Lutfi ALIA ODONTOGENIC CYSTS

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MORPHOLOGICAL AND IMMUNOPATHOLOGICAL FEATURES OF THE ODONTOGENIC CYSTS Lutfi ALIA M.D


CYSTS & NEOPLASMS OF THE JAWS 4th EDITION OF THE WHO CLASSIFICATION - JANUARY 2017


I. EPITHELIAL LINED CYSTS        

1. ODONTOGENIC DEVELOPMENTAL Dentigerous cyst Odontogenic keratocyst Orthokeratinic odontogenic cyst Calcifying odontogenic cyst (Gorlin cyst) Gingival cyst of infants (alveolar cyst) Gingival cyst of the adult Lateral periodontal cyst & Botryoid odontogenic cyst Glandular odontogenic cyst

   

2. ODONTOGENIC NONDEVELOPMENTAL CYSTS: INFLAMMATORY ORIGIN Radicular cyst (apical and lateral) Residual periapical cyst Paradental cyst (Hofrath cyst) Inflammatory collateral cyst

    

3. NON - ODONTOGENIC CYSTS Nasopalatine duct cyst Nasolabial cyst Mid palatal Raphé Cyst of Infants Globulo-maxillary cyst Median mandibular

II NON-EPITHELIAL LINED CYSTS - PSEUDOCYSTS  Simple bone solitary cyst - Post traumatic, - Posthaermorrhagic  Aneurysmal bone cyst III. CYSTS ASSOCIATED WITH THE MAXILLARY ANTRUM IV. CYSTS of SOFT TISSUE, MOUTH, FACE & NECK

V. ODONTOGENIC NEOPLASMES • • • • • • •

• • •

a. MALIGN ODONTOGENIC NEOPLASMS Ameloblastic carcinoma Primary intraosseous carcinoma Sclerosing odontogenic carcinoma * Clear odontogenic cell carcinoma Ghost cell odontogenic carcinoma Odontogenic carcinosarcoma Odontogenic sarcoma b. BENIGN ODONTOGENIC TUMOURS b. 1. EPITHELIAL ORIGIN Ameloblastoma, conventional - Ameloblastoma, unicystic type - Ameloblastoma, extraosseous/peripheral type - Metastasizing (malignant) ameloblastoma Squamous odontogenic tumor Calcifying Epithelial Odontogenic Tumor Adenomatoid odontogenic tumor

b. 2. MIXED (EPITHELIAL – MESENCHYMAL) Ameloblastic fibroma Primordial Odontogenic Tumor * Odontoma - Compound type and Complex type Dentinogenic Ghost cell Tumor *

• • • •

b. 3. MESENCHYMAL ORIGIN Odontogenic fibroma Odontogenic myxoma Cementoblastoma Cemento ossifying fibroma *

• • •

1. Wright JM, Vered M. Update from the 4th Edition of the WHO Classification of Head and Neck Tumours: Odontogenic and maxillofacial bone tumors. Head Neck Pathol. 2017; 11: 68-77.


THE ODONTOGENIC CYSTS


• •

Odontogenic cysts are true cysts, derived from residues of mature odontogenic epithelium, and can have their onset at any age. Dentigerous Cyst, Calcifying Odontogenic Cyst, Paradental Cyst, arise from reduced enamel epithelium. Odontogenic Keratocyst, Orthokeratinized Cyst, Lateral Periodontal Cysts, Gingival Cysts, arise from rests of dental lamina (rests of Serres - dental lamina remnants in soft tissue between the oral epithelium and the periosteum). Radicular Cyst, Residual Cyst and Inflamatory Colateral Cyst, arise from epithelial rests of Malassez (pax epithelialis pediodontii), which are odontogenic epithelium in the periodontal ligament - Hertwig's epithelial root sheath).

Enamel epithelium (above) Dental papilla (below) and odontoblasts - dentine

Dental Lamina (above) Vestibular lamina (below).

