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Case Report

Calcifying Cystic Odontogenic Tumour: A Case Report and Review on Nomenclature

Bhudev Sharma, Sanjeet Singh, Preeti Bhardwaj

Abstract

Calcifying cystic odontogenic tumor is an uncommon odontogenic neoplasm which is included in the heterogenous group of lesions under a broader description of Ghost cell odontogenic tumors. All these lesions are characterised by presence of ghost cell as a common feature. Calcifying cystic odontogenic tumor is a lesion having variable biologic behaviour and had a controversial nomenclature. It can be found in association with other odontogenic tumors. Here a case of multilocular calcifying cystic odontogenic tumor in 19 year old boy involving left mandible is discussed. This article also provides the current update on nomenclature and classification of ghost cell lesions.

Key words: Odontogenic Tumors;Odontogenic Cyst;Dental Cysts;Calcifying;Ghost Cells; Biological Behavior;Nomenclature.

Bhudev Sharma, Sanjeet Singh, Preeti Bhardwaj. Calcifying Cystic Odontogenic Tumour: A Case Report and Review on Nomenclature. International Journal of Oral & Maxillofacial Pathology; 2012:3(1):79-85. ©International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved.

Received on: 23/06/2011 Accepted on: 26/03/2012

Introduction

Calcifying odontogenic cyst (COC) was first described as a distinct clinicopathologic entity by Gorlin et al. in 1962.1 COC is considered as odontogenic lesion. COC is usually an intraosseous lesion but it may also occur extraosseously. COCs are primarily cystic in nature and appears to be non-neoplastic.2,3. COCs can also occur as a solid lesion, some of which are neoplastic in nature. Extremely rare malignant variant is also there. Radiographically, the COC can be well defined unilocular or multilocular lesions that may or may not have radiopaque material. Histologically, COC share the similar features of ameloblatomatous epithelium with ghost cells with or without dentinoid formation. COC is frequently found in association with or exhibits areas, histologically similar to variety of odontogenic tumors, including complex or compound odontoma, ameloblastic odontoma, ameloblastic fibroma, ameloblastic fibro-odontoma and adenomatoid odontogenic tumor.4 There has been extended debate about the biological behavior of these lesions and many nomenclatures and classification have been published. This article presents a case report of COC and also includes the current update on nomenclature and classification of ghost cell lesions.

Case Report

A 19 years old male patient reported to the department of oral medicine, diagnosis and radiology with chief complain of swelling in his left lower back tooth region for past six months. Swelling was initially small for the first two months, and then increased to its present size. There were no accompanying symptoms. The patient was otherwise healthy with no significant medical and family history.

On extra oral examination, a large swelling with size 8 x 6 cm and diffuse borders was observed on left side of face. Superiorly the swelling was extending from ala of nose to pinna of ear, inferiorly extending from lower border of mandible including sub mandibular region and posteriorly involving ramus of mandible. On palpation the swelling was hard, non-tender, without any elevated temperature. Single palpable, mobile, and tender lymph node was also noticed. Mouth opening was normal. On intraoral examination, there was single diffuse swelling extending from distal aspect of tooth #38 to distal aspect of #43, measuring about 7 x 2 cm. Buccal vestibule was obliterated and there was mild swelling on the lingual side.

Aspiration biopsy showed few epithelial cells with inflammatory cells and was suggestive of infected cyst. Radiographic evaluation with the help of Orthopantomograph (OPG) and CT scan showed a radiolucent

multilocular lesion extending from tooth #43 to #38 region extending upto ramus of mandible and also involving lower border of mandible. There was divergence of roots of tooth #35 and #36. Based on the clinical and radiographic findings the differential diagnosis of Odontogenic Keratocyst, Ameloblastoma, Odontogenic Myxoma and Central Giant Cell lesion were given. Patient was sent to department of oral and maxillofacial surgery for incisional biopsy. Histopathological examination showed a cystic cavity lined by stratified squamous epithelium of six to eight cells thick. Epithelium showed prominent palisaded columnar or cuboidal basal cells with hyperchromatic nuclei and reverse of polarity. Budding of basal cells layer was also evident. Overlying epithelial layers were loosely arranged, resembling stellate reticulum like cells. The epithelium also exhibits ghost cell keratinization. Hence a final Diagnosis of Calcifying Odontogenic Cyst was made. After histopathological diagnosis the patient underwent surgical treatment i.e. segmental resection of mandible under general anesthesia.

