Peripheral Giant Cell Granuloma in a Dog Lorraine A. Hiscox, DVM; Yvan Dumais, DMV Summary:
Peripheral giant cell granuloma is considered rare in the dog with little known about the clinicopathologic features. There are few reports in the veterinary literature concerning this benign, reactive lesion, formerly known as giant cell epulis. In humans, the four most commonly described reactive epulides are focal fibrous hyperplasia (fibrous epulis), pyogenic granuloma, peripheral ossifying fibroma, and peripheral giant cell granuloma. This case report describes the diagnosis and surgical management of a peripheral giant cell granuloma in a dog. J Vet Dent 32(2); 103-110, 2015
A 6.6 kg, 12-year-old spayed/female Lhasa Apso was presented for evaluation and treatment of a recurrent, progressive gingival mass. The mass was first noted by the owner 3-years prior to referral presentation. At that time, the mass was reported as small and located near the maxillary incisor teeth. The owner’s general practitioner excised the mass without submission for histopathologic evaluation. The mass recurred 1-year later and a second surgical excision was performed by the general practitioner. Again, histopathology was not obtained. The owner noted recurrence and expansion of the mass approximately 10-months after the second surgical procedure and the patient was referred. At referral presentation, a comprehensive physical examination was within normal limits with the exception of a grade I/VI systolic heart murmur present in the absence of exercise intolerance or coughing. An oral examination in the awake patient revealed a firm, bright red, nodular gingival mass located between the right maxillary third (103) and left maxillary second incisor (202) teeth. There was slight hemorrhage with minimal manipulation. The right maxillary first (101) and second (102) incisor, and the left maxillary first incisor (201) teeth were not visible. The mass involved the hard palate mucosa with a line of demarcation present from the mesiopalatal aspect of the left maxillary third incisor (203) tooth to the level of the right maxillary canine (104) tooth (Fig. 1). The 103 was displaced labially with a mobility index of 1. Regional lymph nodes were not enlarged. Given the duration of the lesion, the differential diagnosis for the oral examination findings included other forms of gingival enlargement such as pyogenic granuloma, focal fibrous hyperplasia, and odontogenic and oral neoplasia.1 Cardiac evaluation prior to general anesthesia was recommended and declined. Clinical staging of the mass included a complete blood count, serum chemistry tests, computerized tomographic (CT) imaging of the mass both pre- and postcontrast administration, CT of the thorax and abdomen in order to screen for metastatatic disease, intraoral radiography, and 103
J VET DENT Vol. 32 No 2 Summer 2015
incisional biopsy for histopathologic evaluation. Preoperative laboratory tests were considered unremarkable with a mild elevation in BUN with concentrated urine (1.042), and elevated globulins which were attributed to mild dehydration and chronic inflammation, respectively. The patient was premedicated with acepromazinea (0.03 mg/kg) and hydromorphoneb (0.1 mg/kg) administered IM. Once sedated, a catheterc was placed in the right lateral saphenous vein and anesthesia was induced with propofold (2.0 mg/kg) IV. A size 7.5, cuffed endotracheal tube was placed and oxygen delivered at a rate of 1L/min and isofluranee between 1.25 and 2% in a semi-closed system. A balanced electrolyte solutionf was delivered at a rate of 2.5 ml/kg/hr based on consultation with a cardiologist in consideration of the
Figure 1 Rostral (A) and palatal (B) photographic views of a peripheral giant cell granuloma in a 12-year-old Lhasa Apso dog. Note the bright pink nodular appearance and displacement of the right maxillary third incisor tooth (103) with apparent absence of the right maxillary first (101) and second (102) incisor teeth. The mass is grossly well-demarcated from the normal mucosa of the hard palate.
unevaluated, pre-existing heart murmur. Electrocardiogram, core body temperature, heart rate, respiratory rate, end tidal carbon dioxide, pulse oximetry, and indirect blood pressure
Figure 2 Intraoral radiographic image of a peripheral giant cell granuloma in a 12-year-old Lhasa Apso dog (A). Note the absence of the right (101) and left (201) maxillary first incisor teeth and displacement of the right maxillary second (102) and third (103) incisor teeth. There are areas of decreased bone density (white arrow) and irregular bone proliferation (gray arrow). A computed tomographic (CT), 3-D reconstructed image shows a 2-cm expansile mass affecting the incisive bone region with secondary osteolysis and periosteal reaction (B). The image confirms the radiographic findings and displacement of the left maxillary second incisor tooth (202).
