Indian Journal of Pathology and Microbiology

: 2015  |  Volume : 58  |  Issue : 4  |  Page : 546--549

Primary Burkitt's lymphoma of the breast without Epstein-Barr virus infection: A case report and literature review

Jianguo Wei1, Caixia Lin2, Chunwei Xu3, Qun Xi4, Cheng Wang1,  
1 Department of Pathology, Shaoxing People's Hospital, Shaoxing, People’s Republic of China
2 Department of Oncology, The People's Hospital of Jiangshan, Jiangshan, Zhejiang, People’s Republic of China
3 Department of Pathology, The General Military Hospital of Beijing PLA, Beijing 100700, People’s Republic of China
4 Department of Ultrasound, The General Military Hospital of Beijing PLA, Beijing 100700, People’s Republic of China

Correspondence Address:
Dr. Chunwei Xu
Department of Pathology, The General Military Hospital of Beijing PLA, Nanmen Warehouse 5, Dongsishitiao Street, Dongcheng, Beijing 100700
People’s Republic of China


Burkitt lymphoma (BL) is a highly aggressive neoplasm, which arising from the germinal center or post germinal center B-cell. Primary breast lymphomas are extremely rare, and the most common histologic type is diffuse large B-cell lymphoma. Primary BL of the breast is much less common than the other types of lymphoma. Here, we report an extremely rare case of a 37-year-old Chinese female with localized bilateral breast, who was referred to our institution for bilateral breast swelling. The left breast tissue ultrasonography showed the short axis measuring 20.3 mm × 18.8 mm and the long axis measuring 22.1 mm × 20.8 mm soft tissue mass. The right breast tissue ultrasonography showed the short axis measuring 30.2 mm × 26.9 mm and the long axis measuring 33.5 mm × 2.18 mm. Coarse needle biopsy of breast masses demonstrated a non-Hodgkin's B-cell lymphoma. The patient underwent a bilateral mastectomy. Histological examination of the tumor showed a characteristic "starry sky" pattern, the medium-sized tumor cells were a monotonous pattern of growth, and there were many abnormal mitotic figures. The neoplastic cells strongly expressed CD20, CD79-μ, MUM-1, PAX-5, CD43 and Bcl-6, Ki-67 were nearly 100% positive, but negative for CD10, Bcl-2 and TdT. By fluorescence in situ hybridization an IGH-MYC gene fusion was detected in the tumor tissue which indicating the presence of a typical BL translocation t(8;14)(q24;q32). The final histopathological diagnosis was primary BL of the breast.

How to cite this article:
Wei J, Lin C, Xu C, Xi Q, Wang C. Primary Burkitt's lymphoma of the breast without Epstein-Barr virus infection: A case report and literature review.Indian J Pathol Microbiol 2015;58:546-549

How to cite this URL:
Wei J, Lin C, Xu C, Xi Q, Wang C. Primary Burkitt's lymphoma of the breast without Epstein-Barr virus infection: A case report and literature review. Indian J Pathol Microbiol [serial online] 2015 [cited 2021 Aug 3 ];58:546-549
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Primary breast lymphoma accounts for only 0.05-0.25% of all breast malignant tumors and 2% of extranodal malignant lymphomas.[1] Most primary breast lymphomas are origin from B-cell, and the most common histologic type is diffuse large B-cell lymphoma (DLBCL), mucosa-associated lymphoid tissue (MALT) lymphoma and follicular lymphoma. Primary Burkitt's lymphoma (BL) of the breast is extremely rare than the other types of B-cell lymphoma and is a highly aggressive non-Hodgkin's B-cell lymphoma with an extremely short doubling time. According to the World Health Organization, BL can be classified into three subtypes: Endemic, sporadic and immunodeficiency-associated BL. Although they are different in geographic distribution and clinical presentation, but they have similar morphology and immune phenotypic features, and all possess translocation of the MYC gene.[2] Here we describe a case of a 37-year-old Chinese female who was admitted to our hospital with painless bilateral breast enlargement. The histopathological, immunohistochemical features and fluorescence in situ hybridization (FISH) analysis of MYC (8q24) of the excised tumor were characteristic of supporting the diagnosis of BL. However, due to its rarity, little is known concerning the origin, natural history and effective treatment of primary BL of the breast. Here, we report a case of a primary BL of the breast and present a brief review of the literature.