Discussion

The term calcifying odontogenic cyst was first suggested by Gorlin et al (1962).1 Although other terms have been proposed to designate this lesion.5-10 Gorlin in his original report suggested that this cyst may represent the oral counterpart of the dermal calcifying epithelioma of Malherbe.11 The COC is predominantly an intraosseous lesion though it can also occur extraosseously. It can occur with wide age range, peak incidence is seen in 2nd and 3rd decade of life with no sex predilection.2 It occurs with about equal frequency in the maxilla and mandible and mostly involves the anterior jaws.9 It can also be associated with other odontogenic tumors. Mostly the lesion is asymptomatic and the swelling is most common complaint and generally not associated with pain. Intra-osseous lesion may produce hard bony expansion whereas peripheral lesions may appear as local gingival growth.12

Radiographically the central lesions are unilocular or multilocular radiolucency with or without well defined margins. Bony expansion may be present. Irregular calcified bodies of varying size and opacity may be seen. Dense opacities are associated with complex odontome. Displacement or teeth and root resorption may also be seen. Peripheral lesions may show either no radiographic features or a superficial erosion of the underlying cortical bone.13 COC may develop from reduced enamel or remnants of odontogenic epithelium in the follicle, gingival tissues or bones.12

The main histopathologic criteria for diagnosis of the COC are almost well established. The cyst lining should show proliferation to the point that it resembles ameloblastoma. Within this proliferation of epithelium, cells undergo characteristic ghost cell keratinization. Dystrophic calcification of the ghost cell can be seen.13 Ghost cells are most remarkable feature of COC. These cells however may also be found in several odontogenic and non odontogenic lesions. The ghost cells consist of enlarged, ballooned, ovoid or elongated elliptoid epithelium. The ghost cell may represent abnormal type of keratinisation with affinity for calcification or squamous metaplasia with subsequent calcification caused by ischemia or may represent the product of abortive enamel matrix in odontogenic epithelium or may be the product of coagulative necrosis of odontogenic epithelium.14

Many investigators have made effort to clarify the nature of ghost cell by using special histochemical methods, transmission electron microscopy, and scanning electron microscopy, and various theories have been proposed without any general agreement. Gorlin et al1, Ebling and Wagner15 Gold8, Bhaskear9, Komiya et al16 and Regezi et al17 all believed that ghost cells represent normal or abnormal keratinisation. Leavy18 investigated ghost cells in odontomas and suggested that they represent squamous metaplasia with subsequent calcification caused by ischemia. This theory was supported by Sedano and Pindborg19 and by Kerebel and Kerebel.20 Sedano and Pindborg thought the ghost cells represented different stages of normal and aberrant keratin formation and that they were derived from metaplastic transformation of odontogenic epithelium. Other investigator suggested or implied that ghost cells may represent the product of abortive enamel matrix in odontogenic epithelium.21

Immunohistochemical studies22,23 demonstrated that most typical denucleated ghost cells reacted very faintly or not at all

with polyclonal cytokeratin antibody, in contrast to the marked reaction of adjacent odontogenic epithelium. The weak immunoreactions of ghost cells suggest that the keratin antigen have been altered. Therefore ghost cells may represent the product of coagulative necrosis of odontogenic epithelium. Immunohistochemical analysis of COC has found that amelogenin protein was expressed chiefly in ghost cells, whereas cytokeratin 19 and bcl-2 protein were chiefly expressed in lining epithelial cells.24 Bcl-2 positivity was found to be more in COC with odontoma than in those without odontoma.24,25 COC with ameloblastomatous, proliferative type and odontoma associated COCs to have higher expression of Ki-67.24,25

Considerable histopathologic diversity has been recognized among lesions referred to as COC or under related diagnostic terms. The term COC has been commonly used since the first description by Gorlin et al in 1962. The COCs shows extreme diversity in its clinical and histopathological features as well as in its biological behaviour. Because of this diversity, there has been confusion and disagreement on the terminology and classification of this lesion. In past few authors have regarded COC as a tumour with a marked tendency for cystic formation.26,10 Fejerskov & Krog (1972) used the term Calcifying ghost cell odontogenic tumor26 (CGCOT) and Freedman et al (1975) referred to it as Cystic calcifying odontogenic tumour (CCOT).10 There were two concepts regarding the nature of COCs. Some authors have regarded COC as a tumour with a tendency for marked cystic formation. Based on this or what can be called a „monistic concept‟ the terms calcifying ghost cell odontogenic tumour (CGCOT)26 and cystic calcifying odontogenic tumour (CCOT)10 were proposed to be substituted for COC. The WHO classification of 199227 is also based on this monistic concept that all COCs are neoplastic in nature, even though most of these lesions are cystic in architecture and appear to be non-neoplastic.

