Abstract Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare clinical entity. This is a case report of a 71-year-old female with a history of bilateral breast augmentation 16 years prior who presented to an outside facility with swelling and erythema of her right breast. She was found to have a mass on imaging. Biopsy was consistent with BIA-ALCL. She was initiated on chemotherapy and eventually was referred to our hospital where she underwent breast implant explantation with total capsulectomy, including removal of the mass. This patient’s erythema could represent another manifestation or treatment effect of BIA-ALCL. Level of Evidence: 5 Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare but treatable disease that was first reported in 1997 and is strongly associated with textured breast implants.1,2 The most common presentation is a peri-prosthetic fluid collection and/or breast mass approximately nine years after implant placement.3,4 As of February 2017, the FDA had 359 reported cases; however these reports can be inaccurate, duplicated, and underreported.1,3 This equates to a lifetime risk of developing BIA-ALCL of 1:30,000 in US women with textured breast implants. There have been 12 deaths worldwide attributed to this disease, however none of these patients received complete surgical excision or targeted therapy and most had a delayed diagnosis or treatment.5 CASE REPORT This research did not require IRB approval but was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The patient gave her informed consent for publication of her case, including the use of photographs. The patient is a 71-year-old Caucasian female with a history of diabetes mellitus, hyperlipidemia, COPD, obesity, sinus bradycardia, paranoid schizophrenia, anxiety, depression, and current tobacco use who underwent bilateral subpectoral breast augmentation in 2000 at an outside facility. She developed breast swelling and erythema of the lower pole of her right breast in May 2016. She also had night sweats and a 40-pound weight loss in the previous year. Her initial workup and treatment were completed at an outside facility. A mammogram was normal. An ultrasound showed a mass from which an fine needle aspiration was performed but the specimen was inadequate for evaluation. Five months later, a CT scan of the chest, abdomen, and pelvis revealed an 8.2 cm right breast mass with axillary lymphadenopathy. A core needle biopsy revealed BIA-ALCL positive for CD30, CD4, CD43, CD45, TIA-1, and EMA and negative for ALK1. FISH was negative for rearrangement of IRF 4 and TP63. A bone marrow biopsy was negative for lymphoma involvement. A PET-CT scan showed FDG avid areas in the right breast mass; right axillary, internal mammary, and supaclavicular lymph nodes; and right breast and abdominal skin. The outside facility initiated the patient on cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) chemotherapy after which she developed significant erythema of her breast (Figure 1). She underwent a second cycle of CHOP and experienced progressive worsening of the erythema, necessitating discontinuation. She was treated with Keflex and local wound care and was switched to Brentuximab. After this infusion, the patient again experienced an exacerbation of the erythema associated with pain, warmth, and swelling of the breast, and blistering in the inframammary fold. She became febrile so she presented to her local emergency department. Her white blood cell (WBC) count was elevated to 18.5, CRP to 341, and ESR to 110. Blood cultures were drawn and ultimately were negative. She was started on Clindamycin and Vancomycin and transferred to our facility. Figure 1. View largeDownload slide (A, B) Preoperative photographs of a 71-year-old woman demonstrating significant swelling and erythema of the right breast, which is involved with BIA-ALCL, 12 days after receiving her first dose of CHOP chemotherapy. Figure 1. View largeDownload slide (A, B) Preoperative photographs of a 71-year-old woman demonstrating significant swelling and erythema of the right breast, which is involved with BIA-ALCL, 12 days after receiving her first dose of CHOP chemotherapy. The next morning her WBC decreased but the erythema persisted so Infectious Diseases was consulted. An ultrasound revealed a 6.4 cm mass and a complex fluid collection tracking to the skin which was aspirated and found to be sterile. A CT scan showed an 8.2 × 3.9 cm mass with marked inflammatory changes involving the right breast, improved axillary adenopathy, and possible bilateral intracapsular implant rupture (Figure 2). A skin biopsy was performed and showed subacute dermatitis and eosinophilic spongiosis with no bacterial or fungal growth, carcinoma, or abnormalities on immunohistochemical staining. Plastic surgery was