Limits...
Promyelocytic Leukemia with No Retinoic Acid Receptor Alpha Abnormality but with RUNX1T1 Insertion to Chromosome 7q: A Classification and Management Dilemma.

Overholt K, Guinipero TL, Heerema NA, Loken MR, Kahwash SB - Case Rep Hematol (2015)

Bottom Line: In this report, we describe the case of a 2-year-old boy who presented with bone pain and was found to have pancytopenia.Gene sequencing results became available after initiating therapy but were not informative.The diagnostic challenges and urgent management issues this unusual case raises may justify including it, along with similar cases, in a separate subtype of acute myeloid leukemia (AML) in future classifications.

View Article: PubMed Central - PubMed

Affiliation: Hematology/Oncology and Blood and Marrow Transplant, Nationwide Children's Hospital, Columbus, OH 43205, USA.

ABSTRACT
A case of acute promyelocytic leukemia (APL) with RUNX1T1 insertion to 7q is described and compared to reported cases of APL with negative retinoic acid receptor alpha (RARA) abnormality. In this report, we describe the case of a 2-year-old boy who presented with bone pain and was found to have pancytopenia. Bone marrow examination showed morphologic and immunophenotypic findings typical of APL, but conventional cytogenetics, fluorescence in situ hybridization (FISH), and real-time polymerase chain reaction (RT-PCR) showed no evidence of RARA rearrangements. The only cytogenetic abnormality found was a small insertion in 7q, and three copies of RUNX1T1. Gene sequencing results became available after initiating therapy but were not informative. We describe the rarity of such cases and discuss how the typical morphologic and immunophenotypic findings of APL, coupled with the definite absence of RARA rearrangement (by FISH and RT-PCR), present a diagnostic and classification dilemma, raising the possibility of an unknown alternative mechanism for the leukemogenesis and maturation arrest seen in other APL variants. The diagnostic challenges and urgent management issues this unusual case raises may justify including it, along with similar cases, in a separate subtype of acute myeloid leukemia (AML) in future classifications.

No MeSH data available.


Related in: MedlinePlus

Initial core biopsy touch imprints. (a) Wright-Giemsa stained blood-dilute touch imprints; note the packed marrow on the left side. (b) Hemorrhagic necrosis on right side of this H&E stained section. (c) Immunoperoxidase staining of core biopsy for CD33; areas not taking the stain represent necrotic marrow. (d) Immunoperoxidase staining for Myeloperoxidase of a section from core biopsy.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4553303&req=5

fig1: Initial core biopsy touch imprints. (a) Wright-Giemsa stained blood-dilute touch imprints; note the packed marrow on the left side. (b) Hemorrhagic necrosis on right side of this H&E stained section. (c) Immunoperoxidase staining of core biopsy for CD33; areas not taking the stain represent necrotic marrow. (d) Immunoperoxidase staining for Myeloperoxidase of a section from core biopsy.

Mentions: The core biopsy touch imprints also were paucicellular (Figure 1(a)), and flow cytometry showed no significant blast/progenitor cell population. Sections from the core biopsy were available the following day, revealing a hypercellular marrow space with an area of coagulative necrosis (Figure 1(b)). The marrow space was dominated by myeloid cells with some maturation and increased cells with cytoplasmic granules. There was a marked decrease in erythroid cells and megakaryocytes. Immunoperoxidase staining confirmed the predominance of myeloid cells (positive CD33 and MPO, Figures 1(c) and 1(d)). The negative staining for T-cell, B-cell, CD61, and CD42b helped exclude other hematopoietic malignancies, and negative results for mast cell tryptase, CD2, and CD25 excluded mastocytosis. A repeat marrow sampling including additional core biopsies was recommended in order to compensate for the inadequate blood-dilute aspirate and repeat immunophenotyping by flow cytometry on a more representative sample. Additional core biopsies were obtained, with one core used to generate a cell suspension of marrow cells by teasing out and disaggregating marrow tissue. This new cell suspension was used for making stained cytospin slides for cell morphology alongside the touch imprints and was utilized for immunophenotyping by flow cytometry and for cytogenetics. The touch imprints from this sample showed predominance of abnormal promyelocytes, with some showing multiple delicate Auer rods (arrow in Figure 2).


