Bilateral primary diffuse large B-cell lymphoma of the breast: diagnostic and surgical management—a case report

Introduction

Primary breast lymphoma (PBL) is a rare type of malignant breast tumor. Its clinical manifestations and imaging features often resemble breast hyperplasia or other breast tumors, making it prone to misdiagnosis. Ultrasound, as a routine examination method for breast diseases, plays a crucial role in the early detection and differential diagnosis of breast lymphoma. The following is a case report of the ultrasonic diagnosis of a case of B-cell non-Hodgkin’s lymphoma (B-NHL) of the breast, combined with a literature review, to discuss its imaging characteristics and key diagnostic points.

PBL accounts for less than 1% of all malignant breast neoplasms. The majority of cases are of B-cell origin, especially diffuse large B-cell lymphoma (DLBCL), followed by follicular, mucosa-associated lymphoid tissue (MALT), and small lymphocytic lymphomas (1-3). Secondary breast involvement by systemic B-NHL is more frequent than true PBL (1,3,4). Accurate diagnosis relies on histopathology, immunohistochemistry (e.g., CD20), and molecular tools such as immunoglobulin heavy/light chain gene rearrangement to confirm B-NHL (3,5).

In previous case series and reports, breast B-NHL usually appears on ultrasound as a hypoechoic, often irregular or oval mass with circumscribed or microlobulated margins; the orientation is usually parallel, similar to benign lesions (1-4,6,7). Lesions can be solitary or multiple, nodular or diffuse; in PBL cohorts, the average tumor size is typically large (5–7 cm) (1,4,8). Compared with invasive ductal carcinoma (IDC), microcalcifications are an uncommon finding (2,7,8). Color Doppler often shows internal blood flow signals, which can sometimes be abundant (3,4,6,8).

When ultrasonography examines axillary lymph nodes, findings such as cortical thickening, loss of the fatty hilum, and abnormal vascularity suggest a high possibility of lymphoma involvement (3,4,7). A 2020 retrospective study by Chen et al., which compared the ultrasound features of 32 patients with pathologically confirmed breast lymphoma and 30 patients with breast IDC, found that breast lymphoma lesions were significantly larger, more likely to be circumscribed, had fewer calcifications, and had richer blood flow signals (8). We present this article in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0133/rc).

Case presentation

A 38-year-old female was admitted to the hospital with the chief complaints of “toothache for 2 months, abnormal vaginal bleeding for 7 days, and heavy bleeding accompanied by dizziness for 2 days”. These systemic symptoms (especially anemia and thrombocytopenia) raised the suspicion of an underlying hematologic malignancy. There was neither personal nor family history of breast tumors or lymphoma. Neither medical attention was sought nor relevant treatment was received before. Physical examination revealed bilateral breast enlargement with palpable masses. The masses were firm in texture, relatively well-defined, without significant tenderness, and no enlarged axillary lymph nodes were palpated. From historical and current information, “thrombocytopenia, severe anemia, vaginal bleeding” was made as the admission diagnosis, prompted further investigation, leading to the breast ultrasound examination.

The patient underwent breast and axillary lymph node ultrasonography. The results indicated Breast Imaging-Reporting and Data System (BI-RADS) category 4 (suspicious) assessment. Disordered breast architecture and heterogeneous echogenicity of the glandular tissue were noted. Both breasts showed a grid-like echo pattern with localized hypoechoic areas: approximately 4.4 cm × 1.1 cm in the left breast and 1.9 cm × 1.0 cm in the right breast. The morphology was relatively regular, oriented parallel to the skin (wider-than-tall), with circumscribed margins and posterior acoustic enhancement. No obvious calcifications or liquefaction areas were seen (Figures 1,2). Color Doppler flow imaging (CDFI) showed relatively abundant arterial blood flow signals within bilateral masses, presenting as high-resistance flow (Figure 3A,3B). Bilateral axillary lymph nodes were visible, with the larger ones measuring 0.6 cm × 0.5 cm on the left and 0.8 cm × 0.4 cm on the right, showing clear structure (Figures 4,5).

Figure 1 Both breasts showed a grid-like echo pattern with localized hypoechoic areas: approximately 4.4 cm × 1.1 cm in the left breast.

Figure 2 Both breasts showed a grid-like echo pattern with localized hypoechoic areas: approximately 1.9 cm × 1.0 cm in the right breast.

Figure 3 CDFI showed relatively abundant arterial blood flow signals within bilateral masses, presenting as high-resistance flow. (A) Resistance index of the grid-like echo pattern in left breast was 0.69. (B) Resistance index of the grid-like echo pattern in right breast was 0.69. CDFI, color Doppler flow imaging.

Figure 4 Bilateral axillary lymph nodes were visible, with the larger ones measuring 0.8 cm × 0.4 cm on the right, showing clear structure.

Figure 5 Bilateral axillary lymph nodes were visible, with the larger ones measuring 0.6 cm × 0.5 cm on the left, showing clear structure.

