International collaborative study on ghost cell odontogenic tumours: calcifying cystic odontogenic tumour, dentinogenic ghost cell tumour and ghost cell odontogenic carcinoma

Background:  Calcifying odontogenic cyst was described first by Gorlin et al. in 1962; since then several hundreds of cases had been reported. In 1981, Prætorius et al. proposed a widely used classification. Afterwards, several authors proposed different classifications and discussed its neoplastic potential. The 2005 WHO Classification of Odontogenic Tumours re-named this entity as calcifying cystic odontogenic tumour (CCOT) and defined the clinico-pathological features of the ghost cell odontogenic tumours, the CCOT, the dentinogenic ghost cell tumour (DGCT) and the ghost cell odontogenic carcinoma (GCOC).
Methods:  The aim of this paper was to review the clinical-pathological features of 122 CCOT, DGCT and GCOC cases retrieved from the files of the oral pathology laboratories from 14 institutions in Mexico, South Africa, Denmark, the USA, Brazil, Guatemala and Peru. It attempts to clarify and to group the clinico-pathological features of the analysed cases and to propose an objective, comprehensive and useful classification under the 2005 WHO classification guidelines.
Results:  CCOT cases were divided into four sub-types: (i) simple cystic; (ii) odontoma associated; (iii) ameloblastomatous proliferating; and (iv) CCOT associated with benign odontogenic tumours other than odontomas. DGCT was separated into a central aggressive DGCT and a peripheral non-aggressive counterpart. For GCOC, three variants were identified. The first reported cases of a recurrent peripheral CCOT and a multiple synchronous, CCOT are included.
Conclusions:  Our results suggest that ghost cell odontogenic tumours comprise a heterogeneous group of neoplasms which need further studies to define more precisely their biological behaviour.     

Ameloblastoma, calcifying epithelial odontogenic tumor, and glandular odontogenic cyst show a distinctive immunophenotype with some myoepithelial antigen expression

Background:  Odontogenic neoplasms have some morphologic overlap with salivary gland neoplasms, many of which show myoepithelial differentiation. In the 1980s, an ultrastructural study identified a population of myoepithelial-like cells in calcifying epithelial odontogenic tumor. Myoepithelial derived tumors have since been shown to have distinct immunohistochemical profiles.
Methods:  We examined a series of odontogenic neoplasms, including 11 ameloblastomas, four calcifying epithelial odontogenic tumors, five glandular odontogenic cysts (GOCs), and five keratocystic odontogenic tumors with a panel of myoepithelial-associated immunohistochemical stains. We also assessed representative control examples of oral mucosa, odontogenic rests, and dentigerous cysts.
Results:  All of the neoplastic and non-neoplastic oral epithelium-derived entities share a p63-positive, high molecular weight cytokeratin (CK5/6)-positive immunophenotype. Calponin reactivity was at least focally present in two of four calcifying epithelial odontogenic tumors, three of five GOCs, and 10 of 11 ameloblastomas; the sole completely non-reactive ameloblastoma represents a lung metastasis. One case of calcifying epithelial odontogenic tumor was focally positive for glial fibrillary acidic protein. However, other more definitive markers of myoepithelial differentiation, including S-100 and smooth muscle actin, were negative. Two of three calcifying epithelial odontogenic tumors and five of five GOCs were also positive for a low molecular weight cytokeratin (CK7).
Conclusions:  Ameloblastomas, GOCs, and calcifying epithelial odontogenic tumors show a distinctive immunophenotype which overlaps with that of myoepithelial-derived salivary gland neoplasms but does not provide definitive support for myoepithelial differentiation.     

Peripheral dentinogenic ghost cell tumor

A case of dentinogenic ghost cell tumor, that has originated peripherally in the jaw, is presented and the literature reviewed with particular reference to the origin of the tumor. The total number of central and peripheral cases reported in the English literature is 10 and although mucosal infiltration is common, peripheral origin of the neoplasm could be verified in only 3 cases.     

