| Session: Ph- chronic myeloproliferative disease |
| Case number: 148 |
Submitter(s): Robert P. Hasserjian.
Clinical history
61 year old woman who developed recurrent skin and mouth infections in 2000 and was found to be neutropenic. Neutropenia persisted and the patient has been dependent on G-CSF support since 2002. Thrombocytopenia, anemia, and mild splenomegaly (spleen dimension 14 cm) developed in 2005 and she became transfusion-dependent. There is no family history of hematologic disorder. The patient is otherwise healthy without lymphadenopathy. The patient has been on no medications aside from G-CSF and erythropoietin.
CBC from 2006 (on G-CSF): WBC 5.4 x 109/L (57% polys, 1% basos, 28% lymphs, 14% monos), HGB 11.5 g/dL, PLT 76 x 109/L. MCV 87.8 fL.
Details of gross/microscopic pathology:
A bone marrow sample from 2000 was hypocellular (30% cellular) with trilineage hematopoiesis, increased early myeloid elements, and multiple lymphoid aggregates (Figure 1). Multiple subsequent bone marrow biopsies between 2000-2005 demonstrated increasing cellularity and progressive reticulin fibrosis. A bone marrow sample from 2005 (slides submitted) is 95% cellular (Figure 2) with grade 3+/4 reticulin fibrosis (Figure 3). A trichrome stain failed to reveal collagen fibrosis. Megakaryocytes are increased with focal clustering and only occasional forms with enlarged, hyperlobated nuclei (Figure 4). Multiple lymphoid aggregates are present (Figure 5), some paratrabecular, composed of a mixture of CD2+ and CD20+/PAX5+ lymphocytes (Figure 6,7). The T-cells are predominantly CD4+, with fewer CD8+ cells. Review of the peripheral smear revealed some hypogranulated neutrophils; there was no leukoerythroblastosis. The bone marrow aspirate was a 'dry tap'; an aspirate smear from 2003 revealed normal myeloid and erythroid maturation with only rare dyserythropoietic cells. There were no ringed sideroblasts on an iron stain.
Immunophenotype (flow cytometry/immunohistochemistry):
Flow cytometry on peripheral blood and on multiple previous bone marrow samples failed to reveal a monotypic B-cell or abnormal T-cell population.
Cytogenetics:
Bone marrow karyotype on multiple occasions: 46, XX.
Molecular analysis:
TCR and IgH gene rearragement studies on peripheral blood are negative. Peripheral blood is negative for JAK2 V617F mutation.
Interesting feature(s) of submitted case:
This case raises the differential of chronic idiopathic myelofibrosis (CIMF), MDS with fibrosis, an unclassified MDS/MPD, and bone marrow lymphoma. The lack of prominent dysplasia (difficult to evaluate in this patient dependent on growth factor therapy) is against MDS, while the relatively normal megakaryocyte morphology and only minimal splenomegaly after 6 years of disease are against CIMF. There is no evidence of lymphoma based on multiple flow cytometric and molecular studies of bone marrow and peripheral blood. Autoimmune myelofibrosis typically occurs in patients with known autoimmune disease, but can occur in patients without such a history (Pullarkat V et al. Am J Hematol 2003; 72: 8).
Proposed diagnosis:
Progressive bone marrow fibrosis, likely immune-mediated (autoimmune myelofibrosis).
Panel diagnosis:
agree with proposed diagnosis
Comments:
PowerPoint:
Presentation Link
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