the mast cells from the leukemic clone [4,6,7]. Concurrent occurrence of SM may defi ne a subset of patients with de novo AML and other myeloid neoplasms who have an adverse prognosis [2].…”

“…It is characterized by the involvement of at least one extracutaneous organ with or without skin infi ltration and in most cases the aggregates of neoplastic cells are readily apparent on tissue sections but their mast cell lineage must be confi rmed by the use of special stains [1]. Bone marrow mastocytosis may be associated with many clonal nonmast cell hematological neoplasms including myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia [2]. Mastocytosis in association with acute myeloid leukemia especially with t (8;21) has been described in earlier studies [2][3][4][5][6] and there is evidence of origin of the mast cells from the leukemic clone [4,6,7].…”