“Highly Cohesive” Silicone Breast Implants: a Histopathologic and Laser Raman Microprobe Analysis

International Journal of Environmental Research and Public Health Article A Case of Silicone and Sarcoid Granulomas in a Patient with “Highly Cohesive” Silicone Breast Implants: A Histopathologic and Laser Raman Microprobe Analysis Todor I. Todorov 1,†, Erik de Bakker 2,3, Diane Smith 4,‡, Lisette C. Langenberg 5, Linda A. Murakata 1,§, Mark H. H. Kramer 6 , Jose A. Centeno 1,k and Prabath W. B. Nanayakkara 4,* 1 Department of Environmental and Infectious Disease Sciences, Division of Biophysical Toxicology, Armed Forces Institute of Pathology, Washington, DC 20306, USA; [email protected] (T.I.T.); [email protected] (L.A.M.); [email protected] (J.A.C.) 2 Department of Plastic Surgery, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands; [email protected] 3 Department of Molecular Cell Biology and Immunology, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands 4 Henry Jackson Foundation, Bethesda, MD 20817, USA; [email protected] 5 Department of Internal Medicine, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands; [email protected] 6 Department of Pathology, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands; [email protected] * Correspondence: [email protected] † Current address: Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Citation: Todorov, T.I.; de Bakker, E.; College Park, MD 20740, USA. Smith, D.; Langenberg, L.C.; ‡ Current address: Center for Device and Radiological Health, US Food and Drug Administration, Murakata, L.A.; Kramer, M.H.H.; Silver Spring, MD 20993, USA. Centeno, J.A.; Nanayakkara, P.W.B. A § Current address: South Jersey Gastroenterology, Marlton, NJ 08053, USA. Case of Silicone and Sarcoid k Current address: Division of Occupational and Environmental Medicine, University of Maryland School of Granulomas in a Patient with “Highly Medicine, Baltimore, MD 21201, USA. Cohesive” Silicone Breast Implants: A Histopathologic and Laser Raman Abstract: Foreign body giant cell (FBGC) reaction to silicone material in the lymph nodes of patients Microprobe Analysis. Int. J. Environ. with silicone breast implants has been documented in the literature, with a number of case reports Res. Public Health 2021, 18, 4526. dating back to 1978. Many of these case reports describe histologic features of silicone lymphadenopa- https://doi.org/10.3390/ijerph18094526 thy in regional lymph nodes from patients with multiple sets of different types of implants, including single lumen smooth surface gel, single lumen textured surface gel, single lumen with polyethylene Academic Editor: Paul B. Tchounwou terephthalate patch, single lumen with polyurethane coating, and double lumen smooth surface. Only one other case report described a patient with highly-cohesive breast implants and silicone Received: 4 March 2021 Accepted: 21 April 2021 granulomas of the skin. In this article, we describe a patient with a clinical presentation of systemic Published: 24 April 2021 sarcoidosis following highly cohesive breast implant placement. Histopathologic analysis and Confo- cal Laser Raman Microprobe (CLRM) examination were used to confirm the presence of silicone in Publisher’s Note: MDPI stays neutral the axillary lymph node and capsular tissues. This is the first report where chemical spectroscopic with regard to jurisdictional claims in mapping has been used to establish and identify the coexistence of Schaumann bodies, consisting of published maps and institutional affil- calcium oxalate and calcium phosphate minerals, together with silicone implant material. iations. Keywords: breast implant; silicone; sarcoidosis; Raman; Schaumann bodies Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. 1. Introduction This article is an open access article Silicone gel breast implants have been subject to controversies since their introduction distributed under the terms and by Cronin and Gerow in the early 1960s [1]. The safety of these implants first came conditions of the Creative Commons into question after several reports were published on a possible association of silicone Attribution (CC BY) license (https:// breast implants and development of connective tissue disease in the 1980s [2–6]. Other creativecommons.org/licenses/by/ possible adverse effects of silicone implants include capsular contracture, rupture [7], 4.0/). Int. J. Environ. Res. Public Health 2021, 18, 4526. https://doi.org/10.3390/ijerph18094526 https://www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2021, 18, 4526 2 of 11 locoregional complications, silicone migration to the lung, skin and lower extremities [8,9], and interference with cancer detection [10]. To reduce these probable adverse effects, “highly cohesive” implants were introduced into the market in 1994. The cohesiveness of the silicone [polydimethylsiloxane (PDMS)] polymer and a specially designed outer membrane in these implants were developed to reduce the incidence of rupture and gel bleeds, characterized