Vol. 117 No. 5 May 2014
Fine needle aspiration cytology in the diagnosis of perioral adverse reactions to cosmetic dermal fillers Karina Morais Faria, DDS, Felipe Paiva Fonseca, DDS, MSc, Wagner Gomes Silva, DDS, Rodrigo Neves Silva, DDS, Pablo Agustin Vargas, DDS, PhD, Oslei Paes de Almeida, DDS, PhD, Marcio Ajudarte Lopes, DDS, PhD, and Alan Roger Santos-Silva, DDS, PhD University of Campinas, Piracicaba, São Paulo, Brazil
Facial cosmetic procedures are increasingly requested, and dermal filler materials have been widely used as a nonsurgical option since the 1980s. However, injectable fillers have been implicated in local adverse reactions. Therefore, the aim of this article was to describe the use of fine needle aspiration cytology (FNAC) in the diagnosis of foreign-body reactions to the perioral injection of dermal fillers. A 69-year-old woman presented with a painful nodule on her right nasolabial fold. Intraoral FNAC was performed, and cytologic smears were examined under optical and polarized light microscopy, showing birefringent microspheres, confirming the diagnosis of an adverse reaction caused by polymethyl methacrylate filler. FNAC is a less invasive method to confirm the diagnosis of adverse reactions caused by perioral cosmetic dermal fillers. (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:e393-e395)
The use of cosmetic fillers has gained widespread acceptance in dermatology and cosmetic facial surgery.1 Various injectable fillers have been used in orofacial tissues for esthetic purposes, including bovine collagen, hyaluronic acid, poly-L-lactic acid, calcium hydroxyapatite, paraffin, silicone, polymethyl methacrylate (PMMA), hydroxyethyl methacrylate, polyacrylamide, and polyalkylimide gel, most of which are well tolerated. However, adverse reactions such as pain, edema, ulceration, itching, scarring, nodule formation, and migration of the injected material have been reported. Granulomatous foreign-body inflammatory reactions are a typical histologic finding in these situations.2,3 The diagnosis of adverse reactions to dermal fillers (ARDF) may be a challenge, because most patients deny the use of cosmetic fillers. In addition, these patients often refuse to undergo biopsy because of the risk of facial scarring. To the best of our knowledge, no previous diagnosis of ARDF has been rendered by means of fine needle aspiration cytology (FNAC).
CASE REPORT A 69-year-old woman complaining of a painful nodule that had been present on her perioral region for about 2 years was referred to our department. The patient’s medical history included systemic arterial hypertension, for which she had been taking losartan and chlorthalidone. She denied drinking alcohol and smoking. The patient denied any history of diabetes, immunosuppression, head and neck trauma, or prior surgical interventions. Oral Diagnosis Department, Semiology and Oral Pathology Areas, Piracicaba Dental School, University of Campinas (UNICAMP). Received for publication Mar 22, 2013; returned for revision Jul 16, 2013; accepted for publication Jul 23, 2013. Ó 2014 Published by Elsevier Inc. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.07.029
A review of symptoms by system was unremarkable. Extraoral examination was performed; there were no changes in skin color or texture, but a discreet asymmetry with increased volume was found in the skin adjacent to the right nasolabial fold (Figure 1, A). No lymphadenomegaly, thyromegaly, or other relevant head and neck abnormalities were observed. Intraoral examination revealed an extension of the skin lesion into the oral mucosa, causing a hardened nodule that was painful to palpation (Figure 1, B). Intraoral FNAC was performed with a 24-gauge needle; the material was smeared on 3 glass slides, which were immediately air fixed for Diff-Quik staining. The cytologic smears showed several bluish to purple microspheres of variable sizes, with a hemorrhagic background (Figure 1, C and D). When examined under polarized light microscopy, several microspheres were birefringent, exhibiting the typical Maltese cross pattern of round particles (Figure 1, E and F). The presumptive diagnosis was a foreign body reaction caused by the dermal application of a cosmetic filler. An intraoral excisional biopsy was performed under local anesthesia for confirmation of the diagnosis (Figure 2, A). Histologically, multiple areas of negative microcystic-like spaces resembling adipocytes were found, limited by fibrous septa, along with focal areas of chronic inflammatory infiltrate with scarce giant cells within and around the spaces (Figure 2, B). The microcystic-like spaces were empty, and the presence of PMMA microspheres could not be observed during the analysis of the histologic sections (Figure 2, C and D). The histologic findings were compatible with a foreign body reaction associated with dermal injection of PMMA, and the diagnosis of ARDF was confirmed. At 6 months follow-up, the intraoral surgical site had completely healed, with no symptoms or signs of remaining nodules.
