Invasive stage III breast implant-associated anaplastic large cell lymphoma successfully treated with incomplete resection

Abstract

A woman with history of bilateral breast augmentation 15 years prior presented with right breast swelling, peri-implant effusion and a palpable inferomedial mass. Effusion aspiration demonstrated pleiomorphic cells consistent with breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Further diagnostic studies confirmed stage III disease with a 4.7 cm right breast mass and fluorodeoxyglucose uptake in an internal mammary chain lymph node. The patient underwent surgery with incomplete resection due to invasion of the chest wall followed by chemotherapy and radiation therapy. BIA-ALCL typically presents as an indolent effusion, however advanced disease carries a worse prognosis. This case highlights successful treatment without recurrence past the one-year mark as well as the need for multidisciplinary management when dealing with advanced disease.

Background

Development of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare but increasingly recognised late complication associated with the use of textured breast implants.^{1 2} The majority of BIA-ALCL cases have been associated with Allergan textured implants, also sold under the McGhan and Inamed brand names, leading to a recall by the Food and Drug Administration (FDA) in 2019.³ This condition typically presents a decade after breast augmentation with peri-implant effusion.⁴

We report a rare presentation of advanced BIA-ALCL with chest wall invasion 15 years after breast augmentation with textured breast implants. This case is unique in describing successful treatment of a T4N1M0 tumour infiltrating the chest wall with incomplete surgical resection. The case highlights the need for early recognition of this condition as well as the technical management of advanced disease by a multidisciplinary team.

Case presentation

The patient is a middle-aged woman in previously excellent health who underwent bilateral cosmetic breast augmentation 15 years prior. McGhan FX 280 mL silicone textured implants were utilized for the procedure.

The patient started to experience tightening around the implants prior to presentation with a subsequently normal mammogram. Five years after this original tightening sensation, she presented with right breast pain, associated swelling, skin changes and a palpable mass on self-exam (figure 1).

Figure 1.

The patient at initial consultation with enlargement of the right breast, palpable fluid collection and inferomedial right breast mass.

Investigations

Mammography demonstrated a 4.7 cm mass with peri-implant effusion in the inferomedial right breast (figure 2). Aspiration of the effusion revealed pleiomorphic cells positive for CD30, CD2, focally and weakly positive for CD45, and ALK-1 negative, consistent with BIA-ALCL.⁵ PET-CT demonstrated fluorodeoxyglucose (FDG) uptake in the right breast mass and internal mammary chain node deep to the right breast (figure 3). This established the tumour as T4N1M0, stage III per National Comprehensive Cancer Network (NCCN) guidelines. Bilateral axillary adenopathy was noted on exam but was not FDG avid.

Figure 2.

Mammography of the right breast displaying a new density in the inferomedial right breast. Density is causing mass effect and flattening of the implant.

Figure 3.

PET-CT displaying FDG uptake in the right breast mass with chest wall involvement (left) and internal mammary chain node deep to the right breast (right). PET-CT, positron emission tomography-computed tomography. FDG, fluorodeoxyglucose.

Due to the rare nature of BIA-ALCL and the patient’s advanced presentation, a multidisciplinary approach was used, with input from plastic surgery, surgical oncology and lymphoma oncology. It was determined that it was appropriate to proceed with resection and adjuvant chemotherapy as recommended by NCCN guidelines.⁵ The surgical team had concerns but not confirmation of chest wall invasion based on preoperative imaging, and surgery was done with curative intent.

Treatment

The patient was taken to the operating room and a right total mastectomy was performed with excision of the pectoralis major and minor muscles including the periosteum of the fourth rib just lateral to the sternum for maximal tumour debulking. The tumour extended into the intercostal muscles and encased the ribs. With intraoperative confirmation of chest wall involvement, the team decided to pursue partial resection followed by chemotherapy rather than a morbid rib resection. Macroscopic residual tumour remained along the chest wall following surgery. Rib resection by thoracic surgery would have been considered at a later date if the patient did not respond to chemotherapy.

Surgical pathology demonstrated an irregularly shaped, 7.0×6.2×5.0 cm solid mass with central haemorrhage and necrosis. Anterior and posterior margins were less than 0.1 cm indicating tumour invasion into the skin, skeletal muscle and posterior margin of the right chest wall. The left breast implant was resected en-bloc and replaced with a Mentor smooth silicone implant. Pathology of the left breast implant capsule was without evidence of malignancy.

