Odontogenic Keratocyst Pathology 

Updated: Dec 22, 2020
  • Print








Odontogenic Keratocyst Pathology. Panoramic film d Odontogenic Keratocyst Pathology. Panoramic film demonstrating mandibular odontogenic keratocysts in nevoid basal cell carcinoma syndrome.


Many odontogenic tumors have been described to have extraosseous equivalents, and although odontogenic keratocysts (OKCs) are regarded primarily as intraosseous lesions, they can also occur in a peripheral location [11] ; nearly three dozen such cases have been reported in the literature, [12, 13] with a mean patient age of 52 years and a slight male predilection. [13] Peripheral odontogenic keratocysts can be seen in association with NBCCS. [12]

The cystic nature of odontogenic keratocyst (OKC) has long been debated, with some investigators classifying the OKC as a benign tumor. [14] In recent years, the WHO has recommended that the term "keratocystic odontogenic tumor" (KCOT) replace the term "odontogenic keratocyst" (OKC), as it better reflects the neoplastic nature of the lesion. [15, 16] Several factors, such as the cyst's aggressive behavior, high mitotic activity histologically, and evidence of associated genetic and chromosomal abnormalities (eg, mutation of the PTCH gene) often seen in neoplasia, serve as the basis for this new classification. [6, 16, 17]




Odontogenic keratocysts (OKCs) account for approximately 3-11% of all cysts in the jaws. [1, 20] They occur in all ages, with a peak incidence in the second and fourth decades of life, [9, 20] with the youngest patient reported at age 5 years. [1] The mean age of patients with multiple odontogenic keratocysts (OKCs), with or without NBCCS, is younger than those with single nonrecurrent OKCs.

Odontogenic keratocyst (OKC) is predominantly a disease of white individuals, primarily Northern Europeans, and there is a reported male-to-female ratio of 1.6:1, [1, 20] although Chirapathomsakul et al reported that OKCs are slightly more common in women than men. [20] Peripheral odontogenic keratocysts (OKCs) have a female predominance with a female-to-male ratio of 2.2:1. [12]



Odontogenic keratocysts (OKCs) are generally thought to be derived from remnants of the dental lamina (rests of Seres), traumatic implantation or down growth of the basal cell layer of the surface epithelium, [1] or reduced enamel epithelium of the dental follicle. [21] Studies have suggested a genetic cause, specifically a PTCH gene aberration, in the etiology of these cysts.





Clinical Features and Imaging

Clinically, odontogenic keratocysts (OKCs) generally present as a swelling, with or without pain. [15, 21] The cyst classically grows within the medullary spaces of the bone in an anteroposterior direction, causing expansion that is at first minimal. [22] Buccal expansion is noted in approximately 30% of maxillary and 50% of mandibular lesions. [21] It has been demonstrated that the collagenase activity in the cysts' epithelium with its resorbative properties appears to regulate the ability of the lesion to grow expansively in bone. [23]

Radiographically, odontogenic keratocysts (OKCs) present as a well-defined radiolucent lesion that is either unilocular or multilocular, with smooth and usually corticated margins, unless they have been secondarily infected (see the images below). [20] In 25-40% of cases, there is an unerupted tooth involved with the lesion [20] ; adjacent teeth may be displaced, but root resorption is rarely seen. Maxillary lesions tend to be smaller than mandibular lesions; however, more extensive involvement can be appreciated in the maxilla because of the cancellous nature of the bone. [15] Larger lesions can cause bony expansion with or without perforation of the cortical plates. [3]

Odontogenic Keratocyst Pathology. I-CAT computed t Odontogenic Keratocyst Pathology. I-CAT computed tomography scan of a multilocular odontogenic keratocyst.
Odontogenic Keratocyst Pathology. I-CAT computed t Odontogenic Keratocyst Pathology. I-CAT computed tomography scan demonstrating extensive compartmentalization of a mandibular odontogenic keratocyst.





Gross Findings

The epithelial lining and connective tissue wall of the odontogenic keratocyst (OKC) is characteristically thin and friable, thus causing the specimen to fragment when treated. [22] Grossly, the lesion often has a bosselated, gray, cystic appearance mimicking the appearance of a glove.


Microscopic Findings


Odontogenic Keratocyst Pathology. Typical odontoge Odontogenic Keratocyst Pathology. Typical odontogenic keratocyst lining. Classic features demonstrating a corrugated parakeratinized surface can be identified. The epithelial lining is supported by a chronically inflamed connective tissue wall.
Odontogenic Keratocyst Pathology. High-power micro Odontogenic Keratocyst Pathology. High-power micrograph of an orthokeratinized odontogenic keratocyst demonstrating corrugated surface keratin with chevron keratinization.


Odontogenic Keratocyst Pathology. An odontogenic k Odontogenic Keratocyst Pathology. An odontogenic keratocyst demonstrating epithelial odontogenic rests in the supporting collagenous wall.


