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Introduction

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Juvenile myelomonocytic leukaemia (JMML) is a rare myelodysplastic/myeloproliferative haematological neoplasm that occurs predominantly in young children, particularly children with one of a number of predisposing inherited conditions [1-4]. Both neurofibromatosis type 1 (NF1 mutation) and Noonan syndrome (PTPN11 mutation) predispose to JMML. Somatic mutations in the same genes are present in other patients with this type of leukaemia.

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Clinical features

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Most affected children are under the age of three years but the age of presentation ranges from early infancy to adolescence. Boys are affected about twice as often as girls. Children present with systemic symptoms and clinical features resulting from anaemia, neutropenia and thrombocytopenia. Hepatomegaly and splenomegaly are usually marked and tonsillar enlargement is common. Lung infiltration leads to cough, tachypnoea and sometimes death from pulmonary insufficiency [5]. In addition, there may be poor growth, fever, an eczematous or maculopapular rash, xanthomas, bloody stools and lymphadenopathy. Rarely central nervous system infiltration has occurred [6]. Children with neurofibromatosis type 1 may have café-au-lait spots, and children with Noonan syndrome display abnormal facies and cardiac anomalies.

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Haematological and pathological features

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There is anaemia and thrombocytopenia. The anaemia is normocytic (the majority), macrocytic (a minority) or microcytic (a small minority). The white cell count is moderately to markedly elevated (Figs 7.1, 7.2, 7.3). The neutrophil count is usually increased. The monocyte count is increased, a count of at least 1 × 109/l being one of the criteria for diagnosis of this condition. There are increased numbers of neutrophil precursors, including some blast cells (usually less than 5% and by definition always less than 20%). Eosinophilia and basophilia are less prominent than in Philadelphia (Ph)-positive chronic myeloid leukaemia. There are usually circulating nucleated red cells. Neutrophils may be dysplastic and monocytes may appear immature or have an increased nucleocytoplasmic ratio.

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Figure 7.1

Peripheral blood film from a child with JMML showing a neutrophil, a promyelocyte and abnormal monocytes. May-Grünwald-Giemsa (MGG), high power.

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Figure 7.2

Peripheral blood film from a child with JMML showing a neutrophil and highly abnormal monocytes, same child as Fig. 7.1. MGG, high power.

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Figure 7.3

Peripheral blood film from a child with JMML showing a dysplastic neutrophil and several blast cells. MGG, high power.

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The bone marrow is hypercellular, due to increased granulopoiesis and, to a lesser extent, increased monocyte production (Fig. 7.4). Dyserythropoiesis and dysgranulopoiesis are common but Auer rods are not seen. Megakaryocytes are often decreased and may be dysplastic. Blast cells (plus promonocytes) are, by definition, less than 20%.

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