The clinical course of the cysts, are correlated with histological type and their complications, than conditioned the surgical strategy. 2. Alia L, Pettini M, Hako L, Schűrfeld K. Orthokeratinized odontogenic cyst vs odontogenik keratocyst. Riv. Ital. Chir.Max-fac. 2000, 1, 36 3. Alia L, Pettini M, Casorelli I, Passali D: Cisti odontogene del mascellare superiore. Riv. Ital. Otorin.Larin. Aud. Fon. 2003. n.2. 89 - 94 4. Kramer IRH, Pindborg J, Shear M: The VHO histoligcal typing of odontogenic tumours. Cancer. 1992, 70, 2998 – 29925. 5. Wright MJ, Vered M.: Update from the 4th Edition of the WHO Classification of Head and Neck Tumours: Odontogenic and Maxillofacial Bone Tumors. Head and Neck Pathology. 2017 Mar;11(1):68-77. (Blue book)


GENERAL CLINICO-PATHOLOGICAL CONSIDERATIONS


 Odontogenic cysts can remain asymptomatic and therefore undetected for long periods of time.  Kelley 1966 and Kramer in 1974: The cyst is a pathological cavity, rounded, which have fluid, semifluid, solid, or semisolid contents.  Well defined with fibrous capsule and lined by stratified squamous epithelium.  Usually radiolucent, exeption Gorlin cyst which may be mixed.  Unilocular, or sometimes multilocular.

 SECRETIONS  Epithelial lining secretes mucus, increase the volume.

 TRANSUDATION & EXUDATION    

Serous, sero-fibrinous, haermorrhagic, purulent … Lymphocites release limphokines. Monocytes release interleukine - 1. Osteoclasts activating factor – OAF.

 INCREASED of OSMOLARITY    

Raises internal hydrostatic pressure. Attracts fluid within cavity. Increase of the osmotic pressure is realted to proteins present in the fluid . Accumulation of the keratine desqumated from parakeratinic and hyperkeratinik layer.

 CELL DETRITIUS  Desquamated epithelial cells of lining, apoptotic cells, necrotic cells.

6. Wright JM, Vered M. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Odontogenic and maxillofacial bone tumors. Head Neck Pathol. 2017; 11:68-77 7. Alia L, Pettini M, Casorelli I, Passali D: Cisti odontogene del mascellare superiore. Riv. Ital. Otorin.Larin. Aud. Fon. 2003. n.2. 89 - 94. 8. Luis V. Sarmiento et all. Prevalence and distribution of odontogenic cysts in a Mexican sample. A 753 cases study. Journ. Clin. Exp. Dent. 2017 Apr. 9 (4): 531 - 538


MATERIALS & METHODS OF THE STUDY

• Our study was performed on 220 cases diagnosed and operates on for a odontogenic cystic lesion in the jaw.

THE PRINCIPAL OBJECTIVE OF THIS REPORT WAS: TO DETERMINE INCIDENCE AND MORPHOLOGICAL & IMMUNOPATHOGICAL FEATURES OF ODONTOGENIC CYSTS


THE CLINICAL DIAGNOSIS OF THE CYSTS WAS BASED:

• • • •

Radiographic findings of the orthopantomographic examination (OPT) in 220 cases. In the 112 cases with CT scan or Magnetic Resonance. In 176 cases, was applied enucleation of cysts. In 44 cases the extirpation with segmental osteoectomy.

Orthopantograme showed unilocular radiolucent lesion in left body of mandible

Three-dimensional CT scan showed perforation of buccal cortical plate

Pre operator situation


PATHOLOGICAL METHODS OF THE STUDY


HISTOPATHOLOGICAL ANALYSES:

• • •

All cysts were routinely fixed in 10 % neutral formalin, processed and embedded in paraffin. The sections coloured with eosine - haematoxylin were reviewed to confirm histological diagnosis. PAS and Trichrome Masson. For the morphologic diagnosis of Odontogenic cysts, were applied the criterion of WHO - 2017. IMMUNOHISTOCHEMICAL STUDY:

Was performed using sensitive biotin-streptavidin imunoperoxidase technique, on 4 μ paraffin sections.

• For analyses of cytokeratins expression, have use the monoclonal antibodies against CK10, CK13, CK14, CK16, CK17. CK19 • For the proliferative index we have use monoclonal antibodies against Mib-1 • Other markers: VEGF, CD34, Bcl-2, p53, p63, CD44, α-SMA, Types I & III collagen, Tenascin, Laminine-1. RESULTS:  ODONTOGENIC DEVELOPMENTAL CYSTS  ODONTOGENIC NONDEVELOPMENTAL CYSTS - INFLAMMATORY ORIGIN

09. Li T. J, et all: Orthokeratinized Odontogenic Cyst: a clinicopathological and immunocytochemical study of 15 cases. Histopathology. 1998, 32, 242 – 245 10. Sadri D, et all: Expression of VEGF in Odontogenic Cysts: Is There Any Impression on Clinical Outcome? Open Dent. Journ. 2016 Dec 30;10:752-759 11. Alia L, Pettini M, Casorelli I, Passali D: Cisti odontogene del mascellare superiore. Riv. Ital. Otorin.Larin. Aud. Fon. 2003. n.2. 89 - 94.

