Breast implant-associated anaplastic large cell lymphoma presenting as a breast mass: A case report and literature review.

First author: data collection, study concept, writing the paper, data interpretation. Second author (Corresponding author): study concept, data collection, data interpretation, writing the paper. Third author: data interpretation, study concept, writing the paper. Fourth author: data collection, data analysis, writing the paper. Fifth author: data collection, writing the paper.

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request, no identifying characteristics were altered.

Ethical approval for this work was given by the “Research Ethics Committee” on May 9th 2023 at our institution: American British Cowdray Medical Center, 154 Carlos Graef Fernandez Av, Mexico City, 05300, Mexico. The reference number for this approval is: CMABC-RC-23-01.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

researchregistry8885.

Fernando Cordera González de Cosío.

BIA-ALCL is a rare neoplasm that should be considered in the differential diagnosis of a breast mass in patients with a history of textured breast implant placement. After diagnostic confirmation, capsulectomy and systemic therapy can be performed with good therapeutic results.

BIA-ALCL was first described in 1997, the relationship of this type of lymphoma with breast implants was recognized by the Food and Drug Administration (FDA) in 2011 and recognized as an independent entity by the World Health Organization (WHO) in 2017 [ 1 , 5 ]. This lymphoma should be suspected in any patient with a history of breast implant placement who develops breast asymmetry >12 months after implant placement, especially after the use of textured implants [ 1 ]. The estimated prevalence in patients with textured breast implants is 3.3 %, the risk of developing BIA-ALCL is up to 67.6 times higher, compared to the risk of primary anaplastic lymphoma of the breast [ 10 ]. BIA-ALCL is frequently localized to pericapsular fibrous tissue or a seroma fluid cavity [ 4 , 5 ]. The most frequent clinical finding (in about 85 % of patients) [ 11 ] is effusion or persistent seroma around the breast implant, appearing on average 8-12 years after implant placement, possibly accompanied by breast asymmetry, pain or tenderness [ 4 , 12 ]. Some similar conditions to rule out include: • Early-onset periprosthetic effusions (less than a year after implant placement): relatively frequent and caused by complications related to surgery or the implant, including friction, irritation, allergic reactions, infection, among others. • Incidental finding of effusion: in asymptomatic patients, a small amount of innocuous periprosthetic fluid (5-10 ml) may be found. • Implant rupture: usually does not increase the total volume of the breast [ 7 ]. Early-onset periprosthetic effusions (less than a year after implant placement): relatively frequent and caused by complications related to surgery or the implant, including friction, irritation, allergic reactions, infection, among others. Incidental finding of effusion: in asymptomatic patients, a small amount of innocuous periprosthetic fluid (5-10 ml) may be found. Implant rupture: usually does not increase the total volume of the breast [ 7 ]. Less frequent findings include a breast mass (8-24%) [ 13 , 14 ], lymphadenopathy or skin rash (4-12%), and systemic symptoms (<5 %) [ 14 ]. Various triggering pathophysiological mechanisms have been proposed to generate chronic inflammatory response in genetically predisposed patients, textured surface is a crucial factor in inducing chronic inflammation, with abundance of T lymphocytes and silicone-laden macrophages promoting additional T lymphocyte chemotaxis [ 1 ]. Other factors include specific materials and manufacturers, with an incidence ranging from 1:36,730 with Siltex to 1:600–800 with Allergan brand BIOCELL implants, voluntarily withdrawn from the market in 2019 [ 15 ]. Ultrasound has a sensitivity of 84 % and a specificity of 75 % for detecting effusions, in cases of presentation as a breast mass, the sensitivity drops to 46 %, in which case, MRI may be required for an adequate evaluation [ 15 ]. Ultrasound usually shows a uniform periprosthetic effusion and inflammatory reaction in the surrounding tissue. Masses are visualized as well-defined solid or hypoechoic oval areas [ 4 ]. Fine needle aspiration biopsy is used to obtain periprosthetic fluid samples (a minimum volume of 50 ml is required to reach diagnostic utility), or a core-needle biopsy of any mass and/or affected lymph nodes, histological confirmation of BIA-ALCL requires CD30 expression, and absence of ALK, essential for differentiation from systemic ALCL [ 8 ]. Once histopathological diagnosis is confirmed, a PET-CT should be performed to identify any capsular masses and involvement of thoracic structures. Pertinent laboratory studies include complete blood count, metabolic panel, lactate dehydrogenase, and hepatitis B serology if adjuvant chemotherapy is being considered [ 14 ]. The most effective therapeutic intervention consists in complete surgical resection of the implant and capsule [ 15 ]. A study by Clemens et al. [ 16 ] reported significantly higher overall survival when complete surgery was compared with incomplete resection or partial capsulectomy, chemotherapy, or radiotherapy ( p  < 0.001), the 10-year overall survival was near to 100 % in patients with complete surgery, compared to approximately 85 % with any other intervention alone. Currently, the NCCN guidelines recommend considering the removal of the contralateral implant, since in 4.6 % of reported cases, evidence of contralateral disease has been found on microscopic analysis [ 14 ]. In cases with evidence advanced disease, the most effective chemotherapeutic regimen consists of CHOP, plus brentuximab vedotin [ 17 ], demonstrating improvement in the duration of remission (48.2 vs 20.8 months with chemotherapy alone) and a reduction of up to 34 % in risk mortality in a 42-month follow-up period [ 18 ]. Reconstruction can be considered immediately for cases presenting in stages (IA-IC) and should be delayed in stages IIA-IV for a period of at least 12 months and up to 5 years depending on the result of radiological follow-up, it is recommended in all cases to avoid textured implants for reconstruction and some authors propose to avoid smooth implants as well due to the lack of evidence that completely excludes them from a causal association with BIA-ALCL, the reconstruction with autologous tissue represents a good alternative [ 12 , 19 ]. The procedure was performed through subareolar incisions, using an approach similar to a standard implant removal procedure. This allowed a complete capsulectomy, complete removal of the breast mass and an excellent postoperative cosmesis, the use of immunotherapy has been purposed as a good option in addition to adjuvant chemotherapy, however it has been rarely used in large series [ 13 ], in this case we found this therapeutic modality to be effective and well tolerated. The estimated median survival is 12 years, with an overall survival of 97 % at 3 years and 92 % at 5 years [ 19 ]. When the disease extends beyond the capsule the 5-year survival can drop to 72 %, the presence of a solid mass is a significant adverse prognostic feature [ 5 , 7 ]. Screening or prophylactic removal of textured implants is not currently recommended, due to the relatively low risk of developing lymphoma. For asymptomatic patients, only awareness and routine medical consultations are required for the prevention of breast cancer [ 20 ].

