ODONTOGENIC KERATOCYST

or KOT

Dr. Mayank Vermani PG 2nd year Deptt. Oral & Maxillofacial Surgery

INTRODUCTION
Term by Philipsen in 1956

Epithelial developmental cyst derived from enamel organ or dental lamina.

Comprises 10-12 % of all cysts of jaw.

WHO- Keratocyst odontogenic tumour

Defined as benign uni or multicystic, intraosseous tumour of odontogenic origin, with a characterstic linning of parakeratenized stratified squamous epithelium which have potential for aggressive & infiltrative behaviour.

UNIQUE

supported by reported cases. Penetrates the cortical bone May extend to the skull base from mandible or to the orbit and infratemporal fossa from the maxilla. (J ORAL AND MAXILLOFAC SURG 64;308316:2006)

Aggressive nature

High recurrence rate

In 1976, Brannon proposed 3 mechanisms for KCOT recurrence: incomplete removal of cyst lining, growth of new KCOT from satellite cysts and development of a new KCOT in adjacent area that is interpreted as a recurrence.

Specific histopathological feature

FREQUENCY
Anywhere b/n 3-10.5% Shears found OKCs about 11.2% in series of 2616 lessions 7-8% by Toller 11% by Marker

Bataineh & Mansour- 11% of all jaw cysts Dammer 13% of all cysts

 Age Peak in 2nd-3rd decade, 5th decade Sex males> females (1.5:1) Site - mandible> maxilla Dammer et al 3:1 Stolinga no predilection Mandi : maxi is 14:68 by stolinga. Half of keratocyst occurs at angle of mandible extends to asc ramus and body.

CLINICAL PRESENTATION
Pain, swelling, facial asymmetry or discharge, paresthesia or may be free of symptoms. Hard swelling with perforation of cortical plate

Maxillary more tends to be infected.

Aggressive odontogenic cyst, due to relatively high reoccurence rate, relatively fast growth & tendency to invade adjacent tissues.

STOELINGA REPORTED AN IMPORTANT CHARACTERSTIC Lack of bony expansion ,

Follows a path of least resistance, Tends to hollow out the mandible. Thereby replacing bone marrow rather than giving rise to periosteal formations

 Bony fenestrations are seen on lingual side of OKCs. rare because of the thick buccal plate to be resorbed. Often associated with impacted or missing

SYNDROMES ASSOCIATED WITH OKC

Gorlin goltz syndrome Skin Oral Facial features Skeletal CNS Nevoid basal cell Carcinoma in pediatric patients(multiple OKCs in 50%)

 Simpson-Golabi-Behmel syndrome (x- linked) Overgrowth Mental retardation Broad & coarse face Flat frontal bone & mid-facial deficient with obvious hypertelorism. Noonan Syndrome Micrognathia, high arched palate, malocclusion, bifid uvula and rarely cleft palate

 Genetic study patched gene (PTCH) gene , tumour suppresor gene participates in tumourogenesis of sporadic neoplasm detected mutations in nevoid basal cell carcinoma Also called as benign cystic neoplasm because the loss of a tumour suppressor gene

HISTOPATHOLOGY
7 Histologic criterion
Lining epithelium thin and uniform, lack of rete pegs, parakeratinized(83%) surface Thin & mitotic activity is high like neoplasm If inflamed Basal cell layer- well defined, palisaded layer, polarized picket fence or tombstone appearance.

Spinous cell layer- intracellular edema. Keratinization parakeratotic but may be orthokeratotic Keratin layer- corrugated Fibrous cyst wall- thin & uninflamed.

Metalloproteinase mediated degradation of collagen in juxtaepithelial regions. Connective tissue wall contains mucopolysaccharides, microcysts(20%) & epithelial islands(50%) and is free of inflamation Daughter or satellite cysts more common in syndromes Lumen- cholesterol & hyaline bodies Electrophoresis- low content of soluble protein

 More aggressive? High mitotic count, higher turnover & active collagenase

Angiogenesis is a feature of benign neoplasm evidence of this in OKC may account for the behaviour

IMMUNOHISTOCHEMISTRY
Variety of immunohistochemical markers including CEA,p53 protein, lectin, lactoferrin, HPV , EGF. Cytokeratin 18 staining was more common in non syndromic patient, c 17 did not

Emmprin level was significantly higher in epithelial linning

In general PCNA, Ki 67 & p53 positive PTCH gene mutation is an important step in pathogenesis

 Two hit hypothesis-arises from precursor cells that contains an inherited first hit
Then only a single mutation required in somatic cell to cause homozygous inactivation and neoplastic progression sporadic OKCs might arise from susceptible cells in which two somatic mutations have occurred , one manifests as allelic loss. Loss of tumour suppresor genes supports the view that OKC is a benign neoplasm.

