clinical and molecular features of keratocystic …international journal of dental sciences –...

International Journal of Dental Sciences – Volume 1 Issue 1- Jan-March 2018

ISSN: Under Process http://www.ijdsjournal.org Page 21

Clinical and Molecular Features of Keratocystic Odontogenic

Tumors Mallavolu Malleswar

1, K.Gnandeep Reddy

2, Avinash Yadlapati

3

Department of Dermatology,Venereology & LeprosyGuntur Medical College,Guntur

INTRODUCTION KCOT’s are positively with the mainly calculated

lesions in oral pathology, which is not a disclosure

allow for their secret medical concert and multipart

tool of pathogenesis. In fact, the exact KCOT facial

appearance are the motivation for several thought

about the true environment and alignment of these

lesions, which are still discussed in the technical

community. Until lately these lesions were recognized

as odontogenic keratocysts , a stint first used by

Philipsen in 1956. In the opening, the term was worn

toward depict several mouth cyst in which keratin was

produced. Though, it became obvious that several

other kinds of jowl cysts, such as rediculer and

remaining cysts, strength reveal keratinization because

in good health, foremost to the assumption to thorough

histological skin tone of OKCs and not single the

occasion of keratin, must be there use to make different

these lesion from other cysts of the mouth. Researchers

quickly implicit that OKCs explain cruel medical

actions and big reappearance charge, aspects which are

not characteristic meant for spare odontogenic cysts.

what's more that, it has be famous to OKCs are between

the majority obvious aspect of nevoid nasal cell

carcinoma condition, and called similar to Gorlin-Goltz

disease.In ending, some studies have exposed that

inherited factors are leader in etiology of these lesions

and that assured mechanisms of pathogenesis, classic for

neoplastic lesion, are also occupied in growth of OKCs.

Hence, into 2005 these lesions be reclassified as

Keratocystic Odontogenic Tumors and distinct as kindly,

odontogenic, uni- otherwise multicystic intraosseous

tumors, with characteristic par keratinized squamous

epithelium coating, have a possible for insistent and

infiltrative development. But, since KCOTs also show a

few cysts-like facial appearances, comprising reaction to

decompression, the tumoral personality of this abrasion

residue the subject of debate among investigators. In this,

we depict the diagnosis and treatment modalities of this

lesion.

2. Etiology and pathogenesis It is extensively received to KCOTs originate starting

odontogenic epithelium. trash of dental lamina, and in

addition proliferations of the basal cell coating of verbal

epithelium, be considered on the similar time as feasible

source of epithelial cells which strength multiply to form

a KCOT. In a latest learning scheduled keratin profile in

KCOTs, it be establish to similar keratins be expressed

in cooperation into KCOTs epithelial cells along with in

the cells of dental lamina in rats, supporting the

hypothesis to KCOTs occur starting its miscellanies. On

the new hand over, there are ideas that the key source of

epithelial cell necessary for KCOT structure is

derivative starting basal cell of verbal epithelium, which

do well keen on the deeper tissues plus structure

microcysts, propose to KCOTs must be consider like

hamartomas. Outcomes of study, presentation that the

main quantity of micro cysts plus epithelial island are

Abstract: The reason of this manuscript is to estimate the features and performance of the odontogenic

keratocyst (OKC), now properly predictable as the keratocystic odontogenic tumour; Odontogenic

keratocyst be a swelling of pointed tooth source through a aggressive clinical performance comprising a

elevated recurrence pace. Though, the recurrence rate after marsupialization shadowed by enucleation is not

suggestively higher than that after aggressive modalities. The most operative treatments are enucleation

complemented with Carnoy’s solution, otherwise marsupialization by later cystectomy. Most talented is the

use of molecular biology to treat such tumours which could ultimately decrease or eradicate the need for

aggressive approaches to accomplish the lesions.

Keywords — KCOTs, Malignant transformation, Marsupialization, NBCC syndrome.

RESEARCH ARTICLE OPEN ACCESS


ISSN: Under Process http://www.ijdsjournal.org 2

located in part of KCOTs ramparts which are in during

speak to by oral mucosa are in union by such an belief.

Also, proliferations of basal epithelial cell of spoken

mucosa keen on the subepithelial mucosal layer be

accepted in NBCCS patients, additional supporting this

possibility. silent, ever since equally kinds of epithelial

cells share a mutual embryogenic origin plus be theme

to general inductive effects, it have been recommended

that these two schemes should not eliminate one another.

