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 Table of Contents  
Year : 2016  |  Volume : 7  |  Issue : 3  |  Page : 111-113

Proptosis, a rare presentation of acute myeloid leukemia − AML M6 in a child

1 Department of Pathology, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India
2 Department of Pediatric Hemato Oncology, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India

Date of Web Publication26-Oct-2016

Correspondence Address:
Julius Scott
Professor of Pediatrics, Head/Division of Pediatric Hemato Oncology, Sri Ramachandra Medical Centre, No. 1, Ramachandra Nagar, Porur, Chennai - 600 116, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1658-5127.192985

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Acute myeloid leukemia (AML) M6 or acute erythroid leukemia is an extremely rare type of AML accounting for 3–4% of all AML cases. In children, AML is even rarer, in accordance to the fact that only 0.5–4.6% of all cancer-affected individuals are children. Proptosis as a sign of AML is well noted; however, proptosis as an extramedullary symptom in the case of AML M6 is very rare. A 3-year-old male child presented with bilateral proptosis. Bone marrow aspirate predominantly showed blasts, which by flow cytometry were concluded to be AML M6. Proptosis as an extramedullary presentation in the case of AML M6 in the pediatric age group was not reported in literature. We are presenting our case for its rarity.

Keywords: Acute erythroid leukemia, erythroblast, myeloblast, proptosis

How to cite this article:
Kesamneni R, Nagarajan P, Johnson T, Scott J. Proptosis, a rare presentation of acute myeloid leukemia − AML M6 in a child. J Appl Hematol 2016;7:111-3

How to cite this URL:
Kesamneni R, Nagarajan P, Johnson T, Scott J. Proptosis, a rare presentation of acute myeloid leukemia − AML M6 in a child. J Appl Hematol [serial online] 2016 [cited 2023 Jan 27];7:111-3. Available from: https://www.jahjournal.org/text.asp?2016/7/3/111/192985

  Introduction Top

Acute myeloid leukemia (AML) M6 or acute erythroid leukemia is an extremely rare type of AML accounting for a mere 3–4% of all AML cases. In children, this is even rarer, in accordance to the fact that only 0.5–4.6% of all cancer-affected individuals are children.[1] Hence, AML M6 is clinically not suspected in regular medical practice. Though proptosis as a sign of AML is well noted, proptosis as an extramedullary symptom in the case of AML M6 was not reported elsewhere. Herein, we report a case of AML M6 in a 3-year-old child in whom the disease primarily presented as bilateral proptosis.

  Case History Top

A 3-year-old male child presented with bilateral proptosis without any start of visual impairment started in both eyes [Figure 1]. There was no history of fever, head injury, bone pain, seizures, loss of consciousness, and bleeding manifestations. His clinical examination revealed splenomegaly. He did not have any other significant findings on clinical examination. Opthalmic examination did not reveal any other abnormalities other than proptosis.
Figure 1: Child with bilateral proptosis

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Laboratory investigations showed hemoglobin level of 100 g/L, total white blood cells (WBCs) count of 2.8 × 109/L and platelet count of 226 × 109/L. Peripheral smear examination revealed microcytic hypochromic red blood cells (RBCs) and some atypical cells resembling blasts with large nucleus, two to three nucleoli, fine chromatin, and moderate basophilic cytoplasm.

Following this peripheral blood picture, bone marrow aspirate was done. Bone marrow aspirate had 93% blasts with large nucleus fine chromatin and moderate basophilic cytoplasm. Some of the blasts showed small cytoplasmic vacuoles and cytoplasmic budding. Binucleated forms were also seen [Figure 2]. Normal hematopoiesis was suppressed. Immunophenotyping of blasts by flow cytometry showed 80.0% blast cells identified in CD45 side scatter as CD45 dim positive and in low side scatter in blast gate. The blast cells expressed myeloid and erythroid markers such as CD117, CD71, glycophorin A, and CD36. They were negative for other lymphoid markers like CD19, CD10, CD20, Tdt, CD3, CD5, CD7, cy CD3, and cy 79a, myeloid markers like cy MPO, CD13, and CD33, monocytic markers like CD11c, CD64, and CD14, megakaryocytic markers like CD61 and CD41, and immature markers like CD34 and HLADR. The scatter parameters and antigen expression profile as studied by flow cytometry of the sample were in favor of AML M6.
Figure 2: (a) Erythroblasts with megaloblastoid forms, nuclear budding, and binucleation. May Grunwald Giemsa (MGG) 100×. (b) Erythroblasts as medium to large cells with round nuclei, fine chromatin, and deep blue agranular cytoplasm with variable cytoplasmic vaculation. MGG 100×. (c) Bone marrow showing diffuse infiltration of large atypical cells with pleomorphic nuclei and scant cytoplasm. H and E 40×. (d) Erythroblasts with diffuse positivity for glycophorin A. Immunohistochemistry − 20×

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Microscopically, the bone marrow biopsy also showed marrow infiltrated by monotonous population of large atypical cells with suppressed normal trilineage hematopoiesis [Figure 2]. By immunohistochemistry, tumor cells were positive for vimentin, CD117, and glycophorin A, and negative for CD45 [Figure 2]. Myeloperoxidase was negative among the erythroblasts; however, few scattered myeloid precursors showed positivity.

Correlating the morphological features in bone marrow aspirate and biopsy with the immunohistochemical and flow cytometry findings, the case was diagnosed to be AML M6. In view of the confirmed diagnosis of leukemia, and considering the financial constraints and that the clinical condition of the child was not stable, neuroimaging was deferred.

The child was started on chemotherapy with cytarabine and daunorubicin. However, even after inducing chemotherapy, and in spite of treatment, the disease worsened, and the child succumbed to the illness.

