Primary intraosseous squamous cell carcinoma arising in an odontogenic cyst: a clinicopathologic analysis of 116 reported cases.

PURPOSE: To review the literature on primary intraosseous squamous cell carcinoma (PIOSCC) associated with odontogenic cyst. METHODS: All well-documented cases of PIOSCC published between 1938 and 2010 were collected. Only cases of PIOSCC arising from the lining of an odontogenic cyst, including the keratocystic odontogenic tumor, were selected. Age, sex, signs and symptoms, affected jaw, cyst type, treatment, histopathology, and outcome were recorded. RESULTS: The mean age was 60.2 years (range 1.3-90). There were 80 (69%) men and 36 (31%) women. Mass and pain were the most common presenting symptoms. The mandible was affected in 92 (79%) patients and the maxilla in 24 (21%). It was a residual/radicular cyst in 70 (60%) patients and a dentigerous cyst or a keratocystic odontogenic tumor in the remaining 40%. The histopathology was well-differentiated SCC in 53 (46%) patients and moderately differentiated SCC in 47 (40%) patients. Fifty-three (46%) patients were treated with surgery alone and 44 (38%) with surgery and radiotherapy. Fifty-eight (62%) patients survived 2 years and 36 (38%) survived 5 years. CONCLUSION: PIOSCC has a predilection for men (M/F ratio of 2.22:1), affects mainly adults in their 6-8th decades, occurs most frequently (79%) in the mandible, and is associated mainly with a residual/radicular cyst. Histologically, the well-to-moderately differentiated SCC was the most common. Surgery alone or combined therapy of surgery and radiation was the most common approach. The prognosis is 62% surviving 2 years and 38% 5 years.

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, Praetorius 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.

Odontogenic cyst with verrucous proliferation.

An unusual case of an odontogenic cyst with verrucous proliferation is described in a 13-year-old girl. This histologically distinctive odontogenic cyst variant does not appear to have been reported previously. The cyst was characterised by a series of verrucous projections in the lumen with hypergranulosis and cells resembling koilocytes, raising the possibility of a viral aetiology. However, no evidence of human papillomavirus (HPV) was found using immunohistochemistry and polymerase chain reaction (PCR) amplification.

The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 3. Immunocytochemistry of cytokeratin and other epithelial cell markers.

Numerous studies of keratin expression by the more common odontogenic cysts were done to determine whether patterns of cytokeratin staining could provide accurate diagnostic markers for the different varieties; to see whether comparative studies with oral mucosa and developing odontogenic epithelium could explain the pathogenesis of the cysts; and whether cytokeratin patterns could provide clues in elucidating the aggressive nature of the OKC. This review was a complex task with a range of at least 19 different cytokeratins being studied and also a broad range of antibodies in use for the same cytokeratin or group of cytokeratins. Moreover, there was not always standardisation of laboratory techniques in the selection and preparation of material. These difficulties were, in general, recognised by the different workers in the field, particularly when there was disagreement on results and caution was expressed about drawing conclusions from some positive findings. It would be fair to conclude that cytokeratin immunocytochemistry has not advanced to any meaningful extent, its use as a diagnostic marker for the OKC nor in eludidating its pathogenesis. With regard to OKC behaviour, it has been pointed out that there was strong reaction of OKC lining for keratin 16, a cytokeratin that has been associated with high proliferative activity. Yet other studies have also shown keratin 16 expression in dentigerous and radicular cysts. Differences in cytokeratin, EMA and CEA immunocytochemical reactivity between the parakeratinised and orthokeratinised varieties of cyst were demonstrated and the suggestion made that the orthokeratinised type has a considerably less aggressive behaviour, is a different entity and should bear a different name. Furthermore, Ki67 positive cells in the parakeratinised OKC linings were considerably more frequent than in the orthokeratinised linings.OKC, dentigerous and radicular cyst epithelium reacted positively for epithelial growth factor receptor (EGFr) but a trend indicating the most intense staining in the OKCs, followed by the dentigerous and then the radicular cyst linings led to the conclusion that the OKCs have an intrinsic growth potential not present in other odontogenic cysts.

The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 2. Proliferation and genetic studies.

Immunocytochemical studies of the expression of PCNA, Ki67 and p53 protein have been done by different groups on sporadic keratocysts (OKCs) and OKCs associated with the naevoid basal cell carcinoma syndrome (NBCCS). These 'markers' have in common that they are all expressed in actively proliferating cells, particularly in neoplasms. The findings were compared with their expression in dentigerous and radicular cysts. While there was some variability in the reported results, probably because of technical inconsistencies and the use of different antibodies, a definite trend emerged. In general PCNA, Ki67 and p53 positivity occurred more frequently and more intensely in the OKCs, and in the syndrome-related more than the solitary, compared with the other cyst types. In the OKCs the positivity was expressed mostly in the suprabasal layers of epithelium whereas in the other cysts types it was mainly in the basal layer that positivity was observed. Other studies showed that the gene for the NBCCS (PTCH), a tumour suppressor gene, mapped to chromosome 9q22.3. PTCH gene mutation has been shown to be an important step in the pathogenesis of the OKC and was thought to have a role in the development of the sporadic as well as the syndrome-related OKCs. The 'two-hits' hypothesis was invoked in support of the view that syndrome-related basal cell carcinomas (BCCs) and OKCs probably arise from precursor cells that contain an inherited 'first hit'. Only a single mutation was then required in the somatic cell to cause homozygous inactivation and neoplastic progression. Sporadic OKCs might arise from susceptible cells in which two somatic mutations or 'hits' have occurred, one of which manifests as allelic loss. The loss of tumour suppressor genes supports the view that the OKC is a benign neoplasm.

The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 1. Clinical and early experimental evidence of aggressive behaviour.

In this, the first of three articles on the aggressive nature of the odontogenic keratocyst (OKC), there is a review of clinical and histological observations which indicated that this was an aggressive lesion with a predilection for recurrence unlike the majority of other jaw cysts. This led to the tentative suggestion that the OKC might be a benign neoplasm. Subsequently there were early laboratory investigations that compared proliferation rates of the OKC epithelium with other jaw cysts, comparative enzyme histochemistry to assess aspects of its metabolism and markers that would enable accurate presurgical diagnosis of this cyst. Comparative studies were also pursued on the walls of the OKC and other jaw cysts to identify factors that might influence the capacity of the OKC to resorb the bone surrounding it. The clinical and laboratory studies reviewed in this section provided cogent presumptive evidence of the distinctively aggressive nature of the OKC that led numbers of investigators to pursue immunocytochemical and genetic studies on this cyst. Parts 2 and 3 of this series review this work.