2.1. Genetic factors in pathogenesis of KCOTs:

Besides of the leap of epithelial cell, the

etiology of KCOTs is powerfully connected to

hereditary factors, in exact to modification of tumor-

suppressor PTCH genetic material, which is a main

division of sonic hedgehog signalling tool. The PTCH

genetic material encodes PTCH trans covering protein,

which, communally by SMO , form a receptor pro SHH

ligands plus overpowers SMO mediate record of cellular

propagation genes. Therefore, lack of PTCH function

results in improved transcription of genes in control for

cell proliferation and, eventually, in tumor formation

2.2. Cell proliferation and apoptosis Besides genetic factors, many study propose to

dysregulation of chamber rotation in addition to increase

may be main for KCOT pathogenesis. It is believed that

KCOTs show augmented chamber creation charge and

that such a phenomenon might be related to its

aggressive growth. Proliferating chamber nuclear

antigen be a protein which is uttered in the focus of

replicating cells. It is measured to be a indication of cell

imitation, but also strength be articulated through DNA

fix procedure and under the pressure of various

expansion factors. In a model of 11 OKCs plus 10

periodical and dentigerous cysts, the maximum number

of PCNA activist cells was recognized in the supra basal

epithelial coating of KCOTs, proposing that these lesion

include upper proliferative activity associated to peri

apical and dentigerous cysts. In adding, it be recognized

to PCNA phrase be extra different in syndromic

compare toward irregular KCOTs.

Figure 1 Immunohistochemical staining of KCOT wall for

p53. Nuclear expression of p53, predominantly in the basal

epithelial layer

Extensive research has dedicated on protein p53 and its

role in these lesions (Figure 1).

3. CLINICAL FEATURES: KCOTs be caring except nearby forceful lesions

with elevated propensity to recur subsequent to surgical

treatment. insistent rising contained by the jaws,

tendency to take up immediate anatomical structures and

infrequent malignant change are aspects which

distinguish KCOTs from other kinds of odontogenic

tumors. However, the majority of KCOTs are

asymptomatic until they reach a significant size. If signs

are present, most of the patients will complain on

swelling, pain and liberation of cystic fluid into the

mouth (Figures 2 and 3).

Figure 2 Painless swelling of the left mandible in a patient

with KCOT.



Figure 3: Panoramic radiograph of the same patient.

Multilocular radiolucency of the left mandibular body

Rarely, involvement of the low-quality alveolar daring

can effect in paresthesia of the minor lip. derived

infectivity of the injury will consequence in signs of

acute irritation. KCOTs tend to produce rather fast

within modularly bone, while bony development befits

clinically obvious only whilst a lesion reaches outsized,

which is a fact that donates to late analysis. Still,

aggressive increase of KCOTs is illustrated by many

case information of these lesions with strange clinical

production. connection of the maxillary sinus keen on

addition near floor of the range might product in

proptosis as a first scientific sign showing tumor

company. Also, infiltration into surrounding soft tissues,

orbit and infratemporal fossa and even involvement of

the skull base has been confirmed.

3.1. Recurrence Moreover insistent increase contained by the

jawbones, one more surprising quality of KCOTs is a

extremely high occurrence of return consequent to

surgical action. declared return rates vary from 3% up to

62%. Such discrepancy in reported consequences could

be additional to dissimilar duration of follow-up periods

and wide range of surgical methods used to treat these

patients. In a classic study from Browne, in a sample of

85 OKCs, recurrence happened in 25%, most of them

within five years subsequent to cyst removal. The

significance of adequate follow-up was proven by

Forssell and colleagues, by the fact that only 3% of

KCOTs reappeared within the first postoperative year,

but after three years reappearance rate rose to 37%.

3.2. Malignant transformation: Regardless of forceful escalation and high return

toll, KCOTs are kind lesions. Still, cases of malevolent

conversion and ensuing advance of squamous chamber

carcinomas be popular in the prose. These tumors are

standard as key intraosseous odontogenic carcinomas,

denoting to squamous cell carcinomas arise in the mouth,

possibly from miscellany of odontogenic epithelium. To

begin analysis of PIOC two main norms should be met:

absence of early involvement with the overlying mucosa

or cover and excepting of metastasis opening a secluded

chief tumor through at most a 6-months evidence

phase.The most extensively used grouping of PIOC is

the one from Waldron and Mustoe (Table 1).

