Histological and immunohistochemical characteristics of capsular synovial metaplasias that form around silicone breast implants

Metaplasia is a reversible phenomenon that usually occurs in response to chronic irritation and/or inflammation. It allows for the substitution of fragile cells with those that are better able to survive under various circumstances. Our study aims to describe the histology of one unusual type of metaplasia results in the formation of a synovial-like membrane typical of joints inside a female patient’s breasts around silicone implants. We analyzed samples from 22 female patients, who underwent delayed-staged breast reconstructions. Attention was paid especially to tissue that was in direct contact with the silicone expander and that was under permanent pressure and friction between the implant and the surrounding tissue. Biopsies of explanted periprosthetic capsules were processed for examination by light microscopy. Immunohistochemical staining (ten different primary antibodies) was performed to examine a variety of cell-specific antigens. At the interface between the tissue capsule and the silicone breast expander, we typically observed a 50–200-μm cellular lining. Thanks to the high cellular density, this cellular layer resembled epithelium. However, there was no basement membrane, and cells were negative for cytokeratin. The cells forming the superficial layer were strongly positive for vimentin and podoplanin and weakly positive for the S100 protein. These cells did not express desmin or smooth muscle actin. Within the most superficial layer (synovial intima), we distinguished two types of cells: phagocytic (CD68-positive) and fibroblast-like synovial cells. We conclude that the cellular lining surrounding silicone breast implants looks like a true synovial membrane resembling a fibrous form of synovium.     

Acceleration of capsule formation around silicone implants by infection in a guinea pig model

Fibrous capsules surrounding silicone implants were investigated in a new guinea pig model to delineate some of the factors leading to capsular contracture. Both the implant surfaces and tissue capsules were examined by light and scanning transmission electron microscopy (STEM + SEM) with x-ray energy spectroscopy (XES). The capsular tissues were qualitatively similar to those recovered clinically, showing dense parallel collagen deposits, fibroblasts, myofibroblasts, macrophages, and foreign-body giant cells. Silicone was positively identified within intercellular vacuoles and the rough endoplasmic reticulum of macrophages by XES. Tissue recovered from the capsules that surrounded implants that were contaminated with S. aureus presented a qualitatively similar histologic spectrum. The contaminated specimens did show an accelerated response. SEM showed a cellular invasion of the silicone envelopes. We conclude that the model accurately simulates the clinical situation and suggests that immune mechanisms may play a key role in capsular contracture.     

"Bleeding" of silicone from bag-gel breast implants, and its clinical relation to fibrous capsule reaction.

We present evidence of the following. 1. Modern silicone bag-gel breast implants leak silicone gel through the bag. 2. The amount of silicone leaked by an intact implant varies from one implant to another, and is not constant for any type or brand. 3. The leaked silicone, together with fibrous thickening and various degrees of inflammation will be found in capsules surrounding the implants if extensive biopsies are taken and many sections are examined.     

Long-term use of polyurethane breast prostheses: a 14-year experience

I have used polyurethane prostheses for the past 14 years, implanting 220 implants into 130 patients who desired breast reconstruction after subcutaneous mastectomy or cancer ablation or simply breast augmentation. I theorize that a polyurethane-covered implant resists contracture, retaining its compressibility because the fibroblasts proliferate into the polyurethane in many different directions. When the fibrils contract, the forces of contracture counterbalance one another, resisting contracture. However, when smooth prostheses are implanted, fibrils are directed in a circular fashion around the implant and naturally contract, leading to firmer breasts. There were 115 prostheses inserted following subcutaneous mastectomy, and 22 percent developed contracted capsules. Seven implants became exposed because of skin necroses; one was removed because of a Staphylococcus infection; and two patients developed a combination of polyurethane and silicone granulomas. These developed only with the earlier implant, where there was shedding of the polyurethane sponge layer and silicone bled from the low-viscosity silicone used in the earlier implants. No granulomas were noted with the currently used Surgitek Replicon implant. Eighty-five breasts were reconstructed after cancer ablation with polyurethane implants, and the contracture rate was 2.3 percent. Other complications were minimal. A smaller group of patients had augmentation mammaplasty, and 20 prostheses were placed in 10 patients. A 15 percent contracture rate was noted in this group. In this study, 82 percent of patients were followed for up to 14 years. Capsular contractures occurred in 30 implants between 1 and 11 years, for an average recurrence at 6.3 years. The overall contracture rate was 13 percent. Other complications were minimal. All implants were placed subcutaneously or subglandularly, and all were drained.     