 Case Report

A 37-year-old Chinese female patient presented with localized bilateral breast swelling for 5 months. She had 10 years history of HBV infection. On physical examination, blood pressure was recorded as 105/84 mmHg, heart rate was 84 beats/min, respiratory rate was 20 breaths per min and temperature was 37°C. The laboratory test results demonstrated a normal red blood count, as well as normal levels of myelogram, but there was a high white blood count, which may be with infections, and the serum lactate dehydrogenase (LDH) was elevated at 843 IU/dL. In addition, the test results for Epstein-Barr virus (EBV) viral capsid antigens were negative. Furthermore, the left breast tissue ultrasonography showed the short axis measuring 20.3 mm × 18.8 mm [Figure 1]a and the long axis measuring 22.1 mm × 20.8 mm [Figure 1]b soft tissue mass, and the left axillary lymph nodes were enlarged and the largest measured 10.7 mm × 10.7 mm in size [Figure 1]c; and the right breast tissue ultrasonography showed the short axis measuring 30.2 mm × 26.9 mm [Figure 1]d and the long axis measuring 33.5 mm × 2.18 mm [Figure 1]e, and the right axillary lymph nodes were enlarged and the largest measured 19.6 mm × 11.8 mm in size [Figure 1]f. Coarse needle biopsy of breast masses demonstrated a non-Hodgkin's B-cell lymphoma. The patient underwent a bilateral mastectomy. Our patient received adjuvant chemotherapy after the operation, she had no local recurrence or metastasis after 9 months follow-up.{Figure 1}

Pathological examination

On gross examination, the excised tumor specimen measured 30 mm in diameter, cross-sections of the tumor revealed a firm, grayish-white, texture medium mass without hemorrhage and necrosis. Microscopically, atypical medium-sized lymphocytes with a widely monotonous growth pattern, diffusely infiltrated between the lactating mammary gland [Figure 2]a, with the starry sky phenomenon [Figure 2]b, numerous mitosis and apoptosis were seen. Immunohistochemical staining was then performed with the primary antibodies as shown in [Table 1]. The results showed that the residual breast acinar cells were positive for CK [Figure 3]a and the neoplastic cells were positive for CD20 [Figure 3]b, CD79-α, MUM-1 [Figure 3]c, Pax-5, CD43 and Bcl-6, Ki-67 were nearly 100% positive [Figure 3]d, but negative for CD3, CD5, CD10, CD21, CD23, CD45RO, CyclinD1, Bcl-2 and TdT. EBV (in situ hybridization) was negative. Analysis using the C-MYC break-apart detection probe (Guangzhou LBP Medical Science Technology Co., Ltd., Guangzhou, China) was also performed and the results revealed that ~90% of the neoplastic cells exhibited red and green signal separation, which indicated that chromosome breakage and translocation of the MYC gene had occurred in the neoplastic cells [Figure 4].{Figure 2}{Table 1}{Figure 3}{Figure 4}


Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma of the B-cell. Three distinct clinical forms of BL based upon the epidemiological distribution are recognized: Endemic, sporadic, and immunodeficiency-associated. Extrandal sites are the most commonly involved with some variation according to the clinical variants. Endemic BL is associated with EBV and is often seen in Africa, and the most common affected sites are the jaws and other facial bones, the distal ileum, cecum, omentum, kidneys, long bones, thyroid, salivary glands and breasts may also be affected either with or without jaw involvement. Sporadic BL is found worldwide, 30% of patients are involved by EBV and the majority presents with abdominal masses, and the ileo-caecal region represents the most frequent site of involvement, similarly to endemic BL, ovaries, kidneys, thyroid and breasts are also frequently involved.[3] Immunodeficiency-associated BL occurs in immunocompromised patients, such as AIDS patients and organ transplant recipients, nodal localization is frequent as well as bone marrow involvement.[4]

Primary BL of the breast is extremely rare, the diagnostic criteria including the histopathological specimens has closed association of mammary tissue and lymphomatous infiltration, absence of coexistent widespread disease except the appearance of ipsilateral axillary lymph nodes, and absence of extramammary lymphoma or systemic lymphoma. Primary BL of the breast have a specific clinical manifestation (often bilateral and massive), with a rapid spread and a poor prognosis, and it usually affects the bilateral breast of puberty, pregnancy or lactation.[1],[5] To the best of our knowledge, only 48 cases of BL of the breast have been previously reported in the English-language literature from 1967 to 2013. Of these 48 cases, 27% (13/48) occurred during pregnancy, 31% (15/48) occurred during the lactational period, and the times of occurrence of the others were not available. The ages of all the patients which were reported ranging from 12 to 36 years. The exact etiology of primary BL of the breast may not be known, and it is of interest that most patients should be diagnosed at pregnancy or lactation, our patient was a lactating woman, so we think hormones may play an important role in the pathogenesis. Some reports pointed out that it may be associated with EBV infection. However, Our patient was negative for EBV. Therefore, we hypothesized that there was no direct relationship between them.

