Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
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Case report
Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update Dimitrios Konstantakis a,1, Panagiota Kosyfaki b, *,1, Harald Ebhardt c, Rainer Schmelzeisen a, Pit Jakob Voss a a b c
Department of Oral and Maxillofacial Surgery, (Head: Prof. Dr. Dr. Rainer Schmelzeisen), Albert-Ludwigs University Hospital Freiburg, Germany Specialist in Prosthodontics, Private Practice, Basel, Switzerland Oral Pathologist, Zentrum für Oralpathologie, Potsdam, Germany
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 8 October 2013 Accepted 17 October 2013
The dentinogenic ghost cell tumor (DGCT) is a relatively uncommon locally invasive neoplasm. This report describes the case of a 20-year-old Caucasian female patient who was diagnosed with an intraosseous DGCT in the left molar region of the mandible. Radiographic analysis revealed a well-circumscribed radiolucent lesion with focal radiopacity. Segmental resection of the mandible was performed by means of piezoelectric surgery. The histopathological examination yielded islands of odontogenic epithelium with clusters of ghost cells and dysplastic dentin, thus enabling the identification of the lesion as DGCT. Long-term surveillance of patients with intraosseous DGCTs is mandatory in order to detect in time any signs of recurrence. A literature update concerning intraosseous DGCTs is also provided. Ó 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Keywords: Dentinogenic Ghost cell Intraosseous Mandible Resection Tumor
1. Introduction The dentinogenic ghost cell tumor (DGCT) is considered to be an occasionally encountered odontogenic neoplasm with a locally invasive behavior (Praetorius and Ledesma-Montes, 2005). In accordance with the World Health Organization (WHO) the principal histologic characteristics of this lesion are strands and islands of ameloblastoma-like epithelial cells infiltrating into connective tissue layer, ghost cell formation and production of variable amounts of dysplastic dentin (Praetorius and Ledesma-Montes, 2005). The DGCT occurs predominantly in later life (Castro et al., 1997; Kim et al., 2001) and current literature reports on two DGCT variants: the intraosseous or central (Stone et al., 1998; Kasahara et al., 2002; Juneja and George, 2009; Singhaniya et al., 2009; Sun et al., 2009) and the extraosseous or peripheral variant (Castro et al., 1997; Iezzi et al., 2007; Candido et al., 2009; Kumar et al., 2010; Bello et al., 2012). Generally, intraosseous DGCT variants occur more frequently than the extraosseous ones (LedesmaMontes et al., 2008; Sun et al., 2009), they are more aggressive and thus necessitate extensive surgical resection (Kasahara et al., 2002; Sun et al., 2009). * Corresponding author. E-mail address: [email protected] (P. Kosyfaki). 1 The authors Dimitrios Konstantakis and Panagiota Kosyfaki contributed equally to this work.
The aim of this case report is to present the surgical clinical management of an intraosseous dentinogenic ghost cell tumor located in the left molar region of the mandible in a 20-year-old Caucasian female patient. In parallel, clinical and radiographic findings as well as histologic features are outlined and discussed along with a review of the existing literature.
2. Case report A 20-year-old Caucasian female patient was referred to the Department of Oral and Maxillofacial Surgery of Albert-Ludwigs University Hospital, Freiburg for evaluation of a lesion in the region of the lower left first and second molar and subsequently for further treatment. According to the documentation of patients’ attending maxillofacial surgeon a biopsy was already carried out in the region of the lesion two weeks ago. The histologic pattern of the lesion was diagnostic of DGCT. The medical history of the patient was non-contributory. The patient complained about mild pain in the left molar region of the mandible and difficulty in mastication. The extraoral examination of the same region revealed a minimal swelling, which was mildly tender and non-fluctuant. There was no evidence of lympadenopathy or neurological signs. Intraorally a mildly painful small-sized enlargement with firm consistency was palpated in the buccal region of the roots of the lower left first and second molar.
1010-5182/$ e see front matter Ó 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jcms.2013.10.011
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
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D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
Fig. 1. Preoperative panoramic radiograph.
The overlying mucosa was intact and in terms of surface texture and color it had a normal clinical appearance. The lower left first and second molars were especially sensitive to percussion, they were vital and showed no mobility. Mouth opening was unrestricted. The panoramic radiograph disclosed a well-circumscribed radiolucent lesion in the left molar region of the mandible (Fig. 1). The osteolytic lesion extended from the upper border of the inferior alveolar nerve canal and involved the lower left first and second molar, causing resorption of the distal root of the first molar and the mesial root of the second molar (Fig. 1). Three-dimensional radiographic analysis by means of cone beam computed tomography (CBCT) demonstrated the actual size and margins of the lesion and revealed concomitant expansion of the buccal and lingual cortical bone (Fig. 2a). Interestingly foci of prominent radiopacity dispersed within the radiolucent mass (Fig. 2a and b) were detected. Based on the clinical and radiographic findings as well as the previous histologic findings a provisional diagnosis of an intraosseous DGCT was made. It was decided that the patient be hospitalized and that segmental resection of the mandible be performed under general nasotracheal anesthesia. The surgical procedure involved segmental mandibular resection with en bloc excision of the left first and second molar by means of piezoelectric bone surgery (Fig. 3a and b). Mobilization of the alveolar inferior nerve and removal of the bone surrounding the nerve followed. Subsequently, bone edges were smoothed away
and wrapping of the nerve with an equine collagen membrane (Tissue Foil EÒ, Baxter, Resorba, Nürnberg, Germany) took place. In order to prevent mandibular fracture due to the substantial bone removal a nine-hole osteosynthesis plate was positioned and fixed with six angle stable screws (Synthes UniLOCK 2.0-System, DePuy Synthes, Johnson and Johnson, Oberdorf, Switzerland) (Fig. 3c). Wound closure was attained with absorbable collagen sponge as well as with resorbable and non-resorbable sutures. After surgery a panoramic radiograph was obtained (Fig. 4). The postoperative course was uneventful. Postoperative histopathological examination of the removed tissue showed a tumor mass, which was composed of connective tissue stroma and numerous odontogenic epithelial cell nests with an ameloblastomatous appearance. The epithelial cells were peripheral columnar cells with hyperchromatic and elongated nuclei with reversed polarization. The arrangement of the epithelial cells in the center of the lesion resembled stellate reticulum. Many clusters of ghost cells were seen, some of which demonstrated dystrophic calcification. Several epithelial cells were transforming into ghost cells. An immature and dysplastic dentinoid matrix was observed in close contact with the proliferative epithelial islands. No mitoses were noticed and there was no evidence of malignant transformation. Gingival tissues were not infiltrated by tumor cells. The lesion appeared to be completely removed. The final diagnosis was DGCT (Fig. 5a and b). After a period of six weeks following the initial surgery the reconstruction of the mandible by means of autogenous iliac bone grafting took place (Fig. 6) in order to enable the future placement of oral implants. A 3-month recall interval including routine clinical and radiographic examination was recommended in order to detect in time any signs of recurrence, metastasis or malignant transformation. The patient remained disease-free 3 months post surgery. 3. Discussion A recent article presented data on intraosseous DGCTs published during the period from 1972 to 2008 (Juneja and George, 2009). In contrast, the present work summarized current scientific knowledge and provided a literature update covering the time period between 2009 and September 2013 (Table 1). The PubMed (Medline) electronic database was explored and relevant dental articles in English were retrieved. In total fifteen cases, including the present case, one retrospective study presenting data on seven cases
Fig. 2. a) Preoperative CBCT view showing marked focal radiopacity and cortical bone expansion. b) Preoperative CBCT view showing marked focal radiopacity.
