Keeping abreast of the expanding literature of implant-associated Anaplastic Large Cell Lymphoma (ALCL)
By Warren R. Heymann, MD
July 6, 2016
Silicone gel implants were removed from the US market in 1992 because of health concerns, only to be reintroduced in 2006, with the provision for increased surveillance of health outcomes (1). I was under the (apparently mistaken) impression that the FDA put the brouhaha of a potential association of silicone breast implants, with ill effects such as cancer or autoimmune diseases, to rest several years ago.
In 2011, the FDA warned of a potential association of breast implants, either saline or silicone, with ALCL, having become aware of approximately 60 such cases. They offered the following recommendation:
Consider the possibility of ALCL when you have a patient with late onset, persistent peri-implant seroma. In some cases, patients presented with capsular contracture or masses adjacent to the breast implant. If you have a patient with suspected ALCL, refer her to an appropriate specialist for evaluation. When testing for ALCL, collect fresh seroma fluid and representative portions of the capsule and send for pathology tests to rule out ALCL. Diagnostic evaluation should include cytological evaluation of seroma fluid with Wright Giemsa stained smears and cell block immunohistochemistry testing for cluster of differentiation (CD) and Anaplastic Lymphoma Kinase (ALK) markers (2).
Most primary breast lymphomas are B-cell lineage; all reported cases of breast implant-associated lymphomas are of T-cell origin. The prognosis of implant-associated ALCL is variable, some with an excellent outcome with just removing the implant itself, while other aggressive cases also require chemotherapy (3). Indeed, there may be two distinct variants as described by Laurent et al (4): 1) in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and 2) infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). They concluded:
In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.
Alcalá et al detailed the case of a 56 year-old woman with a history of bilateral breast reconstruction following breast cancer of the right breast, who developed papules of the right breast, initially thought to be cutaneous metastases. Pathology demonstrated pleomorphic, large, epithelioid lymphocytes, staining positively for CD15 and CD30; ALK-1 was negative. The T-cell receptor g gene rearrangement confirmed a diagnosis of breast implant-associated ALCL. The implants were removed, CHOP chemotherapy administered, however, she developed neutropenia and succumbed to septic shock (5).
The etiology of implant-associated ALCL is unknown, although it is likely multifactorial, being related to chronic inflammation from bacterial antigen stimulation of T-cells.
Since the initial reports, almost 200 patients have been reported worldwide with breast implant-associated ALCL (6). Although rare, given the ever-increasing number of breast implants, for reconstructive or cosmetic indications, the likelihood is that we will be seeing more cases of ALCL in this context. It is our obligation to recognize it, confirm the diagnosis, and advise our patients to get the implant removed, whether or not further chemotherapy is necessary.
1. Balk EM, et al. Long-term health outcomes in women with silicone gel breast implants: A systematic review. Ann Intern Med 2016; 164: 164-75.
2. Anaplastic large cell lymphoma (ALCL) in women with breast implants: Preliminary FDA findings and analyses. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/BreastImplants/ucm239996.htm 2011
3. Letter H, et al. Breast implant-associated anaplastic large cell lymphoma: A case report and literature review. Cureus 2016; 8: e546.
4. Laurent C, et al. Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes. Ann Oncol 2016; 27: 306-14.
5. Alcalá R, et al. Skin involvement as the first manifestation of breast implant-associated anaplastic large cell lymphoma. J Cutan Pathol 2016; 43: 602-8.
6. Kadin ME, et al. Biomarkers provide clues to early events in the pathogenesis of breast implant-associated anaplastic large cell lymphoma. Aesthet Surg J; 2016; 36: 773-81.
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