Ameloblastomatous calcifying odontogenic cyst: a rare histologic variant

Calcifying odontogenic cyst (COC) is an uncommon developmental odontogenic cyst first described by Gorlin in 1962. It is considered as extremely rare and accounts for only 1% of jaw cysts reported. Because of its diverse histopathology, there has always been confusion about its nature as a cyst, neoplasm or hamartoma. Several subclassifications have been proposed. Here, we present a case of calcifying odontogenic cyst with ameloblastic proliferation - an extremely rare histologic variant. The classical histologic features of the lining epithelium in the form of cords and presence of characteristic ghost cells were seen along with ameloblastomatous proliferations. Ameloblastomatous COC microscopically resembles unicystic ameloblastoma except for the ghost cells and calcifications within the proliferative epithelium. The nature of the COC is controversial. The case is presented here for its rarity, and difference between ameloblastomatous COC and ameloblastoma ex COC has been emphasized.     

Peripheral calcifying odontogenic cyst

BACKGROUND: Calcifying odontogenic cyst (COC) is a rare lesion representing about 1% of jaw cysts. It may occur in a central (intraosseous) or peripheral (extraosseous) location. METHOD: A case of peripheral COC located on the gingiva, appearing as a painless, circumscribed, pink nodule has been reported. RESULTS: Peripheral, in contrast to central, COC tends to affect older patients. Peripheral COC is a less aggressive lesion than the central counterpart, and a simple excision biopsy is curative. CONCLUSION: The histological finding of a keratinized epithelium rich in ghost cells has helped in making the diagnosis.     

Initiation of ectopic epithelial calcification in a calcifying odontogenic cyst

Ultrastructural observation was performed on a calcifying odontogenic cyst (COC) associated with an odontoma and arising in the right mandibular region of an 8-year-old Japanese boy. Four types of cells were identified in the epithelial layer of the COC. The basal cells were low columnar in shape and contained some intracellular organelles. They were attached to the neighboring cells with a few desmosomes and resembled inner enamel epithelium of the normal enamel organ. The stellate reticulum-like cells, polygonal in shape, possessed desmosomes and many cytoplasmic projections. Some intracellular organelles and a few bundles of tonofilaments were observed in the cytoplasm. The light oval cells that were pale staining with toluidine blue contained dilated membranous organelles and many relatively evenly distributed tonofilaments. These cells were usually scattered in the vicinity of the focal accumulations of ghost cells, and the cell membrane was discontinuous in parts. The ghost cells contained many bundles of tonofilaments that were 60-240 nm in diameter and arranged in various directions. No intact intracellular organelles were noted in the cytoplasm. They were attached to the neighboring ghost cells with some desmosomes and their cell membrane was discontinuous in parts. A variety of vesicles, 90-450 nm in diameter, were scattered among the tonofilament bundles. Some of these contained needle-like crystals that were considered to be initial calcification sites in ghost cells. These vesicles presented morphological similarities to matrix vesicles, and it is therefore suggested that matrix vesicle-like structures are deeply involved with initiation of calcification of ghost cells in COC.     

The diagnosis and treatment of dentinogenic ghost cell tumor

The purpose of this study is to assess the diagnosis, treatment and prognosis of the dentinogenic ghost cell tumor (DGCT). This is a retrospective study of patients with DGCT who underwent one or multiple surgical interventions during the 10-year period from 1997 to 2007. Seven patients with DGCT were identified under the WHO 2005 classification guidelines. The lesions were located in the maxilla in 4 patients and in the mandible in 3 patients. Five patients experienced recurrences following conservative surgery. They were all treated with aggressive local resection. Two patients had no conservative surgery but aggressive local resection. After 7–105 months’ follow-up, no recurrences were found in any of the patients. Intraosseous DGCT should be treated by resection with an adequate safety margin, of at least 0.5 cm, as recommended for ameloblastoma. Patients with a DGCT should remain in long-term follow-up.     