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
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Fig. 4. Postoperative panoramic radiograph after removal of the lesion and placement of the osteosynthesis plate.
Fig. 3. a) Segmental mandibular resection with en bloc excision of the left first and second molar. b) Macroscopic aspect of the lesion after removal. c) Placement and fixation of an osteosynthesis plate.
(Sun et al., 2009) and seven case reports (Juneja and George, 2009; Singhaniya et al., 2009; Yoon et al., 2010; Cicciu et al., 2012; Ramaglia et al., 2012; Biggs et al., 2013; Park et al., 2013) with histologically confirmed intraosseous DGCT lesions were found. On the other hand, no prospective studies or randomized controlled trials, which represent a high level of evidence, were identified. Although the patient of the present case was 20 years old, as in a similar clinical report (Yun et al., 2007), patients’ age was found to range from 12 years to 51 years with a mean age of 29 years (Table 1). According to other authors for the occurrence of the
intraosseous DGCT patient age can range from 12 years to 75 years with a mean age of 40 years (Juneja and George, 2009). Based on Table 1 eight lesions occurred in the mandible and eight lesions in the maxilla. It must be highlighted, that one research group dealt with two DGCT lesions localized bilaterally in the maxilla of the patient (Ramaglia et al., 2012). A clear predominance existed for male patients (eleven cases) over female patients (four cases). Between the occurrence of a DGCT and the medical history no correlation could be established, as in the present case and two other cases (Ramaglia et al., 2012; Park et al., 2013) the medical history was unremarkable, another patient was reported to be sickle cell carrier (Biggs et al., 2013) and specific information regarding the medical history of patient was not provided for the remaining cases (Juneja and George, 2009; Singhaniya et al., 2009; Sun et al., 2009; Yoon et al., 2010; Cicciu et al., 2012). In general, intraosseous DGCT variants are centrally located in the bone of the jaw (Stone et al., 1998) and show a predilection for the first molar to canine region (Buchner, 1991; Ledesma-Montes et al., 2008; Candido et al., 2009). In the present case the DGCT arose in the mandible in the region of the lower left first and second molars (Fig. 1), a location which has already been described in the literature (Singhaniya et al., 2009). Apart from the symptomatology of the present case, the clinical signs of intraosseous DGCT variants may also include expansion of the jaw, clinically visible swelling, obliteration of the maxillary sinus or infiltration of the soft tissues (Hong et al., 1991; Ellis, 1999; Kim et al., 2001; Sun et al., 2009). Swelling can be painful (Singhaniya et al., 2009; Yoon et al., 2010; Biggs et al., 2013) or painless (Kasahara et al., 2002; Yun et al., 2007; Juneja and George, 2009). In certain cases swelling can be accompanied by pus discharge (Juneja and George, 2009; Singhaniya et al., 2009), tooth displacement or mobility (Yoon et al., 2010; Park et al., 2013). Nevertheless, the DGCT can be asymptomatic and present itself as coincidental radiographic finding during routine patient examination (Ramaglia et al., 2012). The radiographic findings of the present case (Figs. 1, 2a and 2b) were consistent with previously diagnosed intraosseous DGCTs, which appeared radiographically as a mixed radiolucent/radiopaque (Juneja and George, 2009; Singhaniya et al., 2009; Yoon et al., 2010) or as a purely radiolucent lesions (Hong et al., 1991; Kim et al., 2001; Praetorius and Ledesma-Montes, 2005), depending on the amount of calcification. Lesions can be unilocular or multilocular with either well-defined or ill-demarcated margins (Ellis, 1999; Kim et al., 2001; Li and Yu, 2003; Singhaniya et al., 2009; Yoon et al., 2010). Root resorption (Park et al., 2013), as seen in the present case (Fig. 1), displacement of adjacent teeth (Park et al., 2013), resorption of associated impacted teeth
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
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D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
Fig. 6. Postoperative panoramic radiograph after reconstruction of the mandible by means of autogenous iliac bone grafting.
Fig. 5. a) An area of the tumor with stellate reticulum-like epithelial cells (on bottom left), aggregates of ghost cells (in the center) and dysplastic dentin (on the right) are observed (hematoxylin and eosin, [H&E], original magnification 10). b) Higher magnification shows numerous ghost cells and dysplastic dentin ([H&E], original magnification 20).
(Praetorius and Ledesma-Montes, 2005) as well as the presence of impacted teeth involved in the lesion (Juneja and George, 2009; Singhaniya et al., 2009) have also been radiographically observed. In the present case segmental mandibulectomy was performed (Fig. 3a). The reason was that intraosseous DGCT variants display typically a more aggressive behavior than extraosseous DGCT variants (Sun et al., 2009; Bello et al., 2012). Moreover, intraosseous DGCTs have the propensity to recur after treatment (Stone et al., 1998; Kasahara et al., 2002; Li and Yu, 2003; Sun et al., 2009; Biggs et al., 2013; Park et al., 2013). In one retrospective study (Sun et al., 2009), after local curettage a high rate of recurrences has been registered during the follow-up period, that rendered additional surgical retreatment indispensable (Table 1). Furthermore multiple recurrences have been linked with malignant transformation of the DGCT (Li and Yu, 2003; Li and Gao, 2009). Interestingly, apart from recurrence of an intraosseous DGCT on the primary site, distant metastasis of the DGCT to the graft donor site has been recently reported (Park et al., 2013). Thus, nowadays the preferred mode of treatment of intraosseous DGCT variants consists in extensive bone resection (Juneja and George, 2009; Singhaniya et al., 2009; Sun et al., 2009; Cicciu et al., 2012; Park et al., 2013) with adequate safety margins (Kasahara et al., 2002; Sun et al., 2009; Yoon et al., 2010), especially in cases of radiologically
poorly-defined DGCTs (Sun et al., 2009). In cases where bone grafting is necessary, the tumor removal should take place first and then the graft bone should be harvested to avert hematogenous spreading of tumor seeds and contamination of the initial donor site (Park et al., 2013). For patients with recurrent intraosseous DGCTs a close long-term surveillance is highly recommended (Yoon et al., 2010). Yet, only relatively short-term data on follow-up intervals exist up to now (Table 1). On the other hand, the majority of extraosseous DGCTs appear as peripheral lesions in the form of exophytic nodules confined to the gingival mucosa in dentate patients or the alveolar mucosa in edentulous patients (Stone et al., 1998; Sun et al., 2009; Bello et al., 2012). Extraosseous DGCT variants affect mainly the anterior part of the jaw (Candido et al., 2009; Bello et al., 2012) and they are usually asymptomatic (Candido et al., 2009). No changes or only mild erosion of the bone are the general radiographic features of extraosseous DGCTs and saucerization of the underlying cortical bones has also been noticed in some cases (Ellis, 1999; Kim et al., 2001; Praetorius and Ledesma-Montes, 2005; Bello et al., 2012). Conservative localized excision is the treatment of choice for extraosseous DGCT variants (Sun et al., 2009; Bello et al., 2012). Generally after treatment there is no evidence of recurrence (Bello et al., 2012). As far as the age is concerned, there seems to be a relatively wide range of age distribution from 41 to 83 years, with 62 years being the average age for occurrence of the extraosseous DGCT (Candido et al., 2009). According to the WHO (Praetorius and Ledesma-Montes, 2005) the DGCT together with the calcifying cystic odontogenic tumor (CCOT) and the ghost cell odontogenic carcinoma (GCOC) comprise the complex of odontogenic ghost cell tumors. Based on a research of 215 CCOTs (Buchner, 1991), CCOTs represent 1%e2% of all odontogenic tumors and of all CCOTs only 2%e14% are solid tumors (Buchner, 1991; Kasahara et al., 2002; Sun et al., 2009), which were considered to be DGCTs. Due to the similarity of histologic features between the DGCT and the CCOT (Castro et al., 1997; Kim et al., 2001), it is believed that the DGCT is actually the solid, clinicopathological tumor variant of the CCOT (Kim et al., 2001; Sun et al., 2009), which was first described by Gorlin et al. (Gorlin et al., 1962). DGCTs are extremely rare and only few published cases exist to date (Kim et al., 2001; Iezzi et al., 2007). Thus, there is a lack of specific clinical guidelines (Kim et al., 2001; Li and Yu, 2003) and due to the fact that the DGCT can clinically and/or radiographically resemble other odontogenic tumors, the definitive diagnosis relies principally on the histopathological analysis of the lesion (Iezzi et al., 2007). In the present case the histopathological analysis of the DGCT revealed sheets and rounded islands of odontogenic epithelium, surrounded by mature fibrous connective tissue, which is consistent with previous literature (Praetorius and Ledesma-Montes, 2005; Ledesma-Montes et al., 2008). It has been reported, that
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
Research group
N
Age
Gender
Medical history
DGCT location
Clinical signs
Radiographic findings
Initial treatment
RC1
FU1
Retreatment
RC2
FU2
(Present case)
1
20
f
Unremarkable
Mandible
0
3 mo
e
e
e
1
27
m
Sickle cell trait
Maxilla
Well-defined radiolucent/ radiopaque lesion Unilocular lesion
Segmental resection
(Biggs et al., 2013)
Mildly painful swelling Painful swelling
1
3 mo
Hemimaxillectomy
0
12 mo
(Park et al., 2013)
1
25
f
Unremarkable
Mandible
Well-defined multilocular radiolucent lesion
1
2 ys
Partial mandibulectomy
0
3 mo
(Cicciu et al., 2012) (Ramaglia et al., 2012)
1 1
18 12
m f
n.s. Unremarkable
Mandible Maxilla
(Yoon et al., 2010)
1
46
m
n.s.
