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Systemic mastocytosis associated with acute myeloid leukemia: case report and implications for disease pathogenesis☆

https://doi.org/10.1016/j.jaci.2004.02.042Get rights and content

Abstract

Mastocytosis may be associated with clonal nonmast cell lineage hematologic diseases, including myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia. Here we present a patient with the simultaneous diagnosis of mastocytosis and an acute myeloid leukemia, M2 subtype in the French-American-British classification, with t(8;21) carrying a population of immature mast cell precursors, and discuss this presentation in the context of a potential pathogenetic cellular link between this leukemia and mastocytosis.

Section snippets

Case presentation

A 67-year-old woman consulted on April 1999 because of a 4-month history of fatigue, ecchymosis, and spontaneous hematomas in the absence of pruritus, flushing, abdominal pain, or diarrhea. Physical examination was unremarkable except for the presence of ecchymosis and hematoma in the absence of other skin lesions. Peripheral blood analysis revealed the existence of a moderate normocytic anemia (hemoglobin, 96 g/L) and thrombocytopenia (16 × 109 platelets/L; normal values, 150-350 ×109/L)

Differential diagnosis

Differential diagnoses considered in this case included non-MC tryptase-positive hematopoietic neoplasms, mastocytosis associated with clonal non-MC lineage hematologic diseases (AHNMDs), and other pathologic conditions associated with an increase in BM MCs.

Laboratory and other testing and procedures

The results of the immunophenotypic studies performed at diagnosis and during follow-up are summarized in Table I, Table II. As may be seen in Table I, as many as 2 different populations of blast cells in addition to MCs were detected in the BM, their relative distribution varying between samples obtained at different time points. Phenotypically, at diagnosis, blast cells showed expression of myeloid-associated markers (CD13+, CD33+, CD117+, MPO−/+) in the absence of lymphoid-related antigens

Diagnosis with discussion of pathogenesis

A MC hyperplasia within BM may be observed in pathologic conditions other than mastocytosis, including Hodgkin disease,9., 10. non-Hodgkin lymphoma (NHL),11., 12., 13., 14. and myelodysplastic syndromes (MDSs).15., 16. In such diseases, MC morphology is normal, and compact MC aggregates are not present.17 Moreover, BM MCs display a normal immunophenotype, lacking expression of both CD2 and CD25.6., 18.

An increase in serum tryptase levels has been described in ∼40% of patients with AML19., 20.

Final diagnosis with treatment and management plans

In the case reported here, the diagnosis of mastocytosis was confirmed on the basis of 1 major criterion (presence of BM MC aggregates) and 2 minor criteria (morphologically abnormal MCs carrying an aberrant immunophenotype) according to the World Health Organization classification. The small size of BM MC aggregates could be explained by the fact that BM biopsy was performed after a cycle of idarubicin plus ARA-C and response of SM to cytoreductive therapy. In fact, in BM samples studied once

Summary

Mastocytosis may be associated with non-MC lineage hematologic disorders including AML, MDS, MPD, and NHL.21 Among all patients diagnosed with these non-MC lineage hematologic disorders, a few are found to coexist with mastocytosis. Thus, care should be taken in the morphological BM examination to rule out the presence of abnormal MCs. If SM is suspected, a careful histologic and immunophenotypic analysis of MCs is mandatory. Analysis of serum tryptase may help to confirm the coexistence of SM.

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      In contrast, our experience suggests that such evolution should be considered an exceptional event in ISM. In our series, only 4 ISM cases developed a myeloid malignancy (an AML, an MDS, a polycythemia vera, and a MCL); of note, in those 2 cases developing AML and MCL, the D816V KIT mutation, apart from being present in MC, was also positive in highly purified CD34+ hematopoietic precursors, myeloid and lymphoid cells, suggesting the occurrence of D816V KIT mutations in all hematopoietic lineages in both patients, as sporadically mentioned in the literature for individual ISM cases evolving to a more aggressive subtype of the disease6,36-40; however, to establish the impact of presence of D816V KIT mutation in all hematopoietic lineages as a predictor of outcome in ISM, longer follow-up of cases accomplishing this characteristic is mandatory. In a retrospective study in which 58 proved cases of SM were analyzed, Travis et al11 found only 46.5% to remain alive after a median follow-up of 7.6 years.

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    ☆

    Supported by Fondo de Investigaciones Sanitarias (grant no. 01/0413) and Red Española de Mastocitosis (grant no. G03/007) of the Ministerio de Sanidad y Consumo Madrid. R. Núñez-López and A. Prados are recipients of a grant from Instituto de Salud Carlos III, Red Española de Mastocitosis G03/007.

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    Copyright © 2004 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.