Unusual presentation of myeloid sarcoma in a case of acute promyelocytic leukemia with a cryptic PML-RARA rearrangement involving multiple sites including the atrium.

Myeloid sarcoma is an extramedullary tumor mass composed of immature myeloid cells. Myeloid sarcoma may develop de novo, concurrently with acute myeloid leukemia (AML), or at relapse. Although myeloid sarcoma can occur at any site, myeloid sarcoma involving the heart is extremely rare. Reported here is the case of a 30-year-old man, initially diagnosed with acute promyelocytic leukemia (APL) in bone marrow, who presented later with myeloid sarcoma at multiple anatomical sites (left scapula, thoracic vertebra, right atrium, and supraclavicular mass) in multiple relapses. Conventional cytogenetic studies performed on the atrial sample revealed a karyotype with additional material on the short arm of chromosome 7, at 7p22. Fluorescence in situ hybridization studies confirmed a cryptic PML-RARA fusion on the short arm of chromosome 7, as well as a second fusion on one copy of chromosome 15. With the fourth and latest relapse, molecular cytogenetic studies performed on interphase nuclei of the myeloid sarcoma specimen (a supraclavicular mass) showed evidence of six related abnormal clones with a PML-RARA fusion, suggesting clonal evolution. This represents a rare case of APL with a cryptic PML-RARA rearrangement presenting as myeloid sarcoma at multiple relapses and involving multiple anatomical sites, including cardiac atrium.

Acute myeloid leukemia with inv(16) with CBFB-MYH11, 3'CBFB deletion, variant t(9;22) with BCR-ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review.

Coexistence of inv(16) and t(9;22) is a rare chromosomal aberration, one that has been described in chronic myelogenous leukemia (CML), mainly in myeloid blast crisis, and de novo acute myeloid leukemia (AML). Approximately 14 cases have been reported, including only 1 pediatric case. Here we present the case of a 13-year-old boy with a new diagnosis of AML with some features of monocytic differentiation. Conventional cytogenetic analyses on unstimulated blood showed three related abnormal clones with inv(16) in the stemline: 46,XY,inv(16)(p13.1q22)[2]/46,idem,del(7)(q22q32)[16]/46,idem,t(9;22;19)(q34;q11.2;p13.1)[2]. Fluorescence in situ hybridization (FISH) studies on interphase nuclei and previously G-banded metaphases showed a 3'CBFB deletion and confirmed the presence of the Philadelphia chromosome in a t(9;22;19) rearrangement. Deletion 7q31 was also confirmed by interphase FISH analysis. The patient was treated with standard AML chemotherapy plus gemtuzumab as part of a clinical trial. At 10-months follow-up, he was in remission. To the best of our knowledge, this is the first description of a pediatric case of de novo AML with a stemline showing inv(16) along with 3'CBFB deletion, an abnormal clone revealing in addition a del(7)(q22q32), and another clone with a t(9;22;19)(q34;q11.2;p13.1) as an additional abnormality.

A Cryptic t(1;21;8)(p36;q22;q22) in a Case of Acute Myeloid Leukemia with Maturation.

The t(8;21)/RUNX1-RUNX1T1 is found in ~5 percent of cases of acute myeloid leukemia (AML) and in 10 percent of the prior AML with maturation (M2) category of the French-American-British (FAB) classification. While AML with t(8;21) is considered a distinct entity with a favorable prognosis, the clinical consequence of variant translocations is less well defined. In this report we described a 45 year-old male patient having a diagnosis of AML-M2 with morphologic and immunophenotypic features suggestive of t(8;21). However, the initial karyotypic analysis revealed an apparently balanced translocation between 1p36 and 8q22. Further fluorescence in situ hybridization (FISH) studies using the AML1/ETO and the p58 probes from Abbott Molecular, demonstrated a three-way translocation between chromosomes 1, 21, and 8, with single fusion of RUNX1-RUNX1T1 on the derivative chromosome 8 [t(1;21;8)(p36.1;q22;q22)]. The patient was in complete remission after induction therapy followed by consolidation. This report demonstrates the importance of FISH studies for detection of cryptic specific chromosome rearrangements that may have prognostic significance.

Un caso de leucemia mieloide aguda en un paciente con una translocación (1; 21; 8)y una sola fusión AML1-ETO / A case of water myeloid leukemia in a patient with a translocation (1, 21, 8) and one AML1-ETO fusion

The t(8;21) accounts for 5-12% of AML patients, often occurring in the younger population (1). This translocation fuses the AML 1 gene on chromosome 21q22 and the ETO gene on 8q22 resulting in a AML1-ETO hybrid transcript. Under the World Health Organization (WHO) classification, the t(8;21) is distinctly characterized under AML with recurrent aberrations with a favorable prognosis. Variant t(8;21; var) display comparable clinical manifestations compared to the classical translocation; however, they are less defined and their clinicak significance remains arguable. Complex t(8;21) variants account fo approximately 3-4% of all AML1-ETO fusion transcripts with approximately 100 variants described in the literature (1,2). In this article, we discuss a variant (8;21) translocation in AML. Chromosomal analysis of this case using conventional cytogenetics showed an apparently balanced transcolation between the short arm of chromosome 1 at 1p36 and the long arm of chromosome 8 at 8q22. Subsequent FISH studies demonstrated that there was also a fusion of the AML1 and ETO genes on the derivative chromosome 8, a key event in M2, a small ETO signal on chromosome 1, a normal ETO signal on the other homologue 8 and two AML1 signals (a small AML1 signal on the normal copy of chromosome 21). This report demonstrates how important is to do FISH studies to characterize a specific rearrangement in the management of hematological maligancies.

La translocación (8;21) se presenta en un 5-12% de casos de leucemia mieloide aguda y ocurre preponderamente en una población joven de estos pacientes. En esta translocación se fusionan los genes AML1 en el cromosoma 21q22 con el gen ETO en el cromosoma 8 en el locus 8q22 produciendo un gen híbrido AML1-ETO, el cual esta asociado a un pronóstico bastante favorable. En este artículo presentamos un paciente cuyo cariotipo, usando citogenética convencional, mostró una "translocación aparentemente balanceada" entre el brazo corto del cromosoma 1 en la banda 1p36 y el brazo largo del cromosoma 8 en la banda 8q22. Los estudios de FISH usando la sonda de dos colores y doble fusión AML1/ETO determinaron que se trataba de una translocación triple entre los cromosomas 1, 8 y 21 ya que se pudo observar una fusión AML1/ETO el cromosoma 8 derivado, el cual es el evento clave en la translocación típica (8;21). Se observó además una señal de AML1 pequeña en el cromosoma derivado 21, una copia normal completa de AML1 en el homólogo normal 21, una señal pequeña de ETO en el brazo corto del cromosoma 1 así como una copia normal de ETO en el homólogo normal 8. El presente estudio nos permite ver la importancia de FISH en la caracterización de anormalidades cromosómicas así como el monitoreo de enfermedades hematológicas.