then consulted but surgery needed to be delayed given the breast erythema and concern for infection. Figure 2. View largeDownload slide CT scan of the chest demonstrating an 8.2 × 3.9 cm mass with marked inflammatory changes involving the right breast and significant skin thickening. Figure 2. View largeDownload slide CT scan of the chest demonstrating an 8.2 × 3.9 cm mass with marked inflammatory changes involving the right breast and significant skin thickening. The patient completed 12 days of a two-week course of antibiotics secondary to vancomycin-induced thrombocytopenia. While there was residual mild erythema and induration of her breast after 1.5 weeks of treatment, she was taken to the OR for right breast implant explantation and total capsulectomy (Figure 3). There was a significant amount of edema and gelatinous material around the mass which made dissection difficult. The implant was found to be an intact McGhan textured silicone implant that was surrounded by an old hemolyzed hematoma. The left breast implant was left in place given the concern for infection and potential contamination. Pathology revealed a 10.5 × 6.8 × 4.9 cm mass consistent with lymphoma that invaded the capsule and focally extended into fibroadipose tissue. Immunohistochemical stains were performed on the mass and were positive for CD30 and negative for ALK. Microbiology swabs taken from the implant pocket demonstrated no bacterial or fungal growth. Figure 3. View largeDownload slide Right breast capsule and associated mass. Figure 3. View largeDownload slide Right breast capsule and associated mass. The postoperative period was uncomplicated and the patient’s symptoms completely resolved (Figure 4). A PET-CT done three weeks postoperatively showed heterogeneous activity along the implant cavity consistent with inflammation with no or low-level FDG uptake in previous high uptake areas. She went on to complete a total of six cycles of Brentuximab. A repeat PET-CT scan showed stable low-level reactive activity in the right chest wall with no new sites of disease. Approximately 1.5 months after completion of chemotherapy she returned to the OR for explantation of her left breast implant and total capsulectomy. Pathology of the left breast capsule did not show any evidence of lymphoma. She is still doing well eight months after tumor removal with no signs of recurrent disease (Figure 5). Figure 4. View largeDownload slide (A-C) Six week postoperative photographs of a 71-year-old woman who underwent explantation of her right breast implant and total capsulectomy demonstrating complete resolution of swelling and erythema of the right breast. Figure 4. View largeDownload slide (A-C) Six week postoperative photographs of a 71-year-old woman who underwent explantation of her right breast implant and total capsulectomy demonstrating complete resolution of swelling and erythema of the right breast. Figure 5. View largeDownload slide (A, B) Postoperative photographs of a 71-year-old woman eight months after explantation of her right breast implant and total capsulectomy for BIA-ALCL and two months after left breast explanation. Figure 5. View largeDownload slide (A, B) Postoperative photographs of a 71-year-old woman eight months after explantation of her right breast implant and total capsulectomy for BIA-ALCL and two months after left breast explanation. DISCUSSION The patient presented with typical findings of BIA-ALCL, but she also experienced B symptoms and erythema and induration of the affected breast. Cutaneous manifestations have rarely been described in association with BIA-ALCL. In a review of all available case reports in the English language discussing the clinical manifestations of BIA-ALCL (77 total patients), erythema was described in nine patients,6-14 rash in three patients,15-17 pruritus in three patients,16-18 superficial nodules in four patients,12,19-21 ulcer in one patient,22 and poor wound healing in one patient.23 Some of the patients with rash and pruritus did not have these symptoms on the breast. Of the nine patients with erythema, seven had breast erythema as a component of their initial presentation;6-10,13,14 one developed erythema over one month after implant exchange and again three months after explantation and total capsulectomy which was associated with a cutaneous lesion;12 and one developed erythema, swelling, and firmness overlying her transaxillary incision two months after completion of CHOP chemotherapy.11 No other studies mentioned an association between erythema and administration of chemotherapy. The etiology of the cutaneous symptoms in our patient is unclear. It could represent a manifestation of the underlying cancer as it was one of her symptoms upon presentation before receiving any treatment or developing any signs