Postoperative course was complicated by a haematoma secondary to pathological fracture of the right fourth rib. Additionally, the patient developed a nodule along her incision, concerning for progression of residual disease. This area was biopsied, demonstrating pathology consistent with BIA-ALCL. Chemotherapy with brentuximab vedotin, cyclophosphamide, doxorubicin, prednisone (B-CHP) was initiated for five cycles following evacuation and stabilisation of the haematoma. Tumour size decreased noticeably with chemotherapy, however areas of open wound along the incision persisted (figure 4). Positron emission tomography-computed tomography (PET-CT) after three rounds of B-CHP revealed decreased disease burden with low-grade hypermetabolic activity overlying the mastectomy site and right fourth rib with a max standardized uptake value (SUV) of 3.8 compared with 28.9 in the pretreatment PET-CT scan (figure 5). Interval improvement was seen in the right axillary and right internal mammary nodes with corresponding SUV 1.1 and 1.0, respectively.

Figure 4.

Right breast residual wound following total mastectomy and evacuation of recurrent haematoma from pathological rib fracture.

Figure 5.

PET-CT 3 months following resection displaying low-grade hypermetabolic activity over the right mastectomy site and fourth rib with a max SUV of 3.8. At this point, the patient had completed three out of five planned chemotherapy cycles. PET-CT, positron emission tomography–computed tomography. SUV, standardized uptake value.

Due to the aggressive nature of the tumour, it was decided to use consolidative radiation therapy, total dose 36 Gy, directed to the chest wall and adjacent lymph nodes to maximise the chances of long-term remission per NCCN guidelines.⁵

Outcome and follow-up

PET-CT imaging at 8 months following surgical resection revealed no signs of residual or recurrent disease with max SUV of 1.8 over the right fourth rib (figure 6). At 10 months after the initial presentation, the patient had a healed surgical scar and no clinical symptoms of recurrence or residual disease (figure 7).

Figure 6.

PET-CT 8 months following index tumour resection displaying interval improvement of low-grade hypermetabolic activity over the right fourth rib with a max SUV of 1.8. No sign of recurrent or residual disease. The patient completed chemotherapy and consolidative radiation therapy prior to imaging. PET-CT, positron emission tomography–computed tomography. SUV, standardized uptake value.

Figure 7.

Healed surgical wound of the right breast following adjuvant chemotherapy and consolidative radiation therapy.

Right breast reconstruction with a bipedicled deep inferior epigastric perforator (DIEP) flap was performed following successful completion of treatment. Pathology specimens obtained during the procedure of the right chest scar and internal mammary node were benign. The patient will continue to have regular follow-up visits with medical oncology as well as surveillance PET-CT imaging. Mammography of the contralateral breast will be conducted routinely.

Discussion

Since the introduction of silicone breast implants in 1962, breast augmentation has become the leading surgical cosmetic procedure in the USA with 299 715 cases performed in 2019.^{6 7} Approximately 1.5 million patients worldwide receive breast implants each year.⁸ Following the first report published in 1997 BIA-ALCL has become recognised as a rare but serious complication associated exclusively with the use of textured breast implants.^{2 9 10}

BIA-ALCL is a peripheral T cell non-Hodgkin’s lymphoma first recognised by WHO as a unique clinical entity in 2016.¹¹ It is characterised by the presence of pleomorphic CD30 positive, ALK negative lymphoid cells and commonly presents with a delayed peri-implant effusion.^{1 12} Pathogenesis is likely multifactorial with current theories including a chronic inflammatory response due to microtrauma or biofilm formation on the textured implant surface, genetic predisposition, viral infection, an allergic response or chemical carcinogens.^13–20

As of January 2020, the US FDA has received 384 reports of BIA-ALCL in the USA and 733 cases worldwide with 13 and 23 documented deaths, respectively.² In the USA, it had been estimated that women with textured implants have a 1 in 30 000 lifetime risk of developing BIA-ALCL.¹⁰ Among textured implants, risk has been found to vary by manufacturer with the odds ratio of developing BIA-ALCL being 16.52 with Allergan Biocell implants and 23.4 with Silimed implants when compared with Mentor Siltex implants in Australia and New Zealand.²¹ BIA-ALCL cases are likely under-reported overall as a recent prospective cohort study found a BIA-ALCL incidence of 1 in 355 women, of whom over 96% received Allergan Biocell implants.²² An FDA analysis of 573 cases of BIA-ALCL worldwide showed that 83.9% (481) of cases were associated with Allergan breast implants. Based on this information the FDA requested Allergan voluntarily recall their textured implants resulting in these implants being pulled from the market in July 2019.³

BIA-ALCL typically presents as a late onset peri-implant effusion but may also present with a mass.⁴ Less common presentations include capsular contracture,^{23 24} fever, night sweats, weight loss²⁵ or skin lesions.²⁶ Adenopathy is most commonly axillary, however, supraclavicular, mediastinal and internal mammary node involvement has also been reported, and may be associated with poorer outcomes.^27–29 A 2016 review of 95 cases reported a mean 10-year latency between implantation and diagnosis of BIA-ALCL with a mean age at diagnosis of 46 for cosmetic procedures and 57 for breast reconstruction.⁴ Workup of suspected BIA-ALCL begins with ultrasound, or MRI if ultrasonography is equivocal, to assess for fluid collection, masses or lymphadenopathy. Masses should be biopsied, and effusions warrant a minimum 50 mL sample for cytology, CD30 immunohistochemistry and flow cytometry. In cases of confirmed BIA-ALCL, PET-CT should be used for preoperative staging.⁵