Type 1 PIOC arising from odontogenic cyst

Type 2

2A - Malignant ameloblastomas

2B - Ameloblastic carcinoma

Type 3 PIOC arising de novo

a) Keratinizing type

b) Nonkeratinizing type

Type 4 Intraosseous mucoepidermoid

carcinoma

Table 1: Waldron and Mustoes classification of

odontogenic carcinoma

4. Nevoid basal cell carcinoma syndrome:

This syndrome, also called as Gorlin or Gorlin-

Goltz disease be an autosomal leading inborn status

which show tall penetrance and erratic eloquence. The

head heritable fault is alteration in the PTCH genetic

material, which has been plotted to chromosome. As

already cited, this is a tumor-suppressor genetic material,

which explains why prevalence of special kinds of

tumors is the chief clinical feature of this syndrome.

This syndrome is diagnosed in 1 away of 60.000

newborns, but data from several studies propose

substantial geographic and demographic differences,

with prevalence oscillating from 1:56000 to 1:256000.

Gender predilection has not been noted. The most

noticeable clinical manifestations of NBCCS are

occurrence of various basal cell carcinomas along with

KCOTs. These lesion lean to happen at a much younger

period compare toward patients with sporadic tumors.

So, it is not uncommon to see patients with BCCs in

their 2nd or 3rd decades or to diagnose various KCOTs

in children under the age of ten (Figure 4).



Figure 4: Multiple KCOTs in the maxilla and mandible in

a 9-year old girl with NBCC syndrome

Diagnosis is centred on so-called major and minor

diagnostic criteria (Table 2).

Major Minor

Multiple BCCs or one

under the age of 20

KCOT (histological

verification required)

Palmar or plantar pits

Bilamellar calcification

of the falx cerebri

Bifid, fused or

markedly splayed ribs

First degree relative

with NBCCS

Macrocephaly Cleft lip or

palate

Frontal bossing

Hypertelorism Pectus

excavatum / carinatum

Syndactyly of the digits

Radiological abnormalities:

bridging of the sella

turcica,vertebral anomalies

Ovarian fibromas

Medulloblastomas

It is unspecified that identification of NBCCS

might be recognized if two main or one main and two

trivial criterion are encountered. Since mainly of the

lesions associated with the condition are not serious

forecast is generally favourable. while,

medulloblastomas, mean tumors of latter fossa, strength

happen in about 1% to 2% of the patients, frequently

during the first two years of life, again in an age greatly

younger compared to cases not associated to NBCCS.

Though these tumor be usually of desmoplastic type,

which is linked to better consequences, early on death

starting this kind of malignancy are still promising.

NBCCS patients are mostly receptive to ionizing and

UV emission, so rational usage of radiographic imaging

methods and even UV shield of the skin are functional in

decreasing amount of BCCs.

5. Radiographic features: KCOTs be commonly available as surrounding

or ovoid radiolucencies with spongy or scalloped

limitations. As a result, three diverse radiographic type

be general unilocular, multilocular and multilobular

lesions. It have be present designed that multilobular

KCOTs with scalloped limitations are an cause of

unbalanced raise action in diverse parts of the tumoral

barrier, bar this trust requirements spare technological

maintain (Figure 5).

Figure 5: Multilobular KCOT of the anterior maxilla.

Such presentation may be suggestive of a nasopalatine

cyst.

6. Histology: The epithelial coating is slightly thin, generally

consisting of up to eight cell layers, with feature flat

connective tissue edge. It is not extraordinary to sense

impartiality of the epithelial coating from the helpful

stringy partition. The basal epithelial coating comprises

of palisaded cuboidal or columnar cells, which are

frequently overexcited chromatic.

Figure 6: Photomicrograph of a KCOT specimen,

exhibiting formation of satellite microcysts within the

fibrous wall

The external coating is commonly ridged,

containing of compressed, parakeratotic cells. It has

been recognized so as to the mitotic directory in

KCOTs’ epithelial coating is senior associated to

periodical cysts. Higher mitotic commotion was also

witnessed in syndromic compared to irregular lesions.

The stringy coating is thin and frequently exclusive of

provocative get into. Within this element of KCOTs

hedge, proliferations of odontogenic epithelium and

structure of micro cysts force be experiential (Figure 6).



