- Email: [email protected]
Foreign body granulomas in oral tissues as a complication of injectable dermal fillers: A case report
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
Foreign body granulomas in oral tissues as a complication of injectable dermal fillers: A case report Maria Inês Mantuani Pascoalotia, Lilian de Barrosa, Hayder Egg Gomesa, Bruno Sérgio Bahia Lopesd, Leandro Junqueira Oliveiraa,c, Paulo Eduardo Alencar Souzaa,b, Martinho Campolina Rebello Hortaa,b,* a
Graduate Program in Dentistry, School of Dentistry, Pontifical Catholic University of Minas Gerais (PUC Minas), Belo Horizonte, MG, Brazil Oral Pathology Section, School of Dentistry, Pontifical Catholic University of Minas Gerais (PUC Minas), Belo Horizonte, MG, Brazil c Oral and Maxillofacial Surgery Section, School of Dentistry, Pontifical Catholic University of Minas Gerais (PUC Minas), Belo Horizonte, MG, Brazil d Graduate Program in Dentistry, School of Dentistry, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil b
A R T I C LE I N FO
A B S T R A C T
Keywords: Foreign body granulomas Dermal fillers Oral pathology
Injectable dermal fillers have been widely used for aesthetic procedures. However, adverse reactions, such as foreign body granulomas, have been reported. Foreign body granulomas are formed in response to foreign bodies that cannot be phagocytosed by macrophages, triggering a granulomatous inflammatory reaction. Here, we report on a case of foreign body granulomas in oral tissues as a complication of injectable dermal fillers and review the pertinent literature. A 55-year-old woman sought dental assistance, complaining of lip asymmetry. During the intraoral examination, two ill-defined nodules were observed bilaterally in the lower labial and buccal mucosa areas, close to the labial commissure. The patient reported history of aesthetic facial filling in the nasolabial sulcus region, bilaterally. An incisional biopsy was performed, and the anatomopathological examination confirmed the diagnosis of foreign body granulomas. Surgical removal of the lesions was not performed. The patient is under clinical follow-up and, after 2 years, shows no signs of changes or complications.
1. Introduction
2. Case report
The demand for non-surgical aesthetic procedures is increasing worldwide. Injectable dermal fillers have been widely used to attenuate the signs of aging, such as wrinkles or scars. The success of these procedures depends on the application techniques and the type of filler substances used. In the literature, there are several reports on successful cases treated with this aesthetic method, as well as reports regarding complications associated with this procedure [1,2]. Injectable dermal fillers can be classified as biodegradable or nonbiodegradable, and the clinical effects of the products are highly dependent on their categorization [3]. Most fillers appear to be well-tolerated [4,5]. However, adverse reactions, such as pain, edema, ulceration, scarring, migration of the injected filler, and the development of inflammatory nodules and foreign body granulomas, have been reported [6]. Here, we report a case of foreign body granulomas in oral tissues as a complication of injectable dermal fillers.
A 55-year-old, white, female patient, sought dental assistance, complaining of lip asymmetry (Fig. 1A). According to the patient, the lesion was not associated with pain and was noticed approximately one month earlier. During the intraoral examination, two ill-defined nodules were observed bilaterally in the lower labial and buccal mucosa areas, close to the labial commissure. The nodules measured approximately 3 × 2 cm, were lined by normal mucosa, showed firm consistency and were apparently adhered to the underlying musculature (Fig. 1B and C). During the anamnesis, the patient reported a history of aesthetic facial filling approximately 8 years prior to the examination, in the nasolabial sulcus region, bilaterally. According to the patient, the injectable dermal fillers used were hyaluronic acid (Retylane®) and poly (methyl) methacrylate (PMMA) (Artecoll® or Metacril® – the patient was not able to specify which one brand of filler was used). The diagnostic hypothesis of foreign body granulomas as a complication of injectable dermal fillers was established. Under local anesthesia, an incisional biopsy was performed in the posterior region of
⁎ Corresponding author at: Departamento de Odontologia, Pontifícia Universidade Católica de Minas Gerais, Avenida Dom José Gaspar 500, Prédio 46, Sala 101, Belo Horizonte, MG, CEP: 30535-901, Brazil. E-mail address: [email protected] (M.C.R. Horta).
