|Year : 2015 | Volume
| Issue : 1 | Page : 27-29
Mixed phenotype acute leukemia: B/T-cell type-case report and review of literature
Sunita Sharma1, Preeti Rai1, Richa Chauhan1, Jagdish Chandra2
1 Department of Pathology, Lady Hardinge Medical College, New Delhi, India
2 Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, India
|Date of Web Publication||15-Apr-2015|
Department of Pathology, Lady Hardinge Medical College, Shaheed Bhagat Singh Marg, New Delhi - 110 001
Source of Support: None, Conflict of Interest: None
Mixed phenotypic acute leukemia (MPAL), classified under acute leukemia of ambiguous lineage, pose diagnostic dilemma due to multiple lineage-specific antigen expression. World Health Organization has laid down strict criteria for assigning >1 lineage to a single blast population. Most reported cases of biphenotypic acute leukemia belong to myeloid/B-cell lineage or myeloid/T-cell lineage. However, MPAL with B-/T-cell phenotype is very rare. A 5-year-old girl was admitted with fever, petechial rash, pallor, generalized lymphadenopathy, and hepatosplenomegaly. Complete blood counts revealed leukocytosis, anemia, and thrombocytopenia. Bone Marrow Aspiration showed 97% blasts which were negative for myeloperoxidase, and nonspecific esterase. Immunophenotyping showed a single compact population of blasts which expressed CD19, CD79a, CD22, cytoplasmic CD3, and CD7. Thus, flow cytometric immunophenotyping helped to establish a final diagnosis of MPAL: B/T-cell type.
Keywords: Acute leukemia, B/T subtype, mixed phenotype
|How to cite this article:|
Sharma S, Rai P, Chauhan R, Chandra J. Mixed phenotype acute leukemia: B/T-cell type-case report and review of literature. J Appl Hematol 2015;6:27-9
|How to cite this URL:|
Sharma S, Rai P, Chauhan R, Chandra J. Mixed phenotype acute leukemia: B/T-cell type-case report and review of literature. J Appl Hematol [serial online] 2015 [cited 2020 Apr 1];6:27-9. Available from: http://www.jahjournal.org/text.asp?2015/6/1/27/155182
| Introduction|| |
Acute leukemia of ambiguous lineage is a rare entity and constitutes <4% of all cases of acute leukemias.  This entity includes mixed phenotypic acute leukemia (MPAL), acute undifferentiated leukemia, and natural killer lymphoblastic leukemia. MPAL includes biphenotypic acute leukemia (BAL) and bilineage leukemia. European Group for the immunological characterization of acute leukemia (EGIL) classification has been used for the diagnosis of BAL  However, World Health Organization (WHO) has laid down strict criteria for assigning >1 lineage to a single blast population.  Most reported cases of BAL belong to myeloid/B-cell lineage or myeloid/T-cell lineage. ,, However, BAL with B-/T-cell phenotype is very rare. Here, we report a case of B/T-cell mixed phenotype acute leukemia in a child.
| Case report|| |
A 5-year-old girl was admitted with fever, petechial rash, pallor, and progressive weight loss. On examination, she had generalized lymphadenopathy and hepatosplenomegaly.
Her hemoglobin, total leukocyte count, and platelet counts were 44 g/L, 10.3 × 10 9 /L, and 33 × 10 9 /L respectively. Peripheral blood smears revealed 1% blast. Bone marrow aspirate smears showed 97% blasts which were negative for myeloperoxidase (MPO), and nonspecific esterase (NSE). A diagnosis of MPO negative acute leukemia was made [Figure 1].
|Figure 1: ×1000-Wright's Blasts have having high nucleo-cytoplasmic ratio, scant agranular cytoplasm. Nuclei were round with irregular nuclear membrane, slightly condensed chromatin and 0-1 nucleoli|
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Immunophenotyping was performed on the bone marrow aspirate by multicolor flow cytometry using FC 500 flow cytometer (Beckman Coulter). CD45 versus Side Scatter gating strategy showed a distinct population of 96% blasts with dim to moderate expression of CD45.
Single compact population of blasts expressed CD19, CD79a, CD22, cytoplasmic CD3, and CD7. They were negative for TdT, HLA-DR, CD34, CD117, CD13, CD14, CD33, CD10, and cytoplasmic MPO [Figure 2]. Final diagnosis of mixed phenotype acute leukemia: B/T cell type was rendered.
|Figure 2: CD45 vs Side Scatter gating strategy showed a distinct population of 96% blasts with dim to moderate expression of CD45. Single compact population of blasts expressed CD19, CD79a, cytoplasmic CD3, CD7 and CD22|
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| Discussion|| |
A systematic approach is required to diagnose and classify acute leukemias. Most leukemias can satisfactorily be categorized into B-/T-lymphoid or myeloid lineage by immunophenotyping.  However, a few cases pose a diagnostic dilemma due to the absolute lack or multiple lineage-specific antigen expression. These leukemias have been categorized as acute leukemias of ambiguous lineage by the recent WHO classification. 