92 cases 128 cases

41. 8 % 58. 2 %


1. ODONTOGENIC DEVELOPMENTAL CYSTS


92 cases        

Dentigerous cyst Odontogenic keratocyst Orthokeratinic odontogenic cyst Calcifying odontogenic cyst (Gorlin) Gingival cyst of infants Gingival cyst of the adult Lateral periodontal cyst & BOC Glandular odontogenic cyst

2

41. 8 %

39 24 9 7 2 4 6 1

17. 7 % 11. 0 % 4. 1 % 3. 2 % 0. 9 % 1. 8 % 2. 7 % 0. 5 %

1

4 6

7

39

9

24

DC

OKC

OOC

COC

GCI

GCA

LPC

GOC

12. Alia L, Bazat patologjike te semundjeve. Kistet odontogene. Issu.com. Vol 2. 2014


1. 1. DENTIGEROUS (FOLLICULAR) CYST


RESULTS:

39 cases

• • • • •

17. 7 %

The mean age of patients was 52 years (11 – 83 years). < 40 years 60 % of cases. 26 cases males, 13 cases females. 28 cases in the mandible (19 cases location in the mandibular posterior area). 11 cases in the maxilla

Dentigerous cyst encloses the crown of the tooth, and is attached with its neck.

13. Johnson NR. Frequency of odontogenic cysts and tumors: a systematic review. Jorn. Invest.Clin. Dnt. 2014 Feb;5(1):9-14. 14. Alia L, Pettini M, Casorelli I, Passali D: Cisti odontogene del mascellare superiore. Riv. Ital. Otorin.Larin. Aud. Fon. 2003. n.2. 89 - 94 15. Kramer IRH, Pindborg J, Shear M: The VHO histoligcal typing of odontogenic tumours. Cancer. 1992, 70, 2998 – 29920


A normal dental follicle is lined by enamel epithelium, whereas a Dentigerous Cyst is lined by non-keratinized stratified squamous epithelium. Follicular epithelium, it has more potential for growth, differentiation and degeneration.

Non inflammed DC. The wall have a collagenous fibrous connective tissue.

The epithelial lining of inflamed DC was thick with hyperplastic rete ridges.


Dentigerous cyst lined by squamous and mucous secreting cells (Goblet cells).

Pseudostratified ciliated columnar epithelium with Goblet cells.


Epithelial lining containing Rushton bodies (hyaline bodies). Two different histomorphological appearances: granular and homogeneous. Rushton bodies are eosinophilic, straight or curved, irregular or rounded structures within the epithelial lining. Occasional ones had concentric laminations. Electron microscopic studies show the lamellar variant to be composed of alternating electron dense and electron lucent layers, whereas the granular form consists of amorphous material 16. Sarode GS, et all: Pathogenesis of Rushton bodies: A novel hypothesis. Med Hypotheses. 2016 Aug;93:166-9


RB stained positive with orcein

Hyaline bodies stained positive with Masson's Trichrome


IMMUNOHISTOCHEMISTRY


The odontogenic epithelium expresses keratins 7, 10, 13, 14, 17, 19.  Enamel organ was marked for CK14 and for CK19  CK14 stains odontogenic epithelium in all stages of tooth development, including the dental lamina and stellate reticulum.  CK19 is more prominent in later stages.

Expression CK14 in basal and intermediate epithelial lining cells.

CK 19 intense expression (+++). (basal, intermediate and upper cell layer)

17. IOSR Journal of Dental and Medical Sciences . Volume 13, Issue 5 Ver. I. (May. 2014), p. 80-83

Expression of CK19 in epithelial in entire thickness of the epithelium of DC.


Ki-67 < 5 %

Bcl2

P63 (mild 30 – 40 %), moderate (> 50 %)


Cytoplasmic immunostaining COX-2 in the epithelial lining of DC and Unicystic ameloblastoma

CD44s may be useful in detecting the active cells in the odontogenic lesions and to predict the tumor progression.

17. IOSR Journal of Dental and Medical Sciences . Volume 13, Issue 5 Ver. I. (May. 2014), p. 80-83


1. 2. THE ODONTOGENIC KERATOCYST


RESULTS: 24 cases

11, 00 %

• The mean age of patients was 58, 6 years • 18 cases males, 6 cases females. M : F = 3 : 1 • All cases in the mandible

• Philipsen (1956) describes keratin filled jaw cyst in epithelial lining. • Its histological features were established by Pindborg, Shear, Kramer. • OKC arise from rests of the dental lamina, with the presence of the dental papilla and basal cells of oral epithelium.