https://doi.org/10.1016/j.ajoms.2019.09.003 Received 30 May 2019; Received in revised form 17 August 2019; Accepted 10 September 2019 2212-5558/ © 2019 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Maria Inês Mantuani Pascoaloti, et al., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, https://doi.org/10.1016/j.ajoms.2019.09.003
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
M.I.M. Pascoaloti, et al.
Fig. 1. Clinical features. (A) Lip asymmetry. (B and C) Ill-defined nodules in the lower labial and buccal mucosa, bilaterally, lined by normal mucosa, showing firm consistency and adhered to the underlying musculature.
the left side lesion, close to the labial commissure. The material was sent to the Oral Pathology Laboratory of Pontifícia Universidade Católica de Minas Gerais (PUC Minas). The histological examination showed a marked granulomatous inflammation permeating the lamina propria of the oral mucosa, the submucosa and the underlying skeletal striated muscle (Fig. 2A and B). The granulomas were primarily composed of macrophages, scarce epithelioid cells, foreign body multinucleated giant cells, and lymphocytes. Numerous small round cystic spaces, often containing a translucid sphere compatible with a PMMA microsphere, were observed in the cytoplasm of the foreign body multinucleated giant cells or near the giant cells. Fibroblasts and collagen fibers may also be seen at the periphery of the granulomas (Fig. 2C). The anatomopathological examination, together with the clinical history, confirmed the diagnosis of foreign body granulomas as a complication of injectable dermal fillers. The patient was referred for the evaluation of the potential necessity for the surgical removal of the lesions. However, following this evaluation, the surgeon opted not to perform the surgery, due to the extent of the lesions and the intimate associations between the filling material and the anatomical structures, which could result in unnecessary postoperative sequelae. The patient is under clinical follow-up and, after 2 years, shows no signs of changes or complications (Fig. 3A–C).
Fig. 2. Anatomopathological features. (A and B) Granulomas (arrows) permeating the lamina propria of the oral mucosa, the submucosa and underlying skeletal striated muscle (asterisks). (C) Granulomas with epithelioid cells (arrowheads), foreign body multinucleated giant cells (thin arrows) and small round cystic spaces containing structures compatible with PMMA microspheres (thick arrows). Fibroblasts and collagen fibers may also be seen at the periphery of the granulomas (asterisks).
3. Discussion Foreign body granulomas as a complication of dermal fillers are observed in 0.02–1% of patients and may arise months (generally 6–24 months) or even years after the material application [7–9]. The primary factors that influence this host reaction are the amount of material injected, the chemical characteristics of the dermal filler, the biological characteristics of each patient, and the employed technique [2,10]. Clinically, lesions may develop as reddish areas, such as plaques, papules or nodules (ulcerated or non-ulcerated), which harden over time, as a consequence of fibrosis [3]. Either single lesions or multiple lesions may occur, and most are asymptomatic [11]. Because fillers can migrate along tissue planes, the lesions may occur away from the filling area, including intraoral sites [12,13]. This clinical pattern is similar to that observed in the case reported here. Injectable soft tissue fillers can be classified as absorbable (collagen, 2
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
M.I.M. Pascoaloti, et al.
