A “complicated” fracture: a Philadelphia chromosome-positive myeloid sarcoma of the bone

Abstract

Dear Editor, In April 2009, a 19-year-old male presented with progressive pain on his left upper arm. A MRI scan of the arm showed a large tumor of the distal left humerus (Fig. 1a). Because an osteosarcoma was suspected, a biopsy was performed. After the biopsy, the patient presented with a fracture of his arm as a result of minor trauma. This fracture was managed conservatively with an upper arm cast. The biopsy revealed necrotic bone fragments with an infiltration of myeloblasts admixed with immature eosinophils; hence, the diagnosis of a myeloid sarcoma (MS) was established. Besides the pain in his arm, the patient had no complaints, especially no fever, night sweats, weight loss, hemorrhage, or anemia. On physical examination, neither lymphadenopathy and hepatosplenomegaly nor neurological signs were noticed. His peripheral blood counts were normal. A PET scan did not show any other bone lesion. On histological examination, the MS consisted of myelo/monoblasts with expression of lysozyme, partly weak myeloid peroxidase (MPO), and focally CD34 and CD117. A bone marrow aspirate was performed to exclude acute myeloid leukemia (AML). Morphology of the bone marrow did not support a diagnosis of AML or chronic myeloid leukemia (CML), although with flow cytometric immunophenotyping (IPT), a small population (2 %) of aberrant myeloblasts expressing CD15, CD34, and CD117 were found. Intriguingly, cytogenetic analysis of the bone marrow aspirate showed a Philadelphia chromosome (t(9;22)(q34;q11.2)) in 2 of 13 analyzed cells. Subsequent fluorescence in situ hybridization on the tumor biopsy showed that the blasts harbored the BCR-ABL fusion gene (Fig. 1b). PCR performed on peripheral blood and bone marrow showed BCR-ABL levels of 3.3×10 and 1.5×10 copies/ml, respectively. Because of the bad prognosis, the patient was treated with intensive chemotherapy followed by allogeneic stem cell transplantation (SCT) with peripheral blood stem cells from a matched unrelated donor. The therapy was complemented with local radiotherapy of his left arm. During his treatment, the left arm recovered swiftly, and at the time of SCT, he was no longer depending on the cast. Now 2 years after SCT, he is still in remission with an undetectable BCR-ABL level. MS is a rare disease that is reported in 2.5–9.0 % of patients with AML. It can occur concomitantly, following or, rarely, antedating the onset of systemic AML [1]. MS can also occur in the presence of other hematological diseases such as myelodysplastic syndrome and myeloproliferative neoplasia, including CML [2]. Certain known cytogenetic abnormalities, in particular t(8;21), have been associated with a higher incidence of MS [1, 2]. However, the presence of a Philadelphia chromosome t(9;22) is extremely rare and virtually no reports exist on cases in AML with the remainder almost exclusively occurring during CML blast crisis [2]. The phenotype of MS is mostly monoblastic or myelomonocytic, often expressing CD34, CD68, CD99, CD117, MPO, and TdT [2]. In our patient, the MS had this common L. F. J. van Groningen (*) :W. J. F. M. van der Velden Department of Hematology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands e-mail: l.vangroningen@aig.umcn.nl