|Year : 2015 | Volume
| Issue : 3 | Page : 658
CD20 negative primary diffuse large B cell lymphoma of breast: Role of Pax-5
Saumya Shukla, Namrata Punit Awasthi, Pradyumn Singh, Nuzhat Husain
Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
|Date of Web Publication||9-Oct-2015|
Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow - 226 010, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Pax-5 is a B cell marker, the expression of which is detectable in as early as the pro B stage, and subsequently, in all further stages of B cell development except the plasma cells. Malignant lymphomas of breast are uncommon and occur as either primary or secondary lesions. Primary lymphoma is a rare disorder of breast and constitutes less than 0.6% of all breast malignancies and 2.2% of extranodal lymphomas. We report an unusual case of CD20 negative Pax-5 positive primary diffuse large B cell lymphoma (DLBCL) of breast. The case highlights the diagnostic challenge posed by extranodal CD20 negative DLBCL. Pax-5 immunohistochemistry has diagnostic benefit as a B-cell marker in the work-up of undifferentiated malignant neoplasms. Although it is available for nearly a decade now, it is not widely used. Pax-5 is a valuable addition to the armamentarium of markers currently available for lymphoma subtyping.
Keywords: Breast, pax-5, primary lymphoma
|How to cite this article:|
Shukla S, Awasthi NP, Singh P, Husain N. CD20 negative primary diffuse large B cell lymphoma of breast: Role of Pax-5. J Can Res Ther 2015;11:658
| > Introduction|| |
Pax-5, is a relatively new marker for B-lymphoid cells that encodes for B-cell specific activator protein (BSAP). It is a nuclear protein in the paired box containing (Pax) family of transcription factors involved in organ development and tissue differentiation. In diffuse large B cell lymphoma (DLBCL), expression of Pax-5 parallels that of CD20, which is considered to be a pan-B cell marker and is lost in terminally differentiated tumors. , We report an unusual case of CD20 negative Pax-5 positive primary DLBCL of breast. The case highlights the diagnostic challenge posed by extranodal CD20 negative DLBCL.
| > Case report|| |
A 42-year-old woman presented with a breast lump of 6 month's duration. The lump was firm and hard; measured 6 × 5 cm in size. Ancillary investigations did not reveal any organomegaly or lymphadenopathy. A lumpectomy was performed at a peripheral center and reported as infiltrating ductal carcinoma. She was started on adjuvant chemotherapy which included the combination of cyclophosphamide, 5-fluorouracil, and methotrexate. Despite six cycles of chemotherapy, the response was very poor following which the paraffin blocks were sent to our institute for review. The histopathological examination revealed diffuse proliferation of atypical round cells with large areas of necrosis. The mitotic index was high and glandular/tubular differentiation was absent [Figure 1]. A differential diagnosis of carcinoma with small cell morphology, hematolymphoid neoplasm, and sarcoma with small cell morphology was considered. A primary panel of immunohistochemistry was performed, which include cytokeratin, leukocyte common antigen (LCA), synaptophysin, and desmin. The tumor was diffusely positive for LCA. A second line of immunohistochemical staining was performed to further categorize the neoplasm, which included CD20, CD3, CD30, CD15, CD10, ALK1, and Ki-67 proliferation index. The tumor was negative for all these markers and the Ki-67 proliferation index was 60-70%. A third panel of immunohistochemistry was performed, which included CD138 and Pax-5. The tumor cells were positive for Pax-5 and negative for CD138 [Figure 2] and [Figure 3]. Bone marrow examination was normal. Based on the above findings, diagnosis of primary DLBCL of breast was rendered.
|Figure 1: (a) Sheets of monomorphic small, round cells with absence of glandular/tubular differentiation (hematoxylin and eosin (H and E), ×20). (b) Small, atypical cells with scant amount of cytoplasm, vesicular nucleus with conspicuous nucleoli (H and E, ×40)|
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|Figure 2: Immunohistochemistry; cytokeratin: Highlights the entrapped tubules (diaminobenzidine (DAB), ×20), leukocyte common antigen (LCA): Diffuse positive (DAB, ×20), CD20: Negative (DAB,×20), CD3: Negative (DAB, ×20), CD30: Negative (DAB, ×10), and Ki-67 index: 60-70% (DAB, ×20)|
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|Figure 3: Immunohistochemistry; CD138: Negative (DAB, ×20) and Pax-5: Positive (DAB, ×20)|
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| > Discussion|| |
Malignant lymphomas of breast are uncommon and occur as either primary or secondary lesions. Primary lymphoma is a rare disorder of breast and constitutes less than 0.6% of all breast malignancies and 2.2% of extranodal lymphomas. Most breast lymphomas are the non-Hodgkin's type (NHL), which represent approximately 70-90%. In patients diagnosed with NHL, primary involvement of the breast is seen in 0.4-0.7% of the cases. The criteria included for primary breast lymphoma designation are: (1) Normal tissue and lymphomatous infiltrate in close association, (2) no evidence of systemic lymphoma, (3) no concurrent nodal involvement (except axillary nodes), and (4) no previous history of lymphoma.  The present case fulfills these criteria, however, negativity for CD20, which is the most commonly utilized pan B-cell marker makes this case challenging.
Pax-5 is a relatively new marker, the expression of which is detectable in as early as the pro B stage and subsequently in all further stages of B cell development except the plasma cell where it is downregulated. ,, Pax-5 is essential for B lineage commitment and progression of B cell development. In normal lymphoid tissues, Pax-5 is expressed in nucleus of B cells and absent in plasma cells. In reactive lymphoid tissues, intense reactivity of the mantle zone and weak-to-moderate reactivity of the germinal center are noted. Pax-5 is detected in all cases of precursor and mature B cell NHL/leukemia, in Reed-Sternberg cells of Hodgkin lymphoma. Pax-5 expression is absent in less than 5% cases of DLBCL, multiple myeloma, and plasmacytic leukemia.  All the T cell NHLs are negative for Pax-5. The common markers of B cell lineage are CD19, CD20, CD79a, and Pax-5. The sensitivity and the specificity of these markers are variable. ,,
CD20 is an excellent pan B-cell immunophenotypic marker because CD20 is highly expressed on the surface of 90-95% of normal and neoplastic B lymphocytes, however, it is not expressed on immature B precursors and plasma cells. Li et al., have reported 28 out of 1,456 cases (1.9%) of primary DLBCL to be CD20 negative.  Most of these cases have been reported to be plasmablastic variants of DLBCL (primary effusion lymphomas, anaplastic lymphoma kinase positive large B-cell lymphoma, and human immunodeficiency-virus associated plasmablastic lymphoma) and have been reported to have worse outcomes compared to other DLBCL. 
Rituximab is a chimeric monoclonal antibody that recognizes the human CD20 antigen. This drug is commonly used in the treatment of B cell NHLs. CD20 expression is generally reduced or lost following the use of rituximab.  In such cases, recurrences may be difficult to demonstrate by CD20 alone, and hence, Pax-5 would be extremely beneficial.
| > Conclusion|| |
Pax-5 immunohistochemistry has diagnostic benefit as a B cell marker in the work-up of undifferentiated malignant neoplasms. Although it is available for nearly a decade now, it is not widely used. Pax-5 is a valuable addition to the armamentarium of markers currently available for lymphoma subtyping.
| > References|| |
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[Figure 1], [Figure 2], [Figure 3]