substances are more common and intense [9]. The simultaneous use of different types of fillers in combination does not appear to be associated with an increased risk of complications when injected into the same area [14]. However, it is important to know the anatomy of the application site, as well as the appropriate volume of the filler material, to minimize undesired results, such as long-term nodules caused by permanent materials [4]. The clinical differential diagnosis includes a wide spectrum of conditions, from simple lesions, such as salivary gland cysts, to complex diseases, such as orofacial granulomatosis. Therefore, histological examination must be performed to confirm diagnosis [11]. Foreign body granulomas are formed in response to foreign bodies (such as filling materials) that cannot be phagocytosed by macrophages, triggering the release of inflammatory cytokines, which mediate a granulomatous inflammatory reaction characterized by the formation of granulomas containing multinucleated giant cells [7,12]. Lombardi et al. [18] histologically classified injectable filler-associated granulomas in two main types: I) the “classic foreign body granuloma type” (CFBG-type), showing numerous giant cells around foreign bodies (detected in aesthetic fillings using Artecoll®, Arteplast®, Dermalive®, New-fill® or Bioplastique®); II) the “cystic and macrophagic granuloma type” (CMGtype), characterized by several extracellular microcysts on a background of vacuolated macrophages (observed after liquid silicone injections). Liposarcoma represents an important histological differential diagnosis that primarily occurs in association with cystic and macrophagic granuloma type after liquid silicone filling because mononuclear vacuolated macrophages are similar to lipoblasts. In this situation, immunohistochemistry for CD68 and S100 may be employed, since mononuclear vacuolated macrophages in granulomas are CD68 positive and S100 negative and lipoblasts in liposarcomas are CD68 negative and S100 positive [11]. The histological features observed in the case reported here are compatible with the classic foreign body granuloma type, formed by the injection of PMMA, because the granulomas contained multinucleated giant cells and abundant small round cystic spaces inclosing translucid structures with similar sizes and shapes as PMMA microspheres [7,18]. Several therapeutic approaches have been described for the treatment of foreign body granulomas that result from the injection of cosmetic fillers [4,19–21]. In many cases, foreign body granulomas can be treated successfully with intralesional or systemic corticosteroids [4,6,20,22]. Well-circumscribed lesions and cases of widespread lesions that fail repeatedly to respond to conservative therapy can be removed surgically [4]. Surgical removal of granulomas can be difficult because there remains the possibility of finding multiple and/or extensive lesions and inflammatory processes during surgery. These factors can increase the risk of filler migration, the formation of fistulas and the persistence of granulation tissue and can cause marked defects in the region. Thus, surgical excision, when indicated, should be performed by an experienced surgeon [23]. In the case reported, no treatment was undertaken, and no changes were observed after 2 years of follow-up. This clinical stability could be explained by a probable decrease in the migration of the dermal filler particles after reaching the intraoral sites. The filler migration along tissue planes, better denominated as dislocation, may be caused by forces derived from high-volume of filler, high-pressure of injection, skin folding, muscle movement or gravity [13,24]. In conclusion, the professionals responsible for applying these materials for aesthetic purposes must be aware of their properties, injection techniques, and potential complications. Moreover, dentists should be aware that foreign body granulomas in the oral tissues may represent a complication of injectable dermal fillers.
Fig. 3. Clinical features after 2 years of follow-up. The patient shows no signs of changes or complications.
hyaluronic acid, calcium hydroxyapatite and poly-L-lactic acid) and non-absorbable (PMMA), according to the Food and Drug Administration of the United States of America. In another classification system, these materials can be classified according to their duration after application: temporary (absorbable), permanent (non-absorbable) and semi-permanent [14]. According to the patient’s history, the following filling materials were used: Retylane® (hyaluronic acid) and PMMA (Artecoll® or Metacril®). Biodegradable fillers, such as hyaluronic acid (HA), are reabsorbed by the body within a few months, and despite few reports, there may be a hypersensitivity reaction [15]. Artecoll® is composed of PMMA microspheres. Metacril® consists of PMMA and suspended carboxygluconate, which are both considered to be non-biodegradable materials [16,17]. Non-biodegradable materials, such as PMMA, do not generate more foreign body granulomas compared with biodegradable materials, such as HA [10]. However, the foreign body granulomas caused by nonbiodegradable materials tend to exhibit a more marked clinical appearance. Moreover, they also persist in the tissue for longer periods of time and undergo constant changes during their degradation. Because these non-biodegradable materials present a latent phase, months or years can pass before clinical manifestations as foreign body granuloma [8–10]. Because both non-biodegradable and biodegradable substances can induce the formation of foreign body granulomas, this reaction can occur after the application of any dermal filler. However, the clinical manifestations of foreign body granulomas caused by non-absorbable
Consent Written informed consent was obtained from the patient for publication of this case report. 3
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
M.I.M. Pascoaloti, et al.
