Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) - Case Report

1. Abstract

Demand for aesthetic breast surgery is increasing worldwide, both for cosmetic reasons and postoperative breast reconstruction for breast cancer patients. Although the number of women with breast prostheses is steadily increasing, incidence rates for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) are low, with an estimated incidence of 0.1-0.3 per 100,000 women with Common clinical presentation of BIA-ALCL may include breast asymmetry, palpable mass, late seroma, local pain, and firmness. However, cytological examination of seroma fluid may reveal the condition, which should be followed by implant removal and total capsuletomy. In the majority of cases, capsulectomy is curative. Preoperative information about the risk of developing BIA-ALCL is recommended for patients with breast implants. Here, we report two BIA-ALCL cases, where one case was diagnosed after breast cosmetic surgery and the other patient had undergone breast reconstructive surgery with implants after breast cancer treatment.

2. Key words

Breast implant associated anaplastic large cell lymphoma BIA-ALCL; T-cell lymphoma; Breast aesthetic and reconstructive surgery; Capsulectomy

3. Introduction

An estimated 10 million women worldwide have breast implants and approximately 8,000 women undergo breast implantation in Sweden annually (80% aesthetic surgery and 20% reconstruction after breast carcinoma treatment) [1, 4, 5]. Over 1,000 BIA-ALCL caseshave been reported to date, with 24 patient deaths [2, 3, 6]. The first cases of BIA-ALCL were reported in 1995 and 1997 [7, 8]. With an estimated risk of 1-3 women per million per year, BIA-ALCL incidence rates are on the rise as elective breast implantation is more commonly used [9]. Late accumulation of seroma fluid, pain, swelling and induration around an implant of more than 12 months of age may warrant a BIA-ALCL diagnosis. The average onset ofseroma presentation is 8-9 years after implantation (range, 0.2 to 27 years) [10, 11]. The condition begins on the luminal surfaceofthe fibrous capsule surrounding the implant (effusion limited disease, when anaplastic cells are confined to the fibrin layer overlying the capsule) and later may show varying degrees of infiltra- *Corresponding Author (s): Anikó Kovács, Department of Clinical Pathology, Sahlgrensprimarily due to genetic factors (JAK/STAT3 activation and MYC/ TP53 dysregulation, SOCS1 and DNMT3A mutations), Gram-negative biofilm around the implant, type of implant (mainly with textured surfaces), time and geographic differences (highest reported incidence is in Australia and New Zealand and an almost complete absence in Asian countries) [13-19]. Median overall survival rate is nowadays up to 93% and 89% 3- and 5-years after initial diagnosis, respectively [10].

4. Materials and Methods

Two patients aged 38 and 61 were diagnosed with Anaplastic Lymphoma Kinase (ALK)-negative BIA-ALCL at Sahlgrenska University Hospital, Department of Clinical Pathology (Gothenburg, Sweden). The first case developed after aesthetic surgery and the other was diagnosed after reconstructive breast implantation. Both patients had delayed, non-infective fluid collection around the breast implant. BIA-ALCL was diagnosed by cytological assessment of late chronic seroma fluid and later evaluated histopathologically in the fibrous scar tissue of the operation specimen adjacent to the implant. No bacteriological culture/microbiological examination either of seroma fluid or the specimen was performed. The study was approved by the Local Scientific Committee in Gothenburg (DNR: T1033 ad 287-15). The requirement for informed consent was waived by the ethical committee since patient materials were stripped from direct subject identifiers.