Maxilla
(Juneja and George, 2009)
1
14
f
n.s.
Mandible
(Singhaniya et al., 2009)
1
21
m
n.s.
Mandible
Painful swelling Tooth dislocation Tooth mobility Swelling No swelling No tenderness Painful swelling Tooth extrusion with slight mobility Painless swelling Pus discharge Painful swelling Pus discharge
Enucleation and after 6 weeks Medial maxillectomy Partial mandibulectomy
(Sun et al., 2009)
1
37
m
n.s.
Maxilla
Bone expansion
1
51
m
n.s.
Maxilla
n.s.
1
43
m
n.s.
Mandible
Slight pain numbness
n.s.
1
42
m
n.s.
Maxilla
n.s.
1
29
m
n.s.
Mandible
n.s.
1
36
m
n.s.
Mandible
n.s.
Unilocular mixed radiolucent/radiopaque lesion Irregular lesion borders, calcified lumps n.s.
1
18
m
n.s.
Maxilla
n.s.
n.s.
Unilocular radiolucent lesion Two well-defined radiolucent/ radiopaque lesions Ill-defined mixed radiolucent/ radiopaque lesion
Hemimandibulectomy Enucleation Local curettage Conservative surgery
0 0
9 mo 12 mo
e e
e 0
e 18 mo
0
9 mo
e
e
e
Mixed radiolucent radiopaque lesion with impacted 3d molar Unilocular well-defined radiolucent/radiopaque lesion with impacted 3d molar Bone expansion Cortical Bone resorption n.s.
Segmental resection
0
6 mo
e
e
e
Segmental mandibulectomy
0
9 mo
e
e
e
Local curettage
2
n.s.
0
7 mo
Aggressive Local resection Local curettage, Local resection, Segmental resection Local curettage
0
n.s.
Subtotal maxillectomy e
0
14 mo
4
n.s.
Aggressive local resection
0
15 mo
2
n.s.
Partial maxillectomy
0
25 mo
Local curettage
2
n.s.
Segmental resection
0
29 mo
Local curettage
1
n.s.
0
99 mo
Aggressive Local resection
0
n.s.
Aggressive local resection e
0
105 mo
D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
Table 1 Overview of published literature from 2009 to September 2013 on intraosseous histologically confirmed DGCTs lesions.
DGCT: dentinogenic ghost cell tumor, N: number of patients, RC1: number of recurrences following initial treatment, FU1: follow-up time after initial treatment. RC2: number of recurrences following retreatment, FU2: follow-up time after retreatment. m: male, f: female, ys: years, mo: months, n.s.: not specified, e : not performed.
5
6
D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
the epithelium of the tumor islands exhibits an ameloblastoma-like basal cell layer that sometimes can show nuclear polarization (Ledesma-Montes et al., 2008). Furthermore, in the central part of the ameloblastomatous islands, tissue resembling the stellate reticulum of the enamel organ can be identified (Buchner, 1991; Ledesma-Montes et al., 2008). These observations are in accordance with the histologic findings of the present case (Fig. 5a). The presence of ghost cells was ascertained in the present lesion (Fig. 5a and b). Groups of ghost cells or individual ghost cells constitute the distinctive microscopic characteristic of the DGCT (Kim et al., 2001; Ledesma-Montes et al., 2008; Yoon et al., 2010). Ghost cells, are thought to derive either from transformation of epithelial cells (Hong et al., 1991; Kim et al., 2001; Sun et al., 2009; Bello et al., 2012; Ramaglia et al., 2012), degeneration of epithelial cells (Bello et al., 2012) or secondary calcification of metaplastic epithelial cells due to ischemia (Bello et al., 2012). For several researchers ghost cells represent an abnormal or incomplete keratinization process (Fejerskov and Krogh, 1972). In detail, it is has been suggested that, the keratin layer might suffer dystrophic calcification (Fejerskov and Krogh, 1972; Singhaniya et al., 2009; Sun et al., 2009), which can activate a foreign-body reaction in the fibrous tissue wall (Singhaniya et al., 2009). Coagulative necrosis has also been suggested by other authors as origin of the ghost cells (Hong et al., 1991). It must be stressed, that the presence of ghost cells alone is not diagnostic, since ghost cells can be also identified in other neoplasms (Ellis, 1999; Kim et al., 2001). However, ghost cells are a basic prerequisite for the diagnosis of the DGCT (Ramaglia et al., 2012). Dysplastic dentine in varying amounts was observed in the present DGCT (Fig. 5a and b). This juxtaepithelial dentinoid ground substance has been described as an osteoid-like atypical dysplastic dentin containing widely separated cell bodies and collagen, which however lacks the normal tubular characteristic structure of dentin (Stone et al., 1998; Ellis, 1999; Kim et al., 2001). Dysplastic dentine appears as an amorphous irregular eosinophilic mass within the connective tissue and adjacent to the proliferation of the odontogenic epithelial islands (Kim et al., 2001; Praetorius and LedesmaMontes, 2005). Different theories have been developed regarding the origin of dysplastic dentine. Based on these, dysplastic dentine could possibly originate i) from the inductive effect of the odontogenic epithelial component of the tumor (Bello et al., 2012) ii) from the dental lamina remnants (rest of Serres) (Bello et al., 2012) iii) from a metaplastic alteration in the connective tissue stroma without the involvement of granulation tissue (Bello et al., 2012) or iv) from the inductive effect of ghost cells on granulation tissue to lay down osteoid and its subsequent calcification (Singhaniya et al., 2009; Bello et al., 2012). A diagnosis of a CCOT was excluded in the present case because of the very high amount of histologically confirmed dentinoid in the present case, which accounted for the solid structure of a DGCT, in contrast to a cystic structure of a CCOT (Li and Gao, 2009). The presence of dysplastic dentin and large amount of ghost cells seen in the present case differentiated histologically the present DGCT from ameloblastoma (Praetorius and Ledesma-Montes, 2005; Iezzi et al., 2007; Li and Gao, 2009; Singhaniya et al., 2009; Sun et al., 2009) and odontoameloblastoma (Li and Gao, 2009). On the other hand, the “ghost” cells seen in the DGCT resemble closely the analog “shadow” cells present in pilomatrixoma (Stone et al., 1998; Mundinger et al., 2011). Because multiple pilomatrixomas may be linked to various syndromes and rare genetic diseases (Kolomvos et al., 2012) and the present patient had an unremarkable medical history, the possibility of a pilomatrixoma was not considered. Furthermore, lack of ghost cells and dentinoid in basaloid salivary gland tumors, including basal cell adenoma, basal cell
