Silicone Granuloma of the Facial Tissues

Vol. 94 No. 1 July 2002

ORAL AND MAXILLOFACIAL PATHOLOGY Editor: Alan R. Gould

Silicone granuloma of the facial tissues: A report of seven casesGiuseppe Ficarra, MD,a Adalberto Mosqueda-Taylor, DDS,b and Roman Carlos, DDS,c

Florence, Italy; Mexico City, Mexico; and Guatemala City, GuatemalaAZIENDA OSPEDALIERA CAREGGI AND UNIVERSITY OF FLORENCE; DEPARTAMENTO DE ATENCION A LA

SALUD, UNIVERSIDAD AUTONOMA METROPOLITANA XOCHIMILCO; AND HOSPITAL HERRERA, LLERANDI/

AMEDESGUA

The liquid form of silicone, called dimethicone (dimethylpolysiloxane), has been used extensively in somecountries during the past 4 decades for soft tissue augmentation. Although considered biologically inert, this materialhas been reported as potentially inducing, after tissue injection, a granulomatous inflammatory response of variableseverity. Interestingly, a remarkable paucity of reports exists about the development of complications after injections ofliquid silicone into the facial tissues, especially considering its high frequency of use. The purpose of this article is todescribe the clinical and microscopic features of 7 cases of silicone-induced granulomas that developed after injectionof the facial tissues for cosmetic purposes and to discuss the differential diagnosis and management of this condition.(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:65-73)

Silicone (polydimethylsiloxane) is a term applied tocertain polymeric organosilicon compounds that maybe in liquid, gel, or solid forms (Table I).1 The liquidform, called dimethicone (dimethylpolysiloxane), hasbeen used extensively in some countries during the past4 decades for soft tissue augmentation.1-3 Althoughinitial studies supported the belief that this material wasbiologically inert, subsequent reports have shown thatsilicone may induce a granulomatous inflammatory re-sponse of variable severity.1,4,5 Interestingly, a remark-able paucity of reports exists about the development ofcomplications after injections of liquid silicone into thefacial tissues, especially considering its high frequency

of use.6-14 Development of systemic manifestations,such as scleroderma, has been reported in patients whohave received silicone implants. However, these casesremain highly controversial and are still a subject ofdebate and litigation.6,15 The purpose of this article is todescribe the clinical and microscopic features of 7 casesof silicone-induced granulomas that developed afterinjection of the facial tissues for cosmetic purposes andto discuss the differential diagnosis and management ofthis condition.

CASE REPORTSIn Table II, the main clinical characteristics of the 7

patients with silicone granuloma of the facial tissues aresummarized.

Case 1 was presented in part by Dr Giuseppe Ficarra at the Clinico-Pathological Conference of the 10th Meeting of the InternationalAssociation of Oral Pathologists, La Antigua, Guatemala, Sep 17-21,2000.aAdjunct Professor and Director, Section of Oral Pathology andMedicine, Azienda Ospedaliera Careggi and University of Florence,Italy.bProfessor, Department of Oral Pathology and Medicine. Departa-mento de Atencion a la Salud, Universidad Autonoma MetropolitanaXochimilco, Mexico City, Mexico.cAssociate, Department of Pathology. Hospital Herrera, Llerandi/Amedesgua, Guatemala City, Guatemala.Received for publication Dec 11, 2001; returned for revision Jan 11,2002; accepted for publication Feb 15, 2002.Copyright © 2002 by Mosby, Inc.1079-2104/2002/$35.00 � 0 7/14/124459doi:10.1067/moe.2002.124459

Table I. Types of silicone and common applications

Type Applications

Gel Breast implantsLiquid Breast injection (no longer used)

Soft tissue injection (used in some countriesfor cosmetic purposes)

Therapeutic embolizationCardiopulmonary surgery as antifoam agent

Elastomer Breast implantsHeart valves prosthesesFinger joint prosthesesHemodialysis equipment (tubes)

