| Session: Ph- chronic myeloproliferative disease |
| Case number: 182 |
Submitter(s): Shereen Gheith, Dennis Cornfield.
Clinical history
A 45 y.o.man presented in 2/05 with WBC 16,400/uL (33% polys, 16% lymphs, 3% monos, 36% eosinophils, 11% myelocytes); Hb 13.8 g/dL, plt:206,000/uL and mild splenomegaly. In 3/05, BM demonstrated marked hypercellularity with eosinophilia (fig.1,2,3,4). Cytogenetic and FISH studies were negative for BCR/ABL. The differential diagnosis was hypereosinophilic syndrome vs an unspecified myeloproliferative disorder (MPD).He was followed expectantly until 6/05 when he developed SOB and fatigue with Hb 6.3 g/dL. PB smear showed abnormal-appearing eosinophils and nRBCs (fig.6,7). Repeat BM showed similar findings. Cytogenetic studies showed: 46, XY, t (8; 9) (p23; p24). Together with the persistent eosinophilia and markedly hypercellular BM, the diagnosis of chronic eosinophilic leukemia was made.
The patient was treated at various times with imatinib, EPO and hydroxyurea, with no significant improvement. In 4/06, he had an allogeneic BMT with excellent response. CBC 2/07 showed WBC 5,500/uL (55% polys, 36% lymphs, 6% monos, 3% eosinophils); Hb14.4 g/dl; plt 149,000/uL.
Details of gross/microscopic pathology:
1. The BM aspirate smear (fig.1,2) is markedly hypercellular. There is a marked myeloid hyperplasia, left shifted maturation and no increase in blasts. Frequent eosinophils in all stages of maturation are seen. Erythroid elements are relatively decreased in numbers. The M:E ratio is >10:1. Megakaryocytes are present.
2. The BM core biopsy (cord-like fragment; 1.8 X 0.2 cm) is submitted in Bouin's solution.
The BM biopsy (fig. 3,4) is markedly hypercellular (>95%) with marked myeloid hyperplasia, prominent eosinophilia and no increase in blasts. Erythroid elements are relatively reduced in numbers. Megakaryocytes are present with no dysplastic features. A mild increase in reticulin fibrosis is present (fig. 5).
Immunophenotype (flow cytometry/immunohistochemistry):
CD45 against SS: 89% granulocytes, 3% lymphs, 1% monocytes, and 3% cells in the blast gate (CD34% cells<1%). A subset of CD13+ myeloid cells shows reduced CD16 and CD15, suggestive of eosinophils (fig 8, 9,10).
Cytogenetics:
1. BM: 46, XY, t (8; 9) (p23; p24)
2. PB: 46, XY.
Molecular analysis:
1. FISH analyses on the PB and BM were negative for BCR/ABL.
2. FISH for the FIP1L1-PDGFRA fusion gene was negative on BM.
Interesting feature(s) of submitted case:
This case demonstrates:
1. Challenges in diagnosing a Ph(-) chronic MPD with eosinophilia.
2. The differential diagnosis of: 1) chronic MPD with eosinophilia 2) chronic eosinophilic leukemia (CEL) 3) chronic idiopathic eosinophilic syndrome.
3. The importance of cytogenetic and molecular studies in delineating the above entities.
4. The role of t(8;9) (p23; p24) as a novel PCM1-JAK2 fusion gene that further supports a role for deregulated tyrosine kinases in the pathogenesis of Ph(-)MPD.
5. The clinical course and prognosis of CEL associated with t(8; 9)(p23; p24).
Proposed diagnosis:
Chronic Eosinophilic Leukemia with t(8;9)(p23;p24).
Panel diagnosis:
agree with proposed diagnosis
Comments:
Images:
 |
Figure 1 |
 |
Figure 2 |
 |
Figure 3 |
 |
Figure 4 |
 |
Figure 5 |
 |
Figure 6 |
 |
Figure 7 |
 |
Figure 8 |
 |
Figure 9 |
 |
Figure 10 |
Back to Top
Back to Cases by Session
Back to Cases by Contact Submitter