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Primary Breast Lymphoma - An Enigmatic Entity: Series from Tertiary Cancer Care Centre

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Annals of Medicine and Medical Sciences (2026) April 10, 2026 pp. 463 - 467
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Introduction

Primary breast lymphoma (PBL) is a rare presentation of non-Hodgkin lymphoma (NHL) and accounts for 1% of all NHLs, less than 3% of all extranodal lymphomas, and less than 0.5% of all breast malignancies [1-3].

PBL was first defined in 1972 by Wiseman and Liao [4], who established the following diagnostic criteria: the breast as the site of presentation, breast tissue in close relation with lymphomatous infiltration, absence of disseminated disease beyond the ipsilateral axillary lymph nodes, and no previous lymphoma diagnosis. PBL occurs largely in females with few cases reported in males [5]. Radiological findings are usually non-specific with lesions usually being hypoechoic without calcifications or spiculated margins [6].

Most PBLs are of B-cell phenotype, with diffuse large B-cell lymphoma (DLBCL) being the predominant type [7,8]. Less common types include: Follicular lymphoma (FL), Burkitt lymphoma (BL), extranodal marginal zone lymphoma (ENMZL), small-cell lymphocytic lymphoma and anaplastic large-cell lymphoma (ALCL) [9].

The recommended management includes chemotherapy, alone or combined with radiotherapy (RT). Surgery is not recommended as it has no impact on survival or recurrence [10,11]. Central nervous system (CNS) prophylaxis is recommended in high-grade PBL to control CNS involvement. Prognostically, PBL is similar to other lymphomas of similar histological type for which the Ann Arbor staging system or International Prognostic Index are used.

This study presents the types of PBLs seen at our centre, their clinical profile and pathological features along with their management.

Materials and Methods

This was a 10-year retrospective study from 2015-2024. All cases of PBL, diagnosed at our centre during this period, were retrieved from the archives. Only cases meeting the diagnostic criteria laid down by Wiesman & Liao [4], later modified by Hugh et al.,[12] were included in the study. Cases of extramammary lymphomas, secondarily involving breasts, were excluded. The clinical, radiological and pathological data of all cases with PBL, including their follow up and disease progression were collected from the hospital's electronic medical records.

Results

A total of 14 cases PBL were included in the study. All fourteen patients included, were females, aged between 24 and 73 years, (median age:48 years), with 3 of the patients being menopausal, while none were pregnant at the time of diagnosis. In all cases, no prior history of any breast pathology or breast surgery or breast implants could be elicited. All patients presented with a history of lump in the breast.

In the present study, all cases showed unilateral presentation. Mammography was available in six of 14 cases, which showed oval masses with circumscribed margins in 4 cases and indistinct masses in the other two. The Breast imaging reporting & data system (BIRADS) score varied from 3 to 6. Positron emission tomography-computed tomography (PET-CT) report, was available in 8 cases, which revealed single hypermetabolic mass in the breast in 7 cases and single case showing multiple soft tissue densities. The average size of the tumors was 4.4 cm with a maximum dimension of 10.3 cm. Two of these cases showed multiple quadrant involvement. Axillary lymph nodes were palpable in four cases, while 3 cases showed supraclavicular and internal mammary lymph node involvement. One case, in addition, had skin involvement. None of the cases had systemic disease at the time of presentation or on follow-up.

All cases underwent either trucut or excision biopsy followed by IHC analysis to confirm PBL and to further characterize the lymphoma. An extensive IHC panel of B and T cell antibodies was used, including CD20, CD3, CD2, CD7, CD15, CD79a, PAX5, CD30, CD43, CD15, CD10, BCL2, BCL6, MUM1, Ki67 and TdT. CK, and Vimentin were also used where needed. Thirteen of 14 cases showed diffuse expression of CD20, with the only negative case being a T cell lymphoma. The subtyping of NHLs revealed 9 cases of DLBCL, with 3 cases each showing, germinal centre (GC) like immunophenotype, and non-GC or activated B-cell (ABC) like immunophenotype. Two cases of DLBCL were not subclassified, while one case showed an aberrant expression of T cell-associated antigens. Other than DLBCL, 2 cases each of BL & ENMZL along with single case of ALK negative ALCL, were also seen in our cohort (Table 1).