7. Diagnosis: Diagnosis of KCOTs is mostly based on

histological inspection of specimens attained through the

operation. In fact, histological skin touch of KCOTs is

so characteristic that disparity opinion must be rather

simple in mainly of the suitcases. Though, in some

situation, mainly if the tough wall of the scratch

indicates inciting changes, those distinctive aspects

capacity be distorted up to the stage which makes

consistent identification intricate. irritation of the tough

wall generally consequences in main variation of

KCOTs histological skin texture. Proliferation of

epithelial cells and loss of parakeratosis and palisaded

basal coating consequences in a histological seem of

common inflame odontogenic spot. If these variations

influence superior parts of KCOT wall it may be very

complex to form a perfect analysis. In a sequence of 112

OKCs, redness of the tough wall was eminent in as

greatly as 76% of suitcases. While pasting of individual

histological features was obvious in affect portions of

the lesions parapet, it was experimental that in 10 cases

(8.9%) the feature KCOTs exterior was preserved,

despite inciting variations in the behind connective

tissues.

8. Treatment: Problems in exclusion of thin and delicate walls,

incident of multilocular lesions and elevated affinity for

return after the operation are factors which make

surgical conduct of KCOTs extensively more difficult

compared to other cystic lesions of the jaws. immobile,

being a kindly lesion exclusive of significant leaning for

mean conversion, custom use of essential operation

(such as resection of involved jaw) is unconvinced, both

from health and right position of view. Therefore, it is

not unexpected that frequent adjunctive methods have

been industrial for management of KCOTs institute the

stability among valuable decrease of return possibility

and variety of the least forceful surgical process for each

divisible enduring is a essential opinion in behaviour

development for these lesions.

8.1. Enucleation: Bearing in intellect the elevated recurrence toll,

it is established that the ordinary follow of enucleation is

not satisfactory for KCOT conduct. In order to enhance

consequences of enucleation, peripheral ostectomy was

offered, aiming to eliminate miscellany of tumoral tissue

or satellite micro cysts from the edge of the fault,

essentially in multi lobular and multi locular cases.

While it capacity be successful in decrease of return

possibility, lack of capacity to organize the quantity of

impassive bone is measured to be a main drawback of

this development.

8.2. Resection: In distinction to enucleation, resection of the

affect jaw has showed to be very effectual in prevention

of recurrences. In fact, it is the only system for which

case sequence exclusive of recurrences were reported.

Besides resection of bone, deletion of flexible tissues in

get in touch with the lesion is further significant thought

proposed to reduce possibility of return. In a progression

of 31 mandibular KCOTs, insignificant resection of

affect jaw in union with flexible tissue erasure resulted

in careful segregation of recurrences in the training of

the description on period of awake toward eight years.

Figure 7: Excision of soft tissues after removal of the lesion.

9.3. Decompression Another option, which is expansively worn for

ways of great cystic lesion of the mouth, be

decompression, follow with enucleation in the follow

operation. The main reason of such a method is to

reduce the range of the unique lesion, which enables

methodical exclusion at the second-stage surgical

procedure and decreases the danger of damage to instant

anatomical structures.further this, while worn for

KCOTs conduct, decompression generally leads to

thickening of abrasion barrier, which also makes

enucleation of permanent tumoral tissue easier. (Figures

8 and 9).



Fig 8 and 9 Clinical photograph of the lesion, A Caldwell-

Luc approach was used for enucleation at the second stage

surgery.

9.4. Marsupialization It was revealed that marsupialization of KCOTs

consequences in important decrease of Ki-67 in addition

to IL-1α mRNA term in these lesions. As IL-1α utilizes

osteolytic movement, the authors completed that

decreased term of this interleukin may add to the

property of marsupialization. Minor expression of IL-1α

receptor IL-1RI and KGF were also proved in comeback

to decompression.

Surgical field after the application of Carnoy’’’’s solution

Finally, an trial learn showed that helpful difficulty of 80

mmHg better the expression of IL-1α mRNA and

protein into KCOTs epithelial cell, and enhanced the

emission of MMP-1, MMP-2, MMP-3, in adding to

PGE2 in a co-culture of KCOTs fibroblasts plus the

epithelial cell. Based on this, the authors meaningful out

that improved intracystic strain may play a vital role in

OKCs progress via moving the term of IL-1α in

epithelial cells.