Transparency document
Possible causes. Plast Reconstr Surg 2009;123:1842–63. [9] Lemperle G, Gauthier-Hazan N. Foreign body granulomas after all injectable dermal fillers: part 2. Treatment options. Plast Reconstr Surg 2009;123:1864–73. [10] Wiest LG, Stolz W, Schroeder JA. Electron microscopic documentation of late changes in permanent fillers and clinical management of granulomas in affected patients. Dermatol Surg 2009;35:1681–8. [11] Jham BC, Nikitakis NG, Scheper MA, Papadimitriou JC, Levy BA, Rivera H. Granulomatous foreign-body reaction involving oral and perioral tissues after injection of biomaterials: a series of 7 cases and review of the literature. J Oral Maxillofac Surg 2009;67:280–5. [12] Woodward J, Khan T, Martin J. Facial filler complications. Fac Plast Surg Clin N Am 2015;23:447–58. [13] Shahrabi-Farahani S, Lerman MA, Noonan V, Kabani S, Woo SB. Granulomatous foreign body reaction to dermal cosmetic fillers with intraoral migration. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:105–10. [14] Tamiolakis P, Piperi E, Christopoulos P, Sklavounou-Andrikopoulou A. Oral foreign body granuloma to soft tissue fillers. Report of two cases and review of the literature. J Clin Exp Dent 2018;10:e177–84. [15] Molina-Ruiz AM, Requena L. Foreign body granulomas. Dermatol Clin 2015;33:497–523. [16] Rosa SC, De Magalhães AV, De Macedo JLS. An experimental study of tissue reaction to polymethyl methacrylate (PMMA) microspheres (Artecoll) and dimethylsiloxane (DMS) in the mouse. Am J Dermatopathol 2008;30:222–7. [17] Dadzie OE, Mahalingam M, Parada M, El Helou T, Philips T, Bhawan J. Adverse cutaneous reactions to soft tissue fillers—a review of the histological features. J Cutan Pathol 2008;35:536–48. [18] Lombardi T, Samson J, Plantier F, Husson C, Küffer R. Orofacial granulomas after injection of cosmetic fillers. Histopathologic and clinical study of 11 cases. J Oral Pathol Med 2004;33:115–20. [19] Bigatà X, Ribera M, Bielsa I, Ferrándiz C. Adverse granulomatous reaction after cosmetic dermal silicone injection. Dermatol Surg 2001;27:198–200. [20] Carruthers A, Carruthers JDA. Polymethylmethacrylate microspheres/collagen as a tissue augmenting agent: personal experience over 5 years. Dermatol Surg 2010;31:1561–5. [21] Kim KJ, Lee HW, Lee MW, Choi JH, Moon KC, Koh JK. Artecoll granuloma: a rare adverse reaction induced by microimplant in the treatment of neck wrinkles. Dermatol Surg 2004;30:545–7. [22] Thaler MP, Ubogy ZI. Artecoll: the Arizona experience and lessons learned. Dermatol Surg 2010;31:1566–76. [23] Alijotas-Reig J, Fernández-Figueras MT, Puig L. Late-onset inflammatory adverse reactions related to soft tissue filler injections. Clin Rev Allergy Immunol 2013;45:97–108. [24] Laeschke K. Biocompatibility of microparticles into soft tissue fillers. Semin Cutan Med Surg. 2004;23:214–7.
