The experimental production of odontogenic keratocysts

Abstract. In the course of transplantation studies using tooth germs from isologous mice, it was shown that as the tooth germs developed to form teeth, cysts also formed in the epithelium of the enamel organs. It was found that, these cysts were producing keratin. Cysts developed in association with all the developing tooth germs, and by 120 days post-transplantation many of the cysts had completely enveloped the crowns of the developing teeth. It has been clearly demonstrated that in addition to enamel production, tooth germ epithelium is capable of cystic change and keratin formation. As many histological similarities exist between the experimentally induced keratin producing cysts and human odontogenic keratocysts, it is suggested that the development of the experimentally induced cysts from enamel organs actively involved in amelogenesis may be of direct significance to the etiology of human odontogenic keratocysts.     

Familial multiple odontogenic keratocysts

Multiple odontogenic keratocysts (OKCs) are principle features of nevoid basal cell carcinoma syndrome (NBCCS; Gorlin-Goltz syndrome). NBCCS is a genetic disorder transmitted by an autosomal dominant gene with variable expressivity, which is important to recognize when a patient has multiple OKCs. The cysts of the jaws are among the most common findings. Another feature is a certain appearance of the face, such as: large calvaria, high-arched eyebrows, broad nasal root, and mild hypertelorism. Before-therapy diagnosis is, therefore, as important as after-therapy diagnosis. Genetic counseling and examination may also be indicated. The purpose of this paper was to present a family case report of nevoid basal cell carcinoma syndrome with multiple odontogenic keratocysts. The features identified by these combined clinical, imaging, and histologic findings are described, along with a brief mention of the family history and a review of the literature.     

The conservative management of large odontogenic keratocysts

Odontogenic keratocysts, although well recognised to have a high recurrence rate are not invasive tumours and should not be treated by radical surgery with its attendant morbidity. Four cases of successful management by marsupialisation, and three examples of successful enucleation and packing are described, suggesting that conservative methods can be used in the treatment of large odontogenic keratocysts.     

The implications of inflammation in odontogenic keratocysts

The histologic features of 112 odontogenic keratocysts (OKC's) were examined from both a clinical and histopathological perspective with emphasis on the microscopic presence of inflammation and its relationship to transformation of the classic epithelial cyst lining found in OKC's to a nonkeratinized lining characteristic of common inflammatory odontogenic cysts. Eighty-five (76%) of these cases exhibited inflammation. The sensitivity of inflammation as a predictor of this aforementioned transformation is 100%, and its positive predictive value is 88%. The specificity of the same parameters remains high at 73%. Using previous studies, the implications of these findings on the biologic behavior of OKC's is discussed with special reference to therapeutic considerations.     

The implications of inflammation in odontogenic keratocysts

The histologic features of 112 odontogenic keratocysts (OKC's) were examined from both a clinical and histopathological perspective with emphasis on the microscopic presence of inflammation and its relationship to transformation of the classic epithelial cyst lining found in OKC's to a nonkeratinized lining characteristic of common inflammatory odontogenic cysts. Eighty-five (76%) of these cases exhibited inflammation. The sensitivity of inflammation as a predictor of this aforementioned transformation is 100%, and its positive predictive value is 88%. The specificity of the same parameters remains high at 73%. Using previous studies, the implications of these findings on the biologic behavior of OKC's is discussed with special reference to therapeutic considerations.     

Ultrastructure of odontogenic keratocysts.

The ultrastructural features of an odontogenic keratocyst are described. The results of the investigation suggest that the basal lamina complex in the odontogenic keratocyst appears to be morphologically normal. The frequently observed splitting of the epithelium from the capsular tissue is marked by the separation of the epithelium and the basal lamina complex from the connective tissue. The morphologic features of the parakeratinized surface zone of the epithelium suggest that the odontogenic keratocyst may be characterized by "incomplete" parakertinization.     

