Lymphoblastic leukemia with surface light chain restriction: A diagnostic dilemma

Nikhil Rabade; Asma Bibi; Kiran Ghodke; Nikhil Patkar; Prashant Tembhare; Pratibha Amare; PG Subramanian; Sumeet Gujral

doi:10.4103/0377-4929.188129

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CASE REPORT

Year : 2016 | Volume : 59 | Issue : 3 | Page : 410-412

Lymphoblastic leukemia with surface light chain restriction: A diagnostic dilemma

Nikhil Rabade¹, Asma Bibi¹, Kiran Ghodke¹, Nikhil Patkar¹, Prashant Tembhare¹, Pratibha Amare², PG Subramanian¹, Sumeet Gujral¹
¹ Department of Pathology, Hematopathology Laboratory, Tata Memorial Hospital, Mumbai, Maharashtra, India
² Department of Cancer Cytogenetics, Tata Memorial Hospital, Mumbai, Maharashtra, India

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Date of Web Publication

10-Aug-2016

Abstract

Surface light chain expression is a feature of mature B-cell neoplasms. Light chain restriction in precursor B acute lymphoblastic leukemia is infrequently seen. We report a case of a 28-year-old female with non-FAB L3 morphology blasts and immunophenotypic features showing overlap between a precursor and mature B-cell neoplasm.

Keywords: Burkitt, leukemia, light chain restriction

How to cite this article:
Rabade N, Bibi A, Ghodke K, Patkar N, Tembhare P, Amare P, Subramanian P G, Gujral S. Lymphoblastic leukemia with surface light chain restriction: A diagnostic dilemma. Indian J Pathol Microbiol 2016;59:410-2

How to cite this URL:
Rabade N, Bibi A, Ghodke K, Patkar N, Tembhare P, Amare P, Subramanian P G, Gujral S. Lymphoblastic leukemia with surface light chain restriction: A diagnostic dilemma. Indian J Pathol Microbiol [serial online] 2016 [cited 2020 Feb 26];59:410-2. Available from: http://www.ijpmonline.org/text.asp?2016/59/3/410/188129

Introduction

B-cell neoplasms tend to show resemblance to normal stages of B-cell maturation. The WHO 2008 broadly classifies B lymphoid neoplasms into precursor and mature types.^[1] The expression of CD34 and/or terminal deoxynucleotidyl transferase (TdT) is a feature of the former, whereas surface light chain restriction is a feature of mature B-cell neoplasms. Although surface immunoglobulin expression is known to occur in some precursor B-cell acute lymphoblastic leukemias (pre-B-ALL), these cases show heavy chain expression and are typically negative for surface immunoglobulin light chain expression.^[2] Light chain restriction in pre-B-ALL is available in literature as few case reports and small case series only.^[2],[3]

Case Report

A 28-year-old female presented with a history of abdominal pain for a month. Clinical examination revealed the presence of a mass in the hypogastrium along with enlargement of the liver and spleen. Her hemoglobin was 13.4 g/dL, with a platelet count of 269 × 10⁹/L, and leukocytosis (total leukocyte count 19.24 × 10⁹/L). Peripheral blood smear showed the presence of 40% blasts which were negative for cytochemical myeloperoxidase. Serum lactate dehydrogenase (LDH) was markedly elevated (LDH - 3540 U/L, normal range 100–190 U/L). She presented with early features of tumor lysis with raised levels of serum uric acid (9.3 mg/dL, normal range 2.6–6 mg/dL), creatinine (1.4 mg/dL, normal range 0.9–1.3 mg/dL), and low serum calcium (8.1 mg/dL, normal range 8.6–10 mg/dL). However, serum potassium and phosphorus were low. Positron emission tomography–computed tomography scan showed hypermetabolic, bulky, omental, and gastrohepatic soft tissue masses along with a lymphomatous involvement of the liver, spleen, and peritoneal involvement with ascites. Bone marrow (BM) showed the involvement by blasts ranging from intermediate to large in size with moderate cytoplasm and nuclei showing prominent nucleoli. Few blasts showed “hand mirror” shaped morphology and few showed the presence of vacuoles within the cytoplasm [Figure 1]. On flow cytometric immunophenotyping (FCI), the blasts expressed bright CD45, CD19, CD20, CD58, heterogeneous CD34, moderate cytoplasmic CD79a, dim CD22, CD5, and CD43 along with surface kappa light chain restriction [Figure 2]. The blasts were negative for TdT, CD10, CD38, CD200, IgD and other myeloid, and T cell markers. Heterogeneous expression of CD34 favored the diagnosis of a precursor pre-B-ALL.

