Mast cell leukemia
is an extremely aggressive subtype of acute myeloid leukemia
that usually occurs de novo but can, rarely, evolve from transformation of chronic myeloid leukemia
into the more aggressive acute myeloid leukemia
. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis
. The diagnosis of acute mast cell leukemia by the WHO
criteria includes the requirement for a prevalence of 20% neoplastic mast cells
in marrow and 10% in blood. If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.
Cytochemical properties of the leukemic cells must be typical of mast cell derivation (presence of metachromatic
granules staining with alpha-naphthyl chloroacetate esterase, but not with peroxidase). Mast cell tryptase
is an enzyme contained in mast cell granules. Mast cell numbers are best estimated by tryptase immunostaining because very poorly granulated cells may stain very weakly if at all for alpha-naphthol chloroacetate esterase.
The leukemic cells usually are strongly positive for CD13
, and CD117
. Characteristically, basophil (e.g. CD11b
) and monocyte markers (CD14
) are absent. Malignant mast cells overexpress the anti-apoptosis gene, bcl-2.
Acute mast cell leukemia is a rapidly progressive disorder with leukemic mast cells in blood and in large numbers in marrow. The common signs and symptoms include fever, headache, flushing
of face and trunk. The typical cutaneous mast cell infiltrates of urticaria pigmentosa are usually not present before, during, or after diagnosis in patients who have mast cell leukemia. Symptoms include abdominal pain, bone pain, and peptic ulcer which are more prevalent than in other subtypes of acute myeloid leukemia
. These former symptoms are due to relase of a substance called histamine
mast cells. Enlargement of the liver and spleen, or hepatosplenomegaly
is characteristic. The mast cells release also many anticoagulants like heparin
which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage.
Total serum tryptase is elevated in mast cell leukemia. Normal total(alpha + beta) serum tryptase is approximately 6 micro g/L (range 0 to 11 micro g/L). Values of several hundred micro g/L are characteristic of mast cell leukemia. Plasma and urinary histamine levels are frequently elevated in mast cell leukemia. Histidine decarboxylase
(HDC) is the enzyme that catalyzes the reaction which produces histamine from histidine. Measurement of histidine carboxylase in the marrow cells of patients with mast cell leukemia is a very sensitive marker of mast cells.
Immunoglobulin E (IgE
) is important in mast cell function. Immunotherapy with anti-IgE immunoglobulin raised in sheep resulted in a transient decrease in the numbers of circulating mast cells in one patient with mast cell leukemia. Although splenectomy has led to brief responses in
patients with mast cell leukemia no firm conclusions as to the efficacy of this treatment are possible. Chemotherapy with combination of cytosine arabinoside
and either idarubicin
, or mitoxantrone
as for acute myeloid leukemia should be considered.
Acute mast cell leukemia is extremely aggressive and has a grave prognosis. In most cases, multiorgan failure including bone marrow failure develops over weeks to months. Medial survival after diagnosis is only about 6 months.