adenocarcinoma, cellular pleomorphic adenoma, squamous cell carcinoma or basaloid squamous cell carcinoma allowed their accurate separation from the present DGCT (Stone et al., 1998). Because the lesion of the present case had a radiographically well-defined pattern, odontogenic malignancies such as ameloblastic fibro-odonto/dentino sarcoma and non-odontogenic malignancies including chondrosarcoma (Takahama et al., 2012), osteosarcoma (Kämmerer et al., 2012) and metastatic tumors, which appear as ill-defined mixed radiolucent/radioopaque lesions (Yoon et al., 2010) were not taken into consideration. The possibility of chronic suppurative osteomylelitis was excluded due to absence of lymphadenopathy, fever, leukocytosis and predisposing conditions such as trauma, Paget’s disease or diabetes (Yoon et al., 2010). The GCOC is the malignant counterpart of the DGCT and the CCOT (Yoon et al., 2010) and combines cytological and architectural histologic features of malignancy (Yun et al., 2007) that distinguish it from the CCOT or the DGCT (Li and Yu, 2003). These are pronounced mitotic activity, areas of tumor necrosis, nuclear atypia, cytoplasmic pleomorphism and hyperchromatism (Stone et al., 1998; Kim et al., 2001; Li and Yu, 2003). Due to lack of these characteristics in the present case, a diagnosis of a GCOC could not be made. It is worth mentioning, that the GCOC demonstrates a locally aggressive behavior and is characterized by an infiltrative growth pattern with extension into soft tissues (Li and Yu, 2003; Yun et al., 2007; Ledesma-Montes et al., 2008). Distant metastases are reported to be uncommon (Kim et al., 2001; Goldenberg et al., 2004), however they do occur (Stone et al., 1998; Kasahara et al., 2002; Li and Yu, 2003). In such cases wide surgical excision with histologically clean margins is recommended (Goldenberg et al., 2004). Yet, the effectiveness of postoperative radiation therapy with or without adjunctive chemotherapy is questionable (Kim et al., 2001; Goldenberg et al., 2004). 4. Conclusion The present case report illustrated the surgical treatment of an intraosseous DGCT in a 20-year-old patient and provided an insight into the clinical, radiographic and histologic findings of the case. Even if intraosseous DGCTs are rare, the general dental practitioner should not exclude the possibility of encountering a case of DGCT in the daily clinical practice. A thorough clinical and radiographic examination can prevent under-diagnosis of this specific entity. In time referral of the patient for biopsy and histologic analysis, surgical intervention and a long-term follow-up are crucial for the successful treatment of the patient. Conflict of interest The authors declare no conflicts of interest and confirm that no financial and/or personal relationships with other people or organizations exist, that could inappropriately influence this work. Also the authors declare no sources of support in the form of grants. Acknowledgment The authors would like to thank Prof. Dr. Hans-Anton Lehr, Institut für Pathologie im Medizin Campus Bodensee, Friedrichshafen, Germany for his assistance with Fig. 5a and b. References Bello IO, Qannam A, Al-Zahrani A, AlDosari A: Peripheral dentinogenic ghost cell tumor: report of a case and literature review. Int J Surg Pathol 20: 494e499, 2012 Biggs TC, Hayes SM, Harries PG, Salib RJ: Maxillary dentinogenic ghost cell tumour. Ann R Coll Surg Engl 95: 63e65, 2013
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7 Buchner A: The central (intraosseous) calcifying odontogenic cyst: an analysis of 215 cases. J Oral Maxillofac Surg 49: 330e339, 1991 Candido GA, Viana KA, Watanabe S, Vencio EF: Peripheral dentinogenic ghost cell tumor: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108: e86e90, 2009 Castro WH, de Aguiar MC, Gomez RS: Peripheral dentinogenic ghost-cell tumor: a case report. Quintessence Int 28: 45e47, 1997 Cicciu M, Herford AS, Stoffella E, Cervino G, Cicciu D: Protein-signaled guided bone regeneration using titanium Mesh and Rh-BMP2 in oral surgery: a case report involving left mandibular reconstruction after tumor resection. Open Dent J 6: 51e55, 2012 Ellis GL: Odontogenic ghost cell tumor. Semin Diagn Pathol 16: 288e292, 1999 Fejerskov O, Krogh J: The calcifying ghost cell odontogenic tumor - or the calcifying odontogenic cyst. J Oral Pathol 1: 273e287, 1972 Goldenberg D, Sciubba J, Tufano RP: Odontogenic ghost cell carcinoma. Head Neck 26: 378e381, 2004 Gorlin RJ, Pindborg JJ, Odont, Clausen FP, Vickers RA: The calcifying odontogenic cystea possible analogue of the cutaneous calcifying epithelioma of Malherbe. An analysis of fifteen cases. Oral Surg Oral Med Oral Pathol 15: 1235e1243, 1962 Hong SP, Ellis GL, Hartman KS: Calcifying odontogenic cyst. A review of ninety-two cases with reevaluation of their nature as cysts or neoplasms, the nature of ghost cells, and subclassification. Oral Surg Oral Med Oral Pathol 72: 56e64, 1991 Iezzi G, Rubini C, Fioroni M, Piattelli A: Peripheral dentinogenic ghost cell tumor of the gingiva. J Periodontol 78: 1635e1638, 2007 Juneja M, George J: Dentinogenic ghost cell tumor: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107: e17e22, 2009 Kämmerer PW, Shabazfar N, Vorkhshori Makoie N, Moergel M, Al-Nawas B: Clinical, therapeutic and prognostic features of osteosarcoma of the jaws - experience of 36 cases. J Craniomaxillofac Surg 40: 541e548, 2012 Kasahara K, Iizuka T, Kobayashi I, Totsuka Y, Kohgo T: A recurrent case of odontogenic ghost cell tumour of the mandible. Int J Oral Maxillofac Surg 31: 684e687, 2002 Kim HJ, Choi SK, Lee CJ, Suh CH: Aggressive epithelial odontogenic ghost cell tumor in the mandible: CT and MR imaging findings. AJNR Am J Neuroradiol 22: 175e 179, 2001 Kolomvos N, Kamperos G, Theologie-Lygidakis N, Chrysomali E, Iatrou I: Hybrid odontogenic ghost cell tumor and cutaneous pilomatrixoma: a highly unusual coexistence. J Craniofac Surg 23: 1188e1191, 2012