• The OKC is an enigmatic developmental cyst, that deserves special attention. • The term OKC reflect its histiogenesis as well as the characteristic of its keratinized epithelial lining, and a thin corrugated surface layer of parakeratine, but what makes this cyst special, its aggressive clinical behavior and high recurrence rate.

• OKC have occasional association with the Nevoid Basal Cell Carcinoma: (Gorlin – Goltz syndrome).

• Have a PTCH gene (patched - 1 proteine) level disturbance of Chromosome 9 (loss of heterozygosity on the 9q22.3 region) Transmitted as an autosomal dominant trait with high penetrance.

• It’s a dilemma: OKC can be cyst or neoplasm?! 18. Alia L, Pettini M, Hako L, Schűrfeld K. Orthokeratinized odontogenic cyst vs odontogenik keratocyst. Riv. Ital. Chir.Max-fac. 2000, 1, 36


HISTOPATHOLOGY

• • • • • • • •

A thin, uniform lining of stratified squamous epithelium and a thin corrugated surface layer of parakeratine. A spinous cell layer 4 to 8 cells in thickness. Often showing intracellular oedema. The epithelium have a well developed basal layer of cuboidal cells and palisading columnar cells, with polarized and hyperchromatic nuclei. (“picket fence”, or “tombstone” appearance). Mast cells have been shown to be present. A flat subepithelial conjunctive tissue with radially arranged collagen fibers. A relatively thin fibrous capsule that lacks inflammatory cell infiltrate. Presence of islands of odontogenic epithelium. Presence of microcysts in the cystic wall, or Metaplasia of the wall tissues.


HISTOPATHOLOGICAL FEATURES THAT PREDICT RECURRENCES 

    

 

Higher level of cell proliferative activity in the epithelium. Intensive parakeratinization of the surface layer. Subepithelial split of the epithelial lining. Supraepithelial split of the epithelial lining. Budding in the basal layer of the epithelium. Presence of islands of odontogenic epithelium. Presence of daughter cysts within in the fibrous wall. Metaplasia of the wall tissues.

19. Li T. J, et all: Orthokeratinized Odontogenic Cyst: a clinicopathological and immunocytochemical study of 15 cases. Histopathology. 1998, 32, 242 20. Kotwaney S, Shetty P. Orthokeratinized odontogenic cyst: A milder variant of an odontogenic keratocyst. Univers Res J Dent. 2013; 3:101 – 103.


IMMUNOHISTOCHEMISTRY


CK – HMW CK10 positive in the superficial keratin layer.

CK13 higher expression in the cells of suprabasal and upper epithelial layers.

CK17 positive with additional intense staining in the stratum corneum.

CK18 mild (+) intensity and “focal” distribution

CK – MMW CK14 overexpression in the basal, suprabasal cells

CK19 present in the cells of superficial epithelial layer.

CK14, CK17, CK19 are expreesed in the rests of dental lamina.


%

Bcl-2

100 80 60 40 20 0 group1

group 2

Total positivity and negativity of Bcl-2 expression in the study of two groups:

Bcl-2: expression is positive exclusively in the nuclei of basal layer, and subsequently the OKC are seen as cystic lesions but not as odontogenic tumor masse.

Group 1. Odontogenic Keratocyst. n = 20: 85 % positive – 15 % negative Group 2. Ameloblastoma. n = 20: 85 % positive – 15 % negative

21. Li T. J, et all: Orthokeratinized Odontogenic Cyst: a clinicopathological and immunocytochemical study of 15 cases. Histopathology. 1998, 32, 242 22. Razavi SM, et all: Expression of Bcl-2 and epithelial growth factor receptor proteins in keratocystic odontogenic tumor in comparison with dentigerous cyst and ameloblastoma. Dent Res Journ. 2015 Jul-Aug;12(4):342-7


Ki-67 Highest positivity in the nuclei of parabasal and intermediate layer. Fraction of growth > 20 %

Anti-apoptotic p53 in the nuclei of basal, intermediate layer

p63 expressed in the nuclei of basal, parabasal, intermediate layers. (variante TAp63)

23. Kichi E et all: Cell proliferation, apoptosis and apoptosis-related factors in odontogenic keratocysts and in dentigerous cysts. J. Oral Pathol. Med. 2005 May;34(5):280-6. 24. Tosios KI, et all: Immunohistochemical study of bcl-2 protein, Ki-67 antigen and p53 protein in epithelium of odontogenic cysts. J. Oral Pathol. Med. 2000 Mar;29(3):139


Microvessel density in OKC.