  Discussion Top

Acute erythroid leukemia or AML M6 is a very rare type of AML, which accounts for 3–4% of all AML cases.[1] AML M6 has a very broad range of occurrence from mere children to the elderly. The male : female ratio is 2.4:1.[2],[3],[4],[5]

Clinical presentation of AML M6 is highly variable, varying from simple weakness, pallor, and fever to more severe complications such as hemorrhages, hepatosplenomegaly, anemia, and thrombocytopenia. Extramedullary involvement in the case of AML M6 is extremely rare, although a few cases were reported that presented as lymph node enlargement, another presented as hemangioma, and another presented with bilateral ovarian involvement in a 3.5-year-old child.[6],[7]

Proptosis as an extramedullary symptom in the case of AML M6 was not reported elsewhere. Proptosis as a clinical sign generally implies a list of many conditions varying from thyroid disease (exophthalmos) to caroticocavernous fistula to many other conditions such as orbital cellulitis or hematoma, leukemia, meningioma, and orbital tumors.

AML is acute leukemia with a predominant erythroid population. Two subtypes are identified, erythroleukemia (erythroid/myeloid) and pure erythroid leukemia. According to World Health Organization (WHO), erythroleukemia is defined as the presence of ≥50% of erythroid precursors in the entire nucleated cell population and ≥20% myeloblasts in the nonerythroid cells of the bone marrow. Pure erythroid leukemia has >80% of precursors with erythroid lineage with no significant myeloblastic component.[1]

The bone marrow aspirates reveal an increased number of immature erythroid progenitors. Bone marrow aspirate and touch preparations are best for cytological evaluation. The erythroid precursors are dysplastic with megaloblastic nuclei and bi- or trinucleated forms. The cytoplasm may be deeply basophilic, often agranular, and contains small vacuoles that may be periodic acid schiff positive.[1]

The marrow biopsies show diffuse infiltration of undifferentiated cells. Immunophenotypically, the erythroblasts lack myeloid associated markers and are negative with anti-myeloperoxidase (MPO) antibodies. They are positive for antibodies to glycophorin A and hemoglobin A. The myeloblasts can be positive for CD117, CD13, CD33, and myeloperoxidase. To fulfill the most recent WHO definition of acute erythroid leukemia, it is required for erythroid precursors to be ≥50% of all the nucleated cells, and the myeloid blasts should be ≥20% blast of the nonerythroid precursors.[1] AML M6 is a very aggressive disease with a very bad prognosis. There are various factors that influence the prognosis; a few of the factors are as follows: patients belonging to the older age group and abnormalities of chromosome 5 and/or 7.[8],[9],[10] In addition, the median survival of patients with de novo AML M6 and myelodysplastic syndrome–AML M6 was superior to that of therapy-related AML M6.

The standard and most preferred treatment of AML M6 is bone marrow transplant.

We report this case to increase the awareness of the pediatricians and oncologists regarding the unusual presentation of this rare neoplasm.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. Acute myeloid leukemia, not otherwise specified. WHO Classification of Tumours and Lymphoid Tissue. Lyon, France:IARC Press; 2008. page 130.  Back to cited text no. 1
Hasserjian RP, Zuo Z, Garcia C, Tang G, Kasyan A, Luthra R et al. Acute erythroid leukemia: A reassessment using criteria refined in the 2008 WHO classification. Blood 2010;115:1985-92.  Back to cited text no. 2
Liu W, Hasserjian RP, Hu Y, Zhang L, Miranda RN, Medeiros LJ et al. Pure erythroid leukemia: A reassessment of the entity using the 2008 World Health Organization classification. Mod Pathol 2010;24:375-83.  Back to cited text no. 3
Bacher U, Haferlach C, Alpermann T, Kern W, Schnittger S, Haferlach T. Comparison of genetic and clinical aspects in patients with acute myeloid leukemia and myelodysplastic syndromes all with more than 50% of bone marrow erythropoietic cells. Haematologica 2011;96:1284-92.  Back to cited text no. 4
Domingo-Claros A, Larriba I, Rozman M, Irriguible D, Vallespí T, Aventin A et al. Acute erythroid neoplastic proliferations. A biological study based on 62 patients. Haematologica 2002;87:148-53.  Back to cited text no. 5
Olopade OI, Thangavelu M, Larson RA, Mick R, Kowal-Vern A, Schumacher HR et al. Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. Blood 1992;80:2873-82.  Back to cited text no. 6
Colita A, Belhabri A, Chelghoum Y, Charrin C, Fiere D, Thomas X. Prognostic factors and treatment effects on survival in acute myeloid leukemia of M6 subtype: A retrospective study of 54 cases. Ann Oncol 2001;12:451-5.  Back to cited text no. 7
Keifer J, Zaino R, Ballard JO. Erythroleukemic infiltration of a lymph node: Use of hemoglobin immunohistochemical techniques in diagnosis. Hum Pathol 1984;15:1090-3.  Back to cited text no. 8
Haught EA, Johnson MC, Witt PD. Congenital erythroleukemia presenting as a congenital infantile hemangioma. Plast Reconstr Surg 2007;119:70e-72e.  Back to cited text no. 9
Wang HY, Huang LJ, Liu Z, Garcia R, Li S, Galliani CA. Erythroblastic sarcoma presenting as bilateral ovarian masses in an infant with pure erythroid leukemia. Hum Pathol 2011;42:749-58.  Back to cited text no. 10


  [Figure 1], [Figure 2]

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Tejasvini Chandra,Perwez Khan,Lubna Khan,Anshika Gupta
[Pubmed] | [DOI]


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