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Mastocytosis Mast cell leukemia

Mastocytosis is a heterogeneous group of diseases characterised by abnormal proliferation

of mast cells in one or more organ systems, including skin, bone marrow, liver, spleen and

lymph nodes.Median age of systemic mastocytosis 5060 years;

Pathogenesis

Mast cells are derived from pluripotential haemopoietic dells and are the effector cells ofthe immediate allergic reaction via high affinity receptors for IgE. Most varients of systemic

mast cell disease are clonal and a somatic mutation ofc-KIT, the proto-oncogene that

encodes the receptor for stem cell factor, is usually present. These mutations lead to

constitutiveactivation of KIT which causes mast cell proliferation and prevents mast cell

apoptosis.

Clinical symptoms are due to the release of mast cell mediators (including histamine,

tryptase, heparin, TNF-a, PGD2, cytokines and chemokines) which have both local and

systemic effects, and to organ infiltration.

WHO classification of mast cell disease (mastocytosis)

Cutaneous mastocytosis.

Indolent systemic mastocytosis.

Systemic mastocytosis with associated clonal, haematological non-mast

cell lineage disease.

Aggressive systemic mastocytosis.

Mast cell leukaemia. Mast cell sarcoma.

Extracutaneous mastocytoma.

Mast cell leukemia

Is an extremely aggressive subtype ofacute myeloid leukemia that usually occurs de novo

but can, rarely, evolve from transformation ofchronic 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 ofsystemic mastocytosis.

Risk Factors

One-third of patients with malignant mastocytosis acute leukemia develop mast cell

leukemia.

Clinical course

Some patients do not have any symptoms.

Common Signs & Symptoms

Fever/ Weight loss/ Weakness /Flushingand Itching

Low back/muscle/bone pain(osteoporosis)/ Compression of nerves by bone. Peptic ulcers / Hypotension.

Anemia.

http://en.wikipedia.org/wiki/Acute_myeloid_leukemiahttp://en.wikipedia.org/wiki/Chronic_myeloid_leukemiahttp://en.wikipedia.org/wiki/Acute_myeloid_leukemiahttp://en.wikipedia.org/wiki/Systemic_mastocytosishttp://en.wikipedia.org/wiki/Systemic_mastocytosishttp://en.wikipedia.org/wiki/Acute_myeloid_leukemiahttp://en.wikipedia.org/wiki/Chronic_myeloid_leukemiahttp://en.wikipedia.org/wiki/Acute_myeloid_leukemia

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The mast cells release also many anticoagulants like heparin which can lead to serious

bleeding. Liver and splenic dysfunction also contributes to hemorrhage.

Hepatosplenomegaly &Peripheral Lymphadenopathy.

Diagnosing Mast Cell Leukemia

Mast cells are typically 10 to 15 m in diameter, have a round or oval nucleus, and contain

distinctive cytoplasmic granules that are particularly avid for metachromatic dyes.Mast cell leukaemia: defined by 20% MC in BM aspirate and 10% in PB; diffuse infiltration

on trephine biopsy. If the mast cells represent less than 10% of blood cells, the tumor is

called "aleukemic" mast cell leukemia.

Cytochemistry

Cytochemical properties of the leukemic cells must be typical of mast cell derivation

(presence ofmetachromatic granules staining with alpha-naphthyl chloroacetate esterase,

but not with peroxidase).Mast cell tryptase is an enzyme contained in mast cell granules.

Tumor Markers

The leukemic cells usually are strongly positive for CD13, CD33, CD68, and CD117.

Characteristically, basophil (e.g. CD11b, CD25, CD123) and monocyte markers (CD14, CD15)

are absent. The cells usually express CD2 and CD25.

Biochemistry

Total serum tryptase is elevated in mast cell leukemia. (normal 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. Histidinedecarboxylase (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.

Treatment

Because this disease is so rare, standards for treatment do not exist.

Common Treatment Options

Chemotherapy with cytosine arabinosides.

Immunotherapy with antihuman IgE.

Other Treatment Options

A splenectomy has shown positive results in some patients but more studies should be

conducted to prove its value conclusively.

Stem cell transplants might also prove beneficial.

Bone marrow transplant

Prognosis

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.

http://en.wikipedia.org/wiki/Heparinhttp://en.wikipedia.org/wiki/Metachromatichttp://en.wikipedia.org/wiki/Tryptasehttp://en.wikipedia.org/wiki/CD13http://en.wikipedia.org/wiki/CD33http://en.wikipedia.org/wiki/CD68http://en.wikipedia.org/wiki/CD117http://en.wikipedia.org/wiki/CD11bhttp://en.wikipedia.org/wiki/CD25http://en.wikipedia.org/wiki/CD123http://en.wikipedia.org/wiki/CD14http://en.wikipedia.org/wiki/CD15http://en.wikipedia.org/wiki/CD2http://en.wikipedia.org/wiki/CD25http://en.wikipedia.org/wiki/Histidine_decarboxylasehttp://en.wikipedia.org/wiki/Histidine_decarboxylasehttp://en.wikipedia.org/wiki/Histidine_decarboxylasehttp://en.wikipedia.org/wiki/Histidine_decarboxylasehttp://en.wikipedia.org/wiki/CD25http://en.wikipedia.org/wiki/CD2http://en.wikipedia.org/wiki/CD15http://en.wikipedia.org/wiki/CD14http://en.wikipedia.org/wiki/CD123http://en.wikipedia.org/wiki/CD25http://en.wikipedia.org/wiki/CD11bhttp://en.wikipedia.org/wiki/CD117http://en.wikipedia.org/wiki/CD68http://en.wikipedia.org/wiki/CD33http://en.wikipedia.org/wiki/CD13http://en.wikipedia.org/wiki/Tryptasehttp://en.wikipedia.org/wiki/Metachromatichttp://en.wikipedia.org/wiki/Heparin

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