were monitored and recorded every 5-minutesg throughout the procedure. Body temperature was supported with a circulating warm water blanketh. Ampicillin sodiumi (22.0 mg/kg) was administered IV at induction. The CT evaluation revealed an expansile mass approximately 2-cm in diameter, localized in the incisive bone with secondary osteolysis and periosteal reaction (Fig. 2). The transition from affected bone to normal bone was poorly defined. The scan was negative for metastases to areas evaluated (regional nodes, thorax, abdomen). The conclusion of the radiologist was a lesion consistent with neoplasia and fibrosarcoma, osteosarcoma, chondrosarcoma, squamous cell carcinoma, and melanoma were considered the most likely possibilities. Complete oral examination was performed following the CT. All teeth were probed and charted. Generalized severe gingivitis and moderate calculus were recorded. While the teeth were cleaned and polished, additional periodontal therapy was not performed at the request of the owner pending the results of the biopsy of the mass. An intraoral, occlusal radiographic view of the incisive region confirmed the absence of teeth 101 and 201, and 102 was noted to be present but displaced (Fig. 2). A deep incisional biopsy in the region of the central incisor teeth was obtained. Meloxicamj (0.1mg/kg) SQ, tramadolk (4.0 mg/kg) BID X 5-days, and clindamycinl (5.5 mg/kg) BID PO X 7-days were prescribed postoperatively. A soft food diet was advised in the form of meatballs and chew toys and hard treats were prohibited. Samples obtained for histpathology were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned at 5-µm and stained with hematoxylin-eosinphloxine-saffron (HEPS). Histopathologic evaluation revealed a classic peripheral giant cell granuloma (PGCG). Numerous
Figure 3 Histomicrograph of the biopsy specimen from an incisivomaxillary mass in a 12-year-old Lhasa Apso dog showing classic histopathologic characteristics of peripheral giant cell granuloma. There are numerous type I multinucleated giant cells, with up to 20 nuclei within a loose stroma composed of spindle cells and minimal to moderate amounts of collagen. [HematoxylinEosin-Phloxine-Saffron, original magnification = 100 X].
J VET DENT Vol. 32 No. 2 Summer 2015
multi-nucleated giant cells were a prominent feature with up to 20 nuclei. These cells were present within a loose stroma composed of spindle cells with minimal to moderate amounts of collagen (Fig. 3). The patient was admitted for surgery 6-weeks following biopsy. Limited laboratory tests (hematocrit, total protein, blood urea nitrogen, urine specific gravity) were within normal limits. The previously diagnosed prominent gingivitis was considerably improved after dental prophylaxis and antimicrobial therapy. Preoperative sedation and analgesia was provided with acepromazine (0.03 mg/kg), midazolamm (0.1 mg/kg), and hydromorphone (0.1 mg/kg) IM. General anesthesia was induced and maintained as described previously.
Intraoperative analgesia was provided with a fentanyln constant rate infusion, adjusted as needed (2.5-15.0 μg/kg/ hr). Intravenous fentanyl boluses were also admnistered as needed (2.0-5.0 μg/kg). Ketamineo was administered as a single IV dose (7.5 mg/kg). Blood pressure was supported intermittently with glycopyrrolatep (0.002-0.005 mg/kg) IV and dobutamineq (2.0-4.0 μg/kg/min) as a constant rate infusion. Ampicillin (22.0 mg/kg) was administered IV at induction and Q 2-hours intraoperatively. The patient was placed on a ventilatorr due to an irregular breathing pattern. Patient monitoring was accomplished and recorded as described previously. Hematocrit and total protein were also evaluated intraoperatively. Bilateral infraorbital regional blocks were
Figure 4 Lateral (A) and palatal (B) photographic views of a peripheral giant cell granuloma in a 12-year-old Lhasa Apso dog showing intended surgical margins.
Figure 5 Photograph (A) showing extracted tooth root remnants of the transected right maxillary second premolar tooth (106) following resection of a peripheral giant cell granuloma in a 12-year-old Lhasa Apso dog. The postoperative intraoral radiograph (B) confirms resection of the lesion and removal of tooth roots. Note the loose bone fragment (arrow) that was located and removed.