Breast implants are among the most frequently used medical devices for aesthetic and reconstructive purposes [ 1 ]. Annually about 1.5 million women undergo implant placement procedures worldwide [ 2 ]. The incidence of implant-associated anaplastic large cell lymphoma has been estimated between 1:500,000 and 1:3,000,000, with an average age of 50 years at the time of diagnosis [ 3 ]. Currently accepted pathophysiological models postulate that BIA-ALCL develops due to chronic inflammation induced by the material and textured surface of some breast implants [ 4 , 5 ]. The clinical presentation in up to 80 % of cases consists of a seroma surrounding the implant, other clinical features include pain, inflammation or breast asymmetry [ 6 ]. Definitive diagnosis requires immunohistochemical characterization with CD30 positive and ALK negative markers [ 7 ]. Treatment includes capsulectomy, resulting in 93 % of patients free of disease at 3 years. For advanced cases, with bilateral axillary lymph node, bone marrow, or bilateral mammary involvement, adjuvant treatment with immunotherapy and/or chemotherapy may be considered [ 8 ]. This case has been reported in line with the SCARE criteria [ 9 ].

A 44-year-old woman presented with a 3-month history of a right breast mass, medical history was significant for breast augmentation mammoplasty with textured implants 15 years earlier. Family history was significant for leukemia in a paternal aunt. She smoked one cigarette daily for 5 years and stopped smoking one year earlier. Her only medications were antihistamines as needed for seasonal allergic rhinitis. Surgical history included a cesarean delivery at 27 years of age, and a hysterectomy secondary to endometriosis at age 29. On physical examination, bilateral periareolar scars were noted, a palpable 5 cm mass was found in the lower medial quadrant of her right breast, as well as right axillary lymphadenopathy. The overlying skin was normal. Left breast and axilla were normal. Ultrasound and mammography identified a 5 cm tumor in the lower medial quadrant of the right breast that was classified as BIRADS 5 (high suspicion of malignancy), a magnetic resonance imaging (MRI) was ordered for further assessment ( Fig. 1 ). Fig. 1 Magnetic resonance imaging (MRI) of the breast evidencing a right periprosthetic breast mass. Fig. 1 Magnetic resonance imaging (MRI) of the breast evidencing a right periprosthetic breast mass. Ultrasound-guided percutaneous core needle biopsies of the lower medial quadrant mass and right axillary lymph nodes were performed. Pathology review and immunohistochemical analysis confirmed the diagnosis of breast implant-associated anaplastic large cell lymphoma, ALK negative with immunophenotype: CD45, CD43, CD30, EMA, CD4, CD45R0 (positive) TIA-1 (focal positive). A FDG PET-CT identified hypermetabolic lesions in the right breast and right axilla, as well as mild uptake in the bone marrow ( Fig. 2 ). Fig. 2 Initial PET-CT FDG showing uptake in multiple extra-mammary sites. Fig. 2 Initial PET-CT FDG showing uptake in multiple extra-mammary sites. The patient underwent bilateral implant removal and capsulectomies through periareolar incisions, plus en-bloc resection of a solid mass located in the lower medial quadrant next to the right capsule through an additional incision was performed. After a multidisciplinary consultation it was decided that we would not perform a formal mastectomy or an axillary lymph node dissection because the results would not modify the need for adjuvant chemotherapy. In consultation with plastic surgery and the patient we decided not replace breast implants and no further reconstruction procedures were necessary. Bilateral drainages were placed, and surgical wounds were closed with absorbable sutures. The procedure underwent without complications. Neoplastic cells were found invading up to 90 % of the inner lining of the right capsule. All margins were negative. The left capsule was negative for malignancy. Bone marrow biopsy was negative for malignant cells. Immediate recovery was uneventful, and the patient was discharged after one night of hospital stay. She required no blood transfusions. At one week on follow-up visit, the patient was not requiring analgesics, presented no signs of infection, and drainages were removed ( Fig. 3 ). Fig. 3 Bilateral capsulectomies. Fig. 3 Bilateral capsulectomies. Chemotherapy was started two weeks after surgery. Over the following months the patient received adjuvant treatment with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus immunotherapy (brentuximab). After chemotherapy was completed, a FDG PET-CT scan showed no evidence of the hypermetabolic areas previously found. At a 2.5-year follow-up the patient is asymptomatic with no evidence of disease. She currently has complete resolution of her symptoms, good cosmetic results ( Fig. 4 ). Fig. 4 Immediate cosmetic results after bilateral implant removal and capsulectomies. Fig. 4 Immediate cosmetic results after bilateral implant removal and capsulectomies.

All authors declare no conflicts of interest.