Institution: Henry Ford Health System
Additional authors:Javier Arias-Stella, MD Kristin Hunt-Karner, MD Koichi Maeda, MD Kedar Inamdar, MD
Session: AML with myelodysplasia-related changes
HISTORY
A 22-year-old male patient with Fanconi Anemia diagnosed 5 years ago. This diagnosis was established on a bone marrow biopsy performed at a different institution, which showed hypocellular bone marrow (20% cellular) with diepoxybutane (DEB) induced chromosomal breakage by cytogenetic analysis. Additionally the patient had horseshoe kidney and bicuspid aortic valve demonstrated by radiologic studies which further supported the diagnosis of Fanconi anemia. Since his diagnosis, he has required occasional platelet transfusions. Stem cell transplantation as recommended therapy for Fanconi anemia was delayed on multiple occasions due to patient developing recurrent infections in form of gingivitis and increased dental caries that required multiple extractions.
On subsequent follow up, the patient was found with progression of his thrombocytopenia. His baseline platelet count had been around 50 K/uL during the last 3 years whereas his most recent platelet count on 06/2012 was 12, 000/uL. Other laboratory tests at that time showed WBC of 2,400/uL, hemoglobin of 9 g/dL, mean corpuscular volume of 112.1 fl, and absolute neutrophil count of 1.06 K/uL. Patient underwent bone marrow biopsy for assessment of his disease status and for evaluation of progression on 06/2012 (see details below). Clinically, the patient is still requiring occasional platelet transfusion without worsening of his symptoms and is being evaluated for stem cell transplant.DETAILS
Bone marrow biopsy fixed in Bouin’s. The 1.5 cm long core biopsy was decalcified with hydrogen chloride solution.
Core biopsy and clot section show a hypocellular bone marrow (5-10%) with decreased trilineage hematopoiesis. Scattered pockets of cells consisting predominantly of erythroid lineage and clusters of immature myeloid elements are seen. The relatively predominant erythroid component (M:E ratio of 0.7:1 on differential count) exhibits megaloblastoid changes and moderate degree of dyserythropoiesis. The myeloid series is decreased with progressive maturation and no significant dysgranulopoietic changes. Blasts are not increased (1% of differential count from aspirate smears). There are rare unremarkable megakaryocytes. Prussian blue stain shows adequate particulate iron and no ring sideroblasts.IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
CD34 is negative for increased blasts. Flow cytometry was not performed.
CYTOGENETIC FINDINGS
Karyotype: 47 XY +8. Trisomy 8 in 5 out of 20 (25%) metaphase cells analyzed.
Fluorescent in-situ hybridization (FISH) confirms the presence of trisomy 8 in 30 out of 200 (15%) interphase cells analyzed.MOLECULAR FINDINGS
Not performed.
INTERESTING FEATURES
Fanconi anemia patients have a higher risk of developing myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and solid tumors. In most of the cases, the progression to MDS is preceded by the acquisition of chromosomal abnormalities, the most common ones being gain of 1q and 3q and monosomy 7. The only cytogenetic abnormality present in this patient was trisomy 8, which is a common genetic abnormality reported in MDS. Trisomy 8 however lacks a proven prognostic value and is an uncommon finding in this setting. Although, dysplastic changes in other lineages can not be fully evaluated due to decreased numbers, the presence of dyserythropoiesis in conjunction with cytogenetic findings of trisomy 8 would allow a diagnosis of MDS in this particular case.
PROPOSED DIAGNOSIS
Myelodysplastic syndrome in the context of Fanconi Anemia.
CONSENSUS DIAGNOSIS
Fanconi anemia with trisomy 8