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Kumar U, Vij H, Vij R, Kharbanda J, Aparna I, Radhakrishnan R: Dentinogenic ghost cell tumor of the peripheral variant mimicking epulis. Int J Dent 2010: 519494, 2010 Ledesma-Montes C, Gorlin RJ, Shear M, Prae Torius F, Mosqueda-Taylor A, Altini M, et al: International collaborative study on ghost cell odontogenic tumours: calcifying cystic odontogenic tumour, dentinogenic ghost cell tumour and ghost cell odontogenic carcinoma. J Oral Pathol Med 37: 302e308, 2008 Li BB, Gao Y: Ghost cell odontogenic carcinoma transformed from a dentinogenic ghost cell tumor of maxilla after multiple recurrences. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107: 691e695, 2009 Li TJ, Yu SF: Clinicopathologic spectrum of the so-called calcifying odontogenic cysts: a study of 21 intraosseous cases with reconsideration of the terminology and classification. Am J Surg Pathol 27: 372e384, 2003 Mundinger GS, Steinbacher DM, Bishop JA, Tufaro AP: Giant pilomatricoma involving the parotid: case report and literature review. J Craniomaxillofac Surg 39: 519e524, 2011 Park HR, Min JH, Huh KH, Yi WJ, Heo MS, Lee SS, et al: Distant metastasis of intraosseous dentinogenic ghost cell tumour to the donor site of a bone graft. Dentomaxillofac Radiol 42. http://dx.doi.org/10.1259/dmfr.20120172, 2013 Praetorius F, Ledesma-Montes C: Calcifying odontogenic tumor and dentinogenic ghost cell tumor. In: Barnes L, Evenson JW, Reinchart P, Sidranksy D (eds), World Health Organization Classification of Tumors. Pathology and genetics of head and heck Tumors. Lyon, France: IARC Press, 313e314, 2005 Ramaglia L, Esposito D, Bruno MP, Siano M: Dentinogenic ghost cell tumor: histopathology and clinical aspects in pediatric age. Minerva Stomatol 61: 509e517, 2012 Singhaniya SB, Barpande SR, Bhavthankar JD: Dentinogenic ghost cell tumor. J Oral Maxillofac Pathol 13: 97e100, 2009 Stone CH, Gaba AR, Benninger MS, Zarbo RJ: Odontogenic ghost cell tumor: a case report with cytologic findings. Diagn Cytopathol 18: 199e203, 1998 Sun G, Huang X, Hu Q, Yang X, Tang E: The diagnosis and treatment of dentinogenic ghost cell tumor. Int J Oral Maxillofac Surg 38: 1179e1183, 2009 Takahama Jr A, Alves Fde A, Prado FO, Lopes MA, Kowalski LP: Chondrosarcoma of the maxilla: report of two cases with different behaviours. J Craniomaxillofac Surg 40: e71e74, 2012 Yoon HJ, Jayasooriya P, Hong SD, Lee JI, Hong SP: Clinico-pathologic conference: case 5. Dentinogenic ghost cell tumour (DGCT). Head Neck Pathol 4: 347e350, 2010 Yun KI, Lee JA, Lee YS, Kim TJ, Park JU: Dentinogenic ghost cell tumors. J Oral Maxillofac Surg 65: 1816e1819, 2007
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Case report
Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update Dimitrios Konstantakis a,1, Panagiota Kosyfaki b, *,1, Harald Ebhardt c, Rainer Schmelzeisen a, Pit Jakob Voss a a b c
Department of Oral and Maxillofacial Surgery, (Head: Prof. Dr. Dr. Rainer Schmelzeisen), Albert-Ludwigs University Hospital Freiburg, Germany Specialist in Prosthodontics, Private Practice, Basel, Switzerland Oral Pathologist, Zentrum für Oralpathologie, Potsdam, Germany
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 8 October 2013 Accepted 17 October 2013
The dentinogenic ghost cell tumor (DGCT) is a relatively uncommon locally invasive neoplasm. This report describes the case of a 20-year-old Caucasian female patient who was diagnosed with an intraosseous DGCT in the left molar region of the mandible. Radiographic analysis revealed a well-circumscribed radiolucent lesion with focal radiopacity. Segmental resection of the mandible was performed by means of piezoelectric surgery. The histopathological examination yielded islands of odontogenic epithelium with clusters of ghost cells and dysplastic dentin, thus enabling the identification of the lesion as DGCT. Long-term surveillance of patients with intraosseous DGCTs is mandatory in order to detect in time any signs of recurrence. A literature update concerning intraosseous DGCTs is also provided. Ó 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Keywords: Dentinogenic Ghost cell Intraosseous Mandible Resection Tumor
1. Introduction The dentinogenic ghost cell tumor (DGCT) is considered to be an occasionally encountered odontogenic neoplasm with a locally invasive behavior (Praetorius and Ledesma-Montes, 2005). In accordance with the World Health Organization (WHO) the principal histologic characteristics of this lesion are strands and islands of ameloblastoma-like epithelial cells infiltrating into connective tissue layer, ghost cell formation and production of variable amounts of dysplastic dentin (Praetorius and Ledesma-Montes, 2005). The DGCT occurs predominantly in later life (Castro et al., 1997; Kim et al., 2001) and current literature reports on two DGCT variants: the intraosseous or central (Stone et al., 1998; Kasahara et al., 2002; Juneja and George, 2009; Singhaniya et al., 2009; Sun et al., 2009) and the extraosseous or peripheral variant (Castro et al., 1997; Iezzi et al., 2007; Candido et al., 2009; Kumar et al., 2010; Bello et al., 2012). Generally, intraosseous DGCT variants occur more frequently than the extraosseous ones (LedesmaMontes et al., 2008; Sun et al., 2009), they are more aggressive and thus necessitate extensive surgical resection (Kasahara et al., 2002; Sun et al., 2009). * Corresponding author. E-mail address: [email protected] (P. Kosyfaki). 1 The authors Dimitrios Konstantakis and Panagiota Kosyfaki contributed equally to this work.
The aim of this case report is to present the surgical clinical management of an intraosseous dentinogenic ghost cell tumor located in the left molar region of the mandible in a 20-year-old Caucasian female patient. In parallel, clinical and radiographic findings as well as histologic features are outlined and discussed along with a review of the existing literature.
2. Case report A 20-year-old Caucasian female patient was referred to the Department of Oral and Maxillofacial Surgery of Albert-Ludwigs University Hospital, Freiburg for evaluation of a lesion in the region of the lower left first and second molar and subsequently for further treatment. According to the documentation of patients’ attending maxillofacial surgeon a biopsy was already carried out in the region of the lesion two weeks ago. The histologic pattern of the lesion was diagnostic of DGCT. The medical history of the patient was non-contributory. The patient complained about mild pain in the left molar region of the mandible and difficulty in mastication. The extraoral examination of the same region revealed a minimal swelling, which was mildly tender and non-fluctuant. There was no evidence of lympadenopathy or neurological signs. Intraorally a mildly painful small-sized enlargement with firm consistency was palpated in the buccal region of the roots of the lower left first and second molar.
1010-5182/$ e see front matter Ó 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jcms.2013.10.011
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
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D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
Fig. 1. Preoperative panoramic radiograph.
