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SYSTEMATIC REVIEW

Clinical and radiological features of odontogenic ghost cellcarcinoma: review of the literature and report of four new cases

Y Cheng, X Long*, X Li, Z Bian, X Chen and X Yang

Department of Oral and Maxillofacial Surgery, College of Stomatology, Wuhan University, Wuhan, Hubei, PR China 430079

Objectives: To analyse systematically the clinical and radiological features of odontogenic ghostcell carcinoma (OGCC).Methods: Clinical and radiological features of 22 OGCCs (4 new and 18 from the literature) were

analysed.Results: There were 17 (77%) males and 5 (23%) females (male-to-female ratio of 3.4:1). Agesranged from 13 years to 72 years (mean 36.7) with a peak in the fourth (40.9%) and fifth (27.3%)decades. The maxilla was involved in 68% and the mandible in 32%. Our study confirmed thatOGCC is more prevalent in Asians (12/18) than in other racial groups. The mixed radiolucent andradiopaque lesion pattern was the most frequent (14/19) compared with radiolucent lesions (5/19).89% (17/19) showed poorly defined borders and 11% (2/19) showed well defined borders. Rootresorption was reported in 31% (6/19) of patients and tooth displacements in 21%.Conclusions: OGCC demonstrates clinical and radiographic features of a malignant tumour withhigh recurrence.Dentomaxillofacial Radiology(2004) 33, 152157. doi: 10.1259/dmfr/67909783

Keywords: calcifying; odontogenic; carcinoma; cyst; tumour; jaw

Introduction

The calcifying odontogenic cyst (COC), classified as anodontogenic tumour by the World Health Organisation(WHO), was first identified as a distinct entity by Gorlinet al in 1962.1 In 1972, Fejerskov and Krogh2 used the labelcalcifying ghost cell odontogenic tumour. In 1981,Praetorius et al3 recognized four different histologicalpatterns of COC and classified them as type 1A (simpleunicystic), type 1B (odontome-producing), type 1C(ameloblastomatous proliferating) and type 2 (dentino-

genic ghost cell tumour). In their opinion, type 2 sharesmany of the histological features of the cystic variants;however, the solid growth pattern of the type 2 suggeststhat its classification as a neoplasm is more appropriate.Ellis and Shmookler4 used the term epithelial odontogenicghost cell tumour (EOGCT) for the neoplastic variant ofCOC. Although the terminology is inconsistent, ghost cells

are clearly the most distinctive histological feature of thistumour.

Malignant EOGCT is exceedingly rare, with only 18cases reported in the English language literature to date.The first case appeared in 1971 as a photograph in a WHOmonograph on odontogenic tumours, but no clinicalinformation was provided in this example.5 The first welldocumented case of a malignancy arising in a COC toappear in the English language literature was reported by

Ikemura et al in 1985.6 Although case reports havedescribed the malignant tumour using a variety of terms,including malignant COC,6 8 odontogenic ghost cellcarcinoma,911 aggressive epithelial ghost cell odonto-genic tumour,4,12 dentinogenic ghost cell ameloblastoma13

and malignant calcifying ghost cell odontogenic tumour,14

all reported cases demonstrated malignant histologicalfeatures such as infiltration, cellular pleomorphism,numerous mitoses and necrosis.

This paper reports four new cases of this malignancyusing the term odontogenic ghost cell carcinoma (OGCC)and aims at analysing the clinical, radiological and

*Correspondence to: Xing Long Department of Oral and Maxillofacial Surgery,

College of Stomatology, Wuhan University, Wuhan, Hubei, PR China 430079;

E-mail: [email protected]

Received 28 October 2003; revised 24 February 2004; accepted 12 March 2004

Dentomaxillofacial Radiology (2004) 33,Dentomaxillofacial Radiology (2004) 33, 152157q 2004 The British Institute of Radiology

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pathological features to compare with those reported in theEnglish literature (Table 1).

Material and methods

Four cases were retrospectively studied from the Depart-ment of Oral and Maxillofacial Surgery, College ofStomatology, Wuhan University. All cases had beencollected at the hospital during the period 1972 2002following initial or definitive surgery. Radiographicexamination was performed with panoramic and occlusalradiography, Waters position and tomography of themaxilla. Radiographs and clinical follow-up were obtainedfrom the patient file. The surgical specimens of the initialpresentation and subsequent recurrences were fixed in 4%buffered formalin and embedded in paraffin prior to routinehaematoxylin and eosin staining.

