The revised WHO classification on mastocytosis defines four major variants of systemic mast cell proliferative diseases.2
These entities strongly differ with respect to clinical course, extent of organ involvement, and clinical outcome. In general, systemic variants of mastocytosis are characterised by an abnormal accumulation of mast cells in one or more extracutaneous organs. Urticaria pigmentosa-like skin lesions may be present and are often associated with an indolent course of the disease. In about 20% of patients with SM, an associated clonal haemopoietic disorder is diagnosed.3–9
This observation led to the definition of a new entity termed systemic mastocytosis with associated clonal haemopoietic non-mast cell lineage disorder (SM-AHNMD). Quantitatively, SM-AHNMD assumes an intermediate position between the relatively common indolent SM and the rare aggressive SM. The clinical presentation and outcome in the setting of SM-AHNMD is often more related to the associated haematological neoplasm than to the mastocytosis. In most patients with SM-AHNMD, a myeloid neoplasm can be diagnosed. All major subtypes of myeloid malignancies including myelodysplastic and myeloproliferative syndromes have been described.7,9
The AHNMD should be strictly classified according to the WHO or FAB criteria. Even pure cutaneous forms of mastocytosis (urticaria pigmentosa) have been reported to be associated with haematological malignancies, in particular AML.10,11
To the best of our knowledge, approximately 20 cases of SM-AML have been published. In six of these cases, a t(8;21) translocation is reported.3,8,9,12–18
“Our present case validates the usefulness of the diagnostic guidelines included in the WHO system of classification for mastocytosis, even to detect and define a so called occult mastocytosis”
Here, we present an unusual case in which the final diagnosis of SM-AML could be established only in the second (control) bone marrow biopsy specimen after chemotherapy for AML with t(8;21). Apparently, the complete diagnosis was obscured by a diffuse, compact infiltration of an extremely hypercellular bone marrow by myeloblasts. The cytoreductive treatment disclosed multifocal dense infiltrates of mastocytosis in an aplastic bone marrow. The morphological diagnosis in this trephine specimen is that of an isolated bone marrow mastocytosis, which, by definition, belongs to the SM group.
Ideally, the correct diagnosis of SM-AML would have been possible even in the initial biopsy diffusely infiltrated by AML, although compact mast cell infiltrates as the one and only major diagnostic criterion for mastocytosis were not detected. However, two minor diagnostic criteria were fulfilled morphologically, namely spindling in more than 25% of the loosely scattered mast cells and the proof of CD25 expression by mast cells, suggesting their neoplastic nature. Because the transforming point mutation D816V was also detected, three of a total of four minor diagnostic criteria were met, thus enabling the definitive diagnosis of mastocytosis. Our present case validates the usefulness of the diagnostic guidelines included in the WHO system of classification for mastocytosis, even to detect and define a so called occult mastocytosis.
Take home messages
- We describe a 48 year old man with acute myeloid leukaemia (AML) and a type t(8;21) cytogenetic abnormality who had associated bone marrow mastocytosis (SM-AML) that was only detected after successful polychemotherapy in the state of bone marrow aplasia, and persisted after complete remission of AML
- The diagnosis of mastocytosis was based on the dense infiltrate of atypical mast cells, which expressed CD25 (expressed only on neoplastic (not normal) mast cells) and exhibited the transforming somatic mutation D816V of the c-kit gene
- Re-examination of the initial biopsy enabled a diagnosis of SM-AML to be confirmed retrospectively in the initial bone marrow tissue
According to Pullarkat et al
, patients with associated SM and AML t(8;21) have a worse prognosis with standard chemotherapy protocols than patients with AML t(8;21).9
However, our patient is still in complete haematological remission after two years of follow up, although the polychemotherapy was much more effective (and gave a much faster response) on the AML than the mastocytosis, which persisted morphologically for a period of at least 18 months, whereas the AML showed immediate complete remission after induction phase chemotherapy. In this respect, our case confirms the experiences reported by others,17–19
and underlines the resistance of neoplastic mast cells to conventional chemotherapy. The delayed decrease of mast cell infiltration in response to chemotherapy may be explained by the fact that treatment resulted in the depletion of mast cell progenitors but not of mature mast cells. In fact, mast cells are long lived cells and any effect of chemotherapy on their immature progenitors must be expected to lead to a reduction in mast cell numbers only after several months. In this regard, it is also of interest that the last bone marrow biopsy specimen to be analysed contained the transforming D816V mutation, whereas the morphological findings were regarded as not sufficient for a diagnosis of persistent mastocytosis. In fact, this last bone marrow biopsy showed a nearly normal microarchitecture, with intact haemopoiesis and a diffuse moderate increase in loosely scattered mast cells, about 15% of which had a spindle shape appearance and less than 5% of which expressed CD25. These findings may best be interpreted as minimal residual mastocytosis.