Primary Breast Lymphoma in a Young Female: Non-Hodgkin’s Diffuse Large B-Cell Lymphoma in the Presence of Intact Breast Prostheses

Breast implants are among the most frequently used medical devices for esthetic and reconstructive purposes [1]. Primary breast lymphoma (PBL) is a rare type of non-Hodgkin lymphoma that primarily affects the breast. It accounts for less than 1–2% of all non-Hodgkin lymphomas, with diffuse large B-cell lymphoma (DLBCL) being the most common type. PBL is defined by the breast being the main or only site of lymphoma occurrence [2‒5]. The definition of PBL encompasses the co-occurrence of mammary tissue and lymphoid infiltrate nearby, without any indication of widespread lymphoma or a history of extra-mammary lymphoma [6, 7]. Most PBL cases are classified as non-Hodgkin’s B-cell lymphoma, constituting approximately 50% of all breast lymphomas. Among these, DLBCL is the most prevalent subtype [8‒10]. In 1972, Wiseman and Liao [6] introduced the concept of PBL, describing it as lymphoma infiltrating breast tissue, with or without the involvement of regional lymph nodes [11, 12]. PBL symptoms are nonspecific, making diagnosis challenging. PBL typically presents as a painless, palpable mass similar to breast carcinoma. Diagnosis relies on histopathological biopsy and immunohistochemical staining. Less common symptoms include skin changes and nipple involvement [8]. High-grade lymphomas often cause diffuse breast enlargement, whereas lower grade tumors present nodular patterns [13, 14]. PBL can be primary or metastatic, and it is more aggressive with a worse prognosis compared to extranodal non-Hodgkin lymphomas in other areas like the digestive system. Identifying PBL can be complicated, especially when distinguishing it from primary breast carcinoma with concurrent lymphoma [15, 16]. Herein, we present a case of PBL – non-Hodgkin’s DLBCL in a 24-year-old woman who had undergone permanent breast prosthesis placement 2 years before the diagnosis. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000543952).

A 24-year-old female presented to our department with a palpable mass in the right breast. The lesion had initially manifested 4 months prior and had exhibited progressive enlargement. The right axillary and breast masses were accompanied by erythema, cutaneous dimpling in the right breast, and elevated serum prolactin levels. The patient reported no pain or nipple discharge. She denied experiencing thoracic discomfort, weight loss, fatigue, dyspnea, cough, pyrexia, or night sweats. Her medical history included rhinoplasty 6 and 3 years prior, gastric sleeve and abdominoplasty 8 years prior, and breast augmentation 2 years prior. Ultrasonographic examination of the breasts and axillary regions revealed masses in the breast and axilla. Notably, the silicone implants were confirmed to be intact and unaffected (shown in Fig. 1).

A tru-cut biopsy of the masses demonstrated that all tissue cores exhibited intense mitotically active atypical lymphocytic proliferation, consistent with malignant non-Hodgkin’s lymphoma involving the axillary lymph node and right peri-nipple mammary tissue. Furthermore, immunohistochemical analysis revealed that the tumor cells displayed diffuse positivity for the CD20 marker, while the CD3 marker was negative. Ki67 marker was highly positive in more than 95% of the tumor cells. Consequently, the diagnosis was PBL – non-Hodgkin’s DLBCL, with high-grade features. To further evaluate the extent of the disease, a whole-body CT scan with contrast was performed. A relatively large, heterogeneous-density mass was observed in the right breast, exhibiting irregularity at its margins and a non-homogeneous appearance with a necrotic center of decreased density located in the medial aspect of the breast, anterior and superior to the prosthesis, slightly displacing it inferiorly and laterally. It appeared surrounded by edema and measured 4.5 × 4.5 × 5 cm, with some adjacent millimeter-sized nodules. There was a uniform, non-severe thickening of the skin overlying the mass. The prostheses bilaterally appeared intact, without any signs of rupture either intracapsularly or extracapsularly. There were approximately five undifferentiated nodular formations. The CT results confirmed the localized nature of the lymphoma, without distant metastasis (shown in Fig. 2).

A PET scan was performed, which revealed a mass lesion in the right breast measuring 56 × 54 mm, demonstrating high uptake of the radiotracer with a standardized uptake value (SUV) value of 22.5, along with multiple adjacent lymph nodes that were highly metabolically active with an SUV value of 9.5.