Modified from Travis WD, Balogh K, and Abraham JL, 1985.6

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ORAL MEDICINE

ORAL PATHOLOGY

65

Case 1A 56-year-old Italian woman was seen at our clinic with

redness and swelling of the orofacial soft tissues accompaniedby pain and burning sensation. At the time of the first visit,the medical history was negative for relevant systemic dis-eases and the patient did not declare anything remarkable inrelation to the facial problem. She indicated that the facialswellings had a 3-year duration and fluctuated in size. Clinical

examination showed diffuse swelling of the lower contour ofthe face with involvement of the soft tissues overlying themandible and both lips (Fig 1). The swelling was accompa-ined by signs of cellulitis, including redness and warmth, ofthe involved areas. On palpation, multiple ill-defined subcu-taneous masses were appreciated along the inferior border ofthe mandible, both extraorally and intraorally. Intraoral ex-amination revealed a normal appearance of the mucosal sur-

Fig 1. Case 1. Multiple tumefactions are visible on lower contour of face and lips.

Table II. Summary of cases of silicone granuloma of facial tissues

CaseAge/gender/nationality

Reason forsiliconeinjection Anatomic sites Treatment Follow-up result

1 56/female/Italian

Cosmesis Both lips and soft tissuesof lower contour of face

Anti-inflammatorydrugs; systemiccorticosteroid

3 years; persistent disease

2 34/male/Italian

Cosmesis Upper lip Excisional biopsy 2 years; resolution

3 50/female/Mexican

Cosmesis Lower lip and right mentalregion

Local injectionsofcorticosteroids

2 years; stable disease

4 39/female/Mexican

Traumaticdeformity offacial tissues

Lower lip with extensionto labial commissures

Excisional biopsy 3 years; stable disease

5 38/female/Mexican

Cosmesis Lower lip Excisional biopsy 2 years; resolution

6 52/female/Guatemalan

Cosmesis Upper lip Excisional biopsy Lost to follow-up

7 77/female/Guatemalan

Cosmesis Upper lip Excisional biopsy Lost to follow-up

66 Ficarra, Mosqueda-Taylor, and Carlos ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGYJuly 2002

face and presence of fissured tongue. On the basis of theclinical findings, a working diagnosis of Melkersson-Rosenthal syndrome was made. A biopsy specimen was ob-tained from 1 of the subcutaneous masses in the mandibularvestibule. Light microscopic examination revealed skeletalmuscle with surrounding connective tissue infiltrated by his-tiocytes and numerous cystic spaces (Fig 2). The cystic spaces

varied somewhat in size and did not appear to contain residualdroplets of silicone (Fig 3). Varying degrees of fibrosis werepresent among the cystic spaces. Special stains, includingperiodic acid-Schiff (PAS), oil red O, and alcian blue, werenegative. A final diagnosis of silicone granuloma was made.The patient admitted that she had received liquid siliconeinjections into the facial soft tissues for cosmetic purposes 10

Fig 2. Case 1. At low magnification, multiple cystic spaces are evident among connective tissue and skeletal muscle fibers(hematoxylin-eosin stain; original magnification, �4).

Fig 3. Case 1. Numerous round to ovoid empty cavities of varying sizes are visible. Fibrosis, histiocytes, and lymphocytes arepresent between cavities (hematoxylin-eosin stain; original magnification, �10).

Ficarra, Mosqueda-Taylor, and Carlos 67ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGYVolume 94, Number 1

years previously. The patient then was treated with antiin-flammatory drugs and systemic corticosteroid (prednisone 60mg/day), and a partial resolution of symptoms and tumefac-tion was obtained. After 3 years of follow-up, the patient stillshowed persistent disease.

Case 2A 34-year-old transvestite Italian man had received liquid

silicone injections into the lips 7 years previously for cos-metic purposes. A recurrent subcutaneous mass subsequentlydeveloped within the right upper lip, accompanied by localsigns of inflammation (Fig 4). An excisional biopsy was donethat showed the presence of silicone granuloma, and thehistopathologic aspects were similar to those described incase 1 (Fig 5). After 2 years of follow-up, no signs ofrecurrence were observed.

