Breast Implant-Associated Anaplastic Large Cell Lymphoma: What the Primary Care Physician Needs to Know

Abstract

This manuscript aims to outline the pertinent epidemiology, presentation, diagnosis, and treatment of patients who present with breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) as it pertains to primary care, such that the primary care physician (PCP) is able to appropriately care for patients with breast implants and counsel on risks of BIA-ALCL.

Introduction

Since 1997, the number of augmentation procedures in the United States has increased by 207%, according to the American Society for Aesthetic Plastic Surgery.¹ With growing popularity, there is more need for the PCP to have an understanding of potential complications, such that patients with breast implants may be appropriately managed and referred. Of late, there has been increasing media coverage reporting cases of anaplastic large cell lymphoma, a breast implant-associated lymphoma. Given the nature of the disease, it is most commonly diagnosed after symptoms develop, so all healthcare providers need to be alert to those clinical findings. This review aims to outline the pertinent epidemiology, presentation, diagnosis, and treatment of patients who present with breast-implant associated anaplastic large cell lymphoma (BIA-ALCL) as it pertains to healthcare providers, such that physicians are able to provide appropriate care for patients with breast implants, counsel on risks of BIA-ALCL, and ensure timely diagnosis.

Epidemiology

The first reported case of BIA-ALCL was in 1997, with approximately 293 recognized cases in the United States and 779 cases worldwide as of September 3, 2019, according to the American Society of Plastic Surgeons.² The incidence of BIA-ALCL in women with breast implants is estimated at 1 in 4,000–30,000.³ It is important to note that both silicone and saline implants have been implicated in BIA-ALCL, but no cases have been documented prior to the advent of textured implants, suggesting a causal relationship between textured implants and BIA-ALCL (Figure 1).³ Smooth implants have not been associated with BIA-ALCL. On July 24, 2019, at the request of the FDA - Allergan, one of the major breast implant manufacturers - withdrew its BIOCELL^® Textured Implants. At the time of this FDA request, 481 of the 573 known cases were associated with these specific implants. Based on available data, the BIOCELL^® Textured Implants have a six-times higher risk of BIA-ALCL than textured implants from other manufacturers.⁴ The pathophysiology is currently unknown with multiple proposed hypotheses; several of these suggest a chronic inflammatory response involving CD4+ lymphocytes.³

Figure 1.

Photograph of textured breast implant.

Presentation

As patients frequently do not follow-up long-term with the plastic surgeon after breast augmentation or reconstructive procedures, it is important for the PCP and other healthcare professionals to be aware of the association between breast implants and anaplastic large cell lymphoma. Physicians other than plastic and reconstructive surgeons will likely be the first to encounter patients with BIA-ALCL, which may lead to a delay in diagnosis.³ A basic knowledge of the presentation and management of BIA-ALCL by the PCP will minimize this delay.

When following a patient with breast implants, it is important to obtain a specific history regarding the implants, including initial and subsequent surgeries, the location of placement (subpectoral or subglandular), and the type of implant. For BIA-ALCL, onset of symptoms typically occurs greater than one year after implant placement, with the mean time to symptom onset being ten years following placement.³ The majority of patients with BIA-ALCL present with a late-onset (>1 year after placement) seroma that manifests as swelling of the affected breast.⁵ Additionally, on physical exam it is necessary to determine if the implants have changed in texture or firmness, which may be indicative of pathology. One systematic review showed that 66% of patients presented with seroma; 8% with a mass; 7% with both; and 18% with other symptoms, including capsular contracture, axillary lymphadenopathy, skin lesions, and B symptoms.³ Upon presentation, the physician should perform a detailed physical exam, examining the breast for swelling, capsular contracture, cutaneous changes, and regional lymphadenopathy.⁵ Any abnormal findings should prompt further workup and referral to the patient’s plastic surgeon.

Diagnosis

Diagnosis of BIA-ALCL starts with ultrasound, as it has been found to be the most sensitive and specific screening tool in these patients.⁵ If fluid is seen on imaging, the patient should be encouraged to follow-up with their plastic or breast surgeon for further workup, which may include aspiration of fluid and fluid analysis with immunohistochemistry, and flow cytometry to establish the diagnosis of BIA-ALCL.¹ It is important to note that mammogram is not the preferred diagnostic modality, as its sensitivity for identifying BIA-ALCL-associated effusion and mass has been shown inferior to ultrasound.⁶ However, for any change within the breast, particularly with intact breast tissue (augmentation as opposed to reconstruction after mastectomy), it would be encouraged to also obtain a mammogram, particularly if greater than three months has passed since last imaging, so as not to miss the more common diagnosis of breast cancer. Further workup may include excisional biopsies of suspicious lymph nodes, ⁵ and PET/CT may be used for staging to assess for systemic disease.³ Once a cytologic diagnosis of BIA-ALCL is made, the patient should be referred to an oncologist and rported to the PROFILE registry.³ A non-diagnostic workup with high clinical concern should be referred to a specialist to consider additional diagnostic options.

Treatment

Reported to date, BIA-ALCL generally has an indolent course and confers a favorable prognosis. The disease is usually localized to the scar capsule of the implant, and for localized disease, capsulectomy with implant removal is the treatment of choice (Figure 2).³ Additionally, adjuvant radiotherapy may be used for localized disease; whereas, patients with systemic or extensive disease will require chemotherapy and radiotherapy.³ Patients can be counseled that systemic or extensive disease is exceedingly rare with reported incidence of 1 in 250,000.⁶ It is believed that the majority of cases can be managed with surgical excision of implant and capsule alone, while chemotherapy and radiotherapy are reserved for patients with recurrent or more extensive metastatic disease.⁵ At this point in time, chemotherapy has not been found to significantly improve overall survival. As knowledge of this disease is incomplete, a multi-disciplinary, individualized approach should be taken in every case. Following treatment, patients require close follow up with exams every three to six months and imaging every six months for the first two years.³

Figure 2.

Illustration of localized disease within the fibrous capsule of the breast implant, courtesy of the FDA.

Conclusion

At this time, the FDA does not recommend prophylactic screening or implant removal for asymptomatic patients, including those with Allergan BIOCELL^® Textured Implants, due to the low risk of developing BIA-ALCL. ⁴ Further, asymptomatic women without breast changes do not require more than routine breast exams. Despite this, it remains important to discuss the patient’s implants and be able to appropriately care for patients with breast implants. While the PCP is not expected to be an expert on BIA-ALCL, they will likely receive questions from concerned patients with implants. Knowing the basics about BIA-ALCL will allow the PCP to quell many of their patient’s concerns and better care for patients with implants. BIA-ALCL is a rare malignancy associated with textured breast implants. It may occur with both saline and silicone implants, and it usually presents late with a seroma or mass. BIA-ALCL is usually localized and has a favorable prognosis. Most importantly, the patient can always be encouraged to follow up with their plastic surgeon for a more detailed discussion regarding complications of breast implants, as well as for diagnosis and management of BIA-ALCL.