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 of the immediate allergic reaction via high affinity receptors for IgE. Most varients of systemic mast cell disease are clonal and a somatic mutation of c-KIT, the proto-oncogene that encodes the receptor for stem cell factor, is usually present. These mutations lead to constitutive activation 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 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. 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 /Flushing and Itching Low back/muscle/bone pain(osteoporosis)/ Compression of nerves by bone. Peptic ulcers / Hypotension. Anemia.

 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 of metachromatic 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. 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. 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.