骨外型牙源性钙化上皮瘤

骨外型牙源性钙化上皮瘤极为罕见,通过复习1966～2011年英文MEDLINE与1994～2011年中文CHKD中收录的文献,仅有37例骨外型牙源性钙化上皮瘤的个案报告。根据上述资料分析,发现该瘤具有以下临床特点,就诊年龄3～71岁,平均35.8岁;男13例,女19例,男女比例为1∶1.46;肿块直径0.5～4 cm,平均1.76 cm;好发部位主要是牙龈,累及下颌与上颌牙龈的比例为1∶1;组织学特征表现与骨内型牙源性钙化上皮瘤基本相同;复发率为5.4%。因该瘤具有浅表骨侵蚀能力,应行完整的肿瘤切除结合骨面刮治术。     

Cystic variant of calcifying epithelial odontogenic tumor

The calcifying epithelial odontogenic tumor is a rare benign odontogenic neoplasm of the jaw. Clinically, calcifying epithelial odontogenic tumor manifests as an intraosseous lesion (central type) in the majority of cases (95%). Extraosseous or peripheral lesions account for less than 5% of cases. Calcifying epithelial odontogenic tumor can be associated with an impacted tooth and give a radiographic simulation of dentigerous cyst. Most calcifying epithelial odontogenic tumors are solid in nature, histopathologically, and might have few cyst-like spaces within them. However, a true cystic calcifying epithelial odontogenic tumor is a rare possibility. We describe a case of a true cystic variant of calcifying epithelial odontogenic tumor in a 30-year-old male, which to our knowledge, is only the second reported case.     

Histopathologic study of epithelial components in the connective tissue wall of unilocular type of calcifying odontogenic cyst

Histopathologic study of satellite cysts and odontogenic epithelial islands in connective tissue wall of unilocular type of calcifying odontogenic cyst (COC) was made. The material was 13 cases consisting of 3 simple unicystic COCs, 9 odontome producing COCs and 1 ameloblastomatous proliferating COC. Satellite cysts were found in 6 cases, and were histologically classified into following types: simple cystic, odontome producing and ameloblastomatous. Histologic types of satellite cysts did not coincide with those of main cystic lesions in some cases. Odontogenic epithelial islands with or without proliferating feature were found in 9 cases, and were found in all cases with satellite cysts. Melanin and melanocytes were seen in an ameloblastomatous satellite cysts of 1 of 3 pigmented COCs.     

So-called calcifying odontogenic cyst: review and discussion on the terminology and classification

Toida M: So-called calcifying odontogenic cyst: review and discussion on the terminology and classification. J Oral Pathol Med 1998; 27: 49–52. © Munks-gaard, 1998.
The so-called calcifying odontogenic cyst (COC) shows extensive diversity in its clinico-histopathological appearances and biological behaviour. Because of this diversity, there has been confusion and disagreement on the terminology and classification of this lesion. The attempts at classification of COC may be divided into two concepts. The first concept is the "monistic" one that all COCs are neoplastic in nature, even though the majority are cystic in architecture and appear to be non-neoplastic. The second is the "dualistic" concept that COC contains two entities: a cyst and a neoplasm. Although the World Health Organization (WHO) classified COC as an odontogenic tumour in 1992 based on the former concept, current thinking favors strongly the latter one. In this article, several previous classifications of COC in the literature are discussed and a new simple classification scheme based on the "dualistic" concept is proposed.     

Odontogenic ghost cell carcinoma: a case report with immunohistochemical and ultrastructural characterization

Folpe AL, Tsue T, Rogerson L, Weymuller E, Oda D, True LD: Odontogenic ghost cell carcinoma: a case report with immunohistochemical and ultrastructural characterization. J Oral Pathol Med 1998; 27: 185-9. C Munksgaard, 1998. The odontogenic ghost cell tumor (OGCT) is the rare, neoplastic variant of the calcifying odontogenic cyst (COC). To date, there have been only four reports of malignant OGCTs, in five patients. We report an additional case of a malignant odontogenic ghost cell tumor that involved the right maxilla of a 20-year-old man. Our report includes its immunocytochemical and ultrastructural characterization.     

