Anaplastic large cell lymphoma (ALCL) is a rare disease constituting 2 percent of all newly diagnosed non-Hodgkin lymphomas worldwide, with four major variants described in the literature: two distinct forms of systemic ALCL [i.e., anaplastic lymphoma kinase-positive (ALK+) and ALK−]; breast implant-associated (BIA) ALCL, classified as a T-cell lymphoma provisional entity; and primary cutaneous ALCL, which must be distinguished from cutaneous involvement by systemic ALCL.1,2
Breast implant-associated ALCL is a rare T-cell lymphoma that can present as a late effusion, collecting around an implant,3 and came to limited attention only after a U.S. Food and Drug Administration safety communication in 2011.4 Awareness has grown exponentially following new advisory statements by the U.S. Food and Drug Administration,5 numerous government agencies worldwide,6,7 and even media coverage.8
This article describes a case of a patient diagnosed with ALCL after augmentation gluteoplasty with silicone implants. This is the same disease as BIA-ALCL but in another location, never described in the literature, which we call gluteal implant-associated ALCL, thus introducing new important discussions about the understanding of this pathology.
A 63-year-old female patient first came to our institution in early 2015, reporting a silicone augmentation gluteoplasty in 2006 and, after an intramuscular injection on the left buttock in 2013, noted a progressive increasing volume and distortion of that side. Ultrasound and electromagnetic resonance showed a large amount of fluid collection around the implant on the left side and no changes on the right side, with no signs of implant rupture or other alterations (Fig. 1, left). The left side implant was removed, revealing a Silimed (Silimed, Rio de Janeiro, Brazil) gluteal, textured, oval, 350-cc device in an intramuscular location. The capsule was left intact, presupposing a future reimplantation, and the fluid collection sent for laboratory examination. Culture results were positive for Staphylococcus aureus. After a normal postoperative period, the patient was advised to return after 6 months to evaluate the possibility of reimplantation. For personal reasons, she only returned 3 years after surgery, presenting a new and even larger seroma on the left, previously explanted side. A new electromagnetic resonance scan confirmed the presence of thick fluid restricted to the explanted region on the left side, with no involvement of adjacent tissues, and normal appearance on the right, without signs of implant rupture (Fig. 1, right). An 800-ml drainage of fluid accompanied by lumps of yellowish fibrinoid tissue and total capsulectomy was accomplished (Fig. 2). Explantation and total capsulectomy were performed on the right side, presenting a regular capsule and implant aspects. All material was sent for culture and cytologic, pathologic, and immunohistochemical examinations.
Fluid culture results were negative. Sections of the capsule and lumps of fibrinoid tissue presented large “hallmark” cells showing typical horseshoe-shaped nuclei, and the immunohistochemical tests were strongly positive for CD30 and CD4 and negative for ALK, confirming the diagnosis of ALCL on the left side. [See Figure, Supplemental Digital Content 1, which shows (left) a sample from the lumps present on the left pocket, with “hallmark” cells showing a typical horseshoe-shaped nuclei configuration (arrows), characteristic of ALCL. (Right) Cross-section of the fibrous capsule showing a rim of the same population of large pleomorphic cells (hematoxylin and eosin; original magnification, × 40), http://links.lww.com/PRS/D641. See Figure, Supplemental Digital Content 2, which shows immunohistochemical analysis of fibrous capsule sections with neoplastic cells showing (left) membrane and dot-like (arrows) CD30 positivity and (right) membrane CD4 positivity, confirming the diagnosis of ALCL (original magnification, × 40), http://links.lww.com/PRS/D642.] Complementary examinations by positron emission tomography/computed tomography and bone marrow biopsy did not show any other sites involved. No adjuvant treatment was indicated. Up to 6 months postoperatively, she presented a disease-free status, and any surgical intervention or a new implantation was formally contraindicated.
In this case, the patient presented a clinical evolution similar to BIA-ALCL, with no systemic symptoms and with clinical indolence, presenting a progressive effusion around the implant, resulting in a late seroma and leading to buttock asymmetry. In addition, the anatomopathologic cells characteristics and immunophenotyping expression were the same (i.e., CD30+, CD4+, and ALK−), evidencing that gluteal implant-associated ALCL is the same pathologic condition as the BIA-ALCL described in the literature.9
No risk factors have been clearly identified for ALCL, although many have been theorized, including the presence of a subclinical biofilm, response to particulate from textured implants, a consequence of capsular contracture or repeated capsular trauma, and genetic predisposition. However, these observations have not been confirmed in formal epidemiologic studies.10
Previous work comparing the capsules of textured and smooth implants in pigs showed that there are increased lymphocytes on textured breast implants, with a T-cell predominance, further supporting texturing as a link to chronic inflammation and T-cell response.11 If chronic trauma is an etiologic component, we should consider that, anatomically, the gluteal region naturally undergoes more stress in daily life, and this first report somehow contradicts the logic of this interpretation. In contrast, it seems that the majority of implants in gluteoplasty are smooth, but in this case the devices removed were textured, leaving open the understanding of the real role of implant surface in ALCL genesis. Assuming that the implant texturization is an etiologic factor deserves careful consideration because it will imply an obligatory exclusive use of smooth surface implants, which at this moment is not an evidence-based conclusion. Besides this, textured implants are represented by different surface technologies, defined as macrotexture,12 microtexture, and nanotexture,13,14 factors not fully understood in relation to their possible effects on the implant-tissue interface to impact outcomes. Different from the proposed augmentation operations, other implant-associated ALCL cases have been published,15–18 suggesting the presence of an underlying common etiologic factor of unknown nature in the pathogenesis of ALCL. Kadin et al. proposed that BIA-ALCL is linked to chronic bacterial antigen stimulation of Th1/Th17 antigen-driven memory T cells from capsular tissues and surrounding seromas, sustained T-cell proliferation, and subsequent genetic events in the pathogenesis of BIA-ALCL.19
Regarding capsular contracture, the presence of a subclinical biofilm20 is thought to be an important risk factor in BIA-ALCL. In a recent study by Hu et al., the authors compared the implant capsules of patients with BIA-ALCL to those with normal capsular contracture, finding a higher bacterial load and significantly different microbiome in the BIA-ALCL specimens, with a high predominance of the bacterium Ralstonia pickettii.21 The evolution of the disease in an explanted pocket highlights the definitive importance of the total capsulectomy to adequate therapy in better named lymphoproliferative disorders restricted to the capsule.22
The clinical evolution and pathologic and immunohistochemical analysis of this case could confirm the diagnosis of ALCL. For all purposes, this is the same disease, now in a new location, reintroducing important discussions about the understanding of this abnormality and posing certain risks and safety issues for clinical scenarios to be discussed. Thus, all recommendations regarding BIA-ALCL should also be applied to gluteal implant-associated ALCL, such as the rigorous criteria in the asepsis of implant placement and the detailed investigation of all late seroma. The role of implant surface in ALCL genesis demands further studies with regard to an evidence-based decision to adopt smooth implants to prevent the disease. For therapeutic purposes, total capsulectomy seems to be mandatory when treating this type of lymphoproliferative disorder. Regardless of whether it is a BIA-ALCL or a gluteal implant-associated ALCL, we are probably facing an implant augmentation–associated ALCL, and a new international alert should be addressed to the scientific community.
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