Case 3A 50-year-old Mexican woman was seen with an asymp-

tomatic diffuse enlargement of the lower lip that affected theentire vermilion border, adjacent skin, and the labial mucosa,extending to the right mental region (Fig 6). On palpation, thelesion had a homogeneous rubbery consistency. The patientstated that she had received 2 liquid silicone injections ofunknown medical grade in the lower lip 5 years earlier forcosmetic purposes, and she indicated that the lesion had beenslowly enlarging during the last 4 years. A biopsy specimenwas obtained, and microscopic examination revealed numer-ous empty small cystic spaces of varying sizes, surrounded byhistiocytes, which diffusely infiltrated the superficial laminapropria down to underlying adipose tissue and striated mus-

cle. The cystic spaces varied in size and did not stain withspecial stains, including PAS, oil red O, and alcian blue.Foreign body multinucleated giant cells were infrequentlyfound. The patient was treated with 3 injections of 1 mL oftriamcinolone (10 mg/mL) each, 1 every 10 days, after whichminimal reduction of the lesion was observed. She refusedsurgical treatment and is currently asymptomatic, with nochange in size of the lesion over the last 2 years.

Case 4A 39-year-old Mexican woman was seen with a history of

a slowly growing, well-defined lower lip swelling of rubberyconsistency that extended from the midline to 1 cm beyondthe labial commissure and affected both skin and mucosalsurfaces. With a presumptive diagnosis of a labial salivarygland adenoma, the lesion was excised. Histopathologic ex-amination revealed a diffuse granulomatous infiltrate withnumerous multinucleated foreign body giant cells, many ofwhich surrounded vacuoles of varying sizes containing smallfragments of translucent refractile foreign material. Theseparticles were nonbirefringent when viewed with polarizedlight and did not stain with special stains, such as PAS, alcianblue, and oil red O. The lesion extended from the superficiallamina propria deep into the underlying skeletal muscle andwas clearly demarcated from the adjacent fibrous tissue. Thereaction extended beyond the lower surgical margin. Thepatient admitted she received 1 liquid silicone injection in theaffected area 7 years previously during a surgical procedurefor correction of a previous surgical scar caused by a motorvehicle accident. After 3 years of follow-up, the patient stillhas persistent disease.

Fig 4. Case 2. Swelling of upper right lip.

68 Ficarra, Mosqueda-Taylor, and Carlos ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGYJuly 2002

Case 5A 38-year-old Mexican woman underwent injection of liquid

silicone for lower lip augmentation 7 years previously. Thepatient did well for 5 years until she started to notice a gradualsize increase of 2 localized areas of the lip mucosa, resulting innodules, each approximately 2 cm in diameter. Two years afterthe lesions were first noticed, the patient consulted a maxillo-facial surgeon, who performed excisional biopsy of both nod-

ules. Histopathologic examination revealed extensive areasof fibrohistiocytic inflammation that surrounded numerousindividual and empty cystic spaces of varying sizes, givingthe appearance of Swiss cheese, extending from the inter-face with the overlying atrophic squamous epithelium tothe superficial bundles of underlying skeletal muscle. Post-operative follow-up was uneventful, and 2 years later, thepatient remains well without disfigurement.

Fig 5. Case 2. Histopathologic aspect is similar to that depicted in Fig 3 (hematoxylin-eosin stain; original magnification, �10).

Fig 6. Case 3. Diffuse enlargement of lower lip with involvement of entire vermilion border, adjacent skin, and labial mucosa,extending to right mental region.

Ficarra, Mosqueda-Taylor, and Carlos 69ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGYVolume 94, Number 1

Case 6A 52-year-old Guatemalan woman sought medical advice

because of a swelling involving her upper lip of approximately1 month duration. The lesion was firm, mobile, diffuse, andslightly tender on palpation. The clinical diagnosis was salivarygland adenoma or nerve sheath tumor. Excisional biopsy wasdifficult because of the poorly defined limits of the lesion, andfor this reason, it was taken in several pieces. Microscopicexamination revealed the same histopathologic aspects as theprevious cases. Special stains, including PAS, oil red O, andalcian blue, were all negative. On a subsequent visit, the patientadmitted to receiving injection of an unknown substance forcosmetic purposes 1 year before consultation. She commentedthat the substance was injected by a cosmetologist, not a physi-cian. Wound healing was uneventful, and the patient was lost tofollow-up 1 month after consultation.