Based on the ultrasound findings, breast malignancy was initially suspected. Following this, a comprehensive systemic workup was initiated. Bone marrow examination revealed hypercellular marrow (approximately 90%) with sheets of immature lymphoid cells. Flow cytometry identified a 48.6% population of monoclonal CD5–CD10⁺ B-lymphocytes. Cytogenetic and molecular analyses demonstrated a t(8;14)(q24;q32) translocation, MYC rearrangement by fluorescence in situ hybridization (FISH) (23% of cells), and mutations in ID3, KMT2C, ARID1A, and CCND3. Whole-body positron emission tomography-computed tomography (PET-CT) showed diffuse or multifocal hypermetabolism involving the bone marrow, breasts, uterus, bilateral adnexa, gastric wall, and peritoneum, accompanied by ascites. Serum lactate dehydrogenase (LDH) level was elevated at 600 U/L. Contrast-enhanced brain magnetic resonance imaging (MRI) revealed no metastases. Meanwhile, an ultrasound-guided core needle biopsy of the breast mass was performed. Pathology indicated lymphoid hyperplasia. Immunohistochemistry was positive for CD20, negative for CD3 and Cytokeratin (CK, AE1/AE3), and EBER was negative. The Ki-67 (MIB-1) proliferation index was approximately 95%. Combining the clinical and imaging findings, the final diagnosis was breast B-NHL.

The combined findings from the breast biopsy, extensive bone marrow involvement, widespread extranodal disease on PET-CT, and the specific genetic profile [t(8;14) translocation and MYC rearrangement] necessitate a revision of the initial diagnosis. The final integrated diagnosis is systemic Burkitt-like lymphoma with 11q aberration, extensively involving the breast and multiple other extranodal sites, classified as Ann Arbor Stage IV B.

The patient received chemotherapy with the Pola-R-CHP (polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisolone) regimen. During the course of treatment, bone marrow suppression occurred after chemotherapy. Symptomatic treatments such as eltrombopag and Jisaixin were given, and preventive anti-infection measures were also carried out. The patient returned to the hospital for follow-up and assessment every three months. The most recent breast ultrasound did not report any obvious lesions (Figure 6A,6B).

Figure 6 The most recent breast ultrasound did not report any relevant lesions. (A) Low-echoic nodules was identified in the right breast. (B) No significant abnormalities were shown in the left breast.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompany images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

PBL is a rare but distinct extranodal lymphoma subtype, accounting for 0.04–0.5% of all malignant breast tumors (1,4). Over 98% of cases occur in females (9); its clinical and imaging features often overlap with those of breast carcinoma or benign lesions, easily leading to misdiagnosis (1,9,10). While the presentation of bilateral breast masses in this case aligns with the known, albeit uncommon (approximately 10–11%), occurrence of bilateral PBL (1), the educational value of this report extends beyond a mere description of a rare entity. It underscores the diagnostic challenges, highlights the pivotal role of comprehensive systemic staging, and provides a platform to discuss contemporary management paradigms, particularly in the context of evolving therapeutic strategies.

Unusual ultrasound presentation and diagnostic pitfalls: the “grid-like echo” pattern

The initial ultrasound in this case revealed a distinctive “grid-like echo” pattern within the bilateral breast lesions. This sonographic morphology, characterized by intersecting linear hyperechoic strands within a hypoechoic background, is infrequently documented. It may represent the infiltrative growth pattern of lymphoma cells dissecting through the breast parenchyma and Cooper’s ligaments, creating acoustic interfaces distinct from the more common “pseudokidney” or “target-like” signs associated with lymphoma (11). This presentation underscores a key diagnostic pitfall. The well-defined margins, hypoechogenicity, and posterior acoustic enhancement observed can be strikingly similar to a benign fibroadenoma. Conversely, the presence of rich internal vascularity on color Doppler imaging, also observed here, is a feature more commonly associated with malignancy, particularly IDC. The diagnostic challenge lies in this overlap. Unlike IDC, PBL typically lacks spiculated margins, microcalcifications, and significant architectural distortion on mammography (1). The “grid-like echo” pattern, while not pathognomonic, could serve as an additional sonographic clue prompting consideration of a lymphoproliferative disorder in the differential diagnosis of a circumscribed, hypervascular breast mass, especially when bilateral (8).