The Transparency document associated with this article can be found in the online version. Declaration of Competing Interest None. Acknowledgments This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG CDS-PPM-00653-16). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) Finance Code 001. The authors are also grateful to the Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq - 437861/ 2018-0. MCRH is a research fellow of FAPEMIG (CDS-PPM-00653-16). HEG has a PUC Minas fellowship. LB has a CAPES fellowship. References [1] Matarasso SL. The use of injectable collagens for aesthetic rejuvenation. Semin Cutan Med Surg 2006;25:151–7. [2] Sclafani AP, Fagien S. Treatment of injectable soft tissue filler complications. Dermatol Surg 2009;35:1672–80. [3] Funt D, Pavicic T, Maximilian L. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Invest Dermatol 2013;6:295–316. [4] Wolfram D, Tzankov A, Piza-Katzer H. Surgery for foreign body reactions due to injectable fillers. Dermatology 2006;213:300–4. [5] Zimmermann US, Clerici TJ. The histological aspects of fillers complications. Semin Cutan Med Surg 2004;23:241–50. [6] Christensen L, Breiting V, Janssen M, Vuust J, Hogdall E. Adverse reactions to injectable soft tissue permanent fillers. Aesthetic Plast Surg 2005;29:34–48. [7] Lee JM, Kim YJ. Foreign body granulomas after the use of dermal fillers: pathophysiology, clinical appearance, histologic features, and treatment. Arch Plast Surg 2015;42:232–9. [8] Lemperle G, Gauthier-Hazan N, Wolters M, Eisemann-Klein M, Zimmermann U, Duffy DM. Foreign body granulomas after all injectable dermal fillers: part 1.
4
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
Foreign body granulomas in oral tissues as a complication of injectable dermal fillers: A case report Maria Inês Mantuani Pascoalotia, Lilian de Barrosa, Hayder Egg Gomesa, Bruno Sérgio Bahia Lopesd, Leandro Junqueira Oliveiraa,c, Paulo Eduardo Alencar Souzaa,b, Martinho Campolina Rebello Hortaa,b,* a
Graduate Program in Dentistry, School of Dentistry, Pontifical Catholic University of Minas Gerais (PUC Minas), Belo Horizonte, MG, Brazil Oral Pathology Section, School of Dentistry, Pontifical Catholic University of Minas Gerais (PUC Minas), Belo Horizonte, MG, Brazil c Oral and Maxillofacial Surgery Section, School of Dentistry, Pontifical Catholic University of Minas Gerais (PUC Minas), Belo Horizonte, MG, Brazil d Graduate Program in Dentistry, School of Dentistry, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil b
A R T I C LE I N FO
A B S T R A C T
Keywords: Foreign body granulomas Dermal fillers Oral pathology
Injectable dermal fillers have been widely used for aesthetic procedures. However, adverse reactions, such as foreign body granulomas, have been reported. Foreign body granulomas are formed in response to foreign bodies that cannot be phagocytosed by macrophages, triggering a granulomatous inflammatory reaction. Here, we report on a case of foreign body granulomas in oral tissues as a complication of injectable dermal fillers and review the pertinent literature. A 55-year-old woman sought dental assistance, complaining of lip asymmetry. During the intraoral examination, two ill-defined nodules were observed bilaterally in the lower labial and buccal mucosa areas, close to the labial commissure. The patient reported history of aesthetic facial filling in the nasolabial sulcus region, bilaterally. An incisional biopsy was performed, and the anatomopathological examination confirmed the diagnosis of foreign body granulomas. Surgical removal of the lesions was not performed. The patient is under clinical follow-up and, after 2 years, shows no signs of changes or complications.