Orthokeratinised odontogenic keratocysts in Malaysians

The records of the Division of Stomatology, Institute for Medical Research, Kuala Lumpur, Malaysia, were reviewed for the incidence of odontogenic keratocysts of the orthokeratinised variety, during the 20-year-period, 1967 to 1986. Nine cases were found. The clinical, histological and radiological features of these cases are reported. Many features were similar to previous reports of this entity but a peak incidence in the second decade of life, an almost even distribution in the maxilla and mandible, and a distinct predilection for the Chinese were observed. It is suggested that these features may be peculiar to Malaysians.     

Multiple odontogenic keratocysts of the jaws

Single odontogenic cysts are very well documented in the literature. Of those less common reports concerning multiple jaw cysts, many have been associated with systemic conditions or syndromes such as Gorlin-Goltz or basal cell naevus syndrome, Hunter's syndrome and mucopolysaccharidosis, for example, Maroteaux-Lamy syndrome. A case of multiple odontogenic keratocysts unassociated with any syndrome is reported so as to add to the growing number of such cases in the literature. The possibility of this case being a partial expression of the Gorlin-Goltz syndrome is discussed.     

牙源性角化囊肿中PTCH基因的突变检测

目的检测牙源性角化囊肿（OKC）中PTCH基因突变的发生频率、类型及分布特点，分析散发OKC与伴发痣样基底细胞癌综合征（NBCCS）OKC之间的分子病理联系。方法收集8例OKC新鲜病变组织（4例散发，4例伴发NBCCS），提取DNA，采用PCR直接测序法检测OKC病变组织中的PTCH基因突变。结果分别于4例NBCCS—OKC和2例散发OKC中检测到6处PTCH基因突变，2例为错义突变，引起1个氨基酸的改变；其余4例突变分别为1～7个碱基插入或缺失，其中3例引起读码框的改变（移码突变），并导致蛋白质的提前截断，1例导致了2个氨基酸的插入。结论PTCH基因突变不仅常见于NBCCS—OKC，部分散发OKC病变也可以发生该基因的异常。     

The significance of recurrent odontogenic keratocysts in bone grafts

A comprehensive literature review identified 10 reported cases of recurrent odontogenic keratocysts (OKCs) in bone grafts. Seven of them were sufficiently documented for further analysis. All except one of the patients had a long history of repeated recurrences. They were all approached via an extraoral route, avoiding a mucosal perforation, when the bone graft was placed after a segmental resection. In three cases, this was also true for the primary treatment. The origin of the recurrences is considered to be the oral mucosa, almost certainly involving the proliferation of epithelial islands or microcysts that were close to the original OKC. A plea is made to avoid segmental or marginal resections for this lesion and to pay attention to possible epithelial islands/microcysts in the overlying attached mucosa in the case where marsupialization is preferred.     

PTCH gene mutations in odontogenic keratocysts

An odontogenic keratocyst (OKC) is a benign cystic lesion of the jaws that occurs sporadically or in association with nevoid basal cell carcinoma syndrome (NBCCS). Recently, the gene for NBCCS was cloned and shown to be the human homologue of the Drosophila segment polarity gene Patched (PTCH), a tumor suppressor gene. The PTCH gene encodes a transmembrane protein that acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues, including tooth. We investigated three cases of sporadic odontogenic keratocysts and three other cases associated with NBCCS, looking for mutations of the PTCH gene. Non-radioactive single-strand conformational polymorphism and direct sequencing of PCR products revealed a deletion of 5 base pairs (bp) in exon 3 (518delAAGCG) in one sporadic cyst as well as mutations in two cysts associated with NBCCS, a nonsense (C2760A) and a missense (G3499A) alteration. This report is the first to describe a somatic mutation of PTCH in sporadic odontogenic keratocysts as well as two novel mutations in cysts associated with NBCCS, indicating a similar pathogenesis in a subset of sporadic keratocysts.     