There are no tumor markers or imaging characteristics that allow a preoperative diagnosis, and all cases have been diagnosed after surgical resection or at necropsy. The diagnosis is combined with morphology, immunophenotyping and genetic analysis. The tumor of our patient showed a medium-sized and consistent atypical lymphoid cells diffuse infiltration in the breast tissues, typical of starry sky phenomenon, tissue cells engulfing apoptotic bodies, a unique immunophenotype with the expression of CD20, CD79-α, MUM-1, Pax-5, CD43 and Bcl-6, a Ki-67 proliferation index were nearly 100% positive, Bcl-2 and TdT was negative. Interestingly, MUM-1 was strong positive but CD10 was negative, which brings some difficulty for diagnosis. However, FISH analysis of MYC (8q24) was positive. Therefore, the final diagnosis was Primary BL of the breast.

MUM-1 positive but CD10 negative is very rare immunophenotype for BL, only a few reports of BL show that CD10 was negative, and MUM-1 expression of BL was not consistent in the literature. Gualco et al.[6] pointed out nearly 40.5% (90/222) of the BL were positive for MUM-1. Chuang et al.[7] found only 17.5% (5/28) of the BL were positive for MUM-1. The vast majority of BLs have a translocation of the c-MYC proto-oncogene from chromosome 8 to the IGH gene region of chromosome 14b (t[8;14]), and only in a few cases, the c-MYC gene is translocated to the κ-light chain loci on chromosome 2 (t[8;2]) or to the λ-light chain on chromosome 22 (t[8;22]). Dave et al.[8] determined that abnormal MYC gene expression is a sign of BL, which indicates that abnormalities in the MYC gene have become a genetic trait of BL and significant for diagnosis. FISH analysis of our patient's breast mass detected the classical translocations. MYC/IgH fusion gene provide a theoretical basis to diagnosis of BL.

It is important to characterize the lymphoma, with flow and FISH for accurate classification and treatment. Flow cytometry (FCM) is usually better than FISH in lymphoma classification, and compared with FISH, there is no limitation. However, BL have C-MYC amplification, so FISH is better than FCM. The most important thing is that FCM is made with fresh tissue and living cells, we didn't keep fresh tissue, so we did not do it. At present FCM detection have not very big significance for BL, and general patients don't do it, so FISH have extremely important significance in the diagnosis of BL.

The differential diagnosis included DLBCL, MALT, lymphoepithelioma-like carcinoma, and B-cell lymphoblastic lymphoma/leukemia. Although DLBCL and BL may appear a similar morphology with the starry sky phenomenon, medium-sized cells, a high proliferation index and the MYC gene rearrangement, at present, the application of immunohistochemistry is considered to be the most effective method, as the positive results for CD20, CD10 and Bcl-6, but negative for Bcl-2, together with the high Ki-67 proliferation index (usually >95%), which are able to determine a definitive diagnosis for the majority of BL. MALT is the second common type of primary breast lymphoma, which is composed of heterogeous small B-cells including centrocyte-like cells, small B lymphocytesmonocyte-like B-cells and immunoblastic-like cells. In addition, MALT does not express CD10, Bcl-6 and Ki-67 proliferation index that is much lower than that observed in BL. Lymphoepithelioma-like carcinoma is characterized by a carcinoma with stromal heavy lymphocyte infiltration, and immunohistochemical staining for pan-cytokeratin was positive. It is difficult to differentiate BL from B-cell lymphoblastic lymphoma/leukemia according to morphology simply. However, immunohistochemistry is useful for distinguishing them because BL does not express TdT, CD34 and CD99, whereas the latter does.

Recently, there is no unified treatment plan about the primary lymphoma of breast, radiation therapy and chemotherapy are the main treatment. When chemotherapy and radiotherapy can't control the progress of the disease, surgical resection should be considered. The prognosis of early BLs is good. Some authors have reported 5 years survival rates up to 89% and 50% for stages I and II, respectively, but if it involved the multiple organ or tissue, the prognosis is very poor, the median survival time is about 6 months, bone marrow involvement is a signal of poor prognosis, some patients who received CHOP chemotherapy had a better prognosis.[9] Some patients often appear high uric acid and high LDH.[10] Our patient had started in breast surgery in hospital, considering tumor size, the patient's economic, own conditions and their own will, and before surgery, coarse needle biopsy of breast masses demonstrated a non-Hodgkin's B-cell lymphoma. And was not diagnosed with BL, surgical resection was finally chosen and the patient accepted the chemotherapy after surgery. Our patient's LDH was 843 U/L, bone marrow does not be involved, and liver function was normal after four times of chemotherapy, the long-term therapeutic effect and prognosis of our patient will be further followed-up.


Burkitt lymphoma of the breast is an extremely rare but highly invasive neoplasm. The most typical histological feature is a starry star phenomenon, accompanied with hyperplasia of mammary gland and secretion characteristics. The typical phenotype is IgM+/CD10+/Bcl2-/Bcl6+ and almost 100% Ki-67 proliferation index. The immediate diagnosis and timely initiation of chemotherapy may provide a better prognosis, with prolonged progression-free survival.

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