The overlying mucosa was intact and in terms of surface texture and color it had a normal clinical appearance. The lower left first and second molars were especially sensitive to percussion, they were vital and showed no mobility. Mouth opening was unrestricted. The panoramic radiograph disclosed a well-circumscribed radiolucent lesion in the left molar region of the mandible (Fig. 1). The osteolytic lesion extended from the upper border of the inferior alveolar nerve canal and involved the lower left first and second molar, causing resorption of the distal root of the first molar and the mesial root of the second molar (Fig. 1). Three-dimensional radiographic analysis by means of cone beam computed tomography (CBCT) demonstrated the actual size and margins of the lesion and revealed concomitant expansion of the buccal and lingual cortical bone (Fig. 2a). Interestingly foci of prominent radiopacity dispersed within the radiolucent mass (Fig. 2a and b) were detected. Based on the clinical and radiographic findings as well as the previous histologic findings a provisional diagnosis of an intraosseous DGCT was made. It was decided that the patient be hospitalized and that segmental resection of the mandible be performed under general nasotracheal anesthesia. The surgical procedure involved segmental mandibular resection with en bloc excision of the left first and second molar by means of piezoelectric bone surgery (Fig. 3a and b). Mobilization of the alveolar inferior nerve and removal of the bone surrounding the nerve followed. Subsequently, bone edges were smoothed away
and wrapping of the nerve with an equine collagen membrane (Tissue Foil EÒ, Baxter, Resorba, Nürnberg, Germany) took place. In order to prevent mandibular fracture due to the substantial bone removal a nine-hole osteosynthesis plate was positioned and fixed with six angle stable screws (Synthes UniLOCK 2.0-System, DePuy Synthes, Johnson and Johnson, Oberdorf, Switzerland) (Fig. 3c). Wound closure was attained with absorbable collagen sponge as well as with resorbable and non-resorbable sutures. After surgery a panoramic radiograph was obtained (Fig. 4). The postoperative course was uneventful. Postoperative histopathological examination of the removed tissue showed a tumor mass, which was composed of connective tissue stroma and numerous odontogenic epithelial cell nests with an ameloblastomatous appearance. The epithelial cells were peripheral columnar cells with hyperchromatic and elongated nuclei with reversed polarization. The arrangement of the epithelial cells in the center of the lesion resembled stellate reticulum. Many clusters of ghost cells were seen, some of which demonstrated dystrophic calcification. Several epithelial cells were transforming into ghost cells. An immature and dysplastic dentinoid matrix was observed in close contact with the proliferative epithelial islands. No mitoses were noticed and there was no evidence of malignant transformation. Gingival tissues were not infiltrated by tumor cells. The lesion appeared to be completely removed. The final diagnosis was DGCT (Fig. 5a and b). After a period of six weeks following the initial surgery the reconstruction of the mandible by means of autogenous iliac bone grafting took place (Fig. 6) in order to enable the future placement of oral implants. A 3-month recall interval including routine clinical and radiographic examination was recommended in order to detect in time any signs of recurrence, metastasis or malignant transformation. The patient remained disease-free 3 months post surgery. 3. Discussion A recent article presented data on intraosseous DGCTs published during the period from 1972 to 2008 (Juneja and George, 2009). In contrast, the present work summarized current scientific knowledge and provided a literature update covering the time period between 2009 and September 2013 (Table 1). The PubMed (Medline) electronic database was explored and relevant dental articles in English were retrieved. In total fifteen cases, including the present case, one retrospective study presenting data on seven cases
Fig. 2. a) Preoperative CBCT view showing marked focal radiopacity and cortical bone expansion. b) Preoperative CBCT view showing marked focal radiopacity.
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D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
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Fig. 4. Postoperative panoramic radiograph after removal of the lesion and placement of the osteosynthesis plate.
Fig. 3. a) Segmental mandibular resection with en bloc excision of the left first and second molar. b) Macroscopic aspect of the lesion after removal. c) Placement and fixation of an osteosynthesis plate.
(Sun et al., 2009) and seven case reports (Juneja and George, 2009; Singhaniya et al., 2009; Yoon et al., 2010; Cicciu et al., 2012; Ramaglia et al., 2012; Biggs et al., 2013; Park et al., 2013) with histologically confirmed intraosseous DGCT lesions were found. On the other hand, no prospective studies or randomized controlled trials, which represent a high level of evidence, were identified. Although the patient of the present case was 20 years old, as in a similar clinical report (Yun et al., 2007), patients’ age was found to range from 12 years to 51 years with a mean age of 29 years (Table 1). According to other authors for the occurrence of the
intraosseous DGCT patient age can range from 12 years to 75 years with a mean age of 40 years (Juneja and George, 2009). Based on Table 1 eight lesions occurred in the mandible and eight lesions in the maxilla. It must be highlighted, that one research group dealt with two DGCT lesions localized bilaterally in the maxilla of the patient (Ramaglia et al., 2012). A clear predominance existed for male patients (eleven cases) over female patients (four cases). Between the occurrence of a DGCT and the medical history no correlation could be established, as in the present case and two other cases (Ramaglia et al., 2012; Park et al., 2013) the medical history was unremarkable, another patient was reported to be sickle cell carrier (Biggs et al., 2013) and specific information regarding the medical history of patient was not provided for the remaining cases (Juneja and George, 2009; Singhaniya et al., 2009; Sun et al., 2009; Yoon et al., 2010; Cicciu et al., 2012). In general, intraosseous DGCT variants are centrally located in the bone of the jaw (Stone et al., 1998) and show a predilection for the first molar to canine region (Buchner, 1991; Ledesma-Montes et al., 2008; Candido et al., 2009). In the present case the DGCT arose in the mandible in the region of the lower left first and second molars (Fig. 1), a location which has already been described in the literature (Singhaniya et al., 2009). Apart from the symptomatology of the present case, the clinical signs of intraosseous DGCT variants may also include expansion of the jaw, clinically visible swelling, obliteration of the maxillary sinus or infiltration of the soft tissues (Hong et al., 1991; Ellis, 1999; Kim et al., 2001; Sun et al., 2009). Swelling can be painful (Singhaniya et al., 2009; Yoon et al., 2010; Biggs et al., 2013) or painless (Kasahara et al., 2002; Yun et al., 2007; Juneja and George, 2009). In certain cases swelling can be accompanied by pus discharge (Juneja and George, 2009; Singhaniya et al., 2009), tooth displacement or mobility (Yoon et al., 2010; Park et al., 2013). Nevertheless, the DGCT can be asymptomatic and present itself as coincidental radiographic finding during routine patient examination (Ramaglia et al., 2012). The radiographic findings of the present case (Figs. 1, 2a and 2b) were consistent with previously diagnosed intraosseous DGCTs, which appeared radiographically as a mixed radiolucent/radiopaque (Juneja and George, 2009; Singhaniya et al., 2009; Yoon et al., 2010) or as a purely radiolucent lesions (Hong et al., 1991; Kim et al., 2001; Praetorius and Ledesma-Montes, 2005), depending on the amount of calcification. Lesions can be unilocular or multilocular with either well-defined or ill-demarcated margins (Ellis, 1999; Kim et al., 2001; Li and Yu, 2003; Singhaniya et al., 2009; Yoon et al., 2010). Root resorption (Park et al., 2013), as seen in the present case (Fig. 1), displacement of adjacent teeth (Park et al., 2013), resorption of associated impacted teeth
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
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D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
Fig. 6. Postoperative panoramic radiograph after reconstruction of the mandible by means of autogenous iliac bone grafting.
Fig. 5. a) An area of the tumor with stellate reticulum-like epithelial cells (on bottom left), aggregates of ghost cells (in the center) and dysplastic dentin (on the right) are observed (hematoxylin and eosin, [H&E], original magnification 10). b) Higher magnification shows numerous ghost cells and dysplastic dentin ([H&E], original magnification 20).