Two investigators separately evaluated the radiologicalfeatures of the four cases. Consultation with another

observer was made if there was any disagreement.Radiological features were recorded by a majoritydecision.

Case reports

Case 1A 36-year-old Chinese man had been aware of a painlessswelling in his anterior mandible for 2 months. Examin-ation revealed a 5 cm 3 cm 2 cm painless mass in theright and left mandible. Radiographic examination showeda well demarcated radiolucency that extended from the firstpremolar region of the right mandible to the left lateral

incisor region. All of the involved teeth were mobile andexhibited irregular root resorption (Figure 1). The teethwere extracted and a large cyst was enucleated. It wasreported histologically as COC with cystic change. Fiveyears later, the patient presented with a swelling in themandible slightly larger than that at initial presentation.Examination disclosed a 7 cm 5 cm 2 cm firm, solid,mandibular mass. Radiographs demonstrated a large,poorly demarcated mixed radiopaqueradiolucent lesionwith destruction of the buccal and lingual cortical plates.The lesion was treated by mandibular resection.

Histological features of the resected recurrent mandib-ular mass showed epithelial hyperplasia that had a closeresemblance to the follicular and plexiform pattern of

ameloblastoma and duct-like structures of adenomatoidodontogenic tumour. Ghost cells and dentinoid in contactwith the odontogenic epithelium were found in the centreof epithelial masses. Dysplastic epithelium with denselyarranged cells was also found. Most of those cells wereround basaloid cells with nuclear hyperchromatism andmitosis. Some were polygonal epithelial cells with vascularnuclei. There were occasional foci of clear cells.

Case 2A 35-year-old Chinese man sought treatment for a painfulswelling in the right maxilla. Examination revealed a

3 cm 3 cm 2 cm painful mass in the right maxilla.Waters position and occlusal film showed a welldemarcated unicystic radiolucency from the maxillaryright canine to the right second premolar region. Theclinical diagnosis was a periapical cyst and the lesion wasenucleated. At 4 years post operation there was a right

maxillary recurrence. The lesion required more extensivelocal resection. A right maxillectomy was performed.Histologically, the lesion was reported as an ameloblas-toma with cystic change. Nine years after the initialprocedure, the patient returned complaining of swelling inthe palatal and nasal region. Clinical and radiologicalexamination revealed a 10 cm 6 cm 5 cm lesion occu-pying the right maxillectomy cavity (Figure 2). Computedtomography (CT) showed a poorly demarcated multi-locular, osteolytic radiolucency (Figure 3). A soft tissuemass occupying the right maxillectomy cavity measuredapproximately 13 cm 21 cm. A total maxillectomy wasperformed. Histologically, epithelial hyperplasia primarilyformed the follicular pattern of ameloblastoma, but the

plexiform pattern and duct-like structures were also seen.Ghost cells and dentinoid existed in the centre of epithelialmasses. Epithelial cells with nuclear hyperchromatism andmitoses were arranged densely in malignant parts of thelesion. There were occasional foci of clear cells (Figure 4).Ten years later the patient died of cranial metastasis.

Case 3A 33-year-old Chinese man complained of tender swellingon the right side of his face for 6 months. Clinicalexamination revealed a 4 cm 2 cm 2 cm painful massin the right maxilla. Waters position and occlusal filmshowed a well demarcated multilocular radiolucency fromthe maxillary right incisor to the right second premolar

region. Root resorption was found (Figure 5). A subtotalmaxillectomy was performed. Histological examinationshowed a typical COC in the resection. Five years later thepatient sought treatment for a recurrent lesion in the rightmaxilla. Waters position showed a poorly demarcatedosteolytic radiolucency with soft tissue mass occupying theright maxillectomy cavity. A total maxillectomy wasperformed. Histologically, some parts were parenchymaland some were cystic. The characteristics of pathologicalchanges in the parenchyma resembled the first case, but theepithelial arrangement mainly formed duct-like structures,without clear cells. The malignant characteristics ofepithelial cells in the cystic part were not conspicuousand several dentinal masses projected towards the fibrous

capsules.