CD34 expression in OKC wall as circumferential pattern.

Higher expression of VEGF in epithelial, endothelial, miofibroblasts, inflammatory cells, was correlated with greater vascular density and higher inflammatory infiltration.


Subepithelial connective tissue ÎąSMA positive in myofibroblasts

Nonfibrillar expression of Tenascin – continuous immunopositive line in the basement membrane and focal expression in the cyst wall.

The ECM proteins showed a nonfibrillar expression as Tenascin, Fibronectine and Laminine-1 There suggests marked instability in the cystic structure and may contribute to its aggressive behavior.


1. 3. THE ORTHOKERATINIZED ODONTOGENIC CYST


• In 1981, on the basis of differences showed in histological and clinical

RESULTS: 9 cases are OOC

• •

4, 1 %

The mean age of patients was 47 years 6 cases males, 3 cases females, with a M : F ratio 2 : 1 8 cases in the mandible and 1 case in the maxilla.

behaviour, Wright distinguished two different types of OKC: the more common, parakeratotic odontogenic cyst, & the less common, orthokeratotik odontogenic cyst.

• OOC is histologicaly separated from the typical OKC, and constitute a distinct clinico-pathological entity.

• OKC arise from the rests of dental lamina.

Stratified squamous epithelial lining with surface thick layer of orthokeratin, proeminent granulosum layer and cuboidal - flattened basal cells.


HISTOPATHOLOGY


The cavity of OOC is lined by a uniform 4 to 9 cell layers thick regular stratified squamous epithelium.

   

Basal layer exhibits cuboidal or flattened, centrally placed nuclei with less tendency for hyperchromatism. The intermediate layer is made up of polyhedral cells, with eosinophilic cytoplasm. The granulosum layer is proeminent And it’s a thick superficial layer of orthokeratin (onion – skin – like).

 It’s a thin fibrous wall within calcifying foci. 25. Nayak MT et all: Odontogenic keratocyst: Wat is the name? J. Nat. Sci. Biol. Med. 2013 Jul;4(2):282-5. 26. Shear M : The aggressive nature of the odontogenic keratocyst: it is a benign cystic neoplasm? Part 1. Clinical and early experimental evidence of aggressive behaviour. Oral Oncology. 2002; 38:219–226


IMMUNOHISTOCHEMISTRY


CK10 overexpression in the upper layers. CK13 expression In the intermediar and upper epithelial layer.

CK14 In the suprabasal and in the upper epithelial layers. Is found in the keratinocytes of stratified squamous epithelium.

CK19 in basal cells of stratified squamous epithelium

27. Li TJ et all: Orthokeratinized odontogenic cyst: a clinicopathological and immunocytochemical study]. Zhong. Kou Q. Yi Xue ZZ. 2003. 38 (1), 49 – 51. 28. Mario J. Da Silva et all: Immunohistochemical study of the Orthokeratinized odontogenic cyst: A comparison with the odontogenic keratocyst. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. Jan 2003; 94 (6): 732


The ECM proteins showed an fibrillar expression. Fibronectin & Collagen types I - III expressed in a fibrillar aspect.


Ki-67 < 5 %

Expression of p63


1. 4. CALCIFYING ODONTOGENIC CYST (GORLIN CYST - 1962)


RESULTS:

7 cases are COC

3, 20 %

• The mean age of patients was 53 years • 5 cases males, 2 cases females. • 7 cases in the mandible.  Calcifying Odontogenic Cysts are simple cysts lined by squamous stratified epithelium with focal accumulations of the ghost cells. THE GHOST CELLS

 Represent an abnormal type of keratinization, and have an affinity for calcification.  They might represent simple cell degeneration or of enamel matrix.  They might arise from the process of apoptosis of the poorly differentiated odontogenic cells.  They may represent the product of coagulative necrosis of the odontogenic epithelium.

 Ghost cells may be in contact with the connective tissue wall of the cyst where they may evoke a foreign body reaction with the formation of multinucleated giant cells.


Cystic wall lined by prominent odontogenic epithelium

Areas of "ghost" epithelial cells projecting into the lumen

Ghost cells undergoing calcification.


Proliferating odontogenic epithelium forming follicles projecting into the fibrous connective tissue stroma.

