ODONTOGENIC KERATOCYST

Dr. Mayank VermaniPG 2nd yearDeptt. Oral & Maxillofacial Surgery

or KOT

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

• Aggressive nature

• High recurrence rate

• Specific histopathological feature

• 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;308-

316:2006)

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.

FREQUENCY

Anywhere b/n 3-10.5% Shears found OKC’s 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 3:1Stolinga 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 OKC’s. 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 OKC’s in 50%)

Simpson-Golabi-Behmel syndrome

(x- linked)Overgrowth Mental retardationBroad & coarse faceFlat 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

HISTOPATHOLOGY7 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 juxta-epithelial 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 OKC’s 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 (Carnoy’s solution) - Curettage with Thermal (Cryosurgery)

Decompression Decompression and irrigation Decompression and marsupialization

Marsupialization Marsupialization followed by enucleation

Peripheral ostectomy

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

Curettage : defined 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.

EnucleationStudies show that the recurrence rate with alone

Enucleation is high so it is performed with adjunctive therapies.

Treatment No. of patients No. of recurrences

(%)

Enucleation 58 12 20.7

Marsupialization 10 4 40.0

Total 68 16 23.5

(Oral Oncology 46 (2010) 740–742)

Table: Recurrence by treatment modality.

20.7

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

Recurrence by treatment No. Of Recurrences/ Treatments

%Recurrences/ Treatments

Enucleation 6/11 54.5

Peripheral ostectomy 2/11 18.2

Peripheral ostectomy and Carnoy’s solution

0/13 0

Enucleation and Carnoy’s solution

1/2 50

Resection 0/3 0

Recurrence by individual treatment

Peripheral ostectomy 2/24 8.3

Carnoy’s solution 1/15 6.7

Enucleation 7/13 53.8

Resection 0/3 0

54.5

ADJUNCTIVE THERAPHIES

Enucleation followed by curettage

- Curettage with physical mean (Sharp Curette, Rotary bur)

- Curettage with chemical mean (Carnoy’s solution)

- Curettage with Thermal (Cryosurgery)

TREATMENT OF ODONTOGENIC KERATOCYSTS BY ENUCLEATIONAND CARNOY’S SOLUTION.

Treatment type Cysts reported No. recurrences (%)

Curettage 265 19.2

Enucleation alone 387111 28.7

Enucleation and Carnoy’s* 601 1.6

Radical enucleation 61 16.7

Enucleation and cryotherapy

165 31.3

Marsupialisation 4511 24.4

Resection 380 0

1.6

Table : Recurrence rate

Enucleation and carnoy’s 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 LIQUIDNITROGEN 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 20°C ) 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 :e84–e85, 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, 1242–1244)

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 recurrence3. 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.