1. Introduction
2. Case report
The demand for non-surgical aesthetic procedures is increasing worldwide. Injectable dermal fillers have been widely used to attenuate the signs of aging, such as wrinkles or scars. The success of these procedures depends on the application techniques and the type of filler substances used. In the literature, there are several reports on successful cases treated with this aesthetic method, as well as reports regarding complications associated with this procedure [1,2]. Injectable dermal fillers can be classified as biodegradable or nonbiodegradable, and the clinical effects of the products are highly dependent on their categorization [3]. Most fillers appear to be well-tolerated [4,5]. However, adverse reactions, such as pain, edema, ulceration, scarring, migration of the injected filler, and the development of inflammatory nodules and foreign body granulomas, have been reported [6]. Here, we report a case of foreign body granulomas in oral tissues as a complication of injectable dermal fillers.
A 55-year-old, white, female patient, sought dental assistance, complaining of lip asymmetry (Fig. 1A). According to the patient, the lesion was not associated with pain and was noticed approximately one month earlier. During the intraoral examination, two ill-defined nodules were observed bilaterally in the lower labial and buccal mucosa areas, close to the labial commissure. The nodules measured approximately 3 × 2 cm, were lined by normal mucosa, showed firm consistency and were apparently adhered to the underlying musculature (Fig. 1B and C). During the anamnesis, the patient reported a history of aesthetic facial filling approximately 8 years prior to the examination, in the nasolabial sulcus region, bilaterally. According to the patient, the injectable dermal fillers used were hyaluronic acid (Retylane®) and poly (methyl) methacrylate (PMMA) (Artecoll® or Metacril® – the patient was not able to specify which one brand of filler was used). The diagnostic hypothesis of foreign body granulomas as a complication of injectable dermal fillers was established. Under local anesthesia, an incisional biopsy was performed in the posterior region of
⁎ Corresponding author at: Departamento de Odontologia, Pontifícia Universidade Católica de Minas Gerais, Avenida Dom José Gaspar 500, Prédio 46, Sala 101, Belo Horizonte, MG, CEP: 30535-901, Brazil. E-mail address: [email protected] (M.C.R. Horta).
https://doi.org/10.1016/j.ajoms.2019.09.003 Received 30 May 2019; Received in revised form 17 August 2019; Accepted 10 September 2019 2212-5558/ © 2019 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Maria Inês Mantuani Pascoaloti, et al., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, https://doi.org/10.1016/j.ajoms.2019.09.003
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
M.I.M. Pascoaloti, et al.
Fig. 1. Clinical features. (A) Lip asymmetry. (B and C) Ill-defined nodules in the lower labial and buccal mucosa, bilaterally, lined by normal mucosa, showing firm consistency and adhered to the underlying musculature.
the left side lesion, close to the labial commissure. The material was sent to the Oral Pathology Laboratory of Pontifícia Universidade Católica de Minas Gerais (PUC Minas). The histological examination showed a marked granulomatous inflammation permeating the lamina propria of the oral mucosa, the submucosa and the underlying skeletal striated muscle (Fig. 2A and B). The granulomas were primarily composed of macrophages, scarce epithelioid cells, foreign body multinucleated giant cells, and lymphocytes. Numerous small round cystic spaces, often containing a translucid sphere compatible with a PMMA microsphere, were observed in the cytoplasm of the foreign body multinucleated giant cells or near the giant cells. Fibroblasts and collagen fibers may also be seen at the periphery of the granulomas (Fig. 2C). The anatomopathological examination, together with the clinical history, confirmed the diagnosis of foreign body granulomas as a complication of injectable dermal fillers. The patient was referred for the evaluation of the potential necessity for the surgical removal of the lesions. However, following this evaluation, the surgeon opted not to perform the surgery, due to the extent of the lesions and the intimate associations between the filling material and the anatomical structures, which could result in unnecessary postoperative sequelae. The patient is under clinical follow-up and, after 2 years, shows no signs of changes or complications (Fig. 3A–C).