Reactive bone formation at the periphery.

Giant cells surrounding ghost cells in the connective tissue of stroma


IMMUNOHISTOCHEMISTRY


Strong positive for CK 19 The cells of the basal layer of the epithelium.

Strong positive for CK 14 cells of the uper layer of the epithelium

Epithelial expression of p63 Negative Ghost cells


Calcifying Epithelial Odontogenic Tumor: Islands of polyhedral epithelial cells, without palisading or reverse nuclear polarity, with amorphous masses of extracellular matrix that is calcifies. (E & H: x 200)

Calcifying Odontogenic Cyst


Calcifying Epithelial Odontogenic Tumor. Fluorescence of amyloid-like material stained with Thioflavine T


1. 5. LATERAL PERIODENTAL CYST & BOTRYOID ODONTOGENIC CYST


• The first well-documented case of a LPC was reported by Standish & Shafer

RESULTS:

6 cases

2, 70 %

• The mean age of patients was 60 years (30 – 82 years). • 6 cases males. • 6 cases in the mandible. • 1 case is Botryoid Odontogenic Cyst

• •

(1958) LPC arise from the rests of dental lamina. LPC are defined as nonkeratinized and noninflammatory odontogenic developmental cyst, located adjacent or lateral to the root of a vital tooth. These cysts arise along the lateral periodontium, or within the bone between the erupted vital teeth.

LPC located adjacent or lateral to the root of a vital tooth.

The Rx aspect is compatible with a LPC


Epithelial “plaque�

Plaques partly composed of clear cells (glycogen) and mucous cells, in the squamous stratified epithelium.

Unusual invaginating, nodular epithelial.


BOTRYOID ODONTOGENIC CYST

Botryoid Odontogenic Cyst have multilple cyst.

Recurrences of multicystic radiolucent lesions of BOC are common

Botryoid Odontogenic Cyst Multilple cyst cavities lined with thin pavement epithelium with thickened areas (arrows)


1. 6. GINGIVAL INFANTS (NEW BORN) CYST


RESULTS: 2 cases

0, 90 %

The patients are < 4 weeks (male)  

Gingival cyst of infant, or Gingival (alveolar) cyst of infants are mostly found in groups, but also are found as single nodules. Arise from the rests of dental lamina.

Based on histological origin and location in the oral cavity, these cyst can be classified:

- Epstein's pearls (midline of palate) - Bohn's nodules are the white bumps present on the upper gum. - Gingival cyst – alveolar cyst.  

The nodes are a result of cystic degeneration of epithelial rests of the dental lamina (rests of Serres) They are found at the junction of the hard and soft palate, and along lingual and buccal parts of the dental ridges, away from the midline.

  

Gingival cyst of newborn is an oral mucosal lesion of transient nature, that will go away in a few months. It is very common lesion within 3 to 6 weeks of birth, it is very rare to visualize the lesion there after. Clinical diagnoses of these conditions are important in order to avoid unnecessary therapeutic procedure and provide suitable information to parents about the nature of the lesion.

Microscopically the cyst s are lined with a thin layer squamous stratified epithelium and filled with keratin.

32. Wright John M, Merva Soluk-Tekkeşin : Odontogenic tumors: were are we in 2017? Journ. Istan. Univ . Fac Dent 2017; 51 (3 Suppl 1): S10 – S30

The cyst is lined by squamous epithelium and the cyst lumen is filled with keratin.


1. 7. GINGIVAL ADULT CYST


RESULTS: 4 cases

• • • •

1, 80 %

The mean age of patients was 58 years (21 – 78 years) 3 cases males, 1 cases females. 3 cases in the mandible. 1 case in the maxilla.

GAC is a small developmental odontogenic cyst of the gingival soft tissue derived from the rests of the dental lamina.

Containing a lining of embryonic epithelium of cubiodal cells and distinctive focal thikenings, plaque of epitheial lining. A relatively is a thin fibrous capsule with inflammatory cell infiltrate.

Cystic cavity lined by a thin and flattened epithelial lining

Most frequently seen near canine and premolar region. 32. Juliana MM Brod. Gingival ccyst of the adukt. Case report in Dentistry. 2017, 33. Sato H, Kobayashi W, Sakaki H, Kimura H. Huge Gingival Cyst of the Adult: A Case Report and Review of the Literature. Asian J Oral Maxillofac Surg. 2007;19:176–8.