Five patients of DLBCL underwent chemotherapy at our center: using Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, & Prednisone (R-CHOP), with or without etoposide. Intrathecal Methotrexate was given in two cases. Two cases of ENMZL received RT alone (24gy/12 fractions & 40gy/20 fractions). The patient with ALK negative ALCL received 6 cycles of EPOCH.

Follow-up was available in 6 cases, ranging from 4 months to 5 years (median follow-up:12 months), with no evidence of disease recurrence during this duration in all but 2 cases, which showed progressive disease after chemotherapy.

Table 1: Clinico-pathological characteristics of all cases of PBL
Cases 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Age (years) 50 40 73 44 67 43 46 52 64 39 24 54 54 55
BIRADS score NA 6 NA 5 NA NA NA NA 4 NA 4 4 NA 3
Nodal involvement - - - - SCLN IMLN AXLN - - AXLN IMLN - AXLN SCLN - AXLN IMLN SCLN - -
IHC Pos CD20 LCA CD20 BCL6 CD10 Ki-90% CD20 Ki-60% LCA MUM1 BCL6 CD20 BCL2* K-90% LCA CD20 PAX5 OCT2 Ki-70% CD3* CD4* CD7* CD2* CD43* BOB1* CD30* LCA CD20 CD10 cMYC BCL6 Ki-95% CD20 CD10 BCL6 cMYC Ki-95% CD20 BCL2 BCL6 PAX5 CD10 cMYC Ki-90% CD20 BCL2 CD23 MNDA Ki-10% LCA CD3 CD30 Ki-90% CD20 BCL2 BCL6 Ki-90% LCA CD20 CD5 BCL2 MUM1 cMYC Ki-90% CD20 BCL2 MUM1 BCL6 Ki-80% CD20 BCL2 MNDA Ki-5%  
Neg CK CD3 CK SYN CD56 CD30 CD23 CD3 CD5 CD10 CD23 CD34 cMYC EBER CK CD15 EBER S100 CK TdT cyclinD1   CK CD3 BCL2 CD3 CD5 CD30 TdT cyclinD1 LMO2 CD5 MUM1 cyclinD1 CK CD20 EMA CD10 CD15 PAX5 BCL6 ALK CD3 CD5 CD10 MUM1 cMYC CK CD3 CD10 CD8 CK CD5 CD10 cMYC CD5 CD10 BCL6 MUM1 CD43 CD23 cMYC cyclinD1
Diagnosis DLBCL DLBCL - GCB DLBCL DLBCL- ABC DLBCL with aberrant expression of T cell antigens Burkitt lymphoma Burkitt lymphoma DLBCL – GCB ENMZL ALK negative ALCL DLBCL – GCB DLBCL – ABC DLBCL – ABC ENMZL
Treatment NA R-EPOCH 6 cycles NA R-EPOCH + ITMTX 6 cycles R-CHOP 6 cycles NA NA R-EPOCH + ITMTX 2 cycles RT: 24Gy/ 12# 6 MV EPOCH 6 cycles R-CHOP + ITMTX 6 cycles NA NA RT: 40Gy/ 20#
Follow-up NA PD at 6 months NA NED at 5years SD at 18 months NA NA NA NA PD at 18 months NED at 6 months NA NA NED at 4 months

Discussion

The breast is a rare location for the development of a lymphoma. They can be PBL or secondary to systemic disease. PBL is defined as per the definition proposed by Wiseman and Liao [4], which was further modified by Hugh et al.,[12] which requires the presence of an atypical lymphoid population in the breast. Wiseman and Liao [4] suggested, there should be no antecedent diagnosis of lymphoma and no extramammary disease other than ipsilateral axillary nodes. However, Hugh et al.,[12] included cases with supraclavicular and internal mammary nodal involvement and patients having bilateral breast involvement without evidence of distant disease in their study.

PBLs present as a painless, palpable, large, rapidly growing, relatively mobile mass with associated skin retraction, erythema, or peau d’orange with or without ipsilateral axillary lymph nodes [13,14]. It is usually solitary, but can be multiple, as was observed in one of our cases. The B-symptoms associated with lymphomas is rarely seen in PBLs [15]. Bilaterality has been described in 11% of cases [9], however, in the present study, all cases showed unilateral disease.