(Praetorius and Ledesma-Montes, 2005) as well as the presence of impacted teeth involved in the lesion (Juneja and George, 2009; Singhaniya et al., 2009) have also been radiographically observed. In the present case segmental mandibulectomy was performed (Fig. 3a). The reason was that intraosseous DGCT variants display typically a more aggressive behavior than extraosseous DGCT variants (Sun et al., 2009; Bello et al., 2012). Moreover, intraosseous DGCTs have the propensity to recur after treatment (Stone et al., 1998; Kasahara et al., 2002; Li and Yu, 2003; Sun et al., 2009; Biggs et al., 2013; Park et al., 2013). In one retrospective study (Sun et al., 2009), after local curettage a high rate of recurrences has been registered during the follow-up period, that rendered additional surgical retreatment indispensable (Table 1). Furthermore multiple recurrences have been linked with malignant transformation of the DGCT (Li and Yu, 2003; Li and Gao, 2009). Interestingly, apart from recurrence of an intraosseous DGCT on the primary site, distant metastasis of the DGCT to the graft donor site has been recently reported (Park et al., 2013). Thus, nowadays the preferred mode of treatment of intraosseous DGCT variants consists in extensive bone resection (Juneja and George, 2009; Singhaniya et al., 2009; Sun et al., 2009; Cicciu et al., 2012; Park et al., 2013) with adequate safety margins (Kasahara et al., 2002; Sun et al., 2009; Yoon et al., 2010), especially in cases of radiologically
poorly-defined DGCTs (Sun et al., 2009). In cases where bone grafting is necessary, the tumor removal should take place first and then the graft bone should be harvested to avert hematogenous spreading of tumor seeds and contamination of the initial donor site (Park et al., 2013). For patients with recurrent intraosseous DGCTs a close long-term surveillance is highly recommended (Yoon et al., 2010). Yet, only relatively short-term data on follow-up intervals exist up to now (Table 1). On the other hand, the majority of extraosseous DGCTs appear as peripheral lesions in the form of exophytic nodules confined to the gingival mucosa in dentate patients or the alveolar mucosa in edentulous patients (Stone et al., 1998; Sun et al., 2009; Bello et al., 2012). Extraosseous DGCT variants affect mainly the anterior part of the jaw (Candido et al., 2009; Bello et al., 2012) and they are usually asymptomatic (Candido et al., 2009). No changes or only mild erosion of the bone are the general radiographic features of extraosseous DGCTs and saucerization of the underlying cortical bones has also been noticed in some cases (Ellis, 1999; Kim et al., 2001; Praetorius and Ledesma-Montes, 2005; Bello et al., 2012). Conservative localized excision is the treatment of choice for extraosseous DGCT variants (Sun et al., 2009; Bello et al., 2012). Generally after treatment there is no evidence of recurrence (Bello et al., 2012). As far as the age is concerned, there seems to be a relatively wide range of age distribution from 41 to 83 years, with 62 years being the average age for occurrence of the extraosseous DGCT (Candido et al., 2009). According to the WHO (Praetorius and Ledesma-Montes, 2005) the DGCT together with the calcifying cystic odontogenic tumor (CCOT) and the ghost cell odontogenic carcinoma (GCOC) comprise the complex of odontogenic ghost cell tumors. Based on a research of 215 CCOTs (Buchner, 1991), CCOTs represent 1%e2% of all odontogenic tumors and of all CCOTs only 2%e14% are solid tumors (Buchner, 1991; Kasahara et al., 2002; Sun et al., 2009), which were considered to be DGCTs. Due to the similarity of histologic features between the DGCT and the CCOT (Castro et al., 1997; Kim et al., 2001), it is believed that the DGCT is actually the solid, clinicopathological tumor variant of the CCOT (Kim et al., 2001; Sun et al., 2009), which was first described by Gorlin et al. (Gorlin et al., 1962). DGCTs are extremely rare and only few published cases exist to date (Kim et al., 2001; Iezzi et al., 2007). Thus, there is a lack of specific clinical guidelines (Kim et al., 2001; Li and Yu, 2003) and due to the fact that the DGCT can clinically and/or radiographically resemble other odontogenic tumors, the definitive diagnosis relies principally on the histopathological analysis of the lesion (Iezzi et al., 2007). In the present case the histopathological analysis of the DGCT revealed sheets and rounded islands of odontogenic epithelium, surrounded by mature fibrous connective tissue, which is consistent with previous literature (Praetorius and Ledesma-Montes, 2005; Ledesma-Montes et al., 2008). It has been reported, that
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
Research group
N
Age
Gender
Medical history
DGCT location
Clinical signs
Radiographic findings
Initial treatment
RC1
FU1
Retreatment
RC2
FU2
(Present case)
1
20
f
Unremarkable
Mandible
0
3 mo
e
e
e
1
27
m
Sickle cell trait
Maxilla
Well-defined radiolucent/ radiopaque lesion Unilocular lesion
Segmental resection
(Biggs et al., 2013)
Mildly painful swelling Painful swelling
1
3 mo
Hemimaxillectomy
0
12 mo
(Park et al., 2013)
1
25
f
Unremarkable
Mandible
Well-defined multilocular radiolucent lesion
1
2 ys
Partial mandibulectomy
0
3 mo
(Cicciu et al., 2012) (Ramaglia et al., 2012)
1 1
18 12
m f
n.s. Unremarkable
Mandible Maxilla
(Yoon et al., 2010)
1
46
m
n.s.
Maxilla
(Juneja and George, 2009)
1
14
f
n.s.
Mandible
(Singhaniya et al., 2009)
1
21
m
n.s.
Mandible
Painful swelling Tooth dislocation Tooth mobility Swelling No swelling No tenderness Painful swelling Tooth extrusion with slight mobility Painless swelling Pus discharge Painful swelling Pus discharge
Enucleation and after 6 weeks Medial maxillectomy Partial mandibulectomy
(Sun et al., 2009)
1
37
m
n.s.
Maxilla
Bone expansion
1
51
m
n.s.
Maxilla
n.s.
1
43
m
n.s.
Mandible
Slight pain numbness
n.s.
1
42
m
n.s.
Maxilla
n.s.
1
29
m
n.s.
Mandible
n.s.
1
36
m
n.s.
Mandible
n.s.
Unilocular mixed radiolucent/radiopaque lesion Irregular lesion borders, calcified lumps n.s.
1
18
m
n.s.
Maxilla
n.s.
n.s.
Unilocular radiolucent lesion Two well-defined radiolucent/ radiopaque lesions Ill-defined mixed radiolucent/ radiopaque lesion
Hemimandibulectomy Enucleation Local curettage Conservative surgery
0 0
9 mo 12 mo
e e
e 0
e 18 mo
0
9 mo
e
e
e
Mixed radiolucent radiopaque lesion with impacted 3d molar Unilocular well-defined radiolucent/radiopaque lesion with impacted 3d molar Bone expansion Cortical Bone resorption n.s.
Segmental resection
0
6 mo
e
e
e
Segmental mandibulectomy
0
9 mo
e
e
e
Local curettage
2
n.s.
0
7 mo
Aggressive Local resection Local curettage, Local resection, Segmental resection Local curettage
0
n.s.
Subtotal maxillectomy e
0
14 mo
4
n.s.
Aggressive local resection
0
15 mo
2
n.s.
Partial maxillectomy
0
25 mo
Local curettage
2
n.s.
Segmental resection
0
29 mo
Local curettage
1
n.s.
0
99 mo
Aggressive Local resection
0
n.s.
Aggressive local resection e
0
105 mo
D. Konstantakis et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2013) 1e7
Please cite this article in press as: Konstantakis D, et al., Intraosseous dentinogenic ghost cell tumor: A clinical report and literature update, Journal of Cranio-Maxillo-Facial Surgery (2013), http://dx.doi.org/10.1016/j.jcms.2013.10.011
Table 1 Overview of published literature from 2009 to September 2013 on intraosseous histologically confirmed DGCTs lesions.