Although all these methods were evaluated in some

study, presently existing point of attestation is deficient

to suggest any of them as a expected process for KCOTs

conduct. Until more eventual and randomized

experimental trials are implemented, choice of surgical

management will be based on the surgeon’s first variety

and institution-based protocols.

CONCLUSION Suitable to their special medical and organic

skin tone, KCOTs at rest suggest a critical trouble in

verbal and maxillofacial surgical procedure and keep on

to be a theme of argument among researchers and

clinicians. Several aspects of KCOTs pathogenesis

support opinions on their tumoral nature. Though,

response to decompression and significance of

augmented intracystic pressure for their growth specify

that the borderline amongst odontogenic tumors and

cysts might not be as distinctive as we formerly believed.

As present is a consent that typical action options for

cystic lesions of the jaws are not suitable for KCOTs,

extra exertion must be through to create exact diagnosis

in unconfident cases. pertaining to variety of the mainly

suitable conduct modality, it is vital to set up a balance

among of use diminution of return risk and range of

most violent surgical process for every unit patient.

Lastly, better tolerant of KCOTs pathogenesis strength

send clue for fresh handling approach, comprise apply of

survivin and sonic hedgehog signal path inhibitors.

REFERENCES

1. A Textbook of Advanced Oral and Maxillofacial

Surgery by Miroslav Andrić, Božidar Brković,

Vladimir Jurišić, Milan Jurišić and Jelena

Milašin, Page No: 1-32.

2. Ahlfors E, Larsson A, Sjögren S. The

odontogenic keratocyst: a benign cystic tumor? J

Oral Maxillofac Surg 1984;42(1):10–19.

3. Haring JI, Van Dis ML. Odontogenic

keratocysts; a clinical, radiographic and

histopathologic study. Oral Surg Oral Med Oral

Pathol 1988;66:145-153.

4. Cohen MM. Nevoid basal cell carcinoma

syndrome: molecular biology and new

hypotheses. Int J Oral Maxillofac Surg

1999;28(3):216–223.



5. Maurette PE, Jorge J, de Moraes M.

Conservative treatment protocol of odontogenic

keratocyst: a preliminary study. J Oral

Maxillofac Surg 2006;64(3):379–383.

6. Browne RM. The odontogenic keratocyst:

clinical aspects. Br Dent J 1970;128(5):225–231.

7. Brannon RB. The odontogenic keratocyst. A

clinicopathologic study of 312 cases. Part I.

Clinical features. Oral Surg Oral Med Oral

Pathol 1976;42(1):54–72.

8. Dayan D, Buchner A, Gorsky M, Harel-Raviv

M. The peripheral odontogenic keratocyst. Int J

Oral Maxillofac Surg 1988; 17(2):81–3.

9. Worrall SF. Recurrent odontogenic keratocyst

within the temporalis muscle. Br J Oral

Maxillofac Surg 1992;30(1):59–62.

10. Chehade A, Daley TD, Wysocki GP, Miller AS.

Peripheral odontogenic keratocyst. Oral Surg

Oral Med Oral Pathol 1994; 77(5):494–497.

11. Shear M. The aggressive nature of the

odontogenic keratocyst: is it a benign cystic

neoplasm? Part 2. Proliferation and genetic

studies. Oral Oncol. 2002 Jun;38(4):323-31.

Review. Erratum in: Oral Oncol. 2004

Jan;40(1):107

12. Shear M. The aggressive nature of the

odontogenic keratocyst: is it a benign cystic

neoplasm? Part 3. Immunocytochemistry of

cytokeratin and other epithelial cell markers.

Oral Oncol. 2002 Jul;38(5):407-15.

13. Peacock ZS, Cox D, Schmidt BL. Involvement

of PTCH1 mutations in the calcifying epithelial

odontogenic tumor. Oral Oncol. 2010

May;46(5):387-92. Epub 2010 Apr 3.

14. Grachtchouk M, Liu J, Wang A, Wei L,

Bichakjian CK, Garlick J, Paulino AF, Giordano

T, Dlugosz AA. Odontogenic keratocysts arise

from quiescent epithelial rests and are associated

with deregulated hedgehog signaling in mice

and humans. Am J Pathol. 2006 Sep;169(3):806-

14.

15. de Vicente JC, Torre A, Gutiérrez AM,

Lequerica P. Immunohistochemical comparative

study of the odontogenic keratocysts and other

odontogenic lesions. Med Oral Patol Oral Cir

Bucal. 2010 Apr 11.

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