Multiple metabolically active right axillary lymph nodes extending beneath the pectoral muscles were observed, the largest measuring 54 × 42 mm, which also demonstrated high uptake of the radiotracer with an SUV value of 20.

Silicone implants were present bilaterally without any pathological uptake of the radiotracer. Both lung fields appeared normal, and the heart and vessels were unremarkable, with no evidence of pleural effusion or pneumothorax. Additionally, a bone marrow biopsy result was negative, indicating the absence of bone marrow involvement (shown in Fig. 3).

Following diagnosis, the patient underwent eight cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and demonstrated a favorable response to treatment. A CT scan conducted 4 months after the treatment revealed the following: a minor irregularity was observed in the posterior aspect of the right prosthesis, accompanied by slight lateral and downward displacement; the previously identified mass features had resolved, with only a millimetric nodular formation present medial to the prosthesis within the breast tissue, measuring 11 × 9 × 7 mm, necessitating continued follow-up and monitoring; the prostheses on both sides appeared intact, with no evidence of tears inside or outside the capsule; a significant improvement was noted in the undifferentiated nodular formations in the right axilla, where only two millimetric nodules with a reactive appearance were observed and the larger nodules did not exceed 9 mm; previously, approximately five nodes were present, with the largest measuring approximately 4 cm; overall, the remaining findings were stable, with no indications of distant metastases or apparent secondary deposits. The patient’s recovery was monitored through regular follow-ups, including ultrasound and CT scans, which confirmed complete remission.

PBL is a rare condition with unfavorable clinical outcomes. It accounts for less than 0.5% of malignant breast tumors and 2.2% of extranodal lymphomas [17]. While PBL can occur at any age, it predominantly affects postmenopausal women, unlike the case presented which occurred in a patient in their 20s.

PBL typically affects a single breast, with a higher frequency in the upper right quadrant. Bilateral breast involvement is seen in approximately 1%–14% of PBL cases [18]. Multiple studies have indicated a higher prevalence of PBL on the right side [19].

Improved diagnostic techniques have increased the reporting of PBL. This highlights the importance of comprehensive information about this rare disease, which predominantly affects female patients (95%–100%) [8].

Histopathologically, breast tumors can be classified as large-cell B-cell lymphomas, monocytoid B-cell lymphomas, or undifferentiated lymphomas [7]. However, breast implant-associated anaplastic large cell lymphoma should be considered in patients with a history of breast implants who develop breast asymmetry more than 12 months after implantation, especially following the use of textured implants [1].

The majority of PBL patients have DLBCL with B-cell lineage, comprising 40%–70% of all breast lymphomas and exhibiting non-germinal center cell characteristics [8]. Diagnosis of PBL involves radiologic investigations (mammography, ultrasound, MRI, and PET), immunohistochemical biomarkers, and fine-needle aspiration cytology (FNAC) [11]. Accurate diagnosis is crucial for proper staging, grading, and monitoring of treatment response.

Imaging cannot differentiate primary from secondary breast lymphoma, and there are no histomorphological criteria to do so. The role of MRI in diagnosing breast lymphomas is unclear. Due to similar clinical presentations and imaging findings to breast carcinoma, definitive diagnosis relies on histopathology and immunohistochemistry [20, 21].

The optimal treatment for PBL is controversial. Treatment follows guidelines for similar-stage lymphomas elsewhere. Chemotherapy is chosen based on histologic subtype, disease extent, and patient factors. Mastectomy is not beneficial. Nodal status predicts outcomes and recommends radiation and chemotherapy use [17, 22, 23].

Recent therapeutic advances have greatly improved outcomes for patients with PB-DLBCL. Treatment typically includes rituximab-based chemotherapy, intrathecal methotrexate, and radiotherapy, with surgery considered in some cases [24‒26].

This study was conducted at Damascus University and does not require ethical approval for reporting individual cases or case series. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Ahmad Al-Bitar wrote and reviewed the successive versions and participated in their revisions and approved the final version. Amnah Zahreddin, Mohammed Shwin, and Abdullah Barbar participated in writing the report and approved the final version. Alaa Dirani planned and performed the work leading to the report and reviewed the successive versions and participated in their revisions.

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.