| Abstract|| |
The blast crisis of chronic myelogenous leukemia (CML) can be hematological or extramedullary. About 25% of these cases fulfill the criteria for mixed phenotype acute leukemia. We here report a case of a second blast crisis of CML which was extramedullary and was immunophenotypically bilineage T/myeloid.
Keywords: Bilineage leukemia, chronic myelogenous leukemia, extramedullary blast crisis
|How to cite this article:|
Nair IM, Feroze M, Aravindan K P. Bilineage T-lymphoblastic/myeloid extramedullary blast crisis in chronic myelogenous leukemia. Indian J Pathol Microbiol 2016;59:107-9
|How to cite this URL:|
Nair IM, Feroze M, Aravindan K P. Bilineage T-lymphoblastic/myeloid extramedullary blast crisis in chronic myelogenous leukemia. Indian J Pathol Microbiol [serial online] 2016 [cited 2019 Nov 17];59:107-9. Available from: http://www.ijpmonline.org/text.asp?2016/59/1/107/174824
| Introduction|| |
According to World Health Organisation (WHO), chronic myelogenous leukemia (CML) is defined as a myeloproliferative neoplasm that originates in abnormal pluripotent bone marrow stem cells and is consistently associated with the BCR-ABL1 fusion gene located in the translocated philadelphia chromosome. The natural history of untreated CML is bi- or tri-phasic : a0 n indolent chronic phase (CP) is followed by an accelerated phase (AP), a blast phase (BP) or both. The BP can be hematological or extramedullary and in the majority of cases it is myeloid.  Very few cases of bilineage extramedullary blast crisis have been reported.
| Case report|| |
A 38-year-old man was admitted with generalized lymphadenopathy and hepatosplenomegaly. He was a known case of CML CP BCR-ABL positive diagnosed 8 years back and was on imatinib. Two years after the initial diagnosis, he presented in neutropenic sepsis associated with generalized lymphadenopathy and hepatosplenomegaly. His lymph node biopsy from an outside center revealed extramedullary blast crisis which on immunohistochemistry was found to be T-acute lymphoblastic leukemia (ALL). After treating his neutropenic sepsis, he was put on BFM 90 protocol for ALL and attained remission. He continued treatment with imatinib, but he stopped treatment 1-year back.
In the present admission, along with generalized lymphadenopathy and hepatosplenomegaly his peripheral blood showed an elevated total count of 94,100 and a platelet count of 4.1 lakh. His peripheral smear showed 8% blasts. The bone marrow aspirate also revealed <10% blasts which were suggestive of CML in chronic phase CP. Aspirate from his lymph node showed sheets of blasts suggestive of extramedullary blast proliferation. Lymph node excision biopsy and immunohistochemistry was advised for typing of blasts. Meanwhile, a repeat peripheral smear done 5 days after the previous one showed 12% blasts suggestive of AP. Cytochemistry was done on this peripheral smear which clearly showed more than 3% myeloperoxidase (MPO) positive blasts and also occasional blasts with PAS block positivity.
Biopsy of the axillary lymph node showed sheets of blasts [Figure 1]. On immunohistochemistry, many of the infiltrating blasts were CD3 positive whereas CD20 positivity was limited to the normal residual follicles [Figure 2]. Terminal deoxynucleotidyl transferase (TdT) was positive in the immature cells. CD34 as well as MPO were positive in many blast cells [Figure 3]. MPO positivity by immunohistochemistry correlated with cytochemistry done on peripheral smear and a diagnosis of CML blast crisis bilineage type (T-lymphoid and myeloid) was made. Patient was put on chemotherapy as per treatment protocol for ALL and is now in remission.
|Figure 1: Section of lymph node showing architectural effacement and infiltration by uniform blast like cells (H and E ×400)|
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|Figure 2: Left: The tumor cells showing widespread CD3 positivity. Right: Only residual normal follicles are positive for CD20. The tumor cells are negative (Immunohistochemistry ×100)|
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|Figure 3: Left: Some blast stain for the stem cell marker CD34. Right: MPO positivity is seen in many blasts (Immunohistochemistry ×1000)|
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| Discussion|| |
The BP of CML may be diagnosed when (1) blasts are equal to or >20% of peripheral blood white blood cell or of nucleated cells of the bone marrow or (2) when there is an extramedullary blast proliferation.  Extramedullary blast proliferations most commonly present in the skin, lymph node, spleen, bone, or central nervous system. Extramedullary blast crisis is, almost always, followed by hematological blast crisis, so it is considered to be an early sign of blast crisis in the bone marrow. The prevalence of extramedullary blast crisis has been reported to be 7-17% in patients with a BP.  In approximately 70% of cases, the blast lineage is myeloid whereas in nearly 20-30% of cases it is lymphoid.  Approximately 25% of BP cases fulfill the criteria for mixed phenotype acute leukemia (MPAL), but these should be classified primarily as BP with a secondary notation that they have mixed phenotype. 
MPAL can have a separate population of blasts of more than one lineage (bilineage) or a single population of blasts co-expressing antigens of more than one lineage (biphenotypic). The diagnosis of MPAL is done by immunophenotyping. For demonstrating co-expression of lymphoid and myeloid antigens on the same cell flow cytometry is the preferred method. Whereas in cases in which diagnosis requires demonstration of two distinct blast populations, either immunohistochemistry on tissue sections or cytochemical stain for MPO on smear coupled with flow cytometry to detect lymphoid population may be used. 
Consensus criteria for the diagnosis of MPAL were established in 1995 when the European Group for the Immunological Characterization of Leukemias (EGIL) proposed a scoring system for the immunological classification of acute leukemias. This scoring system assigned different scores to several immunological markers based on their lineage specificity. Cytoplasmic markers, including CD3, CD22, CD79a, IgM, MPO, and T-cell receptor, were given a score of 2. Less lineage-specific markers (CD2, CD5, CD8, CD10, CD13, CD19, CD20, CD33, CD65, and CD117) were assigned a score of 1. The least specific markers (CD1a, CD7, CD14, CD15, CD24, CD64, and TdT) were assigned a score of 0.5. This scoring system was adopted in the 2001 WHO classification of tumors of the hematopoietic and lymphoid tissues, with minor modifications. Although the EGIL scoring system defined the lineage determination scores as >2, a modified EGIL (scores of ≥2) has been frequently used to define MPAL. ,
Currently, there is no universal treatment approach for patients with biphenotypic leukemia. But there are case series showing that ALL regimens are more effective in achieving complete remission than acute myeloid leukemia regimens in these cases. 
The present case is a second episode of blast crisis and both of them presented as extramedullary blast proliferation without hematological crisis. The first episode was a T-ALL whereas the second episode was bilineage T/myeloid blast crisis which were diagnosed using immunohistochemistry and correlated well with cytochemistry on peripheral smear. The patient responded to ALL regimen.
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Conflicts of interest
There are no conflicts of interest.
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Indu M Nair
Department of Pathology, Government Medical College, Kozhikode, Kerala
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]