Case 7A 77-year-old woman from Guatemala City was referred

by her dentist who noted several submucosal nodules involv-ing the buccal mucosa bilaterally and the upper lip. Thelesions appeared well circumscribed, relatively mobile, andnontender on palpation. Medical history was remarkable forsevere, incapacitating, and deforming rheumatoid arthritis,diagnosed 15 years previously. On further questioning, thepatient admitted that approximately 5 years before consulta-tion a cosmetologist recommended injections of a “specialsubstance” as a “new harmless method” to correct wrinkles.According to the patient, the substance was manufactured byan unknown South American pharmaceutical company andwas injected by a physician. The name of the “doctor” wasprovided, but it did not appear in the files of the GuatemalanCollege of Physicians. Therefore, it was likely that this personwas not a real doctor, and if so, he was illegally practicing inGuatemala. A biopsy was planned with the clinical diagnosesof orofacial granulomatosis versus silicone granuloma. Mi-croscopic examination revealed findings identical to the casespreviously described. The patient was lost to follow-up 2months after consultation.

DISCUSSIONSilicones are biomaterials ranging from liquid to

solid products and are used widely in medicine. Sili-cone elastomers (solid forms) are found in implantedprosthetic devices, contact lenses, and intravenous fluidtubing, and silicone liquid (dimethylpolysiloxane) isused mainly for soft tissue augmentation.1,2

When first introduced in medical practice, siliconewas considered a safe biomaterial because it did notseem to elicit any pathologic reaction in human tissues.It was used for a variety of cosmetic purposes, such asbreast, facial, and penis augmentation,6,16-18 or for med-ical conditions, such as hemifacial atrophy, Weber-Christian disease, and traumatic deformities of the fa-cial tissues.7,9 However, despite its purported inertbehavior, silicone was soon realized to produce granu-lomas in human and animal tissues. In 1964, Winer et

al19 used the term “siliconoma” to report the granulo-matous reactions in soft tissues of patients who hadreceived liquid silicone injections. Animal experimentsalso showed the production of granulomas in subcuta-neous sites after liquid injections and in viscera whenadministered with intraperitoneal or vascular injec-tion.20 Since 1964, the Federal Drug Administration(FDA), with jurisdiction solely in the United States, haslimited the clinical use of silicone to a few treatmentprotocols and a few experienced investigators. Sincethen, a great reduction in the incidence and severity ofsuch reactions has been observed with use of medical-grade or FDA-investigational formulations of silicone,which produce predictable and self-limited inflamma-tory and fibroplastic responses. The designation ofmedical-grade silicone refers to particle purity, sterilepreparation, and constant viscosity. This silicone isclear, colorless, odorless, and unaffected by storage. Italso is characterized by high water repellency, lowsurface tension, low volatility, heat stability, and theability to remain in liquid form indefinitely.1,2 Despitethese refinements, reports have been seen of severechronic inflammatory reaction to medical-grade sili-cone used by FDA-approved investigators, and thus,this practice has generally been abandoned.7,21 On theother hand, in spite of the limited use of silicone in theUnited States, the clinical use of non-FDA-approvedliquid silicones and other substances for facial tissueaugmentation in Europe, Asia, and Latin America con-tinues.6,11,22,23

The pathogenesis of silicone granuloma is not welldefined. Several investigations have shown that re-peated exposure to silicone gel may induce an antigen-specific lymphocyte-mediated response. However, theresults of these studies, which have been mainly con-ducted to analyze the effects of spillage of siliconegel-filled mammary implants, remain highly controver-sial.24 Tissue reaction to silicone varies in relation tothe form that has been used. Particles of silicone elas-tomer characteristically produce a foreign body giantcell reaction that is particularly evident in lymph nodes.In contrast, when silicone gel or liquid is introducedinto soft tissues, the strong foreign body giant cellreaction seen with silicone elastomer is typically ab-sent. Silicone gel and liquid in tissues usually produceround to oval empty cystic spaces. These spaces may besmall and uniform or large with variation in size andshape, depending on the amount of silicone injectedinto the tissue. Silicone also has the ability of migrationto distant sites. For example, silicone can migrate frombreast gel implants through soft tissues to a variety ofsites, including the upper arm, the chest, the shoulder,and the axillary lymph nodes. Lymph node involve-ment also has been observed in patients with elastomer

