Odontogenic Keratocyst: A Comprehensive Overview

An odontogenic keratocyst (OKC) is a benign yet locally aggressive tumor that develops within the bone, originating from remnants of the dental lamina or tooth germ. It shows a strong tendency to recur and has the potential for malignant transformation. In its early stages, OKC is often asymptomatic, with swelling being the most common clinical sign when symptoms do appear. Accurate diagnosis is essential, involving differential diagnosis and the use of additional diagnostic tools, to ensure proper treatment planning. This helps minimize bone loss and prevents further complications for the patient.

1. Odontogenic keratocyst Presented by Dr. Rahul Srivastava Professor Rama Dental College Hospital & Research Centre Kanpur

2. INTRODUCTION Mikulicz in 1876, first described the odontogenic keratocyst (OKC) as a part of a familial condition affecting the jaws and as a separate entity. He termed it as a “ Dermoid Cyst”. In 1926, Hauer introduced the term “ cholesteatoma ” for it. Later on, the term “ keratocyst “ was coined by Philipsen (1956) and was based on the histologic appearance of the cystic lining. Pindborg and Hansen in 1963 described the essential features of this type of cyst. It is called keratocyst because the cyst epithelium produces a large amount of keratin which fills the cyst lumen.

3. In 2005, WHO reclassified odontogenic keratocysts (OKC) as tumors by modifying the previous two editions of WHO classification. Keratocystic odontogenic tumor (KCOT) was recommended as the appropriate name. However, in 2017, WHO changed odontogenic keratocystic tumor back to odontogenic keratocyst (OKC), which reflects the extensive and continuous investigation of this disease that has been carried on.

4. Molecular and Genetic basis of OKC Gene screening has revealed that PCNA and TP53 play vital roles in the development of odontogenic keratocysts (OKC). PCNA expression is elevated, while tumor suppressor genes like p53 and PTCH1 are often downregulated or mutated in OKC. The p53 protein family, including p53, p63, and p73, is expressed and linked to angiogenesis. M2 polarized macrophages, which promote angiogenesis by releasing factors like VEGF, TGF-β, and MMP-9, are commonly present.

5. Vascular endothelial growth factor (VEGF) plays a key role in initiating blood vessel formation that supports OKC growth. CD34 and CD99 are transmembrane glycoproteins involved in the progression of odontogenic keratocysts (OKC). High CD34 expression in microvessels contributes to cell adhesion and inflammation .

6. CD99, found in the basal and upper basal layers of OKC , may serve as a therapeutic target . Epidermal growth factor receptor (EGFR) expression in the basal and upper basal layers of OKC also stimulates epithelial cell proliferation .

7. CLINICAL FEATURES OKC mostly occurs in adults 30-50 years old, accounting for 14.3% of the total cases of odontogenic tumors. There are generally no obvious symptoms and signs in early-stage OKC, as even if the lesion is large, it still does not cause obvious jaw expansion, making it unnoticeable by facial appearance. They occur twice as often in the mandible as in the maxilla. 4. When OKCs originate from the mandible, the most common location is the posterior sextant, the angle or the ramus .

8. Conversely, the anterior sextant, mainly between canine and lateral incisor, and the third molar region are the most common sites of origin in the maxilla. 6. Large size lesions are particularly common at the angle and ramus of the mandible. 7. In spite of their aggressive behaviour , OKCs, in most cases, cause minimal bone expansion because of their propensity to spread along the intramedullary space of the “growing in the length bone ” .

9. Large lesions, causing significant erosion of cortical plates and involvement of surrounding structures, may be seen in asymptomatic patients. Higher recurrence rates are reported in patients affected by NBCCS and in multilocular lesions. The recurrences might be explained by different causes: Incomplete removal of highly active basal layer of the epithelial cyst lining. Growth of small intramedullary satellite cysts left behind by conservative treatment and development of lesions localised in the adjacent region of the jaws .

10. KCOT cystic lesion contents (aspirate) KCOT contain a very characteristic thick, creamy, dirty white, viscoid suspension of keratin, which has an appearance of pus, but without an offensive smell (Odorless). The smear should be stained and examined for keratin cells. Electrophoresis, will reveal low protein content, with high albumin to globulin ratio. Total protein will be found to be below 4 gm/100 ml, which differentiates the lesion from other cystic lesions. Cholesterol crystals, keratin squames , hyaluronic acid, rushton bodies and heparin and chondroitan sulfate also can be found in the aspirate.