Case 4A 44-year-old Chinese man had been aware of a painlessswelling in his right mandible for 18 months. Examinationrevealed a 3 cm 2 cm 2 cm painless mass in the rightmandible. Lateral oblique projection of the right mandibleshowed a well demarcated unilocular radiolucency in themolar region. Root resorption of the second molar wasvisible. The lesion was enucleated. The pathologicaldiagnosis was calcifying epithelial odontogenic tumour.He had three recurrences, at 1 year, 4 years and 8 years post

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Table 1 Clinical and radiographic features of reported and new cases of odontogenic ghost cell carcinoma

Case No. Authors Age (years)/sex Race Jaw Location Cross midline Border definition Radiolucency Root resorption Tooth disp

1 Pindborg et al 45/M White Mand. N/A N/A N/A N/A N/A N/

2 Ikemura et al 48/F Asian Max. 11 18 No Poorly Mixed No N

3 Ellis and Shmookler 55/F Black Mand. 34 45 Yes Poorly Radiolucent No N4 Ellis and Shmookler 17/M N/A Max. 11 15 No Poorly Mixed No N5 Ellis and Shmookler 46/M White Max. 14 16 No Poorly Mixed No N

6 Grodjesk et al 46/M White Max. 11 18 No Poorly Mixed Yes N7 Scott and Wood 33/M Black Max. 11 18 No Poorly Mixed No N8 McCoy et al 13/F Black Max. 11 17 No Poorly Mixed Yes Ye9 Dubiel-Bigaj et al 42/M N/A Max. 14 16 No N/A N/A N/A N/10 Siar & Ng 39/M Asian Max. N/A N/A N/A N/A N/A N/11 Alcalde et al 72/F Asian Max. 11 16 No Well Mixed No N

12 Folpe et al 20/M N/A Max. 11 18 No Poorly Radiolucent No N13 Lu et al 24/M Asian Max. 11 18 No Poorly Mixed No N14 Lu et al 31/F Asian Max. N/A N/A Poorly Radiolucent No Ye15 Lu et al 19/M Asian Mand. 37 43 Yes Poorly Mixed No N16 Lu et al 39/M Asian Mand. 46 48 No Poorly Radiolucent No N17 Kamijo et al 38/M Asian Max. 13 18 No Well Mixed No N18 Kim et al 33/M N/A Mand. 46 48 No Poorly Mixed Yes Ye19 Case 1 36/M Asian Mand. 31 46 Yes Poorly Mixed Yes Ye20 Case 2 35/M Asian Max. 13 15 No Poorly Mixed Yes N21 Case 3 33/M Asian Max. 11 15 No Poorly Mixed Yes N22 Case 4 44/M Asian Mand. 46 48 No Poorly Radiolucent Yes Ye

M, male; F, female; N/A, not available; Max., maxilla; Mand., mandible; Poorly, poorly defined; Well, well defined

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operatively. These required more extensive local resection.

Thirteen years after the initial procedure, he returnedcomplaining of a recurring mass for 2 months. Panoramicradiography demonstrated a large, poorly demarcatedradiolucency of the mandible from the left secondpremolar to the right ramus (Figure 6). Surgery demon-strated destruction of the buccal and lingual cortical platesof the mandible. Histologically, the characteristics ofpathological changes were the same as the second case.However, no duct-like structures were found.

Discussion

The malignant counterpart of COC is an exceptionally rare

odontogenic tumour, with only 18 cases previouslyreported in the English literature.47,913,1518 This paperpresents four new cases of this unusual tumour. Becausethe radiological and clinical features of the OGCC have notbeen described before, we considered a systematic analysiswas essential.

Although histological criteria have been established forthe diagnosis of the benign COC,5,19 features for the

diagnosis of the malignant form have not yet beendetermined. The histological diagnostic criteria of OGCCis an epithelial lining showing a well defined basal layer ofcolumnar cells, a layer of cells resembling the stellatereticulum of the enamel organ, and masses of ghost cellsthat may be calcified or not, accompanied by atypicalepithelial cell foci presenting mitosis, keratin pearls,necrosis and other malignant features. The four casespresented here fulfilled the criteria of OGCC based on thehistological findings of infiltrative growth, atypical cyto-logical features and ghost cell islands.