DISCUSSION Esthetic procedures to rejuvenate, maintain, and enhance facial appearance are increasingly being requested by patients all over the world.4 In addition to PMMA, e393
ORAL AND MAXILLOFACIAL PATHOLOGY e394 Faria et al.
OOOO May 2014
Fig. 1. A, Discreet facial asymmetry present for 2 years after the application of a cosmetic filler (arrow). B, Intraoral swelling in continuity with the skin nodule (arrow). C, Cytologic smear showing clusters of bluish to purple microspheres of variable size, with a hemorrhagic background (Diff-Quik, original magnification 100). D, Small cluster of sharply round, translucent microspheres under light microscopy (Diff-Quik, original magnification 200). E, Same area observed in Figure 1, C, demonstrating birefringent microspheres under polarized light microscopy (Diff-Quik, original magnification 100). F, Same area observed in Figure 1, D, depicting microspheres highlighting the classic Maltese cross pattern shown by round birefringent particles under polarized light microscopy (Diff-Quik, original magnification 200).
Fig. 2. A, Transoperative image of the intraoral excisional biopsy showing a multinodular soft tissue specimen. B, Histologic features of the biopsy, showing multiple areas of negative microcystic-like spaces resembling adipocytes (hematoxylin-eosin, original magnification 20). C, Histology showing the presence of a foreign body reaction, several negative microcystic-like spaces, giant cells (arrow) around the empty spaces, and a chronic inflammatory infiltrate (hematoxylin-eosin, original magnification 200). D, Higher magnification showing negative microcystic-like spaces and a giant cell (arrow) in detail (hematoxylineosin, original magnification 400).
several other injectable permanent dermal fillers can cause foreign body reactions. The etiology of these dermal granulomas remains unclear, and their occurrence cannot be predicted. Previous studies have found that
granuloma formation is associated with a variety of clinical circumstances, such as host immune responses and local infection. The histologic appearance of these foreign body granulomas seems to be specific for each
OOOO Volume 117, Number 5
CASE REPORT Faria et al. e395
type of injected filler, but identification of the offending agent can be a challenge even for experienced pathologists.5-8 A cosmetic solution composed of 20% PMMA microspheres, 30 to 42 mm in diameter, associated with an 80% bovine collagen solution used as the vehicle, is often injected as a dermal filler in dermatology practice. After dermal injection, the collagen solution is slowly reabsorbed, leaving behind the nonbiodegradable PMMA microspheres. In these circumstances, PMMA microspheres are not broken down and can cause ARDFs.9-11 PMMA is frequently injected for treating nasolabial and lip folds. When ARDF occurs in these regions, it can be confused with other perioral lesions, such as dermal cysts, minor salivary gland tumors, and soft tissue tumors.12-14 In this scenario, FNAC can be useful for guiding the appropriate diagnosis, and the clinical case in question appears to be the first report of its use in the context of ARDF. It is relevant to mention that, in the present case, brisk birefringence could be seen in the PMMA microspheres obtained by FNAC, which was different from what was expected to be observed in histologic sections of PMMA-related ARDF, where birefringence is not typically detected. The lack of birefringence in histologic sections may be due to the fact that PMMA microspheres are lost during histologic processing and the birefringence is not observed because there are no longer any microspheres left. In conclusion, FNAC can be a useful and less invasive method to confirm the clinical suspicion of adverse reactions caused by facial cosmetic dermal fillers.
