Mast cell leukemia

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.{{cite journal |vauthors=Daniel MT, Flandrin G, Bernard J |title=[Acute mast-cell leukemia. Cytochemical and ultrastructural study, about a particular case (author's transl)] |language=fr |journal=Nouv Rev Fr Hematol |volume=15 |issue=3 |pages=319–32 |year=1975 |pmid=54900 }}{{cite journal |vauthors=Le Cam MT, Wolkenstein P, Cosnes A, etal |title=[Acute mast cell leukemia disclosed by vasomotor flushing] |language=fr |journal=Ann Dermatol Venereol |volume=124 |issue=9 |pages=621–2 |year=1997 |pmid=9739925 |url=http://www.masson.fr/masson/58938}} 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.{{cite journal |vauthors=Travis WD, Li CY, Hoagland HC, Travis LB, Banks PM |title=Mast cell leukemia: report of a case and review of the literature |journal=Mayo Clin. Proc. |volume=61 |issue=12 |pages=957–66 |date=December 1986 |pmid=3095598 |doi=10.1016/s0025-6196(12)62636-6}} 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 release of a substance called histamine from neoplastic mast cells.{{cite journal |vauthors=Valent P, Sperr WR, Samorapoompichit P, etal |title=Myelomastocytic overlap syndromes: biology, criteria, and relationship to mastocytosis |journal=Leuk. Res. |volume=25 |issue=7 |pages=595–602 |date=July 2001 |pmid=11377685 |doi=10.1016/S0145-2126(01)00040-6}} 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.{{cite journal |vauthors=Cather JC, Menter MA |title=Red-brown skin lesions and pruritus |journal=Proc (Bayl Univ Med Cent) |volume=13 |issue=3 |pages=297–9 |date=July 2000 |pmid=16389403 |pmc=1317061 |doi=10.1080/08998280.2000.11927693 }} Involvement of the bone can lead to osteoporosis. Abdominal ultrasound or computerized tomography (CT) scanning is used to look for hepatosplenomegaly and lymphadenopathy. Plain radiography and bone densitometry can be used to assess bone involvement and the presence of osteoporosis. Endoscopy and biopsy can be useful if gut involvement is suspected.{{cite book |vauthors=Hoffbrand AV, Catovsky D, Tuddenham E |title=Postgraduate Haematology |publisher=Blackwell |year=2005 |edition=5th}}

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).{{cite book |vauthors=Kufe D, etal |title=Holland Frei Cancer Medicine |publisher=BC Decker |year=2000 |edition=5th}} 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, CD33, CD68, and CD117. Characteristically, basophil (e.g. CD11b, CD123) and monocyte markers (CD14, CD15) are absent. The cells usually express CD2 and CD25.{{cite journal |author=Valent P |title=1995 Mack-Forster Award Lecture. Review. Mast cell differentiation antigens: expression in normal and malignant cells and use for diagnostic purposes |journal=Eur. J. Clin. Invest. |volume=25 |issue=10 |pages=715–20 |date=October 1995 |pmid=8557056 |doi=10.1111/j.1365-2362.1995.tb01948.x|s2cid=23872236 }} Malignant mast cells overexpress the anti-apoptosis gene, bcl-2.{{cite journal |vauthors=Cerveró C, Escribano L, San Miguel JF, etal |title=Expression of Bcl-2 by human bone marrow mast cells and its overexpression in mast cell leukemia |journal=Am. J. Hematol. |volume=60 |issue=3 |pages=191–5 |date=March 1999 |pmid=10072109 |doi=10.1002/(SICI)1096-8652(199903)60:3<191::AID-AJH4>3.0.CO;2-Y|doi-access=free }} A mutation called KIT mutation is detected in most patients.{{cite book |editor=Ansell SM |title=Rare Hematological Malignancies |publisher=Springer |series=Cancer Treatment & Research |year=2008 }}

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.{{cite journal |vauthors=Sperr WR, Jordan JH, Fiegl M, etal |title=Serum tryptase levels in patients with mastocytosis: correlation with mast cell burden and implication for defining the category of disease |journal=Int. Arch. Allergy Immunol. |volume=128 |issue=2 |pages=136–41 |date=June 2002 |pmid=12065914 |doi=10.1159/000059404|s2cid=42677668 }} 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.{{citation|vauthors=Krauth MT, Agis H, Aichberger KJ, etal |title=Histidine carboxylase (HDC) as novel marker of immature neoplastic mast cells in systemic mastocytosis |publisher=Abstracts of the American Society of Hematology 46th Annual Meeting. December 4–7, 2004, San Diego, California, USA |journal=Blood |volume=104 |issue=11 Pt 2 |pages=272b |date=November 2004 |doi=10.1182/blood.V104.11.4755.4755 |pmid=15562525 }}

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.{{cite journal |vauthors=Ribeiro I, Carvalho IR, Fontes M, etal |title=Eosinophilic leukaemia with trisomy 8 and double gammopathy |journal=J. Clin. Pathol. |volume=46 |issue=7 |pages=672–3 |date=July 1993 |pmid=8157759 |pmc=501401 |doi=10.1136/jcp.46.7.672}} Although splenectomy has led to brief responses in patients with mast cell leukemia,{{cite journal |vauthors=Dalton R, Chan L, Batten E, Eridani S |title=Mast cell leukaemia: evidence for bone marrow origin of the pathological clone |journal=Br. J. Haematol. |volume=64 |issue=2 |pages=397–406 |date=October 1986 |pmid=3096368 |doi=10.1111/j.1365-2141.1986.tb04133.x|s2cid=9763026 }} no firm conclusions as to the efficacy of this treatment are possible. Chemotherapy with combination of cytosine arabinoside and either idarubicin, daunomycin, or mitoxantrone as for acute myeloid leukemia has been used. Stem cell transplantation is an option, although no experience exists concerning responses and outcome.

Acute mast cell leukemia is extremely aggressive and has a grave prognosis. In most cases, multi-organ failure including bone marrow failure develops over weeks to months.{{cite book |vauthors=Hoffman R, Benz E, Shattil S, Furie B, Cohen H |title=Hematology: Basic Principles and Practice |publisher=Churchill Livingstone |year=2004 |edition=4th}} Median survival after diagnosis is only about 6 months.

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{{Medical resources

| DiseasesDB = 30102

| ICD10 = {{ICD10|C|94|3|c|81}}

| ICD9 = {{ICD9|207.8}}

| ICDO = {{ICDO|9742|3}}

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| MeshID = D007946

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{{Myeloid malignancy}}

Category:Rare cancers

Category:Acute myeloid leukemia