Breast solitary extramedullary plasmacytoma treated with combined systemic therapy and radiotherapy: diagnostic and therapeutic insights from a rare case

Solitary extramedullary plasmacytoma (SEP) of the breast (or breast plasmacytoma, BP) is a very rare entity, with only very few documented cases in English language medical literature [1]. Epidemiologically, BP accounts for approximately 1.5% of all plasmacytoma cases and 0.2% of breast cancer cases [2]. Its occurrence is poorly understood. The breast tissue, with its rich vascular and lymphatic network, may facilitate the migration of plasma cells. In case of delayed diagnosis, SEP can evolve into multiple myeloma (MM) [1]. Waal et al. demonstrated that more than 50% of solitary plasmacytoma patients develop MM within 2 years after treatment, indicating a significant risk of progression [3]. Radiologically, BP typically appears as intramammary round or oval masses on mammography, and as homogeneously echo-poor or hypoechoic lesions on ultrasound [2].

The main objective was to describe the diagnosis, treatment approach, and clinical outcomes of a rare case of breast SEP, particularly in a patient with a prior ovarian SEP, and to highlight the potential role of combined systemic therapy and radiotherapy in managing such uncommon presentations.

A 41-year-old woman was referred to our Breast Center in December 2023 for a 2-cm mass in the right breast. Patient was previously diagnosed with left ovarian IgG lambda SEP treated by left adnexectomy in 2022. Adjuvant treatment in ovarian SEP is not well-established, and patient had observation alone [4]. This decision was supported by the completeness of her surgical resection, and the absence of MM on metastatic work-up [4]. Breast mammography findings were suggestive of a 4-cm malignant lesion (ACR 4c). Pathological findings from biopsy specimens demonstrated an Epstein-Barr virus (EBV)-positive SEP of the breast (Fig. 1A–D). ¹⁸F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (PET/MRI) ruled out metastatic disease (Fig. 1E). The patient had a hemoglobin level of 12.4 g/dL, creatinine at 50 μmol/L, calcium at 2.21 mmol/L. Proteinuria in a spot sample was 0.04 g/L. The patient had a total gamma-globulin level of 14.3 g/L, including a monoclonal spike of 4.7 g/L, with a Kappa/Lambda free light chain ratio of 9.7/25.7 mg/L. Given the patient’s past history of ovarian SEP diagnosed less than two years earlier and the new diagnosis of breast SEP, the patient was considered to have a relapse. Consequently, systemic treatment, radiation therapy, dose intensification of melphalan, and hematopoietic stem cell autograft were proposed [5, 6].

Figure 1.

Breast solitary extramedullary plasmacytoma treated with combined systemic therapy and radiotherapy: radiologic and pathologic features. A. Hematoxylin-eosin-saffron (HES) stained sections showing plasma cells (blue arrow) with the presence of apoptotic debris (black arrow); B. Immunohistochemistry showing CD138 positivity, consistent with plasmacytomas (blue arrow); C–D. Chromogenic in Situ Hybridization showing the absence of IgG kappa (E) and the presence of IgG lambda (F); E. ¹⁸F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (PET/MRI) axial slices showing hypermetabolic soft-tissue solitary extramedullary plasmacytoma lesion of the right breast (white arrow); F. PET/MRI axial slices showing complete metabolic response at 4-month follow-up imaging

First-line treatment consisted of two cycles of daratumumab, carfilzomib, lenalidomide, dexamethasone (Dara-KRd) resulting in an excellent metabolic response with SUVmax decreasing from 5.5 to 1.4.

After multidisciplinary tumor-board meeting, concurrent radiation therapy (RT) was indicated. RT consisted of 45 Gy in 18 fractions of 2.5 Gy/fraction, resulting in a biological effective dose of 56.3 Gy for α/β 10 (BED10) [7]. This treatment schedule was beneficial in reducing overall treatment duration and improving patient compliance. To minimize radiation-induced toxicity, treatment was delivered four times per week instead of the conventional five, allowing additional time for normal tissue recovery. To ensure accurate and safe RT delivery, daily image-guided radiotherapy (IGRT) and in vivo dosimetry were employed. The patient had already demonstrated excellent clinical tolerance and a favorable metabolic response to the first two cycles of Dara-KRd prior to the initiation of RT, suggesting robust physiological reserve. Close clinical monitoring was maintained throughout the combined treatment phase. The gross tumor volume definition was guided by PET/MRI fusion. The clinical target volume (CTV) encompassed the whole right breast. The planning target volume covered the CTV with a 5-mm margin. The treatment was performed with 6 and 18 megavoltage-photons on a linear accelerator, using the 3-dimensional conformational RT technique. This approach was selected to limit exposure to organs at risk (OARs). While intensity-modulated radiotherapy (IMRT) may be considered a suitable alternative, volumetric modulated arc therapy (VMAT) was not chosen in our case due to its tendency to increase low-dose irradiation. Mean heart dose was 0.7Gy. The V20 of the right lung was 9%. Importantly, the patient did not report any significant fatigue or systemic intolerance during concurrent therapy and presented with grade 1 (CTCAE v5.0) acute radiation-induced dermatitis, managed by local skin care. The combination approach was both feasible and well tolerated in our specific case. Patient Five cycles of Dara-KRd were administered after completion of RT. Therapeutic intensification with melphalan at 200 mg/m² followed by hematopoietic stem cells autograft was delivered. Patient was in complete metabolic response at 4-month follow-up on PET/MRI (Fig. 1F).

Breast SEP is a very rare entity and metastatic work-up should rule out MM [8]. In our case, patient shared similar pathological features between her ovarian and breast SEP. Selective spread to the breast or ovary may have followed a tumoral axis, as seen in Krukenberg tumors or BRCA-associated cancers [9].

Breast solitary extramedullary plasmacytoma is a very rare entity requiring thorough diagnostic evaluation to exclude multiple myeloma. Management should be discussed within a multidisciplinary tumor board involving hematologists, oncologists, and radiation specialists. In our case, combining systemic therapy with involved-field whole breast radiotherapy achieved excellent metabolic response without increasing toxicity. Given the risk of progression to multiple myeloma, close clinical and imaging surveillance is essential. Further studies are needed to establish standardized treatment protocols for this rare presentation.