J VET DENT Vol. 32 No 2 Summer 2015
administered with a combination of lidocaines (1.0 mg/kg) and bupivicainet (1.0 mg/kg) with 0.65 ml delivered per site. The surgical plan was marked allowing for 1-cm margins based on preoperative CT evaluation (Fig. 4). The marked soft tissue was partially incised using a #15 scalpel bladeu followed by full-thickness incisions. A periosteal elevatorv was used to elevate soft tissues from bone. Care was taken to identify, isolate, and ligate the right and left major palatine arteries as they were encountered approximately midway between the center of the palate and the ipsilateral dental arch. A surgical length round burw in a water-cooled highspeed handpiece was used to create peforations in the exposed bone in the same plane as the soft tissue incisions. The soft tissue was retracted to avoid trauma from the surgical bur. The right dental arch was sectioned through 106 and the left side was sectioned through the arch in the absence of teeth. An osteotomex and mallety were used to connect the osteotomy sites and complete the ostectomy. The nasal turbinates were transected using sharp dissection. A small rongeurz was used to grasp the sectioned tissue and remove it en bloc. Hemorrhage was minimal and controlled with gentle pressure using gauze moistened with sterile physiologic saline.aa Removal of the 106 sectioned tooth roots with a dental elevator was verified radiographically (Fig. 5). Osteoplasty to contour bone margins was performed using a football-shaped medium grit diamond burbb. The surgical site was lavaged with sterile saline. Mucosal-submucosal flaps were developed bilaterally with blunt dissection between the submucosa and deeper tissue planes. The infraorbital neurovascular pedicles were not included in the flaps. Flap advancement and mobility were facilitated by incising mucosa caudally, dorsal to the mucogingival line. Additionally, 1-2 mm of palatal marginal tissue was excised to expose palatal bone to support the sutured wound. Two, small perforations were made in the palatal bone using a round surgical bur to provide additional anchorage for placement of the midline sutures for
flap closure. Where possible, the mucosa was closed in 2 layers with monofilament absorbable suturecc in a simple interrupted pattern (Fig. 6).2 The resected specimen was marked for margins and submitted for histologic evaluation (Fig. 7). The aesthetic result of the surgery was evaluated immediately postoperatively and considered good (Fig. 8). The bilateral infraorbital nerve
Figure 6 Photograph showing the T-shaped wound closure following rostral maxillectomy for a peripheral giant cell granuloma in a 12-year-old Lhasa Apso dog.
Figure 7 Dorsal (A) and palatal (B) photographic views of the en bloc specimen following rostral maxillectomy for a peripheral giant cell granuloma in a 12-year-old Lhasa Apso dog. Note the ink-stained areas for marginal assessment.
J VET DENT Vol. 32 No. 2 Summer 2015
Figure 8 Immediate postoperative photograph showing a good aesthetic outcome following rostral maxillectomy for a peripheral giant cell granuloma in a 12-year-old Lhasa Apso dog (A). The 10-day postoperative examination showed the right mandibular canine tooth (404) lateral to upper lip (B). Associated soft tissue trauma appeared absent. The 10-day postoperative examination showed expected healing at the maxillectomy site (C).
blocks were repeated and the patient received meloxicam (0.2 mg/kg) SQ just prior to the conclusion of general anesthesia. Immediate postoperative pain management was provided by the urgent care department of the referral facility. The patient received a ketamine CRI (0.5 mg/kg/hr) and the constant rate infusion of fentanyl was continued at 2.5-5.0 ug/kg/hr PRN. The patient was examined for comfort and the tongue moistened Q 4-hrs. Additionally, intermittent cold compresses were placed over the muzzle for 10-minutes to help control soft tissue swelling. The fentanyl and ketamine were discontinued the following morning based on negative clinical signs for overt pain. The patient did not eat prior to discharge 24-hrs following surgery. Postoperative medications included meloxicam (0.1 mg/kg) PO SID X 5-days, tramadol (3.8 mg/kg) PO BID to TID X 5-days, and clindamycin (5.5 mg/kg) PO BID X 14-days. A soft food diet was advised in the form of meatballs. Chew toys and hard treats were prohibited. An elizabethan collar was recommended at all times during the first week postoperatively, only to be removed during monitored meal times. The histopathology report confirmed that a 2.9-cm mass had been excised and verified the diagnosis of PGCG. The granuloma seemed completely excised based on margin evaluation, however the dorsal aspect had minimal grossly normal marginal tissue. Marginal excision was considered adequate for this type of lesion. Communications in the immediate postoperative period confirmed that the patient was doing well with mention that the recommended dose of tramadol for pain control was reduced due to secondary side effects of sedation. The diet was modified to a homemade diet of chicken and turkey which the dog was content to eat. The 10-day postoperative examination was within normal limits however the owner declined the administration of sedation to allow an oral examination. The right maxillary lip was positioned medial to the right mandibular canine tooth (404) with no evidence of lip trauma. Physical examination was within normal limits and the patient was reported to be doing well at the 3-week postoperative examination. Endodontic therapy of 404 was offered but declined by the owner. The patient was sedated with dexdomitordd (3.0 ug/kg) and butorphanolee (0.3 mg/kg) IM. The incisivomaxillectomy site had uncomplicated healing (Fig. 8). Antisedan was administered to reverse the dexdomitor and the patient was released 30-minutes later. The owner reported that the dog was doing well before the 7-month postoperative examination done under general anesthesia at the hospital of the referring veterinarian. Physical examination was within normal limits and regular dental prophylaxis was recommended. While tooth 404 persisted lateral to the maxillary lip, there was no evidence of skin irritation from the contact. The surgical site had expected healing with no signs of granuloma recurrence. An occlusal radiograph of the surgical area was obtained showing smooth bone margins with no evidence of bony lysis or proliferation (Fig. 9).
