[1492] Juvenile Myelomonocytic Leukemia: Analysis of 7 Cases According to the 2008 WHO Criteria

Brian Y Merritt, Ghadir S Sasa, Choladda V Curry, Donald H Mahoney, Andrea M Sheehan, M Tarek Elghetany. Baylor College of Medicine & Texas Children's Hospital, Houston, TX

Background: Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm seen mostly in children. It poses a diagnostic challenge since most of the diagnostic criteria proposed by the 2008 WHO Classification overlap with reactive conditions or require testing available only in a few research labs.
Design: Our pathology files over 11 years were searched. Relevant clinical and laboratory data were reviewed to include only cases that met the 2008 WHO criteria for JMML at presentation or during the disease course.
Results: Seven patients were identified, 6 meeting WHO criteria at presentation. Median age at diagnosis was 10 months (range 8 weeks-6 years). Splenomegaly was seen in all patients and hepatomegaly in 5. Peripheral blood (PB) had a median white cell count of 17.9x109/L (7.9-23.7x109/L) and a median monocytic count of 4.6x109/L (2.8-8.3x109/L). Thrombocytopenia was present in 6 with a median of 24x109/L (4-92x109/L) and thrombocytosis in one (1500x109/L). Immature granulocytes were seen in 5, and 4 had peripheral blasts (3.5-12.6%), including one with leukoerythroblastic features. Bone marrow (BM) findings included 5 with monocytosis (6.8-20%), 5 with dysplasia of one or more cell lineages, reduced megakaryocytes in 5, reticulin fibrosis in 4, and blasts (including promonocytes) ranging from 3-10%. Two had liver involvement and one lung involvement. Hemoglobin F was 3.0, 7.4, and 32.4% in 3 patients tested (normal 0-2% for age). GM-CSF hypersensitivity was detected in 2 of 2 patients. Cytogenetics and fluorescence in situ hybridization (FISH) performed on all cases showed 3 patients with abnormalities: a trisomy 21 cell line and duplication of 7p, monosomy 7, and a ring chromosome 7 with 7q31 deletion. One had a Noonan's mosaic finding of p.E76K mutation in the PTPN11 gene, and another showed NRAS mutation C.34G>A (p.G12S). Three patients died after 4 weeks, 13 months, and 5 years from diagnosis, respectively, the latter two despite receiving bone marrow transplants.
Conclusions: JMML diagnosis is difficult and requires a combination of clinical, pathologic, and molecular findings. To help distinguish JMML from reactive conditions, we recommend the inclusion of more specific diagnostic criteria, such as molecular abnormalities (NRAS, NF1, PTPN11), thrombocytopenia, splenomegaly, hepatomegaly, decreased BM megakaryocytes, BM fibrosis, BM dysplasia, and increased PB/BM blasts and promonocytes.
Category: Hematopathology

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 236, Monday Morning

 

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