Effects of positive pressure in odontogenic keratocysts

Intracystic fluid pressure is thought to be involved in odontogenic cyst growth. In this study, we investigated the effects of positive pressure on the expression of interleukin-1alpha (IL-1alpha), matrix metalloproteinases (MMPs), and prostaglandin E2 (PGE2) in odontogenic keratocysts to determine whether this pressure stimulates inflammatory cytokine production and signaling of osteoclastogenic events. Positive pressure enhanced the expression of IL-1alpha mRNA and protein in odontogenic keratocyst epithelial cells, and increased the secretion of MMP-1, MMP-2, MMP-3, and PGE2 in a co-culture of odontogenic keratocyst fibroblasts and the epithelial cells. The pressure-induced secretions were inhibited by an interleukin-1 receptor antagonist. Recombinant human interleukin-1alpha (rhIL-1alpha) increased the secretion of MMP-1, MMP-2, MMP-3, and PGE2 in the fibroblasts. Furthermore, in the fibroblasts, rhIL-1alpha enhanced the expression of macrophage colony-stimulating factor (M-CSF) mRNA, and rhIL-1alpha-induced PGE2 increased the expression of nuclear factor kappaB ligand (RANKL) mRNA. Thus, positive pressure may play a crucial role in odontogenic keratocyst growth via stimulating the expression of IL-1alpha in epithelial cells.     

Lectin histochemistry of ameloblastomas and odontogenic keratocysts

The cell membrane carbohydrate components of 10 simple (follicular and/or plexiform pattern) and 5 acanthomatous ameloblastomas, one plexiform unicystic ameloblastoma, one soft tissue ameloblastoma and 11 odontogenic keratocysts were studied in paraffin-embedded tissues using horseradish peroxidase-conjugated lectins. The presence of glucose and mannose was demonstrated by intense labelling with Concanavalin ensiforme (Con A) in 73% of the ameloblastomas examined, while periodate oxidation of the specimens prior to Con A (PA/Con A) stained 53% of the cases. Ameloblastomas did not express receptors for Triticum vulgaris (WGA), Erythrina chrystagalli (ECA), Arachis hypogea (PNA), and Ulex europaeus (UEA-1). The plexiform unicystic ameloblastoma and the soft tissue ameloblastoma examined showed the same cell membrane glycoproteins as the simple and acanthomatous ameloblastomas. Forty-five per cent of the keratocysts demonstrated Con A reactivity from the basal to the keratinized layer, while 72% of these specimens showed positive PA/Con A reactivity from the parabasal to the keratinized layer. Staining with WGA, ECA, PNA, and UEA lectins also revealed the presence of N-Acetyl-glucosamine and fucose oligosaccharides in the plasma membrane of basal, spinous and keratinized cell layers of the odontogenic keratocysts. The distinct cell surface carbohydrate composition of the ameloblastoma and odontogenic keratocyst may be responsible for the differences in biological behavior in these conditions.     

Scanning electron microscopic study of odontogenic keratocysts

Three odontogenic keratocysts were examined with a scanning electron microscope (SEM) on their surface cells, prickle cells, basal cells, and the epithelial-connective tissue interface. The microridges of the surface cells had a short, discontinuous, branched or beaded appearance. Intracellularly, the flattened keratinized cells formed a network consisting of delicate microfilaments. The prickle cells had numerous cytoplasmic projections and a large round nucleus that occupied most of the cytoplasm. The basal cells had two types of cytoplasmic process and a large oval polarized nucleus. The epithelium and the lamina propria were connected by a fibrous and fibrillar network.     

Cartilage in the walls of odontogenic keratocysts

Only one histologically documented case of cartilage in the wall of an odontogenic keratocyst has been reported in the English language literature. Four new cases are presented with the clinical, radiographic and histopathologic features described. To our knowledge this finding has not been reported in association with any other type of odontogenic cyst.     

CEA immunoreactivity in odontogenic tumors and keratocysts

Forty-five oral tumors and cysts were stained immunohistochemically for the presence of carcinoembryonic antigen (CEA). CEA, or a CEA-like antigen that is not nonspecific cross-reacting antigen (NCA), was demonstrated in the majority of aggressive or malignant tumors showing squamous differentiation, including cases of ameloblastoma, odontogenic carcinoma, and squamous carcinoma. CEA immunoreactivity was also found in cases of odontogenic keratocyst and focally in squamous odontogenic tumors but was not found in any of the ameloblastic fibromas, myxofibromas, odontogenic adenomatoid tumors, malignant melanomas, or apical cysts.