On the other hand some authors considered that COC contain two entities: a cyst and a neoplasm,2,14,28,29,30 and this concept is called as „dualistic concept‟. Based on this concept in 1981 Praetorius et al.28 proposed a classification of COC (Table 1) in which they divided COC into two entities and the neoplastic variant was referred as “dentinogenic ghost cell tumour” (DGCT) based on the presence of dentinoid and ghost cell. In 1983, Shear noted the similarity to ameloblastoma and referred to it as Dentinoameloblastoma.31 Scott and Wood were of the opinion that the name dentinogenic ghost cell ameloblastoma was acceptable for aggressive lesions in which ameloblatomatous tumour was present and proposed the name odontogenic ghost cell ameloblastoma for the rare case in which both dentine and enamel were present.32 Ellis & Shmookler29 emphasized the presence of ghost cell keratinisation and proposed the term Epithelial Odontogenic Ghost Cell Tumour (EOGCT) for neoplastic entity. Colmenero et al30 in 1990 termed neoplastic entity as Odontogenic Ghost Cell Tumor (OGCT). Buchner2 (Table 2) and Hong et al.14 (Table 3) have also proposed the classification of COC based on dualistic concept. Hong et al. (1991)14 supported the use of term Epithelial Odontogenic Ghost Cell Tumor” based on the presence of odontogenic epithelial proliferation with some inductive activity and the formation of ghost cells. Hirshberg et al considered COC associated with odontomas to have clinical features sufficiently distinct to categorise them as a separate lesion and named them “Odontocalcifying odontogenic Cyst”.33 Langlaris et al in 1995 proposed the term calcifying odontogenic lesion (COL), including both cystic and neoplastic forms as well as combined lesions containing elements of both.34 Toida M in 1998 suggested another classification based on dualistic concept (Table 4).35 Li and Yu classified the lesions into three categories- cyst, benign tumours and malignant tumours. They suggested that the term COC should be used specifically to designate the unicystic lesions, with or without an associated odontoma.36

This wide range on nomenclature is also reflected in WHO classifications through the years, wherein in 1971 it recognised COC as a non neoplastic cystic lesion and it is defined as “a non-neoplastic cystic lesion in which the epithelial lining shows a well defined basal layer of columnar cells, an overlying layer that is often many cells thick that may resemble stellate reticulum and masses of ghost epithelial cell may be in epithelial cyst lining or in the fibrous capsule. The ghost epithelial cells may become calcified. Dysplastic dentin may be laid down next to the basal cell layer of epithelium.”37

The clinical photograph showing extraoral swelling on the left side of the face (Figure 1). The OPG showing multilocular radiolucency extending from left ramus of mandible to the distal of tooth #43 with divergence of roots of #35 and #36 (Figure 2). The gross specimen showing surgically resected mandible (Figure 3).

The hematoxylin and eosin stained section under high power view showing cystic epithelial lining made up of ameloblast like and stellate reticulum like cells along with few ghost cells (Figure 4) and budding of cystic epithelium (Figure 5).

With time, it became apparent that not all the COCs are cystic. In 1971, the WHO described COC as a “non neoplastic cystic lesion” but classified the lesion as a benign odontogenic tumour.30 In 1992 revision, WHO deleted the term “non-neoplastic” and it again classified the lesion with the benign odontogenic tumour.30 In the WHO Histological Classification of Odontogenic Tumours of 2005, COC was re-named as calcifying cystic odontogenic tumour (CCOT), the benign solid type was referred to as DGCT and the cases previously reported as odontogenic ghost cell carcinoma (OGCC) and malignant epithelial odontogenic ghost cell tumours were re-named by WHO as ghost cell odontogenic carcinoma (GCOC).38

Type 1. Cystic type

  • A. Simple unicystic type
  • B. Odontoma producing type
  • C. Ameloblastomatous proliferating type
  • Type 2. Neoplastic type – Dentinogenic ghost cell tumour ( DGCT)

    Table 1: Classification of the so-called COC as proposed by Praetorius.

  • A. Peripheral (extraosseous) COC
  • 1. Cystic variant
  • 2. Neoplastic (solid) variant
  • B. Central (intraosseous) COC
  • 1. Cystic variant
  • a. Simple (unicystic or multicystic)
  • b. Associated with an odontoma
  • c. Associated with odontogenic tumour (other than odontoma)
  • d. Other variants (such as clear cell variant, pigmented variant)
  • 2. Neoplastic ( solid) variant- known as DGCT or EOGCT
  • 3. Malignant COC
  • Table 2. Classification of so- called COC proposed by Buchner.

    Type 1. Cystic

  • A. Nonproliferative
  • B. Proliferative
  • C. Ameloblastomatous
  • D. Associated with odontoma
  • Type 2. Neoplastic

  • A. Ameloblastoma ex COC
  • B. Peripheral EOGCT
  • C. Central EOGCT
  • Table 3. Classification of so called COC proposed by Hong et al.