Fig. 2. Anatomopathological features. (A and B) Granulomas (arrows) permeating the lamina propria of the oral mucosa, the submucosa and underlying skeletal striated muscle (asterisks). (C) Granulomas with epithelioid cells (arrowheads), foreign body multinucleated giant cells (thin arrows) and small round cystic spaces containing structures compatible with PMMA microspheres (thick arrows). Fibroblasts and collagen fibers may also be seen at the periphery of the granulomas (asterisks).
3. Discussion Foreign body granulomas as a complication of dermal fillers are observed in 0.02–1% of patients and may arise months (generally 6–24 months) or even years after the material application [7–9]. The primary factors that influence this host reaction are the amount of material injected, the chemical characteristics of the dermal filler, the biological characteristics of each patient, and the employed technique [2,10]. Clinically, lesions may develop as reddish areas, such as plaques, papules or nodules (ulcerated or non-ulcerated), which harden over time, as a consequence of fibrosis [3]. Either single lesions or multiple lesions may occur, and most are asymptomatic [11]. Because fillers can migrate along tissue planes, the lesions may occur away from the filling area, including intraoral sites [12,13]. This clinical pattern is similar to that observed in the case reported here. Injectable soft tissue fillers can be classified as absorbable (collagen, 2
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
M.I.M. Pascoaloti, et al.
substances are more common and intense [9]. The simultaneous use of different types of fillers in combination does not appear to be associated with an increased risk of complications when injected into the same area [14]. However, it is important to know the anatomy of the application site, as well as the appropriate volume of the filler material, to minimize undesired results, such as long-term nodules caused by permanent materials [4]. The clinical differential diagnosis includes a wide spectrum of conditions, from simple lesions, such as salivary gland cysts, to complex diseases, such as orofacial granulomatosis. Therefore, histological examination must be performed to confirm diagnosis [11]. Foreign body granulomas are formed in response to foreign bodies (such as filling materials) that cannot be phagocytosed by macrophages, triggering the release of inflammatory cytokines, which mediate a granulomatous inflammatory reaction characterized by the formation of granulomas containing multinucleated giant cells [7,12]. Lombardi et al. [18] histologically classified injectable filler-associated granulomas in two main types: I) the “classic foreign body granuloma type” (CFBG-type), showing numerous giant cells around foreign bodies (detected in aesthetic fillings using Artecoll®, Arteplast®, Dermalive®, New-fill® or Bioplastique®); II) the “cystic and macrophagic granuloma type” (CMGtype), characterized by several extracellular microcysts on a background of vacuolated macrophages (observed after liquid silicone injections). Liposarcoma represents an important histological differential diagnosis that primarily occurs in association with cystic and macrophagic granuloma type after liquid silicone filling because mononuclear vacuolated macrophages are similar to lipoblasts. In this situation, immunohistochemistry for CD68 and S100 may be employed, since mononuclear vacuolated macrophages in granulomas are CD68 positive and S100 negative and lipoblasts in liposarcomas are CD68 negative and S100 positive [11]. The histological features observed in the case reported here are compatible with the classic foreign body granuloma type, formed by the injection of PMMA, because the granulomas contained multinucleated giant cells and abundant small round cystic spaces inclosing translucid structures with similar sizes and shapes as PMMA microspheres [7,18]. Several therapeutic approaches have been described for the treatment of foreign body granulomas that result from the injection of cosmetic fillers [4,19–21]. In many cases, foreign body granulomas can be treated successfully with intralesional or systemic corticosteroids [4,6,20,22]. Well-circumscribed lesions and cases of widespread lesions that fail repeatedly to respond to conservative therapy can be removed surgically [4]. Surgical removal of granulomas can be difficult because there remains the possibility of finding multiple and/or extensive lesions and inflammatory processes during surgery. These factors can increase the risk of filler migration, the formation of fistulas and the persistence of granulation tissue and can cause marked defects in the region. Thus, surgical excision, when indicated, should be performed by an experienced surgeon [23]. In the case reported, no treatment was undertaken, and no changes were observed after 2 years of follow-up. This clinical stability could be explained by a probable decrease in the migration of the dermal filler particles after reaching the intraoral sites. The filler migration along tissue planes, better denominated as dislocation, may be caused by forces derived from high-volume of filler, high-pressure of injection, skin folding, muscle movement or gravity [13,24]. In conclusion, the professionals responsible for applying these materials for aesthetic purposes must be aware of their properties, injection techniques, and potential complications. Moreover, dentists should be aware that foreign body granulomas in the oral tissues may represent a complication of injectable dermal fillers.