or symptoms on infection. A second possible cause is inflammation due to tumor lysis syndrome as the erythema worsened after each round of chemotherapy. Lastly, it could represent an infection as the patient developed a fever and leukocytosis in association with an immunocompromised state and wound healing issues which improved with the initiation of antibiotics. A skin biopsy performed during her hospitalization was negative for cancer or infection, but this was after the initiation of chemotherapy and antibiotics, which could have led to false negative results. Likely the etiology of the erythema was some combination of all three factors which occurred at different times during her treatment course. While this is unclear, it is important to consider breast erythema as a possible clinical manifestation of ALCL moving forward as it may assist in the diagnosis. Unfortunately, these symptoms ultimately led to significant delays in the patient undergoing definitive treatment. A recent study by Hu et al demonstrated that the capsule microbiome in patients with BIA-ALCL is different than patients without tumors with a predominance of Ralstonia species present in ALCL specimens (P < 0.05) and Staphylococcus species in nontumor specimens (P < 0.001).24 These differences implicate a possible infectious etiology in the development of BIA-ALCL and underscore the importance of additional research being conducted in this area. It is possible that our patient had an indolent infection that became activated with the initiation of chemotherapy. This case also highlights the importance of a multidisciplinary approach to the treatment of BIA-ALCL, including early consultation with a plastic surgeon. It is unclear why the outside facility did not pursue further tissue sampling at the patient’s initial presentation after the first specimen was inadequate. Moreover, the patient was not treated per National Comprehensive Cancer Network (NCCN) guidelines. First line therapy is implant explantation with total capsulectomy, including excision of any associated mass and biopsy of suspicious nodes, with consideration for removal of the contralateral implant when present. Chemotherapy should be considered for advanced-stage disease and radiation for residual disease.25 First line chemotherapy for BIA-ALCL is brentuximab, not CHOP as was initially given in this patient, as patients with recurrent or refractory ALCL have demonstrated an excellent response to this therapy.26 The diagnosis, staging, treatment, and surveillance of BIA-ALCL NCCN has recently been nicely summarized by Clemens and Horwitz and should serve as a guide for anyone caring for a patient with this disease.27 CONCLUSIONS BIA-ALCL is a rare clinical entity. The most common presentation is a late-onset seroma and/or a breast mass. Cutaneous manifestations are a rare but important consideration in making the diagnosis and further research assessing potential infectious etiologies should be pursued. Treatment should be under the guidance of a multidisciplinary team with first line therapy being surgery. Disclosures The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. Funding The authors received no financial support for the research, authorship, and publication of this article. REFERENCES 1. Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): By the numbers, and what they mean. https://www.surgery.org/sites/default/files/ALCL-member-information_March_24_2017.pdf. Accessed October 26, 2017. 2. Keech JAJr, Creech BJ. Anaplastic T-cell lymphoma in proximity to a saline-filled breast implant. Plast Reconstr Surg . 1997; 100( 2): 554- 555. Google Scholar CrossRef Search ADS PubMed 3. U.S. Food and Drug Administration Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL). 2017; https://www.fda.gov/medicaldevices/productsandmedicalprocedures/implantsandprosthetics/breastimplants/ucm239995.htm. Accessed April 9, 2017. 4. Brody GS. Anaplastic Large Cell Lymphoma Occurring in Women with Breast Implants: Analysis of 173 Cases. Plast Reconstr Surg . 2015; 136( 4): 553e- 554e. Google Scholar CrossRef Search ADS PubMed 5. Clemens MW. Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): By the numbers, and what they mean. https://www.plasticsurgery.org/for-medical-professionals/quality-and-registries/bia-alcl-by-the-numbers. Accessed September 22, 2017. 6. Hart AM, Lechowicz MJ, Peters KK, Holden J, Carlson GW. Breast Implant-Associated Anaplastic Large Cell Lymphoma: Report of 2 Cases and Review of the Literature. Aesthet Surg J . 2014; 34( 6): 884- 894. Google Scholar CrossRef Search ADS PubMed 7. Bishara MR, Ross C, Sur M. 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Aesthetic Surgery Journal – Oxford University Press
Published: Mar 1, 2018
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