Focal thikenings, plaque of epitheial lining


1. 8. GLANDULAR ODONTOGENIC CYST


RESULTS: 1 cases are COC

0, 50 %

The patient 21 years (male)

    

Is an uncommon jaw bone cyst of odontogenic origin. First described in 1987 by Van Wyk. 1988 Gardner characterized histopathological features and biological behavior. Is a slow growing intraosseous lesion in the anterior mandible. It also has the propensity to grow to a large size and tendency to recur.

 Only 111 cases having been reported.

Kaplan, Anavi, Hirshberg : described ten different histopathologic features. The major criteria:  Squamous nonkeratising epithelial lining, and palisading basal cells.  A thin connective tissue wall.  Epithelium exhibiting variations in thickness along the cystic lining with or without epithelial “spheres” or “whorls” or focal luminal proliferation.  Cuboidal eosinophilic cells or “hobnail” cells.  Mucous cells with intraepithelial mucous pools, with or without crypts lined by mucous-producing cells.  Intraepithelial glandular, microcystic or duct-like structures. The minor criteria include:  Papillary proliferation of the lining epithelium.  Superficial Ciliated cells.  Multicystic architecture within squamous epithelium.  Clear or vacuolated cells in the basal or spinous layers. Epithelial lining of the wall of a sialo-odontogenic cyst

32. Wright John M, Merva Soluk-Tekkeşin : Odontogenic tumors: were are we in 2017? Journ. Istan. Univ . Fac Dent 2017; 51 (3 Suppl 1): S10 – S30


HISTOPATHOLOGY


Metaplastic mucous cells

Pseudoglandular structures with PAS positive mucous cells.

Microcystic area

PAS positive mucous cells within the epithelium


IMMUNOHISTOCHEMISTRY


Basal expression of Bcl‐2, Ki‐67, p53

Ck 19

Cyclin D1 expression


2. ODONTOGENIC NONDEVELOPMENTAL CYSTS - INFLAMMATORY ORIGIN


   

Radicular cyst (apical and lateral) Residual periapical cyst Paradental cyst (Hofrath cyst) Inflammatory collateral cyst

128 cases

58. 2 %

97 cases 23 cases 2 cases 6 cases

44. 0 % 10. 5 % 0. 9 % 2. 7 %

2 6 23

97

RadC

ResC

PC

ICC


2. 1. RADICULAR CYST (APICAL AND LATERAL)


RESULTS: 97 cases RC

44. 00 %

The mean age of patients was 48 years (12 – 82 years) • 5 cases males, 2 cases females. • 61 cases in the mandible (47 cases location was the mandibular posterior area). • 36 cases in the maxilla (more frequent in maxillary anterior zone).

Radicular cyst: Stratified squamous epithelium with rete ridges, and inflamed connective tissue. Juxtaepithelial hyalinization

Radicular cyst at the apex of a non-vital tooth

Radicular Cyst arise from epithelial rests of Malassez (odontogenic epithelium in the periodontal ligament – rests of Hertwig's sheath)

Lateral Radicular cyst of a non-vital tooth

8. Luis V. Sarmiento et all. Prevalence and distribution of odontogenic cysts in a Mexican sample. A 753 cases study. Journ. Clin. Exp. Dent. 2017 Apr. 9 (4): 531 - 538


Rushton bodies or hyaline bodies in Radicular Cyst Are eosinophilic, straight or curved, irregular or rounded structures within in the epithelium.

16. Sarode GS, et all: Pathogenesis of Rushton bodies: A novel hypothesis. Med Hypotheses. 2016 Aug;93:166-9


Mucous metpalsia (stam cells of ERM)

Colesterol cleft and foam cells in the wall.


IMMUNOHISTOCHEMISTRY


Intensa positivity of CK19 in all epithelial layer.

CK18 mild (+) intensity , “focal� distribution

Positivity of p63 in basal and parabasal layers.

CK10 -

E-cadherine membranous positivity in epithelial cells.


2. 2. RESIDUAL PERIAPICAL CYST


RESULTS: 23 cases

• • • • •

10. 50 %

The mean age of patients was 58 years (16 – 89 years) 40 – 60 years 21 cases 19 cases males, 4 cases females. 10 cases in the mandible (location was the mandibular posterior area). 13 cases in the maxilla (location was the maxilla posterior area).

Non-keratinic stratified squamous epithelium lining Residual cyst

 Res. C is the persistence of an apical periodontal cyst that remains after tooth extraction.  ResC, as the name implies, is a radicular, lateral periodental cyst, dentigerous cyst, or any other cyst that has persisted after it’s associated tooth has been lost.  ResC show more predilection in males and they commonly affect the maxillary region.  Usually, Res-C are asymptomatic and calcifications occurring in the residual cysts are quite rare.