钙化上皮瘤及牙源性钙化上皮瘤的临床病理分析

目的：探讨钙化上皮瘤及牙源性钙化上皮瘤的临床表现、诊断及外科处理原则。方法：对13例钙化上皮瘤和4例牙源性钙化上皮瘤患者的临床资料进行回顾性分析。结果：所有患者均经手术治疗。钙化上皮瘤患者平均年龄11．2岁,小于10岁者占69．2％（10例）;位于头颈部8例（61．5％）,四肢4例（30．8％）,躯干1例（7．7％）。牙源性钙化上皮瘤患者平均年龄38．75岁,均位于颌骨。两种肿瘤无明显性别差异,均有复发、恶变的报道。结论：钙化上皮瘤和牙源性钙化上皮瘤在临床表现和病理诊断上具有明显差别,是两种不同的肿瘤;牙源性钙化上皮瘤具有局部浸润性生长,手术切除必须彻底。     

Persistent apical periodontitis associated with a calcifying odontogenic cyst

Aim  To report a case of calcifying odontogenic cyst (COC) that was suggestive of apical periodontitis adjacent to the roots of the maxillary incisor teeth.
Summary  Tooth 21 presented with clinical and radiographic signs of secondary infection, a post within the root canal and substantial internal tooth destruction; it was scheduled for endodontic surgery. Teeth 12 and 22 were root filled following the placement of a calcium hydroxide intracanal dressing for 21 days. Three attempts at root canal disinfection in tooth 11 were unsuccessful, and a persistent purulent drainage precluded completion of root canal treatment. Surgical enucleation of the periapical lesion was undertaken and the tissues submitted for histopathological examination. A diagnosis of COC was established based on the microscopic analysis. COC is an unusual benign lesion that represents 2% of all odontogenic lesions. Depending on the stage of development, it can mimic a large lesion associated with apical periodontitis and should therefore be considered in the differential diagnosis. In the case of COC, the definitive diagnosis can only be made with histopathological analysis.
Key learning points  • Persistent apical periodontitis may be of nonendodontic origin.
• Histological examination is essential to establish the cause of persistent apical periodontitis.
• Calcifying odontogenic cyst can mimic apical periodontitis.     

牙本质生成性影细胞瘤的治疗

目的:探讨牙本质生成性影细胞瘤的诊断、治疗,特别是对复发性牙本质生成性影细胞瘤的治疗。方法:回顾性研究了南京市口腔医院自1997-06～2009-06所收治的8例牙本质生成性影细胞瘤患者,手术切除范围视同于成釉细胞瘤,按临界瘤的治疗方法进行,要有0.5 cm的骨质安全缘。结果:发生在上颌骨4例,下颌骨4例。5例患者为复发性牙本质生成性影细胞瘤,扩大切除后,经过10～124个月的随访,所有病例均无复发。结论:牙本质生成性影细胞瘤的治疗类似于成釉细胞瘤,应确保有0.5 cm的骨质安全缘,对于复发性牙本质生成性影细胞瘤,还应保持长期随访。     

Peripheral calcifying cystic odontogenic tumour and peripheral dentinogenic ghost cell tumour: an updated systematic review of 117 cases reported in the literature

Purpose: To integrate the available data published on peripheral calcifying cystic odontogenic tumour (CCOT) and peripheral dentinogenic ghost cell tumour (DGCT) into a comprehensive analysis of its clinical and radiologic features.

Methods: An electronic search was undertaken in May, 2016. Eligibility criteria included publications reporting cases of peripheral CCOTs/DGCTs having enough clinical, radiological and histological information to confirm a definite diagnosis. Demographic data, lesion site and size, treatment approach and recurrence were analyzed.

Results: Hundred and thirty-eight lesions were found (65 publications), and 117 lesions (63 publications) with enough information were analyzed (55 CCOTs, 50 DGCTs, 12 unknown). Mean age of patients was 51.3?±?23.4 (min–max, 1–92), with higher mean age for the DGCTs variant. The lesions were more prevalent in the mandible, anterior region of the jaws, and in the second, sixth and eighth decades, with an equal sexual distribution. About 20% of all lesions showed signs of erosion of the underlying bone, with a higher rate for DGCTs. The mean lesion size was 1.3?±?0.8 (min–max, 0.4–3.0). Time of follow-up was informed for 37 lesions, with a mean?±?SD of 30.2?±?21.0 months (min–max, 6–84). Almost all lesions were treated by conservative surgery; only three recurrences were reported.

Conclusions: Peripheral CCOTs/DGCTs are rare lesions. Most of the lesions were treated by simple excision with or without curettage of the underlying bone. As the recurrence rate is very low, a conservative approach seems to be enough for the great majority of cases.