by gel leakage through the shell of the implant [11–13]. Several authors reported systemic responses in patients with silicone breast implants, including PDMS prostheses [13–15]. We now report the first case of a patient with highly cohesive breast implants who exhibited a sarcoidosis-like clinical presentation and silicone-containing granulomas at a distant site from her breasts. This case is especially enlightening in the context of the current attention around a number of other reported adverse effects (arthralgia, myalgia, fatigue, pyrexia, sicca) related to breast implants [16]. Therefore, we acknowledge the importance of sharing this account in the present climate of the enhanced understanding regarding exposure to such materials. Case Report A 40-year-old Nigerian born woman, living in the Netherlands since 1985, underwent bilateral breast augmentation in 1996. The implants that she received were the highly- cohesive silicone gel implants (Style-410) (Inamed aesthetics, formerly McGhan Medical, Santa Barbara, CA, USA). Postoperatively, no complications were reported, except for occasional short-lived episodes of breast hardening. In July 2001, she developed stone-hard tender breasts, which were predominantly on the right side. A few weeks later she noticed multiple firm, non-tender skin nodules that were located between the breasts and under the right breast. The nodules were approximately 0.5 cm in diameter, and after several days they began to ulcerate and produced a whitish fluid. She was seen by her plastic surgeon who concluded that she had eczema. In the following eight months, the ulcerations and symptoms worsened, and the implants had to be surgically removed. During the operation the surgeon noted that the fibrous capsule surrounding the implant was severely contracted. A biopsy was taken from the lymph node located in the left axillary and cultures were sent for fungi and mycobacteria. Macroscopic examination of the breast explants showed no obvious leakage. PCR for mycobacteria was negative and cultures for fungi and bacteria were also negative. Six months after the removal of the breast implants, the patient presented to the internal medicine outpatient clinic with an increasing number of nodules scattered all over her body. Her eyes and mouth were dry, her appetite reduced, she lost 2 kg of weight over two months and she complained of extreme lassitude. She had no fever or night sweats but had slight dyspnea on exertion. The patient denied a history of intravenous drug use or liquid silicone injections. On physical examination, she had firm, non-tender skin nodules about 1 cm in diameter on her face (upper eyelids, nose, cheeks), arms, and legs. The nodules were moveable and did not appear to be attached to the skin surface or underlying structures. Both breasts were hard and tender on palpation. In addition, she had swelling in both her upper eyelids, which became so severe that she could barely open her eyes. She also had a moderate visual impairment in her left eye and ophthalmological examination showed features of panuveitis. There was generalized lymphadenopathy. The axillary and inguinal lymph nodes were firm, non-tender, and approximately 2 cm in diameter, while a left supraclavicular lymph node was about 1.5 cm in diameter. Other physical findings included normal heart and lung sounds, mild hepatomegaly and the spleen was not palpable. A chest x-ray and CT scan of the thorax showed multiple enlarged lymph nodes in the hilum and axilla bilaterally, and fine nodular interstitial infiltrates in her lungs. Her sedimentation rate was 23 mm/h (normal < 10 mm/h), c-reactive protein 25 mg/L (normal < 8 mg/L), Hb 7.8 mmol/L (normal 7.5–10 mmol/L), WBC count 4.7 × 109/L (normal 3–10 × 109/L), creatinine 88 µmol/L (normal 60–110 µmol/L), gamma glutamyltransferase Int. J. Environ. Res. Public Health 2021, 18, 4526 3 of 11 201 µ/L (normal 10–50 µ/L), alanine aminotransferase 66 µ/L (normal 4–36 µ/L), and the angiotensin converting enzyme (ACE) level was 63 µ/L (normal < 25 µ/L). The patient was diagnosed with sarcoidosis. No prior family history of sarcoidosis was noted, and the patient did not have a history of autoimmune or autoinflammatory disease. She refused to take prednisone and was treated with minocycline, an antibiotic with presumed anti-granulomatous activity, 100 mg twice per day for 7 months with moderate improvement in her condition. Minocycline has also been shown to have autoimmune and anti-inflammatory diseases [17]. She did not develop any new nodules and the existing nodules became smaller. She also noted a decrease in the amount of dryness of her eyes and mouth. 2. Materials and Methods 2.1. Histology Biopsies were taken from the fibrous capsule surrounding the implants, a lymph node in the left axillary, a nodule on the left lower leg and a nodule on the eyelid. For each type of tissue, sections 4–6 µm in thickness were stained with hematoxylin and eosin (HE) and evaluated using ordinary light microscopy.

Load more