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Year : 2015  |  Volume : 58  |  Issue : 1  |  Page : 127-129
Leukemic phase of pediatric anaplastic large cell lymphoma with unusual immuno-profile and cytogenetic correlation

1 Department of Cytogenetics, Tata Medical Center, Kolkata, West Bengal, India
2 Department of Laboratory Hematology, Tata Medical Center, Kolkata, West Bengal, India
3 Department of Pediatric Hematology, Tata Medical Center, Kolkata, West Bengal, India

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Date of Web Publication11-Feb-2015

How to cite this article:
Gupta A, Parihar M, Mishra DK, Bhattacharyya A. Leukemic phase of pediatric anaplastic large cell lymphoma with unusual immuno-profile and cytogenetic correlation. Indian J Pathol Microbiol 2015;58:127-9

How to cite this URL:
Gupta A, Parihar M, Mishra DK, Bhattacharyya A. Leukemic phase of pediatric anaplastic large cell lymphoma with unusual immuno-profile and cytogenetic correlation. Indian J Pathol Microbiol [serial online] 2015 [cited 2021 Jun 18];58:127-9. Available from: https://www.ijpmonline.org/text.asp?2015/58/1/127/151218


Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase-1 (ALK-1) positive is characterized by expression of CD30, translocations involving ALK-1 gene and account for 10-20% of childhood non - Hodgkin's lymphomas. [1],[2] Bone-marrow is involved in 10-30% of ALCL while frank leukemic phase (LP) is rare. [2],[3] We report a case of 2-year-old child who presented with fever, tachypnoea, generalized lymphadenopathy, hepatosplenomegaly and multiple papules and nodules on her face, trunk, and extremities. Investigations revealed a hemoglobin of 7 g%, very high total leucocyte count (TLC) of 2,24,000/cmm with 64% small atypical monocytoid cells with convoluted grooved nuclei [[Figure 1]a]. Bone marrow aspirate and biopsy were hyper-cellular with 68% small atypical monocytoid cells. Flow cytometry showed these cells to be positive for CD13, CD3 (both surface and cytoplasmic), CD2, CD7, CD4 and negative for CD5, CD8, CD25, CD15, CD33, CD56 and human leukocyte antigen-DR. Right axillary lymphnode biopsy showed loss of architecture due to infiltration of mainly the sinuses by small to medium sized atypical lymphoid cells with convoluted nuclei, open chromatin, conspicuous nucleoli and expressed CD3, CD2, CD43, CD4,EMA, ALK-1 and CD30 by immunohistochemistry [[Figure 1]b and c]. MIB1 proliferation index was 40-50%. Cytogenetic analysis revealed t(2;5)(p23;q35) along with trisomy of chromosome 7 in 19 of 20 metaphases [[Figure 1]d]. A final diagnosis of LP of ALCL, ALK-1 positive was made. The patient died after 33 days of presentation in spite of intensive chemotherapy. LP of ALCL may be seen at presentation or may develop during the treatment or at relapse. Of the 13 pediatric cases of LP of ALCL reported until date only four had LP at initial diagnosis. TLC rarely exceeds more than 1 × 10 6 /cmm. [2],[3] The present case had TLC of 2,24,000/cmm. LP in ALCL has been described predominantly in cases with a small cell variant like the present case while LP in large cell variants has been reported in only three pediatric cases. [3] Immuno-phenotypically ALCL (not in LP) is expresses CD2, CD5, CD7 and CD4 besides being uniformly positive for CD25, CD30, and ALK-1. CD3 is negative in 70-75% of the cases while CD8 is usually negative. [4] In 13 cases of pediatric ALCL in LP, surface CD3 was negative in nine cases, partially expressed in a single case while positive in two cases both of which were small cell variant. CD5 was lost in all the five cases while CD7 was absent in 40% of the cases. CD25 was present in six cases. However, it was negative in the present case with only one such case with CD25 negativity reported literature. CD13 was aberrantly expressed in 83% of the cases. Cytogenetics data was available in 10 of these pediatric cases of which eight cases showed t(2;5)(p23;q35) whereas two cases had variant ALK-1 translocation involving chromosome 2 with chromosome 19. Though trisomy 7 is the most common secondary change in ALCL, it has been described in only three cases of pediatric ALCL in LP with small cell morphology including the present case. [1] Eight pediatric cases of ALCL in LP died of the disease while five were with two not in remission and on treatment, two in complete remission while details of one case was not available. Both the two cases including the present case with trisomy 7 as an additional abnormality died of their disease in spite of aggressive therapy. Whether the presence of trisomy 7 by itself conveys poorer prognosis during the LP remains to be evaluated. To conclude LP is a rare presentation of ALCL. The leukemic cells may show atypical immuno-profile and may present with additional cytogenetic abnormalities whose implication on response to chemotherapy and survival remains unanswered. This warrants high index of suspicion and multidisciplinary for accurate diagnosis.
Figure 1: (a) Peripheral blood smear showing small atypical lymphoid cells with irregular nuclear contours admixed with monocytes (Leishman stain, ×100 oil immersion), (b) biopsy from the right axillary lymph node showing by small to medium sized atypical lymphoid cells (H and E, ×60), (c) immunohistochemistry using anaplastic lymphoma kinase-1 antibody on the right axillary lymph node biopsy (IHC, ×60), (d) karyotype from the bone marrow aspirate cultures showing presence of t (2;5) (p23;q35) (involved chromosomes marked with red ovals and involved regions by arrows) and trisomy of chromosome 7 (marked with green oval) (GTG banded, ×100 oil immersion)

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   References Top

Grewal JS, Smith LB, Winegarden JD 3 rd , Krauss JC, Tworek JA, Schnitzer B. Highly aggressive ALK-positive anaplastic large cell lymphoma with a leukemic phase and multi-organ involvement: A report of three cases and a review of the literature. Ann Hematol 2007;86:499-508.  Back to cited text no. 1
Nguyen JT, Condron MR, Nguyen ND, De J, Medeiros LJ, Padula A. Anaplastic large cell lymphoma in leukemic phase: Extraordinarily high white blood cell count. Pathol Int 2009;59:345-53.  Back to cited text no. 2
Onciu M, Behm FG, Raimondi SC, Moore S, Harwood EL, Pui CH, et al. ALK-positive anaplastic large cell lymphoma with leukemic peripheral blood involvement is a clinicopathologic entity with an unfavorable prognosis. Report of three cases and review of the literature. Am J Clin Pathol 2003;120:617-25.  Back to cited text no. 3
Delsol G, Al Saati T, Gatter KC, Gerdes J, Schwarting R, Caveriviere P, et al. Coexpression of epithelial membrane antigen (EMA), Ki-1, and interleukin-2 receptor by anaplastic large cell lymphomas. Diagnostic value in so-called malignant histiocytosis. Am J Pathol 1988;130:59-70.  Back to cited text no. 4

Correspondence Address:
Dr. Mayur Parihar
Department of Cytogenetics, Tata Medical Center, Kolkata, West Bengal - 700 156
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.151218

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