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  Table of Contents    
LETTER TO EDITOR  
Year : 2016  |  Volume : 59  |  Issue : 2  |  Page : 263-265
Loss of CD20 expression in relapsed diffuse large b-cell lymphoma: Clinical significance of an uncommon pathological finding


1 Department of Pathology, AMRI Hospitals, Kolkata, West Bengal, India
2 Institute of Hematology and Transfusion Medicine, Medical College and Hospital, Kolkata, West Bengal, India

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Date of Web Publication9-May-2016
 

How to cite this article:
Mitra S, Mukherjee S, Bhattacharyya M, Chakraborty H. Loss of CD20 expression in relapsed diffuse large b-cell lymphoma: Clinical significance of an uncommon pathological finding. Indian J Pathol Microbiol 2016;59:263-5

How to cite this URL:
Mitra S, Mukherjee S, Bhattacharyya M, Chakraborty H. Loss of CD20 expression in relapsed diffuse large b-cell lymphoma: Clinical significance of an uncommon pathological finding. Indian J Pathol Microbiol [serial online] 2016 [cited 2019 Dec 11];59:263-5. Available from: http://www.ijpmonline.org/text.asp?2016/59/2/263/182026


Editor,

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma, and rituximab is a chimeric a nti-human CD20 antibody, which has been utilized for the treatment of CD20-positive B-cell lymphomas.[1] We present a case of relapsed DLBCL in a 62-year-old male patient treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) protocol, with loss of CD20 antigenic expression.

The patient presented with abdominal distension, fever, and weight loss of 6 months duration. Ascites was present with no hepatosplenomegaly or superficial lymphadenopathy. Routine laboratory investigations showed no significant anomaly, except elevated lactic dehydrogenase levels in serum and ascitic fluids.

A mass involving the right kidney was detected on computerized tomography of the abdomen, and exploratory laparotomy revealed a right suprarenal mass adherent to adjacent organs. Biopsy taken from the mass showed diffuse infiltration of large atypical lymphoid cells on histopathological examination, with similar cells found in cytological smears prepared from ascitic and pleural fluids. On immunohistochemical staining, the tumor cells were CD45- and CD20-positive and were immunonegative for CD3 and CD30. MIB-1 labeling index was above 80%. The case was diagnosed as a DLBCL with pleural and peritoneal infiltration [Figure 1], [Figure 2], [Figure 3].
Figure 1: (a) Initial biopsy showing diffuse infiltration of large atypical lymphoid cells (H and E, ×400). (b) CD45 positivity in lymphoma cells in initial biopsy (immunoperoxidase, ×400). (c) Second biopsy showing diffuse infiltration of large atypical lymphoid cells (H and E, ×400). (d) CD45 positivity in lymphoma cells in second biopsy (immunoperoxidase, ×400)

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Figure 2: (a) Scattered CD3-positive T-cells in initial biopsy (immunoperoxidase, ×400). (b) CD20 positivity in lymphoma cells in initial biopsy (immunoperoxidase, ×400). (c) Scattered CD3-positive T-cells in second biopsy (immunoperoxidase, ×400). (d) Tumor cells immunonegative for CD20 in second biopsy (immunoperoxidase, ×400)

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Figure 3: (a) Tumor cells immunonegative for CD30 in second biopsy (immunoperoxidase, ×400). (b) Greater than 90% MIB-1 immunostaining in lymphoma cells in second biopsy (immunoperoxidase, ×400). (c) Initial computed tomography scan abdomen showing large right suprarenal mass. (d) Computed tomography scan abdomen after relapse showing left retroperitoneal mass

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Chest roentgenogram, cerebrospinal fluid examination, bone marrow aspiration, and trephine biopsy examination were normal. The patient received 6 cycles of chemotherapy as per R-CHOP protocol with clinical resolution. After 2 months free from symptoms, a repeat ultrasonographic examination of the abdomen showed another abdominal mass with no ascites or pleural effusion. CT scan of the abdomen showed a left-sided retroperitoneal mass. CT-guided fine needle aspiration and Tru-Cut needle biopsy was done from the mass.

Histopathology showed diffuse infiltration of large atypical lymphoid cells with high mitotic activity, similar to that seen in the initial biopsy. The tumor cells were CD45- and CD79a-positive and immunonegative for CD20, CD3, CD30, and EMA. MIB-1 index was more than 90%. Bone marrow aspiration and trephine biopsy showed no evidence of infiltration. The case was finally diagnosed as relapsed DLBCL with loss of CD20 expression. ESHAP (etoposide, methylprednisolone/Solu-Medrol, high dose cytosine arabinoside/HIDAC, and cisplatin) chemotherapy protocol was started with limited clinical response, and the patient currently remains under therapy and observation.