The median age at diagnosis in the Asian population, according to two studies from Japan & South Korea, ranges from 48-53 years [16,17]. This is significantly lower than the median age of 64 years, seen in the Western population [18,19]. A similar finding was observed in our cohort, where the median age was 51 years (Table1). PBL occurs almost exclusively in females with few cases reported in males [20]. All patients in our cohort were females.

The radiological findings of PBLs can be nonspecific and cannot be differentiated from carcinoma breast. Mammograms show a solitary circumscribed mass without calcifications [15,21]. PET-CT, however, is a useful adjunct to rule out systemic disease and evaluate response to chemotherapy. It also adds value in staging and follow-up [22].

90% of PBLs are of B cell origin, with DLBCL being the commonest (50%). Similarly in our study, 13 out of 14 cases (93%) cases were B-cell lymphomas, with a predominance of DLBCL (70%). The lesser common types of B-cell lymphomas seen in breast include FL, ENMZL and BL [23,24]. BL although rare, shows a rapid and aggressive growth and can be fatal [25]. Two cases of BL were seen our study, however, both cases didn’t opt for treatment at our facility and were lost to follow up.

A single case of ALK-negative ALCL was also seen in our study. These T cell origin PBLs have shown higher incidences in post breast implant cases, in the last two decades [26-28]. Our single case of ALK-negative ALCL did not have any history of breast implants. The patient had progressive disease after 18 months, suggesting a poor prognosis when compared to DLBCL.

The frequently used treatment protocol for high grade lymphomas includes chemotherapy using Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, & Prednisone (R-CHOP), with or without etoposide, including intrathecal methotrexate as prophylaxis against CNS metastasis, which may be followed by consolidative RT. A similar treatment regimen was given to at least 6 patients with CNS cover in 3 cases.

Low grade lymphomas are very rare in breast [20], however, two cases of ENMZL were seen in our study. PBL-ENMZL is an indolent lymphoma characterized by small atypical cells with pale cytoplasm and irregular nuclei [29-31]. On IHC, they stain with CD20 and BCL2 with a low KI67 proliferation index as was seen in our study (5% and 10%). Both cases also expressed MNDA. Most PBL-ENMZL can be treated by lumpectomy or local RT or even active surveillance may suffice [23].

Conclusion

The breast is a rare site of involvement by a lymphoma and can be difficult to diagnose without thorough clinical, radiological and pathological workup. The clinical presentation and imaging findings of PBL are nonspecific and may overlap with carcinoma breast. Their treatment is vastly different depending on their grades. Adequate diagnosis requires biopsy and IHC, which is essential to avoid unnecessary surgical intervention. The treatment should be individualized and multimodal.

Abbreviations

PBL-Primary breast lymphoma, DLBCL- Diffuse large b cell lymphoma, ENMZL- Extra nodal marginal zone lymphoma, BL- Burkitts lymphoma, IHC immunohistochemistry, CNS-Central nervous system, GC-Germ cell, ABC-Activated B cell, FL-Follicular lymphoma, BL-Burkitt lymphoma, small-cell lymphocytic lymphoma and ALCL-anaplastic large-cell lymphoma, RT- Radiotherapy, IHC- Immunohistochemistry, BIRADS: Breast imaging reporting & data system, NA: Not available, SCLN: Supraclavicular lymphnode, AXLN: Axillary lymphnode, IMLN: Internal mammary lymphnode, Pos: Positive, Neg: Negative, SYN: Synaptophysin, MNDA- Myeloid cell nuclear differetiation antigen, R: Rituximab, E: Etoposide, P: Prednisone, O: Vincristine, C: Cyclophosphamide, H: Doxorubicin, ITMTX: Intrathecal methotrexate, RT: Radiotherapy, PD: Progressive disease, NED: No evidence of disease, SD: Stable disease.

Declarations

Ethical Approval

NA

Consent for publication

Taken

Acknowledgements

We are indebted to Department of Pathology, Rajiv Gandhi Cancer Institute New Delhi allow us to conduct this study.

Conflict of interest

No

Funding Statement

Nil

Authors’ contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Anila Sharma, Raja Langer, Ankur Kumar and Gurudutt Gupta. The first draft of the manuscript was written by Anila Sharma and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Section

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