5. Case Report

Patient No.1. In 1999, a 44 year old female patient underwent a left sided mastectomy for a luminal A-type of invasive ductal carcinoma NST (No Special Type), grade 2. A simultaneous contralateral prophylactic mastectomy was performed. The patient was initially reconstructed with permanent expander prosthesis bilaterally (Mentor Spectrum - Anatomical: McGhan Style 150 prosthesis) (Picture 1). A left side axillary metastasis of the breast carcinoma was identified in 2001, which was treated by irradiation. Due to complications on the irradiated left side, reconstruction with musculus latissimus dorsi flap was performed with implantation of a permanent prosthesis (McGahn MLP 260 cc) in 2003. The right permanent expander prosthesis was left in place. In neither of the operations were any antibiotics or antiseptic agents used. In 2016, the patient (61 years of age) developed an ALK-negative BIA-ALCL in the thickened fibrotic capsule around the right side implant, which was verified with cytological assessment of the seroma fluid. Both implants were removed together with the fibrotic capsule (Figure 1). The anaplastic lymphoid cells infiltrated the whole thickness of the capsule with tumor necrosis as in stage T3 (Table 1). No lymphadenopathy was found. No further adjuvant therapy was given. She was free of the disease four years later (Picture 2). Patient No.2. The patient underwent bilateral breast augmentation in 2006, and the prostheses were later replaced with bigger ones in 2008. In 2015, the patient experienced swelling of the right breast, which led to replacement of the right side implant again by the private plastic surgeon. In 2016 at the age of 38, an ALK-negative BIA-ALCL was diagnosed in thepatient´s right breast in a late seroma. Bilateral removal of the implants with total capsulectomy was performed (Figure 2). No data about the type of prostheses or the performed surgical procedure was available from the private clinic. Lymphoma cells superficially infiltrated the luminalside of the capsule, as in stage T2 (Table 1). Postoperatively, the patient received radio- and chemotherapy. The patient developed a recurrence of BIA-ALCL medially on the chest wall which indicated a more radical capsulectomy performed by a breast surgeon 7 months later in 2017 and the patient was again treated with radio- and chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone). No lymphadenopathy was identified. The patient is disease free after three years of follow-up.

6. Results

Microscopic analysis revealed monoclonal T-cell proliferation with appearance of pleomorphic epithelioid cells with blast-like morphology. Consequently, severe atypia was found in both cases, both in the seroma fluids and in the fibrotic capsules around the implants. The immunocyto-/histochemical analysis showed positivity for CD45, CD30, CD8, and cytotoxic- associated antigens such as Granzyme, TIA-1 and Perforin in the large anaplastic cells obtained from seroma fluids and in the fibrous capsule of the surgical specimens. Negative results were found for ALK-1, CD3 and CD20. Complete surgical excision, including bilateral total capsulectomy with breast implant removal, had been performed for both patients and they have 3- and 4-year disease-free survival, respectively.

7. Discussion

Approximately 55,000 breast prostheses are implanted for reconstructive and cosmetic purposes in the United States annually [10, 20]. BIA-ALCL is a rare, but highly treatable type of T-cell lymphoma that can develop as late periprosthetic effusion only (measuring from 20 cc to 1,000 cc) or in combination with a palpable mass, or a breast mass alone. It can even present without a seroma or mass, but with detectable lymph node involvement orit can develop in the subcutaneous breast tissue. A case of BIA-ALCL has been reported by a transgender female [21] and gluteal implant associated-ALCL has been also described [22]. BIA-ALCL is a T-cell type of non-Hodgkin lymphoma, which differs from other breast lymphomas, as these are most frequently of B-cell type [9]. It is characterized by the presence of a monoclonal population of uniformly CD30-positive, large anaplastic cells, ALK-negativity and variable expression of T-cell markers and epithelial membrane antigen (EMA). One case with breast implant–associated plasmablastic lymphoma has been reported [23]. In 2016, the World Health Organization (WHO) recognized BIA-ALCL as a provisionally distinct entity, which differs from other ALK-negative ALCLs [11]. Moreover, FDA acknowledged the link between breast implants and ALCL in 2017 [24].

8. Conclusion

Women should be aware of BIA-ALCL preoperatively. Therefore, clinicians should inform patients about the risks of breast implants used in augmentation mammoplasty [34].

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Citation:

Zhiyang Chen. Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) - Case Report. Annals of Clinical and Medical Case Reports 2020