DLBCL accounts for 30–40% of adult non-Hodgkin lymphomas, with a predilection for males and elderly patients. There is marked variability in cellular morphology and variable expression of pan-B cell markers such as CD19, CD20, CD22, or CD79a. There is occasional expression of other markers such as CD5, CD10, BCL2, BCL6, or surface/cytoplasmic immunoglobulin. Proliferative index is usually high with Ki-67 labeling >40% in most cases.[1]

CD20 is a 35 kDa hydrophobic transmembrane protein expressed on pre-B and mature B lymphocytes and is present in approximately 95% of B-cell lymphomas. Rituximab is a murine/human chimeric anti-CD20 monoclonal antibody, which is effective in the treatment of CD20-positive B-cell lymphomas. Complete remission and 5-year event-free survival rates were significantly higher for patients receiving R-CHOP protocol as compared to CHOP protocol. Rituximab acts on CD20-positive cells by several mechanisms, which include antibody-dependent cellular cytotoxicity, complement mediated cytotoxicity, chemo-sensitization, and induction of apoptotic pathways.[1],[2],[3]

Relapse has been noted in up to 30% of DLBCL patients treated with R-CHOP. Rituximab resistance in prior responders is seen in more than 50% of relapses.[2],[4]

Change to a more aggressive phenotype is seen in relapsed cases of indolent lymphomas, however, there is no such histological change for relapsed/resistant DLBCL (RD). Loss of CD20 expression has been documented in several cases of lymphomas treated by rituximab, however, there have been fewer reports of such an antigenic change in RD.[4],[5],[6] Resistance to rituximab is mediated by CD20 loss, attributable to a down-modulation of CD20 mRNA expression or C-terminal deletion mutations of the CD20 gene. Emergence of resistant disease may also result from negative selection pressure, due to the selective elimination of CD20-positive cells by rituximab.[3],[6]

CD20 loss in DLBCL is marked by progressive disease with poor response and survival <1 year.[2],[4],[6] Assessing rituximab resistance is important in determining utility and cost-effectiveness of the treatment. Loss of CD20 can be utilized as a phenotypic marker for this purpose. Interference by circulating serum rituximab does not affect CD20 staining by IHC, and mandatory IHC evaluation of every relapsed case of B-cell lymphoma including DLBCL is recommended to direct further treatment-related decisions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Dunleavy K, Wilson WH. Diagnosis and treatment of diffuse large B-cell lymphoma and Burkitt lymphoma. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, et al., editors. Hematology: Basic Principles and Practice. 6th ed. Philadelphia: Saunders, Elsevier; 2013. p. 1236-41.  Back to cited text no. 1
    
2.
Duman BB, Sahin B, Ergin M, Guvenc B. Loss of CD20 antigen expression after rituximab therapy of CD20 positive B cell lymphoma diffuse large B cell extranodal marginal zone lymphoma combination: A case report and review of the literature. Med Oncol 2012;29:1223-6.  Back to cited text no. 2
    
3.
Wada N, Aozasa K. Loss of CD20 expression after rituximab therapy for B-cell lymphomas: A review of the literature. Cancer Clin Oncol 2012;1:1.  Back to cited text no. 3
    
4.
Jiang Y, Zhao Y, Dong X, Zhang S, Li Y, Wu G. Loss of CD20 expression in relapsed diffuse large B cell lymphoma after rituximab therapy: A case report and review of the literature. Chin Ger J Clin Oncol 2013;12:148-51.  Back to cited text no. 4
    
5.
Ferreri AJ, Dognini GP, Verona C, Patriarca C, Doglioni C, Ponzoni M. Re-occurrence of the CD20 molecule expression subsequent to CD20-negative relapse in diffuse large B-cell lymphoma. Haematologica 2007;92:e1-2.  Back to cited text no. 5
    
6.
Hiraga J, Tomita A, Sugimoto T, Shimada K, Ito M, Nakamura S, et al. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: Its prevalence and clinical significance. Blood 2009;113:4885-93.  Back to cited text no. 6
    

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Correspondence Address:
Subhashis Mitra
Department of Pathology, AMRI Hospitals, Kolkata - 700 029, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.182026

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