70 Ficarra, Mosqueda-Taylor, and Carlos ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGYJuly 2002

finger joint implants. Hematogenous dissemination ofparticles to viscera represents an additional pattern ofsilicone migration. This is seen in patients undergoinghemodialysis and cardiopulmonary bypass, in patientswith cardiac valve prostheses, and also in patients withsoft tissue injection.6 Hematogenous spread of siliconehas been reported in almost every organ, including theliver, kidneys, lungs, brain, pancreas, and bone mar-row.6,25 Silicone injections in facial tissues have been usedextensively for a wide variety of medical and cosmeticpurposes over the last 4 decades. The occurrence of un-desirable reactions is well known and ranges from mildlocal inflammatory reactions to severe facial deformitiesfrom infiltrative granulomatous reactions.6-14 Some inves-tigators consider that these adverse effects have beencaused by the presence of impurities in preparations usedin the past, when adulterants were added to the silicone ina misguided attempt to increase the dermal reaction and to“fix” the silicone within a fibrous capsule.1,26

We present 7 examples of this unusual reaction inpatients who underwent injection of liquid silicone inthe facial tissues 1 to 10 years before development offacial deformity. All cases occurred in patients fromcountries where the exact nature of the silicone injectedis unknown. Because silicone-related complicationstend to appear several years after injection, they willpossibly be observed in future years in those countrieswhere there is lack of strict control in the use ofnon–FDA-approved silicone or other modelatingagents. At least 9 reports about granulomatous inflam-mation after silicone injection of facial tissues exist.6-14

The time interval between silicone infiltration and onsetof symptoms ranged from 5 months to 15 years, whichis similar to that observed in these cases.

The severity of the adverse reaction after infiltrationof silicone is highly variable, ranging from local ery-thema, ecchymosis, hyperpigmentation, and textureproblems (ie, uneven contour) to excessive tissue ele-vation, pain, chronic ulceration, and migratory subcu-taneous masses.1,6,8,10 Although mild inflammatory andfibrous reactions are observed in most cases, Raszewskiet al10 described, 19 years after injection of silicone fornasal bridge augmentation, a locally aggressive fibro-

blastic reaction with infiltration beyond the subcutane-ous tissues of the face, including the left orbit and thefrontal and temporal bones. This complication led toresection of the left upper face and enucleation of theleft eye. On the other hand, it is important to realize thatsilicone can migrate to locations distant from the orig-inal site of application and to lymph nodes, creating apattern of clinical presentation, which may be confusedwith a malignant neoplasm or other granulomatousdiseases if the clinician or pathologist is unaware of thepatient’s previous exposure to silicone.6

Fortunately, silicone granulomas are easily identifiedin most cases with light microscopy.27 Silicone pro-duces a range of histologic reactions in tissues, depend-ing on the form of silicone used and the location of thelesion. The tissue reaction to silicone gel and liquid isdifferent from that produced in response to siliconeelastomer because the exhuberant foreign body giantcell reaction seen with the latter is typically absent inthe former. On the other hand, silicone liquid within thetissue usually shows presence of round to oval cysticspaces, which tend to appear empty on light micro-scopic examination. These may be relatively small anduniform or large and irregular, depending on theamount of material introduced into the tissues. Sur-rounding fibrosis may be induced by migration of sili-cone particles along tissue planes, such as that occur-ring after ruptured breast implants25 or through theproduction of silica from silicone by macrophages.10,28

Silicone has been shown to also enter the blood-stream from soft tissue injection sites and with directintravascular injection. Several fatalities have occurredshortly after soft tissue injections of large amounts ofliquid silicone, some of which was probably injecteddirectly into the bloodstream.6,13

From a clinical point of view, the differential diag-nosis of silicone granuloma includes a variety of con-ditions that are listed in Table III. Labial cases seen aswell-defined nodules suggest a differential diagnosis ofsalivary gland cyst and tumor, soft tissue cyst (dermoidcyst), and tumor.29,30 Cases seen as persistent or recur-rent solid facial swelling or multiple nodules resemblea number of disorders. Recurrent facial erysipelas may

Table III. Differential diagnosis of silicone granuloma

Well-defined single noduleSalivary gland cysts and tumorsSoft tissue cysts (dermoid cyst) or tumors

