| Session: Ph- chronic myeloproliferative disease |
| Case number: 088 |
Submitter(s): Christine F. Garcia, Jason Hyde, Carla Wilson.
Clinical history
3 year old male with a 4 month history of pancytopenia and hepatosplenomegaly. No prior medication use, malignancy, or Down's syndrome. Secondary causes of myelofibrosis (ie ostepetrosis) were excluded. He underwent 3 bone marrow biopsies with similar findings. Current CBC counts as follows: WBC 1.5 K/uL with segs 12%, bands 4%, lymphs 76%, monos 7%, eos 1%, Hgb 8.3 gm/dL, Hct 24.3%, MCV 84.7 fL, RDW 13.7, platelets 5 K/uL.
Details of gross/microscopic pathology:
Peripheral blood smear: normochromic normocytic anemia, with few teardrop and occasional nucleated red blood cells; severely decreased leukocytes with marked neutropenia; no circulating blasts, toxic and/or dysplastic changes; platelets markedly decreased with occasional large forms.[figure1]Bone marrow aspirate smears & touch preparations (bilateral): paucicellar, but with complete maturation of the myeloid and erythroid percursors; no increase in blasts.[figure2]Bilateral bone marrow biopsies (formalin-fixed): The bone marrow cellularity ranges from 0-40% with marked hypocellularity overall. The marrow space is replaced with fibrosis with a few pockets of maturing myeloid and erythroid precursors. Increased number and dilitation of marrow sinuses is noted, as are small clusters of megakarocytes, some of which exhibit atypical morphology. The bony trabeculae are osteosclerotic.[figure3][figure4][figure5]Reticulin stain shows marked reticulin fibrosis.[figure9]
Immunophenotype (flow cytometry/immunohistochemistry):
Flow cytometric studies were performed and detected less than 1% CD34+ blasts. Polytypic B cells comprise 8% of total cells with a kappa:lambda ratio of 1.2:1; approximately 2% of total cells had immunophenotypic characteristics of hematogones. T cells comprise 20% of total cells with a CD4:CD8 ratio of 1.5:1.
Immunohistochemical studies on the bone marrow biopsy section reveal no increase in CD34+ mononuclear cells, however highlight increased neovascularization. CD61 and Factor VIII highlight megakaryocytes, which form small clusters. Rare CD20+ small B cells and scattered small CD3+ T cells are noted; an immunostain for TdT is negative. Tryptase and CD117 stain occasional individually dispersed mast cells in the fibrotic areas. Myeloperoxidase highlights the myeloid predominance within the residual hematopoietic elements.[figure6][figure8][figure7]
Cytogenetics:
Cytogenetic analysis: normal male karyotype (46 XY).
Molecular analysis:
JAK2 mutation analysis was attempted on the paraffin-embedded block however the analysis failed due to insufficient DNA.
Interesting feature(s) of submitted case:
Idiopathic myelofibrosis (IMF) is rare in children with only a few cases reported. Although the diagnostic pathologic findings are similar in adults and children, a less aggressive disease course has been described in children, and reports have suggested that pediatric IMF may represent a distinct clinical-pathological entity as compared with adult IMF.
Proposed diagnosis:
Pediatric idiopathic myelofibrosis.
Panel diagnosis:
Reactive toxic or refractory cytopenia of childhood.
Comments:
Panel comments: JAK2 analysis would be of value.
Images:
 |
Figure 1 |
 |
Figure 2 |
 |
Figure 3 |
 |
Figure 4 |
 |
Figure 5 |
 |
Figure 6 |
 |
Figure 7 |
 |
Figure 8 |
 |
Figure 9 |
Back to Top
Back to Cases by Session
Back to Cases by Contact Submitter