A growth positioned and originating from an epithelial surface or the surface of an organ is described as exophytic. In the oral cavity this would be any lesion that projects above the surface of the gingiva or mucosa.3 Epulis is a descriptive 107
J VET DENT Vol. 32 No 2 Summer 2015
term for a localized exophytic growth on the gingiva and is not a definitive diagnosis. There are two categories of epulides: reactive and peripheral odontogenic tumours but strictly speaking, any growth present on the gingiva may be described as an epulis including malignancies.4,5 The four most common reactive epulides described in humans are: focal fibrous hyperplasia, pyogenic granuloma, peripheral ossifying fibroma, and PGCG.6 Epulides are considered common in the dog with focal fibrous hyperplasia being the most common reactive epulis. Epulides of odontogenic origin are considered rare in the dog.7 There are few reports of PGCG in the veterinary literature and this lesion is considered rare. A survey of 1002 canine oral and pharyngeal lesions identified 6 cases of PGCG and an earlier report identified 1 case in 377 dogs.8,9 More recently, in a review of 2609 canine epulis cases received by a veterinary biopsy service over a period of almost 11-years, 26 cases of PGCG were identified with a prevalence of 0.99%.8 In this same study, almost 30% of dogs were under the age of 6-years with no sex predilection. The age range at presentation was reported to be 6.3 to 11-years in a different study.5 The human literature differentiates giant cell lesions of the jaws as central giant cell granuloma (CGCG) and PGCG
(exophytic origin). The CGCG is reported to be more prevalent in children with a propensity for females, and more frequently diagnosed in the mandible. This locally invasive but nonmalignant lesion may also affect other bones in the craniofacial region.10 Some investigators consider it a variant of giant cell tumor that affects long bones and prefer the term giant cell lesion with no distinction of granuloma. PGCG is considered relatively common in humans, representing approximately 7% of all benign jaw tumors.1,11,12 It develops on the gingiva and alveolar ridge and is believed to originate from the periosteum or periodontal ligament in response to local irritants including trauma, tooth extraction, poorly finished restorations, plaque, calculus and impacted food. The lesion can present at any age but is reported more commonly in people in their 50s and 60s, again with a slight female tendency and predilection for the mandible.1,10,13 The clinical appearance of the lesion varies from smooth, welldemarcated sessile or pedunculated, to a multi-lobular and irregularly delineated deep red-to-bluish mass that tends to be soft and friable, hemorrhages easily, and is slow growing.12,14 Degradation of red blood cells with accumulation of hemosiderin contributes to the bluish discoloration of the mass. Bony involvement is rare although there may be superficial
Figure 9 Photographs taken 7-months following rostral maxillectomy for a peripheral giant cell granuloma in a 12-year-old Lhasa Apso dog showing the right mandibular canine tooth (404) lateral to the upper lip with no apparent trauma (A). The maxillectomy site appears to have uncomplicated healing based on oral (B) and radiographic (C) examinations.