Promyelocytic Leukemia with No Retinoic Acid Receptor Alpha Abnormality but with RUNX1T1 Insertion to Chromosome 7q: A Classification and Management Dilemma.

Overholt K, Guinipero TL, Heerema NA, Loken MR, Kahwash SB - Case Rep Hematol (2015)

Initial core biopsy touch imprints. (a) Wright-Giemsa stained blood-dilute touch imprints; note the packed marrow on the left side. (b) Hemorrhagic necrosis on right side of this H&E stained section. (c) Immunoperoxidase staining of core biopsy for CD33; areas not taking the stain represent necrotic marrow. (d) Immunoperoxidase staining for Myeloperoxidase of a section from core biopsy.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4553303&req=5

fig1: Initial core biopsy touch imprints. (a) Wright-Giemsa stained blood-dilute touch imprints; note the packed marrow on the left side. (b) Hemorrhagic necrosis on right side of this H&E stained section. (c) Immunoperoxidase staining of core biopsy for CD33; areas not taking the stain represent necrotic marrow. (d) Immunoperoxidase staining for Myeloperoxidase of a section from core biopsy.
Mentions: The core biopsy touch imprints also were paucicellular (Figure 1(a)), and flow cytometry showed no significant blast/progenitor cell population. Sections from the core biopsy were available the following day, revealing a hypercellular marrow space with an area of coagulative necrosis (Figure 1(b)). The marrow space was dominated by myeloid cells with some maturation and increased cells with cytoplasmic granules. There was a marked decrease in erythroid cells and megakaryocytes. Immunoperoxidase staining confirmed the predominance of myeloid cells (positive CD33 and MPO, Figures 1(c) and 1(d)). The negative staining for T-cell, B-cell, CD61, and CD42b helped exclude other hematopoietic malignancies, and negative results for mast cell tryptase, CD2, and CD25 excluded mastocytosis. A repeat marrow sampling including additional core biopsies was recommended in order to compensate for the inadequate blood-dilute aspirate and repeat immunophenotyping by flow cytometry on a more representative sample. Additional core biopsies were obtained, with one core used to generate a cell suspension of marrow cells by teasing out and disaggregating marrow tissue. This new cell suspension was used for making stained cytospin slides for cell morphology alongside the touch imprints and was utilized for immunophenotyping by flow cytometry and for cytogenetics. The touch imprints from this sample showed predominance of abnormal promyelocytes, with some showing multiple delicate Auer rods (arrow in Figure 2).

Bottom Line: In this report, we describe the case of a 2-year-old boy who presented with bone pain and was found to have pancytopenia.Gene sequencing results became available after initiating therapy but were not informative.The diagnostic challenges and urgent management issues this unusual case raises may justify including it, along with similar cases, in a separate subtype of acute myeloid leukemia (AML) in future classifications.

View Article: PubMed Central - PubMed

Affiliation: Hematology/Oncology and Blood and Marrow Transplant, Nationwide Children's Hospital, Columbus, OH 43205, USA.

ABSTRACT
A case of acute promyelocytic leukemia (APL) with RUNX1T1 insertion to 7q is described and compared to reported cases of APL with negative retinoic acid receptor alpha (RARA) abnormality. In this report, we describe the case of a 2-year-old boy who presented with bone pain and was found to have pancytopenia. Bone marrow examination showed morphologic and immunophenotypic findings typical of APL, but conventional cytogenetics, fluorescence in situ hybridization (FISH), and real-time polymerase chain reaction (RT-PCR) showed no evidence of RARA rearrangements. The only cytogenetic abnormality found was a small insertion in 7q, and three copies of RUNX1T1. Gene sequencing results became available after initiating therapy but were not informative. We describe the rarity of such cases and discuss how the typical morphologic and immunophenotypic findings of APL, coupled with the definite absence of RARA rearrangement (by FISH and RT-PCR), present a diagnostic and classification dilemma, raising the possibility of an unknown alternative mechanism for the leukemogenesis and maturation arrest seen in other APL variants. The diagnostic challenges and urgent management issues this unusual case raises may justify including it, along with similar cases, in a separate subtype of acute myeloid leukemia (AML) in future classifications.

No MeSH data available.


Related in: MedlinePlus