4. Gladstone HB, Cohen JL. Adverse effects when injecting facial fillers. Semin Cutan Med Surg. 2007;26:34-39. 5. da Costa Miguel MC, Nonaka CF, dos Santos JN, Germano AR, de Souza LB. Oral foreign body granuloma: unusual presentation of a rare adverse reaction to permanent injectable cosmetic filler. Int J Oral Maxillofac Surg. 2009;38:385-387. 6. Bigatà X, Ribera M, Bielsa I, Ferrándiz C. Adverse granulomatous reaction after cosmetic dermal silicone injection. Dermatol Surg. 2001;27:198-200. 7. 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. 8. Medeiros CC, Cherubini K, Salum FG, de Figueiredo MA. Complications after polymethylmethacrylate (PMMA) injections in the face: a literature review. Gerodontology. 2013 [e-pub ahead of print]. 9. Carruthers A, Carruthers JD. Polymethylmethacrylate microspheres/collagen as a tissue augmenting agent: personal experience over 5 years. Dermatol Surg. 2005;31:1561-1565. 10. Lemperle G, Romano JJ, Busso M. Soft tissue augmentation with Artecoll: 10-year history, indications, techniques, and complications. Dermatol Surg. 2003;29:573-587. 11. Requena L, Requena C, Christensen L, Zimmermann US, Kutzner H, Cerroni L. Adverse reactions to injectable soft tissue fillers. J Am Acad Dermatol. 2011;64:1-34. 12. Gelfer A, Carruthers A, Carruthers J, Jang F, Bernstein SC. The natural history of polymethylmethacrylate microspheres granulomas. Dermatol Surg. 2007;33:614-620. 13. Dadzie OE, Mahalingam M, Parada M, Helou T, Philips T, Bhawan J. Adverse cutaneous reactions to soft tissue fillersda review of the histological features. J Cutan Pathol. 2008;35: 536-548. 14. Hoffman C, Schuller-Petrovic S, Soyer HP, Kerl H. Adverse reactions after cosmetic lip augmentation with permanent biologically inert implant materials. J Am Acad Dermatol. 1999;40: 100-102.
REFERENCES
Reprint requests:
1. Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal fillers: review. Dermatol Surg. 2005;31:1616-1625. 2. Zimmermann US, Clerici TJ. The histological aspects of fillers complications. Semin Cutan Med Surg. 2004;23:241-250. 3. Feio PS, Gouvêa AF, Jorge J, Lopes MA. Oral adverse reactions after injection of cosmetic fillers: report of three cases. Int J Oral Maxillofac Surg. 2013;42:432-435.
Alan Roger Santos-Silva, DDS, PhD Área de Semiologia Faculdade de Odontologia de Piracicaba - UNICAMP Av. Limeira, 901 Bairro Areão, Piracicaba, São Paulo 13414-903 Brasil [email protected]
Fine needle aspiration cytology in the diagnosis of perioral adverse reactions to cosmetic dermal fillers Karina Morais Faria, DDS, Felipe Paiva Fonseca, DDS, MSc, Wagner Gomes Silva, DDS, Rodrigo Neves Silva, DDS, Pablo Agustin Vargas, DDS, PhD, Oslei Paes de Almeida, DDS, PhD, Marcio Ajudarte Lopes, DDS, PhD, and Alan Roger Santos-Silva, DDS, PhD University of Campinas, Piracicaba, São Paulo, Brazil
Facial cosmetic procedures are increasingly requested, and dermal filler materials have been widely used as a nonsurgical option since the 1980s. However, injectable fillers have been implicated in local adverse reactions. Therefore, the aim of this article was to describe the use of fine needle aspiration cytology (FNAC) in the diagnosis of foreign-body reactions to the perioral injection of dermal fillers. A 69-year-old woman presented with a painful nodule on her right nasolabial fold. Intraoral FNAC was performed, and cytologic smears were examined under optical and polarized light microscopy, showing birefringent microspheres, confirming the diagnosis of an adverse reaction caused by polymethyl methacrylate filler. FNAC is a less invasive method to confirm the diagnosis of adverse reactions caused by perioral cosmetic dermal fillers. (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:e393-e395)
The use of cosmetic fillers has gained widespread acceptance in dermatology and cosmetic facial surgery.1 Various injectable fillers have been used in orofacial tissues for esthetic purposes, including bovine collagen, hyaluronic acid, poly-L-lactic acid, calcium hydroxyapatite, paraffin, silicone, polymethyl methacrylate (PMMA), hydroxyethyl methacrylate, polyacrylamide, and polyalkylimide gel, most of which are well tolerated. However, adverse reactions such as pain, edema, ulceration, itching, scarring, nodule formation, and migration of the injected material have been reported. Granulomatous foreign-body inflammatory reactions are a typical histologic finding in these situations.2,3 The diagnosis of adverse reactions to dermal fillers (ARDF) may be a challenge, because most patients deny the use of cosmetic fillers. In addition, these patients often refuse to undergo biopsy because of the risk of facial scarring. To the best of our knowledge, no previous diagnosis of ARDF has been rendered by means of fine needle aspiration cytology (FNAC).