11. Panoramic radiography Radiographically , OKCs appear as a well-defined unilocular or multilocular radiolucency bounded by corticated margins. On panoramic radiography, mandibular unilocular OKCs may show few and incomplete septa within the lesions; this finding is more common in larger than in smaller OKCs. Cropped panoramic radiograph shows a large OKC with well-defined and lobulated margins occupying the body of the mandible. 

12. Cone Beam and Multidetector Computed Tomography In the mandible, the OKCs have a tendency to grow predominantly mesiodistally along the length of the bone, causing minimal expansion of the buccal and lingual cortical plates. However, in some cases, the OKC may expand and erode the cortices. In contrast, large OKCs in the maxilla more frequently present a hydraulic expansion of the alveolar bone with remodelling , thinning, scalloping and perforation of the cortices. In addition, when OKCs originate from the alveolar bone subjacent to the maxillary sinus, its floor is lifted and lumen is reduced.

13. Cone Beam and Multidetector Computed Tomography On CT images, OKCs typically manifest as osteolytic lesions that exhibit a unilocular or a predominantly unilocular morphology with few and incomplete septa. The multilocular presentation with adjacent satellite cysts (daughter cysts) is possible, particularly in large lesions. In these cases, loculations are usually large and few (soap-bubble appearance).

14. Magnetic resonance imaging Most of the OKCs present intermediate or high signal intensity on T1-weighted sequences and heterogeneous signal intensity (from low to high) on T2-weighted sequences. MRI with diffusion-weighted imaging (DWI) and calculation of apparent diffusion coefficient (ADC) is sensitive to physiological parameters such as tissue cellularity , nucleus-to-cytoplasm ratio and integrity of cell membranes, thus providing information about the microstructure of living tissues. ADC value of OKCs is usually significantly lower than that of cystic/predominantly cystic ameloblastomas .

15. Multiple odontogenic keratocysts (OKCs) The presence of multiple OKCs is considered one of the major criteria for the diagnosis of Nevoid basal cell carcinoma syndrome ( NBCCS) and their occurrence may be the first sign of the disease. NBCCS, also known as Gorlin–Goltz syndrome, is an autosomal dominant multisystemic disease characterised by multiple nevoid basal cell carcinoma, multiple OKCs, palmar or plantar pits, calcifications of falx cerebri and skeletal abnormalities, such as bifid, fused or splayed ribs. Multiple OKCs are also observed in other syndromes, such as Noonan syndrome, Ehlers– Danlos syndrome and oral-facial-digital syndrome.

16. Differential diagnosis for odontogenic keratocyst   Odontogenic myxoma Central giant-cell granuloma Adenomatoid odontogenic tumor Traumatic bone cyst Lateral periodontal cyst Gorlin's cyst Multicystic ameloblastoma Ameloblastic fibroma

17. HISTOLOGIC FEATURES The odontogenic keratocyst wall is usually rather thin unless there has superimposed inflammation. The lining epithelium is highly characteristic, and is composed of: A parakeratinized surface which is typically corrugated, rippled or wrinkled. A remarkable uniformity of thickness of the epithelium, usually ranging from 6 to 10 cells thick. A prominent palisaded , polarized basal layer of cells often described as having a ‘picket fence’ or ‘tombstone’ appearance.

18. These cysts are formed with a stratified squamous epithelium that produces orthokeratin (10%), parakeratin (83%), or both types of keratin (7%). No rete ridges are present; therefore, the epithelium often sloughs from the connective tissue (94% of the time). The epithelium is thin, and mitotic activity is frequent; therefore, OKC grows in a neoplastic fashion and not in response to internal pressure. In the presence of an intense inflammatory process, the adjacent epithelium loses its keratinized surface, may thicken and develop rete processes or may ulcerate.

19. The lumen of the keratocyst may be filled with a thin straw colored fluid or with a thicker creamy material. Sometimes the lumen contains a great deal of keratin, while at other times it has little. Cholesterol, as well as hyaline bodies at the sites of inflammation, may also be present.

20. The epithelial lining is uniformly thin, generally ranging from 8–10 cell layers thick. The basal layer exhibits a characteristic palisaded pattern with polarized and intensely stained nuclei of uniform diameter. The luminal epithelial cells are parakeratinized and produce an uneven or corrugated profile.

21. MANAGEMENT OF ODONTOGENIC KERATOCYSTS Numerous surgical methods have been practiced in the management of odontogenic keratocysts (OKC). These methods are divided into: 1- Conservative methods include simple enucleation and marsupialization /decompression. 2- Adjuvant methods such as peripheral ostectomy , cryotherapy (liquid nitrogen) and Carnoy’s solution are considered aggressive forms of treatment which have shown more promising outcomes. 3- Radical methods involve mainly resection which yields the lowest RR however causes significant morbidity.

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