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Auer Rods in the Mature Neutrophils of Acute Biphenotypic Leukemia: About One Case

El Bayed Sakalli H*, Ouazzani Touhami K, Oukkache B

Laboratory of Hematology, Hospital Center Ibn Rochd, Casablanca, Morocco

*Correspondinguthor:
El Bayed Sakalli H
Laboratory of Hematology
Anbar Hospital Center Ibn Rochd Casablanca
Morocco
Tel: 0661483661
E-mail: [email protected]

Received date: 28/01/2019; Accepted date : 04/04/2019; Published date: 11/04/2019

Visit for more related articles at Journal of Clinical and Medical Case Studies

Abstract

Introduction: Auer rods are crystalline inclusions, pathognomic of myeloid differentiation of the leukemic blasts. Their presence in maturing myeloid cells and monocytes is rare. In this study, we report a rare and uncommon case of acute biphenotypic leukemia with Auer rods in fagot present in the mature neutrophils. Case report: 21 years old men admitted at the hospital with a tumor syndrome, the hem gram detected a leukocytosis at 79 500/μl with 96% blasts, a normochromic normocytic anemia at 8.3 g/dl and a thrombocytopenia at 40 000/ul. The myelogram revealed a rich marrow of 92% of heterogeneous size blasts with a cross linked chromatin nucleus and basophilic cytoplasm.The neutrophils with mono or bilobed nucleus characterized by the presence of Auer bodies in fagot. The immunophenotyping showed acute biphenotypic leukemia and the medullary karyotype showed a trisomy 4, a deletion of the chromosome 16 in q22, the translocation. Discussion: The presence of Auer rods in neutrophils is an uncommon phenomenon, evocative of nucleo cytoplasmic asynchronism, where the nuclear maturation has occurred, their presence is linked to a favorable prognosis of the disease. Auer rods in fagot are characteristic of acute promyelocytic leukemia but as illustrated by our patient, they cannot be considered specific It has been observed that their presence in neutrophils is linked, in most cases, to acute myeloblastic leukemia with acute promyelocytic leukemia and acute myeloblastic leukaemia with maturation M3 and rarely M1 and myelodysplastic syndrome.

Keywords

Auer rods, Acute biphenotypic Leukemia, Mature neutrophils, Fagot, Leukemic blast

Abstract

Introduction: Auer rods are crystalline inclusions, pathognomic of myeloid differentiation of the leukemic blasts. Their presence in maturing myeloid cells and monocytes is rare. In this study, we report a rare and uncommon case of acute biphenotypic leukemia with Auer rods in fagot present in the mature neutrophils.

Case report: 21 years old men admitted at the hospital with a tumor syndrome, the hem gram detected a leukocytosis at 79 500/μl with 96% blasts, a normochromic normocytic anemia at 8.3 g/dl and a thrombocytopenia at 40 000/ul.

The myelogram revealed a rich marrow of 92% of heterogeneous size blasts with a cross linked chromatin nucleus and basophilic cytoplasm.The neutrophils with mono or bilobed nucleus characterized by the presence of Auer bodies in fagot. The immunophenotyping showed acute biphenotypic leukemia and the medullary karyotype showed a trisomy 4, a deletion of the chromosome 16 in q22, the translocation.

Discussion: The presence of Auer rods in neutrophils is an uncommon phenomenon, evocative of nucleo cytoplasmic asynchronism, where the nuclear maturation has occurred, their presence is linked to a favorable prognosis of the disease.

Auer rods in fagot are characteristic of acute promyelocytic leukemia but as illustrated by our patient, they cannot be considered specific It has been observed that their presence in neutrophils is linked, in most cases, to acute myeloblastic leukemia with acute promyelocytic leukemia and acute myeloblastic leukaemia with maturation M3 and rarely M1 and myelodysplastic syndrome.

Introduction

Auer rods are stem-shaped crystalline inclusions corresponding to small rods normally present in the myeloid blasts; consist of the fusion of several azyrophilic granules, named according to JHON AUER [1,2]. These inclusions contain enzymes such as acid phosphatase, peroxidase, and esterase and may represent abnormal derivatives of cytoplasmic granules. The finding of Auer rods instained blood smears helps to differentiate acute myelogenous Leukemia from acute lymphoblastic leukemia. We report a rare and unusual case of acute biphenotypic leukemia with Auer rods in fagot present in the mature neutrophils [3].

case report

A 21 year old man, without a specific pathological history. Presented to hospital, with a left sub-maxillary tumefaction gradually increasing in volume in a context of fever. The clinical exam show: Slightly colored conjunctivitis, no gingival hypertrophy, two left lateral cervical adenopathies of 3 cm and 1 cm, axillary and inguinal measuring 2 and 3 cm respectively, no hepatomegaly or splenomegaly, Absence of cutaneo-mucous hemorrhage. Laboratory studies were performed and showed a hyperleukocytosis at 79.5 × 103/μl with 96% of blasts, a normocytic normochromic anemia at 8.3 g/dl, a thrombocytopenia at 40000/μl. The neutrophils level of 800/μl, the lymphocytes level of 2390/μl. The subsequent bone morrow aspirate was hyper cellular with 91% of heterogeneous size blasts, a cross-linked chromatin nucleus; a nucleolate with a basophilic cytoplasm sometimes containing grains and rarely Auer rods, a myeloperoxidase was positive. The examination of peripheral blood film demonstrated marked dysgranulopoiesis have signs of dysplasia: Monolobed or bilobed nucleus with highly condensed chromatin and cytoplasm, sometimes containing Auer rods. Immunopheno typing was in favor of acute biphenotypic leukemia with the presence of a blastic population expressing the following markers: CD2; CD3; CD7; CD13; CD33; CD34; CD117; HLA-DR; TdT. The medullary karyotype showed à trisomy 4, a deletion of chromosome 16 in q22, a translocation. Serological assessment was performed and showed negative anti HCV; negative HIV; positive Ag HbS; Ag Hbe; positive Ac negative anti Hbe. He received the National protocol ALL with complete remission after first induction.