    1. Cyst: Calcifying ghost cell odontogenic cyst (CGCOC)

    2. Neoplasm

  • A. Benign: Calcifying ghost cell odontogenic tumour (CGCOT)
  • a. Cystic variant: cystic CGCOT
  • b. Solid variant: solid CGCOT
  • B. Malignant: malignant CGCOT
  • 3. Combined lesion- each of the categories described above (CGCOC, CGCOT and malignant CGCOT) associated with the following lesions

    α. Odontoma

    β. Ameloblastoma

    γ. Other odontogenic lesions

    Table 4: Classification of so- called COC by Toida M.

    1. Non-neoplastic (simple cystic) variants

  • a. With nonproliferative epithelial lining
  • b. With nonproliferative (or proliferative) epithelial lining associated with odontomas
  • c. With proliferative lining
  • d. With unicystic, plexiform ameloblatomatous proliferation of epithelial lining.
  • 2. Neoplastic Variants

  • A. Benign type (CGCOT)
  • a. Cystic subtype ( cystic CGCOT)
  • α) SMA ex epithelial cyst lining

    b. Solid subtype (solid CGCOT)

    α) peripheral Ameloblastoma like

    β) SMA-like

    B. Malignant type (malignant CGCOT or OGCC)

    a. cystic subtype

    b. solid subtype

    (Note: SMA- Solid Multicystic Ameloblastoma)

    Table 5: Classification suggested by Reichart PA and Philipsen HP in 2004

    Group 1: Simple cysts

  • 1. Calcifying odontogenic cyst
  • Group 2. Cysts associated with odontogenic hamartomas or benign neoplasms: calcifying cystic odontogenic tumours (CCOT).

  • 1. CCOT associated with an odontome
  • 2. CCOT associated with adenomatoid odontogenic tumour
  • 3. CCOT associated with Ameloblastoma
  • 4. CCOT associated with ameloblastic fibroma
  • 5. CCOT associated with ameloblastic fibroodontoma
  • 6. CCOT associated with odontoameloblastoma
  • 7. CCOT associated with odontogenic myxofibroma
  • Group 3. Solid benign odontogenic neoplasm with similar cell morphology to that in COC, and with dentinoid formation

  • 1. Dentinogenic ghost cell tumour
  • Group 4. Malignant odontogenic neoplasms with feature similar to those of dentinogenic ghost cell tumour

  • 1. Ghost cell odontogenic carcinoma
  • Table 6: Classification of the odontogenic ghost cell lesions by Praetorius, 2006

    Since then at least two more classification system have been proposed (Table 5 & 6).39,40 The WHO in 2005 defined CCOT as „a benign cystic neoplasm of odontogenic origin, characterized by an Ameloblastoma-like epithelium with ghost cells that may calcify‟.38 Calcifying cystic odontogenic tumour (CCOT) can occur intra or extraosseously and they can be further subdivided into.41 Type 1: Simple cystic CCOT (Includes pigmented and clear cell variants). Type 2: Odontoma associated CCOT. Type 3: Ameloblatomatous proliferating CCOT. Type 4: CCOT associated with benign odontogenic tumours other than odontoma. The recommended treatment protocol for CCOT is conservative surgical enucleation. Since rare recurrences have been reported, a follow-up period of 10 years has been suggested.39

    Conclusion

    To summarise & conclude the present case of COC now termed as Calcifying Cystic Odontogenic Tumour which is usually seen in anterior jaws region but here the lesion was involving both anterior and posterior jaws is reported. The lesion is characterized by the presence of ghost cells having varied histochemical properties and with variable biologic behaviour.

    Author Affiliations

    1. Dr.Bhudev Sharma, Reader, 2. Dr.Sanjeet Singh, Senior Lecturer, Department of Oral & Maxillofacial Pathology, DJ College of Dental Sciences & Research, Modi Nagar, U.P. India, 3. Dr.Preeti Bhardwaj, Reader, Department of Orthodontics, Kothiwal Dental College & Research Centre, Moradabad, U.P. India.

    Acknowledgement

    We would like to thank all the staff members from Department of Oral & Maxillofacial Pathology for their support & cooperation.

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  • Corresponding Author

    Dr. Bhudev Sharma,

    Reader,

    Dept. of Oral & Maxillofacial Pathology,

    DJ College of Dental Sciences & Research,

    Ajit mahal, Niwari Road,

    Modi Nagar - 201204, UP, India.

    Email: drbhudevsharma@yahoo.com

    Ph: +91 9971004394

    Source of Support: Nil, Conflict of Interest: None Declared.

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