Differential Diagnosis

Implant rupture must be ruled out in the presence of a large fluid effusion surrounding the implant. Effusions that develop within 1 year of surgery may indicate a postsurgical hematoma or effusion, but periprosthetic fluid collection that has developed more than 1 year after surgery may indicate BIA-ALCL.16 BIA-ALCL can typically be differentiated from other breast masses based on physical examination and history of breast augmentation surgery. Fibrocystic breast disease may present with multiple bilateral round or rope-like masses that fluctuate in size with hormonal stimulation associated with menstrual cycles. Primary breast malignancies tend to present as a hard irregularly-shaped mass, nipple retraction, or bloody nipple discharge.

Diagnosis

Initial diagnostic testing could include imaging such as ultrasound or magnetic resonance imaging (MRI) of the affected breast and ipsilateral axilla to assess for effusion and lymphadenopathy.19 Mammography has not been shown to be superior to ultrasound or MRI.16,19 If fluid is found, a fine needle aspiration (>50 mL) should be performed to collect a sample for cytologic pathology.16,19 Likewise, fluid can be collected during a capsulectomy procedure. Cells that have invaded the surface of the capsule, breast parenchyma, or regional lymph nodes can be collected for tissue sampling.

On cytology analysis, the cells will appear as large, pleomorphic cells with large nuclei and an increased amount of cytoplasm.9 All ALCL lymphomas, including BIA-ALCL, can usually be distinguished by the presence of “hallmark” cells, which are cells with horseshoe-shaped nuclei.9


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A key differentiating factor between BIA-ALCL and other forms of non-Hodgkin lymphoma is that BIA-ALCL is negative for anaplastic lymphoma kinase (ALK), while most other forms of non-Hodgkin lymphoma are ALK positive.9 The most common marker for BIA-ALCL is an increased CD30 count, often with CD43 and CD4 elevated as well, which can be noted with immunophenotyping.9 Other markers expressed with BIA-ALCL include T-cell intracellular antigen 1 (TIA-1), granzyme B, and epithelial membrane antigen.20 Additionally, BIA-ALCL will not have Reed-Sternberg cells, which are pathognomonic for Hodgkin lymphoma.9

Treatment

Once BIA-ALCL is diagnosed, the recommended treatment is to remove the implant with a total capsulectomy and removal of any associated solid tumors.19 In a total capsulectomy, both the implant and the entire surrounding fibrous capsule are removed to help prevent reoccurrence or continued symptomatology. Removal of the contralateral implant should also be strongly considered.21 A study by Clemens et al demonstrated that in the absence of a tumor mass, total capsulectomy resulted in complete remission in 93% of cases at 3 years.21

Cases of reoccurrence or metastasis are most commonly related to an incomplete or partial capsulectomy. In uncomplicated cases, surgery is the only treatment indicated. If the disease has metastasized to regional lymph nodes, chemotherapy treatment is warranted in the form of CHOP, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone.17,22 Radiation therapy may also be considered as adjuvant treatment. Total mastectomy is not required as the lymphoma cells do not invade the surrounding breast tissue.23

The Ann Arbor staging system is utilized to predict lymphoma disease prognosis. Since BIA-ALCL typically remains contained to the surrounding fibrous capsule, about 85% of cases are staged as IE.23 About 15% of cases will indicate spread beyond the fibrous capsule into regional lymph nodes and will be staged as IIE.23 It is very rare for the disease to spread outside of the regional lymph nodes. If the disease is confined to the capsule and appropriately excised, the 5-year survival rate is approximately 90%.17 An updated staging system for malignant lymphoma based on Lugano classification also is available.24

Conclusion

BIA-ALCL is a rare but potentially fatal outcome of breast implantation. Nurse practitioners and physician assistants working in aesthetic or reconstructive surgical specialties should educate patients about this disease entity during presurgical counseling sessions and incorporate this risk into shared decision making when selecting implant type. The cause of BIA-ALCL appears to be multifactorial and more research should be done to confirm true incidence rates and explore possible pathways of development. It is prudent to continue recommending against textured implants and to investigate any case of breast edema or effusion occurring in relation to implant insertion since the prognosis is most favorable with early and complete surgical intervention.  

Kristen Grippe, MPAS, PA-C, is an associate professor in the Physician Assistant Department at Gannon University in Erie, PA, and a physician assistant at Spartansburg Medical Center in Spartansburg, PA. Elisabeth Duer, MPAS, PA-C, currently works at Rehabilitation and Fitness Consultants, PLLC, and at AdventHealth Altamonte Springs Hospital, in Florida.

References

1. Cook JA, Sasor SE, Tholpady SS, Chu MW, Momeni A. Complexity of health news reporting on breast implant‐associated anaplastic large cell lymphoma. Breast J. 2019;25(1):163-165. doi:10.1111/tbj.13189.

2. American Society of Plastic Surgeons. 2019 national plastic surgery statistics. Published 2019. Accessed February 25, 2021.https://www.plasticsurgery.org/news/plastic-surgery-statistics

3. American Society of Plastic Surgeons. 2020 national plastic surgery statis­tics. Published 2019. Accessed May 3, 2021. https://www.plasticsurgery.org/news/plastic-surgery-statistics

4. Swerdlow SH, Campo E, Pileri S, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390. doi:10.1182/blood-2016-01-643569.

