| Session: Myelodysplastic syndrome |
| Case number: 097 |
Submitter(s): Tove V. Isaacson, Charles F. Timmons.
Clinical history
An 18-year-old male, born with no thumbs and diagnosed with Fanconi anemia at age nine, presented to the emergency department with intractable nose bleeds. A complete blood count included the following data: WBC 2.4 K/mm3, RBC 2.24 M/mm3, HGB 5.9 g/dL, HCT 19.7%, MCV 87.7 fl, platelets 101 K/mm3. Review of a peripheral blood smear revealed occasional blasts. A bone marrow biopsy was performed for further evaluation.
Details of gross/microscopic pathology:
The peripheral blood smear showed marked anisopoikilocytosis and polychromatophilia. Circulating nucleated red blood cells had occasional megaloblastoid morphology. Dysplasia in neutrophils included hypogranulation and hyposegmentation. Many platelets were large and hypogranular. Circulating micromegakaryocytes were noted. Blasts observed were intermediate to large sized cells with small amounts of gray cytoplasm and round to oval nuclei with immature chromatin and variably prominent nucleoli. A differential count revealed 3% blasts, 42% segmented neutrophils, 43% lymphocytes, 12% monocytes and 6 nRBC/100 WBC.
The aspirate smear was aspicular and hemodilute. A differential count revealed 1% blasts, 43% neutrophils and granulocytic precursors, 17% erythroid precursors, 33% lymphocytes, 6% monocytes and 1% eosinophils.
The bone marrow core biopsy was 100% cellular. Megakaryocytes appeared increased in number with several small, hypolobate forms noted. Granulocytes showed progressive maturation. There was mild erythroid expansion. Immature blast forms did not appear increased.
Immunophenotype (flow cytometry/immunohistochemistry):
Flow cytometry found no definitive evidence of a hematolymphoid malignancy.
A reticulin stain performed on a bone marrow biopsy section revealed marked reticulin fibrosis.
Cytogenetics:
Cytogenetic analysis demonstrated the following karyotype: 46,XY,trp(1)(q12,q32).
Molecular analysis:
At 9 years of age, DEB (diepoxybutane) induced chromosome breakage studies revealed increased spontaneous and DEB-induced breakage of the patient's metaphase spreads, a diagnostic feature of Fanconi anemia. Although an attempt was made to identify the mutated gene complementation group, poor growth of in vitro cultured cells precluded further analysis.
Interesting feature(s) of submitted case:
Patients with Fanconi anemia have a median survival of approximately 30 years. Bone marrow failure is a major early event which occurs in most patients within the first ten years of life, and evolution into myelodysplastic syndrome and/or acute myeloid leukemia (the two most common malignancies in patients with Fanconi anemia) both serve as clinical predictors of outcome. The most frequent chromosomal abnormalities noted in Fanconi anemia-associated leukemias are duplication of 1q and monosomy 7.
Proposed diagnosis:
Fanconi anemia with evolution to myelodysplastic syndrome.
Panel diagnosis:
agree with proposed diagnosis
Comments:
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