Fig. 3. Clinical features after 2 years of follow-up. The patient shows no signs of changes or complications.
hyaluronic acid, calcium hydroxyapatite and poly-L-lactic acid) and non-absorbable (PMMA), according to the Food and Drug Administration of the United States of America. In another classification system, these materials can be classified according to their duration after application: temporary (absorbable), permanent (non-absorbable) and semi-permanent [14]. According to the patient’s history, the following filling materials were used: Retylane® (hyaluronic acid) and PMMA (Artecoll® or Metacril®). Biodegradable fillers, such as hyaluronic acid (HA), are reabsorbed by the body within a few months, and despite few reports, there may be a hypersensitivity reaction [15]. Artecoll® is composed of PMMA microspheres. Metacril® consists of PMMA and suspended carboxygluconate, which are both considered to be non-biodegradable materials [16,17]. Non-biodegradable materials, such as PMMA, do not generate more foreign body granulomas compared with biodegradable materials, such as HA [10]. However, the foreign body granulomas caused by nonbiodegradable materials tend to exhibit a more marked clinical appearance. Moreover, they also persist in the tissue for longer periods of time and undergo constant changes during their degradation. Because these non-biodegradable materials present a latent phase, months or years can pass before clinical manifestations as foreign body granuloma [8–10]. Because both non-biodegradable and biodegradable substances can induce the formation of foreign body granulomas, this reaction can occur after the application of any dermal filler. However, the clinical manifestations of foreign body granulomas caused by non-absorbable
Consent Written informed consent was obtained from the patient for publication of this case report. 3
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
M.I.M. Pascoaloti, et al.
Transparency document
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The Transparency document associated with this article can be found in the online version. Declaration of Competing Interest None. Acknowledgments This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG CDS-PPM-00653-16). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) Finance Code 001. The authors are also grateful to the Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq - 437861/ 2018-0. MCRH is a research fellow of FAPEMIG (CDS-PPM-00653-16). HEG has a PUC Minas fellowship. LB has a CAPES fellowship. References [1] Matarasso SL. The use of injectable collagens for aesthetic rejuvenation. Semin Cutan Med Surg 2006;25:151–7. [2] Sclafani AP, Fagien S. Treatment of injectable soft tissue filler complications. Dermatol Surg 2009;35:1672–80. [3] Funt D, Pavicic T, Maximilian L. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Invest Dermatol 2013;6:295–316. [4] Wolfram D, Tzankov A, Piza-Katzer H. Surgery for foreign body reactions due to injectable fillers. Dermatology 2006;213:300–4. [5] Zimmermann US, Clerici TJ. The histological aspects of fillers complications. Semin Cutan Med Surg 2004;23:241–50. [6] Christensen L, Breiting V, Janssen M, Vuust J, Hogdall E. Adverse reactions to injectable soft tissue permanent fillers. Aesthetic Plast Surg 2005;29:34–48. [7] Lee JM, Kim YJ. Foreign body granulomas after the use of dermal fillers: pathophysiology, clinical appearance, histologic features, and treatment. Arch Plast Surg 2015;42:232–9. [8] Lemperle G, Gauthier-Hazan N, Wolters M, Eisemann-Klein M, Zimmermann U, Duffy DM. Foreign body granulomas after all injectable dermal fillers: part 1.
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