Previously classified either as an in-situ effusion or infiltrative mass, it is now believed that BIA-ALCL behaves similarly to a solid tumour and is best understood as a spectrum of disease staged using the tumour, lymph node, metastasis (TNM) solid tumour staging system first proposed by the MD Anderson Cancer Center in 2016 and now included in NCCN guidelines.^{5 30} Complete capsulectomy and implant removal has been established as standard of care with higher overall survival compared with partial capsulectomy, chemotherapy or radiation therapy.³⁰ Advanced disease states may need to be treated with radiotherapy or chemotherapy with B-CHP being the current first line therapy, based on the ECHELON-2 trial for treatment of CD30-positive peripheral T-cell lymphoma.³¹ Potential experimental treatments for B-CHP non-responders include IL-2Rα antibodies, JAK-STAT3 pathway inhibitors such as ruxolitinib, and PD1/PD-L1 axis modulators.^{15 32–34} Potential options for reconstruction following successful treatment include augmentation with smooth implants, autologous flaps, mastopexy and fat grafting. Reconstruction can be considered immediately in patients with disease confined to the capsule and should be delayed 6–12 months in patients with extensive disease.³⁵

BIA-ALCL typically has an indolent course, however advanced disease presentations have resulted in death.^{2 25} While 5-year survival in patients with seroma is 100%, estimates in patients with a mass have varied from 2-year survival of 52.5% in patients with infiltrative disease to 5-year survival of 75% in patients with a mass.^{36 37} In a review by Leberfinger et al,⁴ only 8% of patients presented with stage III or higher disease. Advanced disease states are associated with a longer interval from diagnosis to surgery and are associated with lower rates of complete tumour extirpation. Published literature on advanced cases is rare, with a 2018 literature review by Collins et al, showing only 13 cases with stage III–IV MDACC TNM disease.³⁸ BIA-ALCL with invasion of the chest wall is a rare entity, and surgical approaches using both combined chest wall resection and reconstruction as well as chest wall-sparing surgery with adjuvant chemotherapy and radiation therapy have been reported.^{39 40} Additional reports of advanced cases are needed to better understand disease progression and optimise treatment strategies.

Patient’s perspective.

My breast first started swelling and then I noticed a palpable lump and called the doctor. The lump grew and swelling increased rapidly as I waited for my mammogram. I had a difficult time getting an appointment because it was around the time of Breast Cancer Awareness month and a backlog of appointments from COVID-19. I called several times trying to ask for an earlier appointment because I could tell something was very wrong. After I finally got the mammogram, they scheduled a biopsy right away. The day of the biopsy I asked the doctor what she thought it was and she told me that she thought it might be BIA-ALCL. That was the first time I’d ever heard that term. She said she’d tell pathology to be sure to test for it. It ended up taking longer than expected to get the pathology results back – I think because they wanted to verify that this is what it really was. Later, another pathology lab independently verified it as well.

The surgery was more invasive than originally planned because the cancer had already spread. The recovery from the surgery and the broken rib was some of the hardest parts of my treatment because I was in a lot of pain and couldn’t use my dominant arm for a long time. The cancer came back during the short time we were waiting for the incisions to heal to get me into chemo—it was so aggressive. They went ahead and started chemo to knock the cancer back, and, amazingly, I could see that it was working because the swelling/tumour began to shrink within a short time frame. A part of my incision and a drain hole healed very, very slowly during chemo so for months I had an open wound that required a lot of help from the surgeons and wound care at home. I really couldn’t wear a prothesis for the first 6 months after surgery due to the open wounds. After chemo I had a month of radiation. A few months later I received a clear result from my PET scan! About a year after my initial surgery I was finally able to have partial reconstruction, but I will still need more surgery to be whole. What else will be required in the future is still a bit unknown.

The teamwork and coordination between all my doctors were a vital part of my success. They worked carefully together to make sure the overall treatment plan was effective. I feel incredibly fortunate.

Learning points.

• Use of textured breast implants, specifically Allergan brand, significantly increases the risk for development of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

• Presentations involving a mass or infiltrative disease carry a worse prognosis compared with an isolated seroma.

• Early diagnosis and complete resection, when possible, are essential for successful treatment of BIA-ALCL.

• Delayed fluid collections in patients with breast implants should be aspirated and sent for cytology for BIA-ALCL workup.

• Patients with advanced disease not amenable to complete tumour resection may benefit from adjuvant chemotherapy and radiation.

Ethics statements

Patient consent for publication

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