5. US Food and Drug Administration. Medical device reports of breast implant-associated anaplastic large cell lymphoma. Published July 24, 2019. Accessed February 25, 2021. https://www.fda.gov/medical-devices/breast-implants/medical-device-reports-breast-implant-associated-anaplastic-large-cell-lymphoma  

6. Clemens M. BIA-ALCL resources: by the numbers, and what they mean. Plastic Surgery Connect by American Society of Plastic Surgeons. Published February 24, 2020. Accessed February 25, 2021. https://www.plasticsurgery.org/for-medical-professionals/health-policy/bia-alcl-physician-resources/by-the-numbers

7. US Food and Drug Administration. The FDA requests Allergan voluntarily recall Natrelle BIOCELL textured breast implants and tissue expanders from the market to protect patients: FDA safety communication. Published July 24, 2019. Updated June 1, 2020. Accessed February 25, 2021. https://www.fda.gov/medical-devices/safety-communications/fda-requests-allergan-voluntarily-recall-natrelle-biocell-textured-breast-implants-and-tissue

8. Collett D, Rakhorst H, Lennox P, Magnusson M, Cooter R, Deva A. Current risk estimate of breast-implant associated anaplastic large cell lymphoma in textured breast implants. Plast Reconstr Surg. 2019;143(Suppl 3):30S-40S. doi:10.1097/PRS.0000000000005567

9. de Leval L. Breast implant-associated anaplastic large cell lymphoma and other rare T-cell lymphomas. Hematol Oncol. 2019;37(Suppl 1):24-29. doi:10.1002/hon.2582

10. Turner S, Inghirami G, Miranda R, Kadin M. Cell of origin and immunologic events in the pathogenesis of breast-implant associated large-cell lymphoma. Am J Pathol. 2020;190(1):2-10. doi.10.1016/j.ajpath.2019.09.005

11. Santanelli di Pompeo F, Sorotos M. EURAPS editorial: BIA-ALCL, a brief overview. J Plast Reconstr Aesthet Surg. 2018;71(6):785-787. doi:10.1016/j.bjps.2018.04.012

12. Ramos-Gallardo G, Cuenca-Pardo J, Rodríguez-Olivares E, et al. Breast implant and anaplastic large cell lymphoma meta-analysis. J Invest Surg. 2017;30(1):56-65. doi:10.1080/08941939.2016.1215576

13. Jones P, Mempin M, Hu H, et al. The functional influence of breast implant outer shell morphology on bacterial attachment and growth. Plast Reconstr Surg. 2018;142(4):837-849. doi:10.1097/PRS.0000000000004801

14. Ghione P, Cordeiro PG, Ni A, et al. Risk of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) in a cohort of 3546 women prospectively followed after receiving textured breast implants. Hematol Oncol. 2019;37(52):97-98. doi:10.1002/hon.62_2629

15. de Boer M, van Leeuwen FE, Hauptmann M, et al. Breast implants and the risk of anaplastic large-cell lymphoma in the breast. JAMA Oncol. 2018;4(3):335-3341. doi: 10.1001/jamaoncol.2017.4510

16. Quesada A, Medeiros LJ, Clemens MW, Ferrufino-Schmidt MC, Pino-Oviedo S, Miranda RN. Breast implant-associated anaplastic large-cell lymphoma: a review. Mod Pathol. 2019;32(2):166-188. doi:10.1038/s41379-018-0134-3

17. Clemens M, Jacobsen E, Horwitz S. 2019 NCCN consensus guidelines on the diagnosis and treatment of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). Aesthet Surg J. 2019;39(Suppl 1):S3-S13. doi: 10.1093/asj/sjy331

18. Letter H, Rop B, Edison MN, Turner P. Breast implant-associated anaplastic large cell lymphoma: a case report and literature review. Cureus. 2016 Mar 26;8(3):e546. doi: 10.7759/cureus.546

19. Kricheldorff J, Fallenberg EM, Solbach C, Gerber-Schäfer C, Rancsó C, von Fritschen U. Breast implant-associated lymphoma. Dtsch Arztebl Int. 2018;115(38):628-635. doi:10.3238/arztebl.2018.0628

20. Dashevsky BZ, Gallagher KM, Grabenstetter A, et al. breast implant‐associated anaplastic large-cell lymphoma: clinical and imaging findings at a large US cancer center. Breast J. 2019;25(1):69-74. doi:10.1111/tbj.13161

21. Clemens MW, Medeiros LJ, Butler CE, et al. Complete surgical excision is essential for the management of patients with breast implant-associated anaplastic large-cell lymphoma. J Clin Oncol. 2016;34(2):160-168. doi:10.1200/JCO.2015.63.3412

22. Hallquist Viale P. Breast implants and lymphoma: what is the risk for your patient? J Adv Pract Oncol. 2017;8(6):565-567. doi.org/10.6004/jadpro.2017.8.6.1

23. DePaola NE, Coggins H. Breast implant-associated large-cell lymphoma: what we know. J Adv Pract Oncol. 2019;10(1):54-61. doi.org/10.6004/jadpro.2019.10.1.4

24. Munakata W, Terauchi T, Maruyama D, Nagai H. Revised staging system for malignant lymphoma based on the Lugano classification. Jpn J Clin Oncol. 2019;49(10):895-900. doi:10.1093/jjco/hyz111