Institution: Penn State Hershey Medical Center
Additional authors:Michael G. Bayerl, M.D., Jozef Malysz, M.D.
Session: AML with myelodysplasia-related changes
HISTORY
A previously healthy 12 year-old African American male presents with several days of cough, vomiting and high fevers and was found to be pancytopenic: WBC 1.3 K/dL, Hgb 6.4 g/dL, MCV 94.4 fL, Plt 69 K/dL. His family history is significant for a half-sister who was diagnosed with monosomy 7 associated acute myeloid leukemia 2 years previously.
DETAILS
Bone marrow aspirate and clot section: Hypocellular marrow with increased and highly dysplastic megakaryocytes forming clusters, decreased myeloid lineage, no increase in blasts but limited dysplastic maturation to segmented neutrophils and decreased erythroid lineage with megaloblastic maturation and occasional irregular budding.
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Immunohistochemistry for myeloperoxidase, CD68 and lysozyme highlight the markedly decreased myelopoiesis. Flow cytometry did not demonstrate an increase in blasts or a phenotypically abnormal population of cells.
CYTOGENETIC FINDINGS
45,XY,-7[8]/90,XXYY,-7,-7[1]/46,XY[11] FISH analysis confirmed the monosomy 7 clone.
MOLECULAR FINDINGS
None.
INTERESTING FEATURES
Familial monosomy 7 syndrome associated with myeloid neoplasm is extremely rare, with only 14 kindreds reported. It follows an autosomal dominant inheritance pattern with variable penetrance. The precise molecular mechanism of this disease is uncertain at this time. In this case, since the siblings did not share the same father, the mother is an obligate carrier.
PROPOSED DIAGNOSIS
Familial monosomy 7 syndrome associated myelodysplastic syndrome.
CONSENSUS DIAGNOSIS
Familial monosomy 7 syndrome associated with childhood myelodysplastic syndrome
| Bone marrow aspirate: Numerous small and/or mononuclear megakaryocytes, few erythoid precursors and virtually no myeloid precursors. |  |
| Bone marrow aspirate smear: Megaloblastic erythropoieis. |  |
| Bone marrow aspirate: Extremely limited granulopoiesis including a bilobed neutrophil. |  |
| Bone marrow clot section: Hypocellular marrow with increased, clustered and dysplastic megakaryocytes, reduced erythropoiesis and virtually no myelopoiesis. |  |