Figure 1: Hand mirror-shaped blast. Occasional blast with cytoplasmic vacuoles

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Figure 2: CD45 versus side scatter gating (red - blasts, blue - lymphocytes, and green - granulocytes) B-cell lineage blasts with bright CD45 expression blasts expressing heterogeneous CD34 with bright CD20, lack of CD10, and CD38 along with surface kappa light chain restriction

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Immunoglobulin levels were not evaluated in the present case. Serum globulin levels, however, were within normal limits (2.9 g/dl). Light chain expression was studied on the blasts by FCI and not in serum. Hence, heavy chain subtyping was not done. Cytogenetic studies revealed hypodiploidy and monosomy of chromosome 22 and absence of c-MYC translocation. Postinduction BM was in remission with no evidence of minimal residual disease on FCI.

Discussion

Early stages of B-cell maturation occur in the bone marrow. These B-cell precursors, also known as hematogones, can be divided into three stages of maturation identified by their patterns of surface antigen expression. High level of CD20 expression that usually occurs in stage three hematogones coincides with surface immunoglobulin expression.^[4]

Surface light chain restriction is a feature of mature B-cell malignancies and has been reported in pre-B-ALL cases associated with MLL gene rearrangements.^[3],[5],[6] MLL gene rearrangement, especially t (9;11), often seen in B-ALL with surface light restriction was not detected in the present case. MLL gene rearrangement is more frequently seen in infantile leukemia rather than adults and has a poor prognosis. Classical FAB L3 morphology, i.e. abundant deep basophilic cytoplasm with vacuoles, seen in Burkitt lymphoma (BL) was also not seen in our case. The clinical features along with bright expression of CD20, CD45, and kappa light chain restriction seen in our case were suggestive of a high-grade lymphoma such as BL. Expression of CD34 or TdT and lack of MYC translocation can differentiate between BL and pre-B-ALL.^[1] This distinction is crucial as the treatment for BL differs from that of pre-B-ALL. CD10 a germinal center marker frequently seen in BL was not expressed in the present case. Although CD34 expression has been reported in BL,^[2] hypodiploidy, monosomy 22, and lack of MYC translocation seen in our case favored a diagnosis of pre-B-ALL with surface light chain restriction.

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Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Swerdlow SH, Campo E, Harris NL, Pileri SA, Stein H, Thiele J, et al. WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. Lyon: IARC; 2008.
2.	Kansal R, Deeb G, Barcos M, Wetzler M, Brecher ML, Block AW, et al. Precursor B lymphoblastic leukemia with surface light chain immunoglobulin restriction: A report of 15 patients. Am J Clin Pathol 2004;121:512-25.
3.	Vasef MA, Brynes RK, Murata-Collins JL, Arber DA, Medeiros LJ. Surface immunoglobulin light chain-positive acute lymphoblastic leukemia of FAB L1 or L2 type: A report of 6 cases in adults. Am J Clin Pathol 1998;110:143-9.
4.	McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood 2001;98:2498-507.
5.	Kim B, Lee ST, Kim HJ, Lee SH, Yoo KH, Koo HH, et al. Acute lymphoblastic leukemia with mature B-cell phenotype and t (9;11;11)(p22;q23;p11.2): A case study and literature review. Ann Lab Med 2014;34:166-9.
6.	Tsao L, Draoua HY, Osunkwo I, Nandula SV, Murty VV, Mansukhani M, et al. Mature B-cell acute lymphoblastic leukemia with t (9;11) translocation: A distinct subset of B-cell acute lymphoblastic leukemia. Mod Pathol 2004;17:832-9.