The imperative of comprehensive staging and revised diagnosis

A pivotal lesson from this case is the demonstration of how initial diagnostic impressions can be radically altered by exhaustive systemic evaluation. The breast core biopsy confirmed a high-grade B-cell lymphoma. However, subsequent bone marrow biopsy revealed near-total replacement by immature lymphoid cells. Critical cytogenetic and molecular analyses identified a t(8;14)(q24;q32) translocation and MYC gene rearrangement, alongside mutations in ID3, KMT2C, ARID1A, and CCND3. This genetic profile, coupled with a CD10⁺, B-cell lymphoma 2 (BCL2)⁻ immunophenotype and an exceptionally high Ki-67 index (~95%), is classic of Burkitt lymphoma (BL) or Burkitt-like lymphoma with 11q aberration (12,13). Furthermore, whole-body PET-CT revealed extensive extranodal involvement, confirming widespread systemic disease. Consequently, the diagnosis was revised from a primary breast DLBCL to systemic BL/lymphoma with 11q aberration, Ann Arbor Stage IV B, presenting with prominent breast involvement. This reclassification has profound therapeutic implications, as it shifts the management from a regimen designed for DLBCL to an intensive, multi-agent chemotherapy protocol appropriate for BL, underscoring that what appears to be a “primary” breast lymphoma may, in fact, be the initial manifestation of a systemic disease (14).

Contemporary management principles: from surgery to systemic therapy

The management of PBL, and by extension systemic lymphomas presenting in the breast, has undergone a fundamental paradigm shift. Robust evidence confirms that the cornerstone of treatment for aggressive lymphomas is systemic chemotherapy (1,4). R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) remains the global first-line standard for DLBCL (15,16). For high-risk or specific subtypes like BL, more intensive regimens are employed. In this context, the role of surgery is confined to obtaining adequate tissue for definitive histopathological and molecular diagnosis via core needle or excisional biopsy (1,17). Radical surgical resection (e.g., mastectomy) provides no survival benefit and is not indicated (4,18). The surgeon’s critical responsibility transitions to performing a diagnostic biopsy and ensuring seamless referral to a hematology-oncology team within a multidisciplinary team (MDT) framework.

Central nervous system (CNS) prophylaxis: a critical consideration in high-risk disease

For patients with high-risk features, CNS prophylaxis is a vital component of management. Involvement of certain extranodal sites, including the breast, is associated with an elevated risk of CNS relapse (19,20). Our patient, with bilateral breast and extensive bone marrow involvement, falls into a high-risk category. The CNS International Prognostic Index (CNS-IPI) is a validated tool to stratify this risk (19,21). Although consensus on the optimal prophylactic method is lacking, common strategies include intrathecal (IT) chemotherapy (e.g., methotrexate, cytarabine) or high-dose systemic methotrexate (HD-MTX) that crosses the blood-brain barrier (19,22). Guidelines suggest considering CNS prophylaxis for patients with breast involvement (23).

The evolving landscape: novel agents and future directions

Despite the efficacy of R-CHOP, a significant proportion of patients experience refractory or relapsed (R/R) disease (24). The treatment landscape is rapidly evolving with the integration of novel immunotherapies. For R/R DLBCL, options now include antibody-drug conjugates (ADCs) like polatuzumab vedotin, bispecific T-cell engagers (e.g., glofitamab), and chimeric antigen receptor (CAR) T-cell therapy, which have shown promising results in clinical trials (15,24). The recognition of distinct genetic subtypes of DLBCL may pave the way for more personalized, biologically driven therapies in the future (15).

Consideration of rare entities and diagnostic nuances

Throughout the diagnostic process, vigilance for other rare lymphomas is essential. In patients with a history of breast implants, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) must be considered in the differential diagnosis; its management typically involves implant removal with complete capsulectomy (25,26).

In conclusion, this case of bilateral breast lymphoma, ultimately diagnosed as systemic BL, serves as a compelling clinical lesson. It highlights: (I) the diagnostic ambiguity of the “grid-like echo” ultrasound pattern and its role in the differential diagnosis with breast carcinoma; (II) the absolute necessity of comprehensive staging, including bone marrow examination and advanced cytogenetics, to avoid misdiagnosing a systemic lymphoma as a primary breast tumor; (III) the exclusively diagnostic role of surgery; and (IV) the modern treatment paradigm centered on risk-adapted intensive chemotherapy, CNS prophylaxis for high-risk patients, and the evolving role of novel immunotherapies. A heightened awareness of these principles within a robust MDT is paramount to optimize outcomes for this rare and challenging disease.

Conclusions

Surgery plays a critical role in the differential diagnosis of breast B-NHL by providing the necessary tissue for definitive pathological confirmation. Typical sonographic features include a solitary, well-defined, hypoechoic mass with homogeneous internal echogenicity and rich vascularity. Definitive diagnosis relies on pathology and immunohistochemistry. The cornerstone of treatment is systemic chemotherapy, and radical surgical resection does not improve patient survival. Therefore, the indispensable role of surgery lies in its diagnostic, not therapeutic, capacity. Clinical awareness of breast lymphoma should be heightened to avoid misdiagnosis and missed diagnosis. A multidisciplinary approach integrating imaging, pathology, and oncology is paramount for optimal management.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0133/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0133/prf

Funding: This study was supported by the China-Japan Friendship Hospital Talent Recruitment Project (No. 2019-RC-2).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0133/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompany images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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