Persistent or recurrent solid facial swelling or multiple nodulesInfections: recurrent facial erysipelas, tuberculosis, lepromatous leprosy, South American blastomycosis, trichinosisInflammatory disease: allergic contact dermatitis, facial edema with eosinophilia, cheilitis glandularis apostematosa, Ascher’s syndromeOrofacial granulomatosis: Crohn’s disease, Melkersson-Rosenthal syndrome, sarcoidosisForeign body granulomas: paraffinoma, talc granuloma, silica, silicone, bovine collagen, etc

Ficarra, Mosqueda-Taylor, and Carlos 71ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGYVolume 94, Number 1

result in persistent lymphedematous swelling of theaffected part. Typically, patients with erysipelas reportrepeated bouts of swelling with pain, fever, and ery-thema. Other infectious diseases that may give similarfeatures are tuberculosis (lupus vulgaris), lepromatousleprosy, South American blastomycosis, and trichino-sis.29 Among inflammatory diseases sharing this patternof clinical presentation are allergic contact dermatitis,facial edema with eosinophilia, cheilitis glandularisapostematosa, and Ascher’s syndrome. Facial edemawith eosinophilia, a rare disorder first described in1985,31 is characterized by diffuse nonpitting edema ofthe face associated with marked peripheral-blood eo-sinophilia. The edema is episodic initially but eventu-ally persistent. Skin biopsy reveals perivascular infil-trates of lymphocytes admixed with small numbers ofeosinophils. Cheilites glandularis apostematosa is char-acterized by inflammation and hypertrophy of the mi-nor salivary glands in the lower lip.29 Ascher’s syn-drome affects the upper lip, producing nodularsubmucosal swelling (double lip). This rare syndromeis also characterized by blepharochalasis, inflammationof accessory lacrimal glands, and thyromegaly.32 Oro-facial granulomatosis, such as Crohn’s disease, Melk-ersson-Rosenthal syndrome, and sarcoidosis, also maybe confused with silicone granuloma. Crohn’s diseaseinvolving the oral mucosa may result in progressiverubbery swelling of the buccal surfaces. On histologicexamination, noncaseating granulomas are seen in thesubmucosa.33 Melkersson-Rosenthal syndrome is aunique disorder with the triad of facial nerve palsy,lingua plicata (fissured tongue), and solid facial swell-ing.34,35 The complete syndrome is, however, rarelyseen, and orofacial swelling remains the sine qua non ofthe disease and precedes other features in approxi-mately 40% of cases. Sarcoidosis may involve the lipsor facial skin, producing characteristic shiny purple-rednodules.29 Foreign body granulomas paraffinoma andtalc granuloma and granulomatous response to silica,silicone, and bovine collagen can be differentiated fromsilicone granuloma through their histologic aspects anduse of polarized light.36 Finally, for extensive and ag-gressive cases, such as that reported by Raszewski etal,10 low-grade fibrosarcoma and desmoid fibromatosisshould be considered in the differential diagnosis.

Treatment of soft tissue silicone granuloma is diffi-cult, and surgical excision is warranted when possi-ble.7,12,14 For well-circumscribed nodular lesions, sur-gical excision represents a reasonable and effectiveapproach as it has been observed in some of our pa-tients. Instead, for widespread lesions, complete eradi-cation of the granulomatous tissue is highly improbableand surgery may lead to scarring and fistulas. Eventhough corticosteroids have produced beneficial effects

in the treatment of some granulomatous diseases,19

their efficacy appears limited and their therapeutic roleis not well defined by appropriate studies. Prednisonehas mainly been used in doses ranging from 1 mg/d to60 mg/d, with transient improvement of patient signsand symptoms. Successful response has been reportedrecently by Senet et al12 with the use of minocycline forthe treatment of 2 cases of cutaneous silicone granulo-mas, and these authors suggested that the beneficialeffects of minocycline are related to its antiinflamma-tory or immunomodulating effects and to antigranulo-matous properties, which have been shown in vitro.37,38

Liquid silicone injections remain controversial, par-ticularly in those countries where there is inadequateinvestigation and control of biomaterials used for softtissue augmentation. In our patients and in most previ-ously reported cases, the medical grade of the injectedsilicone was unknown.

We thank Drs J. C. Lopez Noriega and C. Liceaga forcontributing cases 2 and 3.

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products injected for soft tissue augmentation. J Am Acad Der-matol 1989;21:992-8.