Capsular contracture in silicone gel and saline-filled breast implants after reconstruction

Comparisons between results with randomly allotted silicone-gel and saline-filled prostheses in breast reconstruction after mastectomy led to the following conclusions. Neither prosthesis type is ideal. Leakage from saline-filled implants occurred in 2 of the 37 implants, with resultant deflation. Silicone prostheses had a significantly higher rate of capsular contracture [surgeon's evaluation: 54 percent capsular contracture for silicone-gel compared with 20 percent for saline-filled prostheses (p = 0.006); patients' evaluation for the same figures: 54 percent compared with 29 percent (p = 0.03)]. Other authors have shown the presence of silicone in the tissue around silicone-gel-filled silicone implants, but less or none around saline-filled silicone implants. Since the only difference between the two groups was the randomly allotted implants, we assume that the free silicone around silicone-gel-filled prostheses is the major cause of capsular contracture. Since the saline-filled implants showed a 20 percent capsular contracture rate, there could be other causes of capsular contracture in this study. For prevention of contracture, improved implant encapsulation and use of a less reactive filling substance seem to offer possibilities. Surgical technique should aim to preserve the integrity of the prosthesis.     

Aspergillus colonization associated with bilateral silicone mammary implants

A case of Aspergillus niger fungal colonization associated with bilateral inflatable silicone mammary implants is reported. Painful fibrous capsular contractures without clinical evidence of infection or inflammation characterized the presenting symptoms. Operative findings included a cheesy-white exudate that surrounded the implants and turbid fluid within the implants. All specimens yielded a heavy growth of Aspergillus niger. Special stains of the fibrous capsules were negative for fungal invasion. The etiology and pathogenesis of Aspergillus colonization in this patient are postulated.     

The effectiveness of sodium 2-mercaptoethane sulfonate (mesna) in reducing capsular formation around implants in a rabbit model

The development of capsular contracture is the most common complication associated with the insertion of breast implants. The authors studied the role of sodium 2-mercaptoethane sulfonate (mesna) in reduction of capsular formation in a rabbit model. Two 40-cc textured saline implants were placed dorsally into each of the 20 rabbits in the study. At the time of insertion of the implants, 10 ml of a 10% solution of mesna was instilled into one of the pockets and normal saline was instilled into the other. The implants were removed and a capsulectomy was performed at 5 months. The capsules were examined histologically for qualitative differences between the two groups. Quantitative analysis of the thickness of the capsule and the myofibroblast populations was also performed and compared between the two groups. The mean total thickness of the capsule around the implants was 496.8 microm in the mesna-treated group compared with 973.7 microm in the saline-treated group (p < 0.001). Likewise, the thickness of the myofibroblast layer was reduced in the mesna-treated group at 283.2 microm versus 555 microm in the saline-treated group (p < 0.0001). The capsules were also relatively less vascular in the mesna-treated group. Because of its ability to reduce the extent of capsular formation and to diminish development of myofibroblasts in the capsules, mesna would appear to be a useful adjunct in the prevention of capsular contracture formation.     

The biophysical and histologic properties of capsules formed by smooth and textured silicone implants in the rabbit.

Capsular contracture remains the major complication of reconstructive and aesthetic breast surgery. The purpose of this investigation was to determine if a silicone implant with a textured surface will form a capsule of significantly different biophysical and histologic properties than conventional smooth silicone. Thirty smooth and 30 textured silicone tissue expanders were implanted under the panniculus carnosus of rabbits. After 3 months, measurements related to contracture were performed on anesthetized animals in an investigator-blinded, controlled manner. Intraexpander pressures were measured as saline was injected over time. We found a significant correlation between intraexpander pressures, applanation tonometry, and Baker class. Histology revealed a thicker, more adherent, and inflammatory capsule around the textured silicone implants as compared with the smooth silicone implants. Dynamic pressures were plotted against volume of saline within the two types of implants. Statistical analysis revealed that the textured implants form a tighter and thicker capsule than the smooth implants after 3 months of observation (p less than 0.005).     

A clinical comparison of the tendency to capsular contracture between smooth and textured gel-filled silicone mammary implants.