RADIOGRAPHS

STOELINGA JW(2001) DEVIDED RADIOGRAPHIC PRESENTATION OF OKC

4 CATEGORIES UNILOCULAR i.e. a more or less round configuration with or without well defined radiographic margin. Scalloped i.e radiolucency with a festooned margin

Mulilobular i.e. two or more lobes were seen with no bony septae dividing the lobes.
Multilocular i.e. separate locules were seen seemingly divided by bony septae

 No expansion of bone at all both lingual and buccal expansion may occur

Roseberg et al found some degree of expansion in all case, large sized unilocular lession showed minimal expansion. Downward displacement of inferior alveolar canal and resorption of the lower cortical plate of mandible may be seen Mental foramen may not be seen . Rosenberg et al reported one case in which there was superior displacement of mandibular canal

 Scalloping of border common,Ill defined periphery EFFECTS- displacement of impacted Resorption, Extrution, Mobility 1/3rd have lingual expansion

TREATMENT
-CONSERVATIVE
-RADICAL

ADVANTAGES OF CONSERVATIVE THERAPY

Preservation of bone, soft tissue and teeth.
Avoid damage to the adjacent anatomic structures. Reduction in cost, hospital admission and reconstruction procedures. Functional integrity is maintained. Reconstruction itself has failures/pitfalls.

Various Conservative treatment modalites are:

Enucleation

enucleation alone enucleation followed by curettage

- Curettage with physical mean (Sharp Curette, Rotary bur) - Curettage with chemical mean (Carnoys solution) - Curettage with Thermal (Cryosurgery)

Decompression Marsupialization
Marsupialization followed by enucleation

Decompression and irrigation Decompression and marsupialization

Peripheral ostectomy

Enucleation : It is defined as to remove whole or clean, as a tumor from its envelope.

Curettage : dened as the removal of growths or other material from the wall of a cavity . . . as with a curette. Marsupialization : It implies the exteriorization of a cyst or an enclosed cavity by resecting a portion of its wall and suturing the cut edges of the remaining wall to adjacent soft tissue, thereby creating a pouch. Decompression : It is accomplished by opening into a cystic cavity, followed by placement of a drainage tube to allow the opening to persist.

According to Tucker et al : Decompression and marsupialization, although serving the same function and relying on the same basic principle of bone regeneration, are two entirely different techniques as marsupialisation is a one-stage operation; decompression is a two-stage procedure.

Enucleation
Studies show that the recurrence rate with alone

Enucleation is high so it is performed with adjunctive therapies.

Table: Recurrence by treatment modality.
Treatment Enucleation Marsupialization Total No. of patients 58 10 68 No. of recurrences 12 4 16 (%) 20.7 20.7 40.0 23.5 (Oral Oncology 46 (2010) 740742)

Table . RECURRENCE (J Oral Maxillofac Surg 63:635-639, 2005)

Recurrence by treatment

No. Of Recurrences/ Treatments

%Recurrences/ Treatments

Enucleation Peripheral ostectomy

6/11 2/11

54.554.5 18.2

Peripheral ostectomy and Carnoys solution

Enucleation and Carnoys solution Resection Recurrence by individual treatment Peripheral ostectomy Carnoys solution

0/13

1/2

50

0/3

2/24 1/15

8.3 6.7

Enucleation
Resection

7/13
0/3

53.8
0

ADJUNCTIVE THERAPHIES
Enucleation followed by curettage
- Curettage with physical mean (Sharp Curette, Rotary bur) - Curettage with chemical mean (Carnoys solution)

- Curettage with Thermal (Cryosurgery)

TREATMENT OF ODONTOGENIC KERATOCYSTS BY ENUCLEATION AND CARNOYS SOLUTION.

Table : Recurrence rate Treatment type Curettage Cysts reported 265 No. recurrences (%) 19.2

Enucleation alone
Enucleation and Carnoys*

387111
601

28.7
1.6 1.6

Radical enucleation
Enucleation and cryotherapy

61
165

16.7
31.3

Marsupialisation
Resection

4511
380

24.4
0

Enucleation and carnoys sol cont.. It act as cauterizing agent that denaturates proteins, nucleic acid and almost all other organic molecules. Penetrates tissue and cause rapid local fixation. Eliminate residual epithelial remnants that left after enucleation. Applied for 3 min before enucleation. (Clinic Oral Invest ,14;27-34:2010)

USE OF ENUCLEATION AND LIQUID NITROGEN CRYOTHERAPY

Liquid nitrogen kill the epithelial remnants or satellite cysts. Intact osseous frame work allows osteoconduction. Cryosurgery causes necrosis in bone and cell death (below 20C ) by forming intracellular and extracellular ice crystal plus osmotic and electrolyte disturbances. Relative lack of bleeding and scarring. Due to difficulty in controlling the amount of liquid nitrogen applied to the cavity, the resultant necrosis and swelling can be unpredictable.

