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CASE REPORT
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Transformation of diffuse large B-cell lymphoma to lymphoblastic lymphoma


1 Department of Pathology, Maulana Azad Medical College, New Delhi, India
2 Department of Medicine, Maulana Azad Medical College, New Delhi, India
3 Department of Radiotherapy, Maulana Azad Medical College, New Delhi, India

Date of Submission11-Jan-2021
Date of Acceptance30-Apr-2021
Date of Web Publication22-Nov-2021

Correspondence Address:
Meeta Singh,
Department of Pathology, Maulana Azad Medical College, New Delhi
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_66_21

 > Abstract 


Transformations in diffuse large B-cell lymphoma (DLBCL) are extremely rare. Here, we are presenting a very rare case of DLBCL transforming into lymphoblastic lymphoma (LBL) diagnosed by fine-needle aspiration cytology (FNAC) and flow cytometry. A 31-year old male on antiretroviral therapy and a known case of diffuse large B-cell lymphoma diagnosed 1 year back on cervical lymphadenopathy, presented with left axillary swelling for 3 months. FNAC and Flow cytometry were performed from the left axillary swelling which confirmed the diagnosis of LBL.

Keywords: Diffuse large B-Cell Lymphoma, flow cytometry, fine-needle aspiration cytology, lymphoblastic lymphoma, transformation



How to cite this URL:
Kushwaha P, Singh M, Mallya V, Jain S, Aggarwal S, Singh K. Transformation of diffuse large B-cell lymphoma to lymphoblastic lymphoma. J Can Res Ther [Epub ahead of print] [cited 2021 Dec 6]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=330930




 > Introduction Top


Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma and the most common type of non-Hodgkin lymphoma (NHL) worldwide, representing approximately 30%–40% of adult NHL.[1]

Transformations in DLBCLs are extremely rare with only scant literature available on transformation of DLBCL to lymphoblastic lymphoma (LBL).[2]

Here, we are presenting a very rare case of DLBCL transforming into LBL diagnosed by fine-needle aspiration cytology (FNAC) and flow cytometry.


 > Case Report Top


A 31-year-old male on antiretroviral therapy presented with cervical lymphadenopathy 1 year back. Excision biopsy of cervical lymph node was done and was diagnosed as DLBCL (CD 19+, CD20+, CD 10-, MUM 1+, and BCL 6-) [Figure 1]. He was started on chemotherapy, RCHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). Having received three cycles of chemotherapy, the patient now presented with left axillary swelling for 3 months. On examination, 6 cm × 6 cm well-defined, non-tender swelling was palpable. He was referred for FNAC of the swelling.
Figure 1: (a) Biopsy showed monomorphic population of large cells with high N:C ratio, prominent nucleoli (H and E, ×400). (b and c) Immunohistochemistry with DAB as chromogen (×600) – These cells showed strong expression of CD20 (b) and MUM1 (c)

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FNAC was performed from the left axillary swelling using 23G needle attached with disposable 20 ml syringe, under aseptic precautions as per the standard technique. FNAC yielded blood mixed aspirate, multiple air-dried smears were prepared and stained with Giemsa. Cell block was prepared and stained with H and E.

Giemsa-stained smears showed large lymphoid cells with high N: C ratio and moderate amount of cytoplasm, some of the cells showed prominent nucleoli with blastoid morphology [Figure 2]. Complete blood count showed pancytopenia with the absence of blasts.
Figure 2: Fine-needle aspiration cytology showed large lymphoid cells with high N:C ratio and moderate amount of cytoplasm, some of the cells showed prominent nucleoli with blastoid morphology (arrow) in hemorrhagic background (MGG, ×600)

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Sample for flow cytometry was also obtained during FNAC in a plastic vial containing 1 ml sheath fluid. Flow cytometry immunophenotyping showed gated cells having moderate-to-high forward scatter and positivity for CD45, CD19, CD20, HLADR, CD34, Tdt, and kappa restriction [Figure 3]. These gated cells did not express CD3, CD4, CD7, CD8, CD38, CD56, and lambda confirmed on Trucut biopsy.
Figure 3: Flow cytometry immunophenotyping showing cells expressing CD45, CD19, CD20, HLADR, and CD34 and showing kappa restriction

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Based on the cytological and flow cytometry findings and the patient being a known case of DLBCL, diagnosis of transformation of DLBCL to LBL was rendered.