2. Selmanowitz VJ, Orentreich N. Medical grade fluid silicone: amonographic review. J Dermatol Surg Oncol 1977;3:597-611.

3. Brown JB. Studies of silicones and Teflon as subcutaneousprostheses. Plast Reconstr Surg 1961;28:86-92.

4. Hench LL. Biomaterials. Science 1980;208:826-31.5. Ben-Hur N, Neumen Z. Siliconoma: another cutaneous response

to dimethylpolysiloxane. Plast Reconstr Surg 1965;36:629-34.6. Travis WD, Balogh K, Abraham JL. Silicone granulomas: report

of three cases and review of the literature. Hum Pathol 1985;16:19-27.

7. Achauer BM. A serious complication following medical-gradesilicone injection of the face. Plast Reconstr Surg 1983;71:251-3.

8. Mastruserio N, Pesqueira MJ, Cobb MW. Severe granulomatousreaction and facial ulceration occurring after subcutaneous sili-cone injection. J Am Acad Dermatol 1996;34:849-52.

9. Pearl RM, Laub DR, Kaplan DN. Complications following sili-cone injections for augmentations of the contours of the face.Plast Reconstr Surg 1978;61:888-91.

10. Raszewski R, Guyuron B, Lash RH, et al. A severe fibroticreaction after cosmetic liquid silicone injection. J Craniomaxil-lofac Surg 1990;18:225-8.

11. Bigata X, Ribera M, Bielsa I, Ferrandiz C. Adverse granuloma-tous reaction after cosmetic dermal silicone injection. DermatolSurg 2001;27:198-200.

12. Senet P, Bachelez H, Ollivaud L, Vignon-Pennamen D, Duber-tret L. Minocycline for the treatment of cutaneous silicone gran-ulomas. Br J Dermatol 1999;140:985-7.

13. Ellenbogen R, Ellenbogen R, Rubin L. Injectable fluid siliconetherapy. Human morbidity and mortality. JAMA 1975;234:308-9.

14. Rees TD, Ballantyne DL, Seidman I. Eyelid deformities causedby injection of silicone fluid. Br J Plast Surg 1971;24:125-8.

15. Sanchez-Guerrero J, Colditz GA, Karlson EW, et al. Siliconebreast implants and the risk of connective-tissue diseases andsymptoms. N Engl J Med 1995;332:1666-70.

16. Symmers W. Silicone mastitis in topless waitresses. Br Med J1968;3:19-22.

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18. Bigata X, Ribera M, Bielsa I, Ferrandiz C. Adverse granuloma-tosis reaction after cosmetic dermal silicone injection. DermatolSurg 2001;27:198-200.

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34. Rubino I, Ficarra G. Sindrome di Melkersson-Rosenthal. Descri-zione di due casi. Minerva Stomatol 1994;43:595-9.

35. Rogers RS. Melkersson-Rosenthal syndrome and orofacial gran-ulomatosis. Dermatol Clin 1996;14:371-9.

36. Shapiro PE. Noninfectious granulomas. In: Elder D, Elenitsas R,Jaworsky C, Johnson B Jr, editors. Lever’s histopathology of theskin. 8th ed. Philadelphia: Lippincott-Raven; 1997. p. 317-40.

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38. Tilley BC, Alarcon GS, Heyse SP, et al. Minocycline in rheu-matoid arthritis. A 48-week, double blind, placebo-controlledtrial. Ann Intern Med 1995;122:81-9.

Reprint requests:

Dr Giuseppe FicarraSection of Oral Pathology and MedicineDepartment of Odontology and StomatologyViale Morgagni 8550134 Florence Italygificarr@tin.it

CALL FOR REVIEW ARTICLES

The January 1993 issue of Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology,and Endodontics contained an Editorial by the Journal’s Editor in Chief, Larry J. Peterson, thatcalled for a Review Article to appear in each issue.

These Review Articles should be designed to review the current status of matters that areimportant to the practitioner. These articles should contain current developments, changingtrends, as well as reaffirmation of current techniques and policies.

Please consider submitting your article to appear as a Review Article. Information forauthors appears in each issue of Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology,and Endodontics.

We look forward to hearing from you.

Ficarra, Mosqueda-Taylor, and Carlos 73ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGYVolume 94, Number 1