CASE REPORT A 69-year-old woman complaining of a painful nodule that had been present on her perioral region for about 2 years was referred to our department. The patient’s medical history included systemic arterial hypertension, for which she had been taking losartan and chlorthalidone. She denied drinking alcohol and smoking. The patient denied any history of diabetes, immunosuppression, head and neck trauma, or prior surgical interventions. Oral Diagnosis Department, Semiology and Oral Pathology Areas, Piracicaba Dental School, University of Campinas (UNICAMP). Received for publication Mar 22, 2013; returned for revision Jul 16, 2013; accepted for publication Jul 23, 2013. Ó 2014 Published by Elsevier Inc. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.07.029
A review of symptoms by system was unremarkable. Extraoral examination was performed; there were no changes in skin color or texture, but a discreet asymmetry with increased volume was found in the skin adjacent to the right nasolabial fold (Figure 1, A). No lymphadenomegaly, thyromegaly, or other relevant head and neck abnormalities were observed. Intraoral examination revealed an extension of the skin lesion into the oral mucosa, causing a hardened nodule that was painful to palpation (Figure 1, B). Intraoral FNAC was performed with a 24-gauge needle; the material was smeared on 3 glass slides, which were immediately air fixed for Diff-Quik staining. The cytologic smears showed several bluish to purple microspheres of variable sizes, with a hemorrhagic background (Figure 1, C and D). When examined under polarized light microscopy, several microspheres were birefringent, exhibiting the typical Maltese cross pattern of round particles (Figure 1, E and F). The presumptive diagnosis was a foreign body reaction caused by the dermal application of a cosmetic filler. An intraoral excisional biopsy was performed under local anesthesia for confirmation of the diagnosis (Figure 2, A). Histologically, multiple areas of negative microcystic-like spaces resembling adipocytes were found, limited by fibrous septa, along with focal areas of chronic inflammatory infiltrate with scarce giant cells within and around the spaces (Figure 2, B). The microcystic-like spaces were empty, and the presence of PMMA microspheres could not be observed during the analysis of the histologic sections (Figure 2, C and D). The histologic findings were compatible with a foreign body reaction associated with dermal injection of PMMA, and the diagnosis of ARDF was confirmed. At 6 months follow-up, the intraoral surgical site had completely healed, with no symptoms or signs of remaining nodules.
DISCUSSION Esthetic procedures to rejuvenate, maintain, and enhance facial appearance are increasingly being requested by patients all over the world.4 In addition to PMMA, e393
ORAL AND MAXILLOFACIAL PATHOLOGY e394 Faria et al.
OOOO May 2014
Fig. 1. A, Discreet facial asymmetry present for 2 years after the application of a cosmetic filler (arrow). B, Intraoral swelling in continuity with the skin nodule (arrow). C, Cytologic smear showing clusters of bluish to purple microspheres of variable size, with a hemorrhagic background (Diff-Quik, original magnification 100). D, Small cluster of sharply round, translucent microspheres under light microscopy (Diff-Quik, original magnification 200). E, Same area observed in Figure 1, C, demonstrating birefringent microspheres under polarized light microscopy (Diff-Quik, original magnification 100). F, Same area observed in Figure 1, D, depicting microspheres highlighting the classic Maltese cross pattern shown by round birefringent particles under polarized light microscopy (Diff-Quik, original magnification 200).
Fig. 2. A, Transoperative image of the intraoral excisional biopsy showing a multinodular soft tissue specimen. B, Histologic features of the biopsy, showing multiple areas of negative microcystic-like spaces resembling adipocytes (hematoxylin-eosin, original magnification 20). C, Histology showing the presence of a foreign body reaction, several negative microcystic-like spaces, giant cells (arrow) around the empty spaces, and a chronic inflammatory infiltrate (hematoxylin-eosin, original magnification 200). D, Higher magnification showing negative microcystic-like spaces and a giant cell (arrow) in detail (hematoxylineosin, original magnification 400).