Discussion

Auer rods are unusual cytoplasmic inclusions corresponding to small rods of 2 to 4 μm long; result the defects in the formation, the aggregation and the concentration of the peroxidase granules in the leukemic blast. A pink, round or rod shaped, splinter like inclusion seen in the cytoplasm of lymphoblasts in immatures granulocytes, and occasionally in monocytes precursors in the peripheralcirculation of 10% to 30% of patients with acute non- lymphocytic leukemia and acute promyelocytic leukaemia. These azyrophilic inclusions result from the crystallization of myeloperoxidase granules; they are pathognomonic of acute myeloid leukemia. The ultrastructure of Auer rods is different in different sub-types of the disease and it is suggested here that this may be a consequence of the Auer rods consisting of different crystalline forms of the enzyme myeloperoxidase [2-5]. Auer rods are seen in several types of AML. They have the peculiarity of bundling in APL [1,2,6]. They are very importance in the diagnosis because they indicate both the lineage and the neoplastic nature of the observed state. Their presence provides two importants information: it is a malignant disease, and it is myeloid. Their interest is proved in the diagnosis of acute promyelocytic leukemia (Figure 1) [1,5,7].

clinical-and-medical-case-studies-mature-neutrophils

Figure 1: Myelogram (staining MGGx100) showing the presence of Auer rods in fagot in mature neutrophils.

Auer rods in a bundle in neutrophils are a rare finding and their presence in neutrophils is suggestive of nucleo-cytoplasmic asynchrony; where the nuclear maturation has occurred, their presence is linked to a favorable prognosis of the disease, several studies have demonstrated that Auer rods confer a favorable prognosis independently of the cytogenetic [1,4]. There is statistical evidence to indicate that patients with Auer rods have a more favorable prognosis than those without. It is proposed that an investigation of the factors that determine the form, if any, of the crystallization of myeloperoxidase will lead to a better understanding of the molecular events underlying the different types of AML.

The rate of remission is significantly higher in patients with Auer rods, these latters are of great prognostic importance concerning both the induction success and the duration of remission. Auer rods are therefore useful for differentiating patients either with poor or good prognosis [8]. The presence of Auer rods in mature neutrophils is extremely rare, but in most cases is associated with acute myeloblastic leukemia often with t (8,21) or Acute promyelocytic leukemia and acute myeloblastic leukaemia with maturation M3 and rarely M1 and myelodysplastic syndrome or acute promyelocytic leukemia in the course of treatment differentiating trans retinoic acid (ATRA), where the level of Auer rods in PNN increases in patients after induction of trans-retinoic acid remission (ATRA) (Table 1) [9-12].

Author, Year Number of cases Type of cell showing Auer roods Other morphological features Immunophenoyp / cytogenetics
Dmitrienko [1] 1 Neutrophils Dysplasic Mixed lineag (T/ myeloid) with Normal Kanyotype
Manish [2] 1 Neutrophils Pseudo-pelger huet anomaly AML with aberrant CD19 and AML1-ETO fusion product
Davies and shmitt [3] 1 Neutrophils   ND
Stass [4] 10 Neutrophils Correlate with AML-M2 ND
Kato [5] 1 Neutrophils Correlate with AML ND
Kanoh [6] 1 Neutrophils and monocytes Pseudo-Pelger-Huet ND
Ashihara [7] 1 Neutrophils Correlate with AML-M3 (APML) T (15,17)
Anand [8] 1 Neutrophils   ND
Kalle [9] 1 Neutrophils MDS transforming to AML T (8,21)
Dawson [10] 1 Neutrophils   Normal kanyotype
Guerin [11] 1 Neutrophils Dysplasia (hypogmular, Pseudo-Pelger-Huet) Complex kanyotyp
Ohnishi [12] 1 Neutrophils and metamyelocytes Correlate with AML-M1 Trisomy4
ND: Not Done, AML: Acute Myeloid Leukemia, MDS: Myeloidsyplastic Syndrome, APML: Acute Promyelocytic Leukemia.

Table 1. Brief summary of the cases documented in the literature showing Auer rods, in cells other than explosions.

ATRA is used as a therapeutic agent in patients with APL to induce the differentiation of leukemic cells. Neutrophils in the bone marrow and blood of patients during ATRA treatment occasionally contain Auer rods, consistent with their derivation from leukemic cells. Although ATRA is effective in inducing differentiation of APL cells, it is incapable of inducing complete neutrophils morphologic maturation.

After a brief review of the literature, the presence of Auer rods in mature neutrophils is related to chromosome 16 abnormalities (deletion or inversion).

Conclusion

Generally, in conclusion, the presence of Auer rods in neutrophils is certainly of great utility since it is associated with a good prognosis independently of cytogenetic. Their presence in neutrophils and other cells clearly shows that these cells are part of a malignant clone. However, their role in the diagnosis orientation and clinical implications is still uncertain. In the long term this may in turn lead to a therapeutic advance.

References