J VET DENT Vol. 32 No. 2 Summer 2015
erosion.1,15,16 The lesions vary in size from < 1-cm to 5-cm with the vast majority of the lesions (95%) reported to be less than 1.5-cm.17 The histologic features of the PGCG are described as numerous multinucleated giant cells (MNGC) amidst lymphocytes, plasma cells, and macrophages in the submucosal stroma.5,9 In a report describing the lesion in dogs, 2 types of PGCG are highlighted, namely the ‘classic’ and the ‘collision’. The collision PGCG has areas of stellate mesenchymal cells in fibrous stroma with regularly spaced blood vessels that is suggestive of the fibromatous epulis of periodontal ligament origin (also known as peripheral odontogenic fibroma - an odontogenic epulis). For both types of PGCG, collision and classic, the MNGC is the most prominent histologic feature with two types described based on nuclear appearance and cytoplasmic staining. The metabolically active (Type I) MNGC exhibits larger nuclei with distinct nucleoli and more basophilic cytoplasm while the degenerating MNGC (Type II) is smaller and exhibits more eosinophilic cytoplasm with condensed hyperchromatic and irregular nuclei.8 While the definitive origin of the MNGCs is unknown, there is the possibility of osteoclastic derivation which is supported by positive staining of some of the MNGCs with tartrate resistant acid phosphatase (TRAP).8 Others believe these cells come from the mononuclear phagocyte system.1 The recommended treatment for this mass, both in the human and veterinary literature, is local excision to the level of underlying bone with thorough curettage of the bone and removal of any identifiable local irritants.8,10,17 Reported recurrence rates in humans are widely variable with 10% given as the average.1 Recurrence may be related to failure to remove the source of irritation.11 In the review of 26 canine cases, there were 2 recurrences within 2-months of surgery.8 Regardless of species, there were no features that distinguished recurrent cases and none of the lesions classified as ‘collision’ recurred. Intraoral radiography plays a key role in evaluation and advanced imaging further aids in clinical staging and determination of pre-surgical planning to attain negative margins. It is imperative for early identification and treatment based on the benign but chronically progressive and locally destructive potential of PGCG. Failure to treat appropriately can result in potentially painful secondary complications such as bone loss with tooth displacement and exfoliation, all of which were present in the case reported here. Additionally, surgical management is made technically more difficult with the increasing size of the lesion. The CT evaluation in this case identified a 2-cm mass, affecting the surgical plan of 1-cm surgical margins based on the history of recurrence and progressive growth. As in this case, medial displacement of the maxillary lip may occur following oral reconstruction resulting in one or both mandibular canine teeth contacting the lateral aspect of the lips. This complication may result in discomfort, skin irritation, or ulceration. The owner should be warned of this complication before surgery. Further, the clinician should address this complication intraoperatively when it is apparent that the reconstruction has compromised the lip vestibule. Crown reduction and vital pulp therapy has an excellent 109
J VET DENT Vol. 32 No 2 Summer 2015
prognosis, especially under controlled conditions. Most owners understand that this procedure may be necessary based on the size of the lesion and the necessity for complete removal, especially when discussed during the preoperative consultation. In this instance, the owner did not express concern over the cosmetic appearance of the dog and there was no trauma to the lip. An additional potential complication with this procedure is nose droop that can be managed by placement of sutures bilaterally in the lateral nasal cartilage and remaining rostral bone to support the nose.2 Nose droop was not a complication in this case. The PGCG diagnosed in this patient displayed the familiar histologic features without evidence of the peripheral odontogenic fibroma and so was defined as ‘classic’. The mass was also consistent with what has been described in the literature based on clinical appearance and biologic behavior. There was no definitive source of irritation identified other than calculus and plaque which may have played a role as local irritants. This report emphasizes the importance of a timely diagnosis with histopathologic confirmation and adequate surgical margins to prevent recurrence. Ultimately, the surgical margins are related to the size and location of the lesion. Incisivomaxillectomy in this case was considered appropriate given the historical tendency for recurrence along with the extent and destructive nature of the lesion. __________________________________________________ c d e f g h i j k l m n o p