Incidence of BAL is 1.2-3.4% of all acute leukemias ,, and 1.72% in children.  Saint Jude's criteria and EGIL scoring systems were used to assign lineage to leukemia before WHO laid down specific criteria in 2008.  WHO specifies MPO to be used as the most specific marker for myeloid lineage demonstrated by cytochemistry, immunophenotyping or immunohistochemistry. Furthermore, myeloid lineage can be assigned if blast population is positive for two of the following markers: NSE, CD11c, CD14, CD64, and lysozyme. Cytoplasmic CD3 is lineage specific for T cells. For B cells, multiple antigens are required for lineage confirmation. A strong CD19 expression along with strong expression of CD79a, cytoplasmic CD22 or CD10 is essential for B cell lineage. If the expression of CD19 is weak, then two of the above markers are required to assign B-cell lineage.
In the present case, single population of blasts was observed. It expressed cytoplasmic CD3, CD7 fulfilling the criteria for T cell lineage. Furthermore, the same population expressed CD19, CD79a, and CD22. Thus, B-cell lineage was also assigned to this population. Hence, a diagnosis of MPAL B-/T-cell type was made.
On extensive search of reported cases of this entity, only 13 cases were found, out of which 7 cases were in the pediatric age. ,, In a series of 32 cases of BAL, Gujral et al., reported 3 such cases.  All achieved complete remission. A recent study advocated administration of acute lymphoblastic leukemia (ALL) type of induction therapy that has activity against both lymphoid and myeloid leukemias.  Present case was started on ALL induction therapy; however she was lost to follow-up. Cytogenetics could not be performed as the patient couldn't afford the expenses.
Mixed phenotypic acute leukemia is a rare entity and also putative cell of origin in MPAL is unknown. Flow cytometry is critical in establishing a diagnosis of MPAL. The most common cytogenetic alteration reported in MPAL are t(9,22)(q34;q11) BCR-ABL1, and 11q23 mixed lineage leukemia rearrangement.  The current WHO guidelines should be used for diagnosis instead of the EGIL criteria. Cases falling into a different WHO category should not be classified as MPAL. Though rare, MPAL should be considered when aberrant expression is obtained by flow cytometry.
| References|| |
Borowitz MJ, Bene MC, Harris NL, Porwit A, Matutes E. Acute leukemias of ambiguous lineage. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008. p. 150-5.
Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995;9:1783-6.
Owaidah TM, Al Beihany A, Iqbal MA, Elkum N, Roberts GT. Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system. Leukemia 2006;20:620-6.
Weir EG, Ali Ansari-Lari M, Batista DA, Griffin CA, Fuller S, Smith BD, et al. Acute bilineal leukemia: A rare disease with poor outcome. Leukemia 2007;21:2264-70.
Rubnitz JE, Onciu M, Pounds S, Shurtleff S, Cao X, Raimondi SC, et al. Acute mixed lineage leukemia in children: The experience of St Jude Children's Research Hospital. Blood 2009;113:5083-9.
Gujral S, Polampalli S, Badrinath Y, Kumar A, Subramanian PG, Raje G, et al. Clinico-hematological profile in biphenotypic acute leukemia. Indian J Cancer 2009;46:160-8.
Costa ES, Thiago LS, Otazu IB, Ornellas MH, Land MG, Orfao A. An uncommon case of childhood biphenotypic precursor-B/T acute lymphoblastic leukemia. Pediatr Blood Cancer 2008;50:941-2.
Matutes E, Pickl WF, Van't Veer M, Morilla R, Swansbury J, Strobl H, et al. Mixed-phenotype acute leukemia: Clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 2011;117:3163-71.
Al-Seraihy AS, Owaidah TM, Ayas M, El-Solh H, Al-Mahr M, Al-Ahmari A, et al. Clinical characteristics and outcome of children with biphenotypic acute leukemia. Haematologica 2009;94:1682-90.
Manola KN. Cytogenetic abnormalities in acute leukaemia of ambiguous lineage: An overview. Br J Haematol 2013;163:24-39.
[Figure 1], [Figure 2]