The aim of this prospective, controlled clinical investigation was to find out if there is a difference in the capsular contracture rate between silicone implants with a smooth or textured surface as the only difference. Twenty-five women with bilateral mammary hypoplasia underwent mammary augmentation. All got a textured implant on one side and a smooth implant on the other. The implants were placed subglandularly. Follow-up examinations were done on six occasions. Three parameters were used for estimation of the tendency to capsular contracture: (1) the patient's opinion on differences in hardness of the breasts, (2) the investigator's classification of capsular contracture, and (3) applanation tonometry. At the end of the follow-up period, after 1 year, all parameters showed with no doubt that the breasts augmented with textured implants had a lower tendency to develop contracting capsules than the breasts augmented with smooth implants.     

Experimental effects on surrounding fibrous capsule formation from placing steroid in a silicone bag-gel prosthesis before implantation.

Soft-gel miniprostheses of silicone were implanted subcutaneously into 75 male rats. Groups of prostheses were preinjected with saline, a commercial form of triamcinolone acetonide, or a suspension of crystalline triamcinolone acetonide. The softness of the prosthesis mound later was measured objectively, and the capsules surrounding the implants were analyzed by histology, SEM, and chemistry, at various intervals up to 120 days after implantation. The control implants developed a normal laminar capsule. With an incidence increasing up to 100 percent at 120 days, the steroid-treated implants were surrounded by capsules lacking an inner membrane. The inner membrane of the laminar capsule had a high protein content (relative to normal tissue) and a relatively reduced collagen content, while the diffuse capsule resulting from the TA treatment had a high protein content and a high collagen content (about the same as normal tissue). No differences were found in the softness of the mounds of the implanted prostheses. The effect of the TA treatment was explained on the basis of its collagenolytic effect, which could gradually erode the normal capsule membrane. Capsule firmness could not be related to the architecture or the protein or collagen content in our findings. We hypothesize that normal capsule firmness may be related to the amount and kind of interconnection between the loose outer zone of connective tissue and the surrounding tissue.     

Label‐free stimulated Raman scattering imaging reveals silicone breast implant material in tissue

Millions of women worldwide have silicone breast implants. It has been reported that implant failure occurs in approximately a tenth of patients within 10 years, and the consequences of dissemination of silicone debris are poorly understood. Currently, silicone detection in histopathological slides is based on morphological features as no specific immunohistochemical technique is available. Here, we show the feasibility and sensitivity of stimulated Raman scattering (SRS) imaging to specifically detect silicone material in stained histopathological slides, without additional sample treatment. Histology slides of four periprosthetic capsules from different implant types were obtained after explantation, as well as an enlarged axillary lymph node from a patient with a ruptured implant. SRS images coregistered with bright‐field images revealed the distribution and quantity of silicone material in the tissue. Fast and high‐resolution imaging of histology slides with molecular specificity using SRS provides an opportunity to investigate the role of silicone debris in the pathophysiology of implant‐linked diseases.     

Tissue reactions to breast implants coated with polyurethane.

The histological features noted in the capsules from 7 polyurethane coated silicone breast prostheses are described. The polyurethane provoked a definite foreign body reaction and was slowly degraded, with some particles ejected from the capsule into the surrounding tissues. Separation of the polyurethane coating from the silicone prosthesis and the degradation of the polyurethane took about two years. Another much more resistant foreign material was found to occur in conjunction with the polyurethane in the capsules. It may be an adhesive or flakes off the silicone shell. Vacuolated spaces were noted in the inner layers of 3 capsules; it was assumed that they contained liquid silicone.     

Interrelationship of capsule thickness and breast hardness confirmed by a new measurement method

All implants initiate a foreign-body response that leads to their encapsulation by scar tissue. In order to better understand this encapsulation process and the differences between soft (comfortable) and firm (contracted) breasts, we studied 22 patients who had come in for reaugmentation during a 2-year period. The capsules removed were prepared and measured using a new method. The capsules were (1) removed and stored in physiologic solution until the time of measurement (30 minutes to 2 hours) and (2) measured using a Mitutoyo dial-thickness gauge (MDTG) that employs a uniform pressure of 85 gm. The measurements revealed that soft breasts (Baker 1) have the thinnest scar-tissue capsules, which ranged in thickness from 0.002 to 0.010 inches. Firm breasts yielded the thickest capsules. Baker 3 measured between 0.010 and 0.078 inches thick, and Baker 4 measured between 0.018 and 0.162 inches thick. We also compared the precision of measurement between the MDTG and a standard (screw-type) micrometer by taking a series of readings on a soft, pliable substance (textured silicone rubber).     

