Myelodysplastic Syndrome Case 158
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1 Myelodysplastic Syndrome Case 158 Dong Chen MD PhD Division of Hematopathology Mayo Clinic
2 Clinical History 86 year old man Persistent borderline anemia and thrombocytopenia. His past medical history was significant for coronary artery disease, stroke and epilepsy. A bone marrow study was performed to evaluate his hematological status.
3 Hematology Lab Results CBC: Hgb: 13.0 g/dl Hct: 38.1% MCV: 88.3 fl RDW: 15.7% WBC: 7.7 x10(9)/l PLT: 102 x10(9)/l WBC Differential (%): Neutrophils 63 Lymphocytes 21 Monocytes 13 Eosinophils 2 Basophils 1 NRBC: 0 Blast: 0
4 Peripheral Blood Smear 400X
5 Bone Marrow Smear 600X Bone Marrow Aspirate and Biopsy
6 Iron Stain 600X BE/CLE Stain 600X
7 Bone Marrow Biopsy 100X
8 Bone Marrow Biopsy 400X
9 CD34 (200X) CD61 (100X) MPO (100X) CD163 (200X)
10 Cytogenetic Study 45,X,-Y,add(21)(q22) [16]/46,XY [4]
11 Possible t(1;21)(p35-36;q22) FISH Study
12 The Proposed Diagnosis Slightly hypercellular bone marrow (40%) with no morphologic or immunohistochemical features of myelodysplasia. Clonal cytogenetic abnormality of uncertain clinical significance.
13 Four years later, this patient developed high grade MDS or AML and died. Bone Marrow Biopsy Follow Up Myelobasts in Periperal Blood (10-15%)
14 The Unique Features Unexplained persistent cytopenia. No clear morphologic evidence of MDS. Definitive clonal cytogenetic abnormalities. Unclassifiable by either WHO or FAB classification system. Progression to overt MDS/AML.
15 Pertinent Questions Prevalence? Clinical outcome? Explanations? What to do?
16 Recurrent Chromosomal Abnormalities in Patients with Morphologically Unremarkable Bone Marrows Patients 7514 BMs with Cytogenetic Studies Other (including +15) 27% Del(20q) or monosomy 20 18% Monosomy 7, der(1;7), del(7q) 15% Complex 20% Del(13q) 4% Del(5q) or a translocation involving 5q 7% Trisomy 8 9% Steensma PD. et al. Leukemia Research, (3):235-42
17 The Clinical Outcome Patients (55) Dead (22) 20 months F/U Alive (32) AML (1) Cytopenia (6) Other Causes (16) Not Followed (22) Followed (10) AML (1) MDS (2) Persistent Cytopenia (7) Steensma PD. et al. Leukemia Research, (3):235-42
18 Possible Explanations The chromosomal abnormalities precede the detectable bone marrow abnormalities. Amount of disease in the bone marrow is minimal. Inadequate bone marrow sampling for morphologic component.
19 Cytogenetic Abnormality Malignancy A fleeting abnormality. May not associate with hematological malignancy, e.g. -Y, +15. Hanson CA. et al. Isolated trisomy 15: A clonal chromosme abnormality in bone marrow with doubtful hematologic significance. Am J Clin Pathol (in press)
20 Conclusion What to do? A BM cytogenetic analysis is necessary in the diagnostic evaluation of patients with persistent unexplained cytopenias even if the bone marrow appears morphologically unremarkable. An abnormal cytogenetic result should not be automatically equated to a malignant process. Continued follow-up is critical.
21 Acknowledgement Curtis A. Hanson MD Division of Hematopathology, Mayo Clinic David P. Steensma MD Division of Hematology-Oncology, Mayo Clinic Gordon W. Dewald PhD and Kazunori Kanehira MD Division of Laboratory Genetics, Mayo Clinic
22 Reference Clonal cytogenetic abnormalities in bone marrow specimens without clear morphologic evidence of dysplasia: a form fruste of myelodysplasia? Steensma PD, et. al. Leukemia Research. 2003, 27(3): Genetic testing in the myelodysplastic syndromes: molecular insights into hematologic diversity. Steensma DP. 2005, 80(5): Identical fusion transcript associated with different breakpoints in the AML1 gene in simple and variant t(8;21) acute myeloid leukemia. de Greef GE, et. al. Leukemia. 1995, 9(2):282-7 Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Espanol de Citogenetica Hematologica. Sole F. et al. Br J Haematol. 2000, 108(2): WHO Pathology and Genetics : Tumors of Haematopoietic and Lymphoid Tissue Isolated trisomy 15: A clonal chromosme abnormality in bone marrow with doubtful hematologic significance. Hanson CA. et al. Am J Clin Pathol (in press)
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