Hydromorphone Hydrochloride, Sandoz Canada Inc, QC Becton-Dickinson, Intravenous Catheter, Utah Diprivan AstraZeneca, Mississauga, ON IsoFlo ®, Abbott Animal Health, St. Laurent, QU Lactated Ringers, Baxter, Mississauga, ON Vet600A, Goldway, Fl. Gaymar T/Pump warm water recirculator, Paragon Medical, Fl. Ampicillin, Novopharm Ltd., Toronto, ON Metacam injectable, Boehringer Ingelheim, Burlington, ON Ultram, Jansen Inc., Toronto, ON Antirobe, Pfizer, Kirkland QC Midazolam, Sandoz, Boucherville, QC Fentanyl, Summit Pharmacy, Aurora, ON Vetalar ® Bioniche, Belleville, ON Glycopyrrolate, Omega, Montreal, QU Dobutamine, Sandoz, Boucherville, QU
s t u v w x
Penlon, model # AV800, Dispomed, QU Lidocaine, AstraZeneca, Mississauga, ON Bupivicaine, AstraZeneca, Mississauga, ON Scalpel blade, Almedic, Montreal, QC Ex 1, Periosteal Elevator, (#9 Molt), Cislak, Niles, IL Round bur #2, surgical length, Henry Schein, Concord, ON Osteotome, Serona Animal Health, Mission, BC Mallet, Serona Animal Health, Mission, BC Rongeur, Almedic, Montreal, QC 0.9% Physiologic Saline, Baxter Corporation, ON 016 M Football, Maxima Diamonds, Henry Schein, Concord, ON Monocryl, Ethicon, Johnson & Johnson, Somerville, NJ Dexdomitor, Pfizer, Kirkland, QC Butorphanol, Wyeth, Guelph, ON Antisedan, Pfizer, Kirkland, QC
aa bb cc dd ee z
From the Dentistry Service, Faculty of Veterinary Medicine, University of Montreal, 1525, rue des Veterinaires, St. Hyacinthe, Quebec, J2S 2M2, Canada. Email: [email protected]
References 1. Sood S, Gulati A, Yadav R, Gupta S. Peripheral Giant Cell Granuloma: A review. Indian Journal of Multidiscipilinary Dentistry. 2012 Feb-April: p. 435-440. 2. Lantz G. Maxillectomy techniques. In Verstraete FLBA, editor. Oral and Maxillofacial surgery in Dogs and Cats. Europe: Elsevier ; 2012. p. 451-466. 3. Sarabadani J, Ghanbariha M, Khajehahmadi S, et. al.. Consistency rates of clinical and histopathologic diagnoses of oral soft tissue exophytic lesions. JODDD. 2009 Summer: p. 86-89. 4. Gardner D. Epulides in the Dog: A Review. J Oral Pathol Med. 1996; 25(32-7). 5. Yoshida K, Yanai T, Iwosaki T, et al. Clinicopathological study of canine oral epulides. J Vet Med Sci. 1999: p. 897-902. 6. Zhang W, Chen Y, An Z, et. al.. Reactive gingival lesions: A retrospective study of 2439 cases. Quintessence International. 2007: p. 103-110. 7. Fiani N, Verstraete FJ, Kass PH, Cox DP. Clinicopathologic characterization of odontogenic tumours and focal fibrous hyperplasia in 152 cases (1995-2005). JAVMA. 2011 February: p. 495-500. 8. Desoutter AV, Goldschmidt MH, Sanchez MD. Clinical and histologic features of 26 canine peripheral giant cell granulomas (formerly giant cell epulis). Vet Pathol. 2012 March: p. 1018-1023. 9. Valentine BA, Eckhaus MA. Peripheral giant cell granuloma (giant cell epulis) in two dogs. Vet Pathol. 1986: p. 340-341. 10. Motamedi MH, Eshghyar N, Jafari SM, al e. Peripheral and central giant cell granulomas of the jaws: A demographic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007: p. e39-343. 11. Pour MA, Rad M, Mojtahedi A. A survey of soft tissue tumor-like lesions of oral cavity: A clinicopathological study. Iranian Journal of Pathology. 2008: p. 81-87. 12. Kumar KA, Humayun S, Kumar BP, Rao JB. Reparative giant cell granuloma of the maxilla. Ann. Maxillofac Surg. 2011 Jul-Dec: p. 181-186. 13. Falaschini S, Ciavarella D, Mazanti R, et al. Peripheral giant cell granuloma: immunohistochemical analysis of different markers. Study of 3 cases. Avances en odontoestomatologia. 2007: p.189-196. 14. Flaitz C. Peripheral giant cell granuloma: a potentially aggressive lesion in children. Pediatric Dentistry. 2000: p. 232-233. 15. de Matos FR, Benevenuto TG, Nonaka CF, et. al.. Retrospective analysis of histopathologic features 288 cases or reactional lesions in gingiva and alveolar ridge. Applied immunohistochem mol morphol. 2013. 16. Penarrocha-Diago MA, Cervera-Ballester J, Maestre-Ferrin L, Penarrocha-Oltra D. Peripheral giant cell granuloma associated with dental implants: Clinical case and literature review. Journal of Oral Implantology. 2012: p. 527-532. 17. Sahingur SE, Cohen RE, Aguirre A. Esthetic management of peripheral giant cell granuloma. J Periodont. 2004: p. 487-492.
J VET DENT Vol. 32 No. 2 Summer 2015