Textured-surface saline-filled silicone breast implants for augmentation mammaplasty

The earliest silicone breast implants were smooth-surface, silicone rubber devices filled with either silicone gel or saline. Because of persistent problems with capsular contracture, polyurethane-covered silicone implants were developed as an alternative. Particularly in the short run, these alternatives proved highly successful at reducing the incidence of capsular contracture. By 1990, polyurethane-covered implants were rapidly becoming the preferred implant choice of many plastic surgeons, but for legal, regulatory, financial, and safety reasons they were withdrawn from the market by Bristol-Myers in 1991. Meanwhile, during the late 1980s, surface texturing and improved materials became available on other silicone breast implants and expanders. Most studies suggest that textured-surface silicone gel-filled implants, saline-filled implants, and tissue expanders have less frequent capsular contracture than their smooth-surface counterparts.     

The incidence of experimental contracture varies with the source of the prosthesis

Nominally equivalent gel-filled miniprostheses supplied by three different manufacturers were placed subcutaneously in rats under identical conditions in a double-blind comparison. The incidence of experimental contracture, defined by grossly visibly asymmetrical distortion of the implant, was 0, 9, and 91 percent for the different manufacturers, consistent with previous observations. Differences among the different implants with respect to the density of the fibrillar capsule structure, the cellularity, and the amount of extruded gel did not correlate with the incidence of contracture. Contracture rate was inversely proportional to the relative degree of filling of the prostheses, as reflected in deviations from the nominal hemispherical shape, and to the viscosity of the gel filling. For implants of the same type, the incidence of contracture was higher when the prosthesis was underfilled. Contracted capsules were more fibrous and contained more cells with microfilament bundles. It is concluded that the physical and geometric properties of silicone implants are critical in the expression of contracture and that these properties vary significantly among prosthesis manufacturers.     

Calcification properties of saline-filled breast implants

Three patients requested explantation of their saline-filled breast implants. Bilateral calcification had occurred in all six implants. Four of the implants were manufactured by McGhan Corporation (Santa Barbara, Calif.), and two, by the Simaplast Company (Toulon, France). All implants had been inserted in the subglandular plane and had been in place for 7 to 23 years. At the time of explantation, patients were 32, 34, and 44 years old. Calcification on the surface of the implants and capsules was analyzed. Implant surface calcification was clinically evident on all six implants, appearing as ivory-colored, tenaciously adherent deposits, only on the anterior surface of the implant. Capsular calcification, which was observed only microscopically, was characterized by poorly organized, irregularly shaped, calcified agglomerates; this calcification also occurred only on the anterior surface of the capsule, adjacent to the area of calcification on the implant. Ultrastructural analysis of scrapings from the implant surface showed large, electron-dense aggregates of crystals, with individual crystals measuring approximately 40 x 10 x 10 nm. In contrast, capsular calcification was characterized by two patterns of deposition, spherulitic aggregates of needle-shaped crystals and areas of metaplastic bone. The individual crystals were approximately 40 x 10 x 10 nm. Energy-dispersive x-ray spectroscopy of specimens from the areas of calcification on the implant and capsule surfaces demonstrated calcium and phosphorus. Electron diffraction of crystals from the implant and capsule surfaces demonstrated the D-spacings characteristic of calcium apatite. There were many differences between the calcification properties of these six saline implants and those of silicone gel implants. For example, mineralization has not been observed on the surface of gel implants, but in these saline implants it occurred primarily on the implant surface. Also, capsular calcification has been observed clinically in gel implants across the surface of the capsule (except at the site of attachment of a Dacron patch), but in this study it was observed only microscopically and was located on the anterior surface of the capsule, adjacent to the area of calcification on the implant. In addition, crystals 100 times larger than those observed on the six saline implant capsules have been observed on the surface of gel implant capsules. A model is presented to explain the mechanism of calcification associated with breast implants and to explain the observed differences between saline-filled and gel-filled implants.     

