Bone marrow neoplastic
Bone marrow - neoplastic myeloid
MDS / MPN
Juvenile myelomonocytic leukemia
Author: Nikhil Sangle, M.D.
Topic Completed: 1 August 2011
Minor changes: 20 January 2022
Revised: 31 December 2018, last major update August 2011
Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.
PubMed Search: Juvenile myelomonocytic leukemia [title] (JMML)
Table of Contents
Definition / general | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Sangle N. Juvenile myelomonocytic leukemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/myeloproliferativeJMML.html. Accessed January 28th, 2022.
Definition / general
- JMML
- Formerly called juvenile chronic myelogenous leukemia
- Resembles CMML more than CML
- 70% are children less than 3 years old, range of 1 month to teenagers
- 10% associated with neurofibromatosis 1 and deletion of NF1 gene
- Due to stem cell defect causing deranged hematopoiesis
- Varied clinical presentation may include failure to thrive, malaise, fever, bleeding, pallor, lymphadenopathy and hepatosplenomegaly; less frequently skin, lung and GI involvement; rarely CNS involvement (J Pediatr Hematol Oncol 2007;29:770)
- Most patients die of disease, although it may wax and wane
- Diagnosis: absolute monocyte count > 1 × 109/L AND < 20% blasts + promonocytes in marrow AND no Philadelphia chromosome AND no BCR-ABL AND at least two of the following: HbF increased for age, myeloid precursors in blood smear, WBC > 10 × 109/L, clonal abnormality or GM-CSF hypersensitivity of myeloid progenitors in vitro (Leukemia 2003;17:277, Table)
- Typically WBC is 20 - 30 × 109/L with granulocytes and monocytes, occasional dysplasia but not prominent
Case reports
- Related to EBV infection (Leuk Res 2008;32:181)
Treatment
- Bone marrow transplant (Blood 2005;105:410)
- Cord blood may provide graft versus leukemia effect (Pediatr Blood Cancer 2008;50:665)
- Rarely transforms to AML but fatal if untreated
- Bad prognosis if age > 2 years, high HbF and low platelet count (Blood 1997;89:3534)
Microscopic (histologic) description
- Peripheral blood: leukocytosis with neutrophilia, monocytosis, nucleated red blood cells
- Bone marrow: hypercellular with granulocytic hyperplasia, 5 - 30% monocytes, decreased megakaryocytes, blasts + promonocytes < 20%, dysplasia not prominent, reticulin fibrosis rare
- Phenotyping: no specific immunophenotypic abnormality
Microscopic (histologic) images
Images hosted on PathOut server:
Peripheral blood:
Increased leukocytes, primarily monocytes
(3 at top) and neutrophils / myelocyte and
monocytes are at lower left, also 2 late
polychromatic normoblasts
Bone marrow biopsy:
Markedly cellular marrow with numerous
myelocytes, also scattered erythroid
precursors with clear cytoplasm and
round dense nuclei, megakaryocytes are reduced
Bone marrow smear:
Numerous myelocytes
and a few monocytes,
only slightly increased
blasts
4 year old child with isolated monosomy 7 of childhood, anemia, thrombocytopenia and leukocytosis:
Peripheral blood
shows mature
monocytes and
neutrophils
Bone marrow biopsy is markedly hypercellular
with immature neutrophils and monocytes,
scattered erythroid precursors and reduced
megakaryocytes
Bone marrow smear shows
increased monocytes, promonocytes
and large multinucleated polychromatic
erythroid precursors
Stains:
Fetal hemoglobin of
peripheral blood shows
50% of cells contain
HbF (Kleihaur-Betke stain)
Positive stains
- CD68 and lysozyme helpful to identify the monocytic component
- Cytochemical stains for NSE, alpha naphthyl acetate esterase / butyrase helpful to identify monocytic cells
Molecular / cytogenetics description
Molecular description:
Cytogenetics description:
- Somatic mutations in NRAS, Kras or PTPN11 occur in 60% of cases
- PTPN11 mutations also occur in Noonan syndrome (Blood 2005;106:2183), no FLT3 activation (Haematologica 2007;92:1557)
Cytogenetics description:
- Usually normal, occasionally monosomy 7
- NO Philadelphia chromosome or BCR-ABL
Differential diagnosis
- Wiskott-Aldrich syndrome: atopic dermatitis-like eczema, no intracellular WASp expression, WASp gene mutation (J Pediatr Hematol Oncol 2007;29:836)
Additional references