Gender distribution of all the reported lesions showed amale predilection of 3.4:1, although this difference is not

statistically significant. This is different from its benigncounterpart, which has been reported as equally commonin both men and women by other authors.8,14,20,21

The age distribution of the patients in the present studyranged widely from 1372 years, with a peak in the fourth(40.9%) and fifth (27.3%) decades. This is different frombenign COC, which has a peak in the second decade.8,20

This shows that the OGCC occurs approximately twodecades later than the benign COC. The reason may be thatthe OGCC apparently arises from malignant transform-ation of a pre-existing benign COC. The mean age in thepresent study was 36.7 years. It is similar to benign COC(34 years).8,14,20,21 Judging from the number of previouslypublished cases, it is interesting that the OGCC appears to

be more common in Asians than other races, although thetrue prevalence remains unknown. Of the 18 previouslyreported cases in the English language literature, whereracial data are provided (14 cases), eight have occurred inAsians, three in Caucasians and three in Blacks. All fourcases presented here occurred in Asians. The predomi-nance of OGCC in Asians is in keeping with thedemographics of the benign COC, which is also morecommon in Asians. This suggests that ethnic origin mayplay a role in the incidence of OGCC, but the number ofcases published in the English literature is too small todraw definite conclusions.

Figure 1 Case 1. A well demarcated radiolucency that extended fromfirst premolar region of the right mandible to the left lateral incisor region

Figure 2 Case 2. Mixed lesion occupying the right maxillectomy cavity

Figure 3 Case 2. CT showing a poorly demarcated multilocularradiolucency occupying the right maxillectomy cavity




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Of the 22 OGCC reported, 15 (68.2%) were in themaxilla and 7 (31.8%) in the mandible. There was a clear

predilection of OGCC for the maxilla (ratio 2.1:1),

differing from the site distribution of the benign COCwhich occurs equally in both the maxilla and mandible. 8,20

In the maxilla, OGCC was not restricted to only one regionsuch as incisorcanine, premolar and molar region, but

rather involved an extensive region. Of the 13 cases in the

maxilla where anatomical location is provided, eight were

located in the incisorcanine, premolar and molar region;

three in incisorcanine, premolar region; and two inpremolar molar region. Twelve cases showed destruction

of the maxillary sinus with obliteration. The lesions in the

maxilla did not cross the midline. On the other hand, in the

mandible, of the six cases where anatomic location was

provided, three were restricted to the molar region andthree crossed the midline but were located betweenbilateral premolar region of mandible.

The OGCC usually appeared as a painful, hard swellingin the maxilla or mandible with osseous destruction, andwith paresthesia being a frequent finding. It may havecause expansion of the mandible or maxilla.

Of 22 OGCC, only 19 cases reported radiologicalfeatures. From them, mostof the lesions (14cases) appearedas mixed radiolucent radiopaque lesions. Only a few (fivecases) were totally radiolucent. The border of the OGCCwas usuallypoorly demarcated exceptfor two cases where itwas a moderately well defined border. Varying degrees of

maxillary sinus involvement, from encroachment tocomplete obliteration, have also been described.

It was difficult to make a diagnosis of OGCC based onradiographic features alone. OGCC showed radiographicfeatures of a malignant tumour and was not specific. Otherpossible diagnoses of malignant tumours included osteo-sarcoma and malignant ameloblastoma. A diagnosis ofOGCC was possible only after the resected specimen wasexamined histologically.

Resorption of the roots of the teeth associated with thelesion was reported in six cases. Tooth displacement wasseen in four cases. Two cases were associated with an

Figure 4 Case 2. Epithelial cells with nuclear hyperchromatism and mitoses were arranged densely in the malignant parts of the lesion (haematoxylinand eosin 40 )

Figure 5 Case 3. A well demarcated multilocular radiolucency from themaxillary right incisor to the right second premolar region

Figure 6 Case 4. A large, poorly demarcated radiolucency of mandiblefrom left second premolar to right ramus

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unerupted canine in the maxilla. However, the actualnumber of these complications is probably higher, becausethe number of OGCC is small and it is possible that someauthors did not describe these features even though theywere seen in radiographs.

At the present time, it is impossible to predict the

biological behaviour of the OGCC. Five of 21 have beenassociated with long-term survival without recurrencefollowing definitive surgery, while 16 of 21 have had apoor clinical outcome with locally recurrent disease or

metastasis (Table 1). Recurrence is common after initialoperation. Therefore, OGCC showed both clinical andradiographic features of a malignant tumour with highrecurrence.

In summary, this study has systematically analysed theexisting English literature on OGCC and provided precise

information on the clinical and radiographic features ofO GC C. M ost o f t he O GC C a pp ea re d a s m ix edradiolucent and radiopaque lesions with poorly demarcatedborders.

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