Cluster of cholesterol cleft in the wall and in the cystic cavity .

Rushton bodies in the epithelial lining of a Residual cyst


2. 3. PARADENTAL CYST (HOFRATH CYST)


RESULTS: 2 cases

0. 9 %

2 cases males (38 and 43 years) In the third vital molars of mandible.

Paradental cyst in the periodontal space of mandibular third molar.

 Hofrath, in 1930, reports some cases of jaw cysts, located distally to third mandibular molar, complicated with pericoronitis.  Is an inflammatory odontogenic cyst, which arise from reduced enamel epithelium.  Was lined by epithelial cells with characteristics of the junctional / sulcular epithelium.  Maruyama S. 2015: This cyst can be considered as a kind of inclusion cyst arising in the periodontal pocket, frequently of the mandibular third molars of young adults.

Non-keratinized stratified squamous epithelium, showing hyperplasia. Connective tissue presenting oedema, hyperemic vessels, areas of hemorrhage, and inflammatory mononuclear cell infiltrates. 31. Maruyama Satoshi et all. Paradental cyst is an inclusion cyst of the junctional/sulcular epithelium of the gingiva: histopathologic and immunohistochemical confirmation for its pathogenesis. Elsevier Vol. 120 No. 2 August 2015


IMMUNOHISTOCHEMISTRY


CK 13 + CK10 -

CK 14 +

CK 19 +


Hyaline bodies within in lining epithelia: granular materials or circumscribed with condensed rims (PAS positive); some contained nuclear traces or calcified materials in the center.


IMMUNOHISTOCHEMISTRY

CK 13 ++

CK 19 ++

CK 14 +

In the connective tissue of the cyst wall, are conglomerates of round-shaped calcified materials, positive for CK13, indicating that they were derived from lining epithelial cells.


2. 4. INFLAMMATORY COLLATERAL CYST


RESULTS: 6 cases

2. 7 %

The mean age of patients was 58 years (22 – 80 years) 5 cases males, 1 case female. 6 cases in the mandible. 

The pathogenesis of these cysts is most likely to be originated from the inflammatory proliferation of epithelial rests of Malassez.

95 % of cases located in the mandible, 5 % in the maxilla.

 The minor variations in the clinical appearance of the Inflammatory collateral cyst make it feasible to consider two groups separately: - associated with first and second permanent molars of the mandible - associated with the third mandibular molar, affected with pericoronitis. - The common location is on the buccal aspect of the molar teeth.

 This is an inflammatory cyst which develops on the lateral surface of a tooth root with a vital pulp. 

The consistent finding of a hyperplastic, non-keratinized stratified squamous epithelium with an intense inflammation in the connective tissue, is in accordance with the hypothesis that inflammation is important for the development of these cysts.

 Vedtofte and Praetorius suggested the use of the descriptive term Inflammatory Paradental Cyst. 

because of its inflammatory origin and also due to its location at the side of the tooth (suggested by Main 1985) should be avoided to prevent confusion with the developmental Lateral Periodontal Cyst. The other term used to describe this entity was Mandibular infected buccal cyst.

32. Vedtofte P. and Praetorius F. The inflamatory paradental cyst. Oral. Surg. Oral Med Oral Pathology. 1989 Aug. 68 (2): 182 - 188

Cystic lining with dense inflammatory infiltrate.


CONCLUSIONS

1. Odontogenic cysts are the most frequent lesions of the jaws, and their constant epidemiological and morphological update, is necessary and indispensable. 2. In the 4th Edition of WHO classification – January 2017: Calcified Cystic Odontogenic Tumor is now classified as a Calcifying Odontogenic Cyst. Keratocystic Odontogenic Tumor, is listed as Odontogenic Keratocyst of developmental odontogenic cysts. 3. It is important morphologically and clinically relevant to separate Odontogenic Keratocyst (OKC) from the Orthokeratinized Odontogenic Cyst (OOC), and also from other odontogenic cysts.

4. Cytokeratins expression studies have been done to evaluate diagnostic accuracy, role in pathogenesis, elucidate behaviour, and role in treatment protocols. 5. Radicular Cyst and Dentigerous Cyst are the most prevalent odontogenic cyst in our study. Due to their etiology, inflammation, dental pulpar necrosis and impacted teeth, so radicular cyst and dentigerous cyst and inflammatory collateral cyst, could be prevenible.


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