DGCT: dentinogenic ghost cell tumor, N: number of patients, RC1: number of recurrences following initial treatment, FU1: follow-up time after initial treatment. RC2: number of recurrences following retreatment, FU2: follow-up time after retreatment. m: male, f: female, ys: years, mo: months, n.s.: not specified, e : not performed.
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the epithelium of the tumor islands exhibits an ameloblastoma-like basal cell layer that sometimes can show nuclear polarization (Ledesma-Montes et al., 2008). Furthermore, in the central part of the ameloblastomatous islands, tissue resembling the stellate reticulum of the enamel organ can be identified (Buchner, 1991; Ledesma-Montes et al., 2008). These observations are in accordance with the histologic findings of the present case (Fig. 5a). The presence of ghost cells was ascertained in the present lesion (Fig. 5a and b). Groups of ghost cells or individual ghost cells constitute the distinctive microscopic characteristic of the DGCT (Kim et al., 2001; Ledesma-Montes et al., 2008; Yoon et al., 2010). Ghost cells, are thought to derive either from transformation of epithelial cells (Hong et al., 1991; Kim et al., 2001; Sun et al., 2009; Bello et al., 2012; Ramaglia et al., 2012), degeneration of epithelial cells (Bello et al., 2012) or secondary calcification of metaplastic epithelial cells due to ischemia (Bello et al., 2012). For several researchers ghost cells represent an abnormal or incomplete keratinization process (Fejerskov and Krogh, 1972). In detail, it is has been suggested that, the keratin layer might suffer dystrophic calcification (Fejerskov and Krogh, 1972; Singhaniya et al., 2009; Sun et al., 2009), which can activate a foreign-body reaction in the fibrous tissue wall (Singhaniya et al., 2009). Coagulative necrosis has also been suggested by other authors as origin of the ghost cells (Hong et al., 1991). It must be stressed, that the presence of ghost cells alone is not diagnostic, since ghost cells can be also identified in other neoplasms (Ellis, 1999; Kim et al., 2001). However, ghost cells are a basic prerequisite for the diagnosis of the DGCT (Ramaglia et al., 2012). Dysplastic dentine in varying amounts was observed in the present DGCT (Fig. 5a and b). This juxtaepithelial dentinoid ground substance has been described as an osteoid-like atypical dysplastic dentin containing widely separated cell bodies and collagen, which however lacks the normal tubular characteristic structure of dentin (Stone et al., 1998; Ellis, 1999; Kim et al., 2001). Dysplastic dentine appears as an amorphous irregular eosinophilic mass within the connective tissue and adjacent to the proliferation of the odontogenic epithelial islands (Kim et al., 2001; Praetorius and LedesmaMontes, 2005). Different theories have been developed regarding the origin of dysplastic dentine. Based on these, dysplastic dentine could possibly originate i) from the inductive effect of the odontogenic epithelial component of the tumor (Bello et al., 2012) ii) from the dental lamina remnants (rest of Serres) (Bello et al., 2012) iii) from a metaplastic alteration in the connective tissue stroma without the involvement of granulation tissue (Bello et al., 2012) or iv) from the inductive effect of ghost cells on granulation tissue to lay down osteoid and its subsequent calcification (Singhaniya et al., 2009; Bello et al., 2012). A diagnosis of a CCOT was excluded in the present case because of the very high amount of histologically confirmed dentinoid in the present case, which accounted for the solid structure of a DGCT, in contrast to a cystic structure of a CCOT (Li and Gao, 2009). The presence of dysplastic dentin and large amount of ghost cells seen in the present case differentiated histologically the present DGCT from ameloblastoma (Praetorius and Ledesma-Montes, 2005; Iezzi et al., 2007; Li and Gao, 2009; Singhaniya et al., 2009; Sun et al., 2009) and odontoameloblastoma (Li and Gao, 2009). On the other hand, the “ghost” cells seen in the DGCT resemble closely the analog “shadow” cells present in pilomatrixoma (Stone et al., 1998; Mundinger et al., 2011). Because multiple pilomatrixomas may be linked to various syndromes and rare genetic diseases (Kolomvos et al., 2012) and the present patient had an unremarkable medical history, the possibility of a pilomatrixoma was not considered. Furthermore, lack of ghost cells and dentinoid in basaloid salivary gland tumors, including basal cell adenoma, basal cell
adenocarcinoma, cellular pleomorphic adenoma, squamous cell carcinoma or basaloid squamous cell carcinoma allowed their accurate separation from the present DGCT (Stone et al., 1998). Because the lesion of the present case had a radiographically well-defined pattern, odontogenic malignancies such as ameloblastic fibro-odonto/dentino sarcoma and non-odontogenic malignancies including chondrosarcoma (Takahama et al., 2012), osteosarcoma (Kämmerer et al., 2012) and metastatic tumors, which appear as ill-defined mixed radiolucent/radioopaque lesions (Yoon et al., 2010) were not taken into consideration. The possibility of chronic suppurative osteomylelitis was excluded due to absence of lymphadenopathy, fever, leukocytosis and predisposing conditions such as trauma, Paget’s disease or diabetes (Yoon et al., 2010). The GCOC is the malignant counterpart of the DGCT and the CCOT (Yoon et al., 2010) and combines cytological and architectural histologic features of malignancy (Yun et al., 2007) that distinguish it from the CCOT or the DGCT (Li and Yu, 2003). These are pronounced mitotic activity, areas of tumor necrosis, nuclear atypia, cytoplasmic pleomorphism and hyperchromatism (Stone et al., 1998; Kim et al., 2001; Li and Yu, 2003). Due to lack of these characteristics in the present case, a diagnosis of a GCOC could not be made. It is worth mentioning, that the GCOC demonstrates a locally aggressive behavior and is characterized by an infiltrative growth pattern with extension into soft tissues (Li and Yu, 2003; Yun et al., 2007; Ledesma-Montes et al., 2008). Distant metastases are reported to be uncommon (Kim et al., 2001; Goldenberg et al., 2004), however they do occur (Stone et al., 1998; Kasahara et al., 2002; Li and Yu, 2003). In such cases wide surgical excision with histologically clean margins is recommended (Goldenberg et al., 2004). Yet, the effectiveness of postoperative radiation therapy with or without adjunctive chemotherapy is questionable (Kim et al., 2001; Goldenberg et al., 2004). 4. Conclusion The present case report illustrated the surgical treatment of an intraosseous DGCT in a 20-year-old patient and provided an insight into the clinical, radiographic and histologic findings of the case. Even if intraosseous DGCTs are rare, the general dental practitioner should not exclude the possibility of encountering a case of DGCT in the daily clinical practice. A thorough clinical and radiographic examination can prevent under-diagnosis of this specific entity. In time referral of the patient for biopsy and histologic analysis, surgical intervention and a long-term follow-up are crucial for the successful treatment of the patient. Conflict of interest The authors declare no conflicts of interest and confirm that no financial and/or personal relationships with other people or organizations exist, that could inappropriately influence this work. Also the authors declare no sources of support in the form of grants. Acknowledgment The authors would like to thank Prof. Dr. Hans-Anton Lehr, Institut für Pathologie im Medizin Campus Bodensee, Friedrichshafen, Germany for his assistance with Fig. 5a and b. References Bello IO, Qannam A, Al-Zahrani A, AlDosari A: Peripheral dentinogenic ghost cell tumor: report of a case and literature review. Int J Surg Pathol 20: 494e499, 2012 Biggs TC, Hayes SM, Harries PG, Salib RJ: Maxillary dentinogenic ghost cell tumour. Ann R Coll Surg Engl 95: 63e65, 2013
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