Odontogenic Keratocyst Pathology. Parakeratinized Odontogenic Keratocyst Pathology. Parakeratinized odontogenic keratocyst. Note the prominent parakeratinized corrugated surface, flat epithelial-connective tissue interface, prominent hyperkeratotic basal epithelial layer, and minimal keratinaceous and proteinaceous debris in the lumen.
Odontogenic Keratocyst Pathology. Odontogenic kera Odontogenic Keratocyst Pathology. Odontogenic keratocyst demonstrating an orthokeratinized surface, a prominent granular layer with acanthosis, and relatively flattened basal epithelial layer cells.



In a review of 183 cases of odontogenic keratocysts (OKCs), 17.1% of cases showed koilocytosis, which raises the possibility of a papillomavirus (HPV) etiology for the lesion [29] ; however, HPV has not been identified in odontogenic keratocysts (OKCs) using molecular and immunohistochemical methods. The OKC lining may rarely show epithelial dysplasia, and the lesion does have the potential to evolve into ameloblastoma or squamous cell carcinoma. [30]



Strong p63 staining has been demonstrated in the epithelium of odontogenic keratocysts (OKCs), especially in the suprabasal layer of the epithelium. [31] It has been postulated that p63 plays a role in blocking apoptosis-inducing and growth inhibitory actions, which may facilitate the proliferative potential of epithelial cells due to its capability of blocking wild type p53, thus enhancing the biologic aggressiveness of these cysts. [31, 32, 33]

Matrix metalloproteinases (MMPs) are enzymes thought to play an important role in regulating the integrity and composition of the extracellular matrix (ECM) and consequently degradation, proliferation, differentiation, and cell death. [17] MMP-1, synthesized by a variety of normal cells including epithelial cells, is one of the major proteases that can degrade the triple helical domain of type I fibrillar collagen, which is responsible for connective tissue strength and rigidity. MMP-1’s expression is thought to be associated with odontogenic keratocyst (OKC) degradation of the organic bone matrix, favoring dissemination of these cysts through the trabecular spaces. [17] With immunohistochemistry, MMP-2s have also been observed to reside in the basement membrane of odontogenic keratocysts (OKCs), and they have been implicated in the degradation of the extracellular matrix surrounding the cysts. [17]  Thus, deregulation of desmosome proteins and extracellular matrix are important changes in the pathobiology of odontogenic keratocysts. [34]

Vascular endothelial growth factors (VEGFs) comprise a family of multifunctional proteins and act as a sensitive measure of the angiogenic potential of a lesion. [35] VEGFs have been implicated in the pathogenesis of cystic tumors and radicular cysts, [35] and they have been documented to be intensely expressed in odontogenic keratocysts (OKCs). [15, 35]

The TrkB and p-Akt signaling appear to be overexpressed in odontogenic keratocysts relative to ameloblastic carcinoma. [36]



A number of studies have examined the expression profile of p53, proliferating cell nuclear antigen (PCNA), and Ki-67 in odontogenic keratocysts (OKCs). These markers have been reported to be expressed more strongly in these cysts than in other types of odontogenic cysts. [37, 38]  Increased Ki-67 labeling and its expression in the suprabasal cell layers of the epithelial lining in odontogenic keratocysts may play a role in its clinical aggression. [39]  Single nucleotide polymorphisms within a variety of genes have also been associated with certain types of odontogenic lesions. [33]


The biologic mechanism associated with the expression of p53 protein in the epithelium of odontogenic keratocysts (OKCs) is not well understood, but the aggressive behavior and high recurrence rate of these lesions may be related to the expression of this protein. [33, 41] In a study performed on 37 odontogenic keratocyst (OKC) cases by Gurgel et al, 91.9% of the cases were strongly positive for p53 in the suprabasal layers of the cystic epithelium, [31] but no significant difference in p53 immunostaining was observed between odontogenic keratocysts (OKCs) associated with NBCCSs or sporadic OKCs [31, 41] It remains unclear whether p53 positive immunostaining in odontogenic keratocysts (OKCs) is because of gene mutation or simply a product of accumulation of normal p53 protein in the site. [31]

The NBCCS or PTCH gene has been mapped to chromosome 9q22.3-q31, which functions as a tumor suppressor. Studies on NBCCS and occasional solitary odontogenic keratocysts (OKCs) suggest that the PTCH gene might play a role in the development of sporadic OKCs. [15] Sun et al reported 26 PTCH1 mutations in odontogenic keratocysts (OKCs). [42]


Prognosis and Predictive Factors


Treatment of odontogenic keratocysts (OKCs) remains controversial, and management modalities can be categorized as either "conservative" or "aggressive," [44] based on multiple factors including lesional size, anatomic relationship, recurrence pattern, and the cyst's association with NBCCS. [16] Multiple surgical management techniques have been reported, including marsupialization, enucleation, enucleation with the use of Carnoy's solution, decompression, marginal or radical surgical resection, and bone implantation. [43]

There is very little information in the literature defining whether the size of an odontogenic keratocyst (OKC) can affect its potential to recur. [16, 45] In a report by Zhao et al, of 489 patients treated for odontogenic keratocysts (OKCs), 255 had follow-up over a period of 3 to 29 years, in which no correlation could be made as to recurrence potential based on lesion location. [43]