(J Oral Maxillofac Surg 59:720-725, 2001)

USE OF METHYLENE BLUE FOR PRECISE PERIPHERAL OSTECTOMY OF KERATOCYSTIC ODONTOGENIC TUMOUR
After the tumour has been enucleated, the surface of the bone cavity is dyed with a 1% solution of methylene blue.
The bone stains heavily and peripheral ostectomy is possible that will remove any residual peripheral neoplastic tissue. (British Journal of Oral and Maxillofacial Surgery 49 :e84e85, 2011)

 DECOMPRESSION AND IRRIGATION Growth of cysts is believed to occur by a combination of osmotic pressure and pressure resorption, coupled with release of prostaglandins and growth factors. Decompression decreases the amount of interleukin that is released.
Disadvantages

Selected group of patients treated.

Cooperation of the patient is required.

Frequent return to hospital is required.

At least 19 months are required for treatment. (J oral and Maxillofac Surg, 62:651,2004)

DECOMPRESSION AND MARSUPIALIZATION

the earliest advocated treatment.

first suggested by Partsch (Partsch 1 procedure)

the partsch 2 procedure is enucleation and primary closure)

What Marsupialization/Decompression does?

higher levels of interleukin-1 (an inflammatory, multifunctional cytokine) decrease significantly after marsupialization. (J Oral Pathol Med 31:526,2002) Post decompression specimen indicating a return to more normal oral epithelium. (J Oral Maxillofac Surg 58:935, 2000)

 Resolution of the lesions with a recurrence rate of 0%. with marsupialization and decompression
(J Oral Maxillofac Surg 62:651, 2004)

MARSUPIALIZATION FOLLOWED BY ENUCLEATION

Marsupialization followed by enucleation can be performed for any reduced OKC small enough to be removed completely.

It is also reserved for cases in which the cyst size has not decreased significantly after a certain point.

THE SONIC HEDGEHOG (SHH) PATHWAY

Alterations in the SHH signaling pathway genes cause a number of developmental defects.

(Medical Hypotheses (2006) 67, 12421244)

INHIBITION OF SHH SIGNALING PATHWAY BY CYCLOPAMINE (MOLECULAR TREATMENT STRATEGY OF ODONTOGENIC KERATOCYST)

Cyclopamine

( Genes Dev. 2002 16: 2743-2748)

RESECTION
Three different types of resections (mostly applicable for the mandible) can be performed: En bloc resection or a marginal (segmental) resection without disruption of the bone continuity Partial resection with the continuity defect Total resection ( maxillectomy, mandibulectomy ) in extreme cases.

 Enbloc resection or resection without continuity defects is the removal of the lesion and of a defined measureable perimeter of adjacent bone along with the lesion while the bony continuity is maintained36

Serious consideration should be given to en bloc resection in the following cases: 1) when OKC recurs despite previous enucleation with an adjunctive procedure;
2) when OKC recurs despite previous marsupialisation followed by enucleation with an adjunctive procedure; 3) in cases of multilocular (multilobular) aggressive intraosseous OKC;

4) in cases of multiple nonsyndromic and syndromic keratocysts of nevoid basal cell carcinoma syndrome; or
5) in a diagnosed OKC exhibiting particularly aggressive clinical behavior (eg, growth, destruction of adjacent tissues) that should require resection as the initial surgical treatment

 Bataineh et al (1998) found following advantages of treatment of keratocyst by resection with continuity defects: 1. Eradication of the pathologic lesion 2. Reduction of the potential for recurrence 3. Preservation of the continuity of the mandible, Thus ,maintaining jaw function and shape.

RECURRENCE
Recurrence rate of OKC has been reported to range from5% ,58.3%(Myoung et et al)72to 100%(Blanas et al).67 High rate of recurrence likely comes from -presence of remnants of residual epithelial islands and/or satellite or daughter cysts (microcysts) in the adjacent overlying attached mucosa, - connective tissue of the cyst wall, or an adjacent osseous margin. Other causes of recurrence - the thin and fragile cystic lining, a high mitotic index of the epithelial cells and elevated prostaglandin levels.