several other injectable permanent dermal fillers can cause foreign body reactions. The etiology of these dermal granulomas remains unclear, and their occurrence cannot be predicted. Previous studies have found that
granuloma formation is associated with a variety of clinical circumstances, such as host immune responses and local infection. The histologic appearance of these foreign body granulomas seems to be specific for each
OOOO Volume 117, Number 5
CASE REPORT Faria et al. e395
type of injected filler, but identification of the offending agent can be a challenge even for experienced pathologists.5-8 A cosmetic solution composed of 20% PMMA microspheres, 30 to 42 mm in diameter, associated with an 80% bovine collagen solution used as the vehicle, is often injected as a dermal filler in dermatology practice. After dermal injection, the collagen solution is slowly reabsorbed, leaving behind the nonbiodegradable PMMA microspheres. In these circumstances, PMMA microspheres are not broken down and can cause ARDFs.9-11 PMMA is frequently injected for treating nasolabial and lip folds. When ARDF occurs in these regions, it can be confused with other perioral lesions, such as dermal cysts, minor salivary gland tumors, and soft tissue tumors.12-14 In this scenario, FNAC can be useful for guiding the appropriate diagnosis, and the clinical case in question appears to be the first report of its use in the context of ARDF. It is relevant to mention that, in the present case, brisk birefringence could be seen in the PMMA microspheres obtained by FNAC, which was different from what was expected to be observed in histologic sections of PMMA-related ARDF, where birefringence is not typically detected. The lack of birefringence in histologic sections may be due to the fact that PMMA microspheres are lost during histologic processing and the birefringence is not observed because there are no longer any microspheres left. In conclusion, FNAC can be a useful and less invasive method to confirm the clinical suspicion of adverse reactions caused by facial cosmetic dermal fillers.
4. Gladstone HB, Cohen JL. Adverse effects when injecting facial fillers. Semin Cutan Med Surg. 2007;26:34-39. 5. da Costa Miguel MC, Nonaka CF, dos Santos JN, Germano AR, de Souza LB. Oral foreign body granuloma: unusual presentation of a rare adverse reaction to permanent injectable cosmetic filler. Int J Oral Maxillofac Surg. 2009;38:385-387. 6. Bigatà X, Ribera M, Bielsa I, Ferrándiz C. Adverse granulomatous reaction after cosmetic dermal silicone injection. Dermatol Surg. 2001;27:198-200. 7. 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. 8. Medeiros CC, Cherubini K, Salum FG, de Figueiredo MA. Complications after polymethylmethacrylate (PMMA) injections in the face: a literature review. Gerodontology. 2013 [e-pub ahead of print]. 9. Carruthers A, Carruthers JD. Polymethylmethacrylate microspheres/collagen as a tissue augmenting agent: personal experience over 5 years. Dermatol Surg. 2005;31:1561-1565. 10. Lemperle G, Romano JJ, Busso M. Soft tissue augmentation with Artecoll: 10-year history, indications, techniques, and complications. Dermatol Surg. 2003;29:573-587. 11. Requena L, Requena C, Christensen L, Zimmermann US, Kutzner H, Cerroni L. Adverse reactions to injectable soft tissue fillers. J Am Acad Dermatol. 2011;64:1-34. 12. Gelfer A, Carruthers A, Carruthers J, Jang F, Bernstein SC. The natural history of polymethylmethacrylate microspheres granulomas. Dermatol Surg. 2007;33:614-620. 13. Dadzie OE, Mahalingam M, Parada M, Helou T, Philips T, Bhawan J. Adverse cutaneous reactions to soft tissue fillersda review of the histological features. J Cutan Pathol. 2008;35: 536-548. 14. Hoffman C, Schuller-Petrovic S, Soyer HP, Kerl H. Adverse reactions after cosmetic lip augmentation with permanent biologically inert implant materials. J Am Acad Dermatol. 1999;40: 100-102.
REFERENCES
Reprint requests:
1. Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal fillers: review. Dermatol Surg. 2005;31:1616-1625. 2. Zimmermann US, Clerici TJ. The histological aspects of fillers complications. Semin Cutan Med Surg. 2004;23:241-250. 3. Feio PS, Gouvêa AF, Jorge J, Lopes MA. Oral adverse reactions after injection of cosmetic fillers: report of three cases. Int J Oral Maxillofac Surg. 2013;42:432-435.
Alan Roger Santos-Silva, DDS, PhD Área de Semiologia Faculdade de Odontologia de Piracicaba - UNICAMP Av. Limeira, 901 Bairro Areão, Piracicaba, São Paulo 13414-903 Brasil [email protected]