The patient succumbed to the illness few days after the diagnosis, no bone marrow could be performed or treatment could be started.


 > Discussion Top


The most common histological transformation in malignant lymphoproliferative diseases is the high-grade transformation also known as Ritcher's transformation of chronic lymphocytic leukemia[3] into DLBCL, plasmacytoma, acute lymphoblastic leukemia (ALL), or histiocytic sarcoma.[4] The transformation of follicular lymphoma (FL), marginal zone lymphoma, and lymphoplasmacytoid lymphoma into DLBCL is also well recognized.[5]

It has been reported that patients with HIV infection and autoimmune diseases show abnormal B-cell populations due to immunosuppression or antigen overexposure, both in circulation and in affected organs which may transform into clonal cells under antigen drive, ultimately leading to independent B-cell neoplasms to develop.[6],[7]

Transformation of FL and mantle cell lymphoma into a B-LBL/leukemia occurs rarely and has been documented for a limited number of cases.[8],[9]

However, transformations in DLBCL are extremely rare and on extensive literature search, single case of transformation of DLBCL to LBL has been reported, in which lymphoblastic transformation from a triple-hit DLBCL occurred[2] along with occasional case reports of transformation of DLBCL to lymphoblastic leukemia.[5],[10]

Transformation of DLBCL to LBL confers very poor prognosis. These cases often lead to extensive peripheral blood and bone marrow involvement.[2] Treatment of such cases is initiated according to the ALL protocol.[10]

Clinical, morphologic, cytogenetic, and immunophenotypic evaluations are necessary to fully characterize this type of transformation in lymphoma.[2] FNAC with flow cytometry is a useful adjunct to early diagnosis.


 > Conclusion Top


Clinical, morphologic, and immunophenotypic evaluations are necessary to fully characterize transformation of DLBCL to Lymphoblastic Lymphoma. FNAC with flow cytometry is a useful adjunct to its early diagnosis.

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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology 2018;50:74-87.  Back to cited text no. 1
    
2.
Hiemcke-Jiwa LS, Leguit RJ, van der Veken LT, Buijs A, Leeuwis JW, de Boer M, et al. Lymphoblastic lymphoma with a triple-hit profile: A rare but distinct and relevant entity. Hum Pathol 2017;63:171-6.  Back to cited text no. 2
    
3.
Martinez-Climent JA, Alizadeh AA, Segraves R, Blesa D, Rubio-Moscardo F, Albertson DG, et al. Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations. Blood 2003;101:3109-17.  Back to cited text no. 3
    
4.
Wetzler M, Kurzrock R, Goodacre AM, McLaughlin P, Ku S, Talpaz M. Transformation of chronic lymphocytic leukemia to lymphoma of true histiocytic type. Cancer 1995;76:609-17.  Back to cited text no. 4
    
5.
Au WY, Srivastava G, Wong KY, Chung LP, Ma SK, Wan TS, et al. Transformation of diffuse large B-cell lymphoma into pre-B acute lymphoblastic leukemia: Clinicopathologic features and clonal relationship. Hum Pathol 2004;35:900-3.  Back to cited text no. 5
    
6.
Bahler DW, Swerdlow SH. Clonal salivary gland infiltrates associated with myoepithelial sialadenitis (Sjögren's syndrome) begin as nonmalignant antigen-selected expansions. Blood 1998;91:1864-72.  Back to cited text no. 6
    
7.
Stott DI, Hiepe F, Hummel M, Steinhauser G, Berek C. Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjögren's syndrome. J Clin Invest 1998;102:938-46.  Back to cited text no. 7
    
8.
Slot LM, Hoogeboom R, Smit LA, Wormhoudt TA, Biemond BJ, Oud ME, et al. B-lymphoblastic lymphomas evolving from follicular lymphomas co-express surrogate light chains and mutated gamma heavy chains. Am J Pathol 2016;186:3273-84.  Back to cited text no. 8
    
9.
Kallen ME, Rao NP, Kulkarni SK, Pullarkat ST, Said J, Tirado CA, et al. B-lymphoblastic transformation of mantle cell lymphoma/leukemia with “double hit” changes. J Hematopathol 2015;8:31-6.  Back to cited text no. 9
    
10.
Benedek I, Lázár E, Pakucs A, Köpeczi JB, Benedek I, Jakab S, et al. Transformation of aggressive non-hodgkin lymphoma in acute lymphoblastic leukemia. J Interdiscip Med 2017;2:72-6.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

 
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