Serum proteins and paraproteins in women with silicone implants and connective tissue disease: a case-control study

Prior studies have suggested abnormalities of serum proteins, including paraproteins, in women with silicone implants but did not control for the presence of connective-tissue disease (CTD). This retrospective case-control study, performed in tertiary-care academic centers, assessed possible alterations of serum proteins, including paraproteins, in such a population. Seventy-four women with silicone implants who subsequently developed CTD, and 74 age-matched and CTD-matched women without silicone implants, were assessed in the primary study; other groups were used for additional comparisons. Routine serum protein determinations and high-sensitivity protein electrophoresis and immunofixation electrophoresis were performed for detection of paraproteins. Women with silicone implants, either with or without CTD, had significantly lower serum total protein and alpha1-globulin, alpha2-globulin, beta-globulin, gamma-globulin, and IgG levels compared with those without silicone implants. There was no significant difference, however, in the frequency of paraproteinemia between women with silicone implants and CTD (9.5%) and age-matched and CTD-matched women without silicone implants (5.4%) (odds ratio, 1.82; 95% confidence interval, 0.51-6.45). Paraprotein isotypes were similar in the two groups, and the clinical characteristics of the 13 women with paraproteinemia were comparable with an independent population of 10 women with silicone breast implants, CTD, and previously diagnosed monoclonal gammopathies. In summary, this first comprehensive study of serum proteins in women with silicone implants and CTD found no substantially increased risk of monoclonal gammopathy. Women with silicone implants, however, had unexpectedly low serum globulin and immunoglobulin levels, with or without the subsequent development of CTD. The causes and clinical implications of these findings require further investigation.     

Inhibitory avoidance memory retention in the elevated T-maze is impaired after perivascular manipulation of the common carotid arteries

Perivascular manipulation promoted by the positioning of a silicone collar around the common carotid arteries causes local inflammation and has been suggested as an animal model of atherosclerosis. This manipulation induces biochemical and morphological changes that are similar to those observed in the early stage of atherosclerosis in humans. Based on evidences showing that atherosclerosis is associated with cognitive deficits in humans, we presently investigated the temporal consequences of the bilateral positioning of silicone collars around the common carotid arteries (n = 15) on inhibitory avoidance memory retention in male Wistar rats tested in the elevated T-maze. The effects of this procedure were compared to those observed in sham-operated animals (n = 15) and to those observed in animals submitted to permanent bilateral occlusion of the common carotid arteries (n = 16). Additionally we studied the effects of the pretreatment with the non-selective anti-inflammatory drug indomethacin (n = 13) or the selective COX-2 inhibitor celecoxib (n = 12) and compared the effects to those of the pretreatment with vehicle (n = 11). The results showed that the silicone collar implants induced deficits in memory retention when animals were tested 2 and 4, but not 15 or 30, days after surgery. Permanent bilateral occlusion of the common carotid arteries impaired avoidance retention up to 30 days after surgery. Pretreatment with indomethacin (2 mg/kg/day) or celecoxib (5 mg/kg/day) post surgery and up to 3 days thereafter did not prevent memory deficits caused by silicone collar implants. Our data suggest that the prostanoids that participate in the inflammatory process triggered by the placement of the silicone collar do not seem responsible for the deficit in memory retention observed during the first days after collar placement.     

Connective tissue of capsules surrounding lavsan under conditions of long-term implantation]

An experimental study of the capsules formed around the net lavsan prostheses at periods of from 7 days to 5.5 years demonstrated that in the process of prolonged implantation morphology and metabolism of the capsule connective tissue underwent changes which could be associated with the release from the implants of low molecular products producing a damaging effect on the tissues surrounding the implant.     

Biodurability of retrieved silicone gel breast implants

This study analyzed the shells of single-lumen silicone gel breast implants within the general context of device durability in vivo. The investigation included the major types of gel-filled implants that were manufactured in the United States in a 30-year period. The implants analyzed were Cronin seamed (two explants and one control), Silastic 0 and Silastic I (18 explants and seven controls), and Silastic II (22 explants and 43 controls). The biodurability of the explants was investigated with measurements of the mechanical and chemical properties of the various types of silicone gel control and explanted shells, with implantation times ranging from 3 months to 32 years. The shell properties measured for the controls and explants included the stress-strain relationships, tensile strength, elongation, tear resistance, moduli, cross-link density, and amount of extractable material in the shell. In addition, the mechanical properties of shells that had been extracted with hexane were analyzed for both explants and control implants. The silicone gel explants investigated in this study included some of the oldest explants of the various major types that have been tested to date. For assessment of long-term implantation effects, the data obtained in this study were combined with all known data from other institutions on the various major types of gel implants. The study also addressed the failure mechanisms associated with silicone gel breast implants. The results of the study demonstrated that silicone gel implants have remained intact for 32 years in vivo and that degradation of the shell mechanical and chemical properties is not a primary mechanism for silicone gel breast implant failure.