Background

Odontogenic cysts are common cysts occurring in the oral cavity. There are two broad categories. In general, periapical cysts located at the tooth root tip and are associated with a nonvital tooth. Dentigerous cysts surround the crown of an impacted tooth and are associated with a vital tooth.

Inflammatory Cysts	Periapical cysts Paradental cysts
Developmental Cysts	Dentigerous cysts Odontogenic keratocyst Calcifying odontogenic cyst Lateral Periodontal cyst Glandular odontogenic cyst

OUTLINE

Pathogenesis
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

 

PATHOGENESIS
CALCIFYING ODONTOGENIC CYSTS
Expression of Hard a-Keratins in Pilomatrixoma, Craniopharyngioma, and Calcifying Odontogenic Cyst. Kusama K, Katayama Y, Oba K, Ishige T, Kebusa Y, Okazawa J, Fukushima T, Yoshino A. Department of Oral Pathology, Meikai University School of Dentistry, Saitama, Japan.	Am J Clin Pathol. 2005 Mar;123(3):376-81. Abstract quote   To examine the properties of shadow and ghost cells, 3 kinds of antibodies were raised against human hair proteins and their immunoreactivity was examined in tumors expressing those cells: pilomatrixoma, 14 cases; craniopharyngioma, 17 cases; and calcifying odontogenic cyst (COC), 14 cases. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses demonstrated that 2 polyclonal antibodies, PA-HP1 and PA-HP 2, reacted strongly with type I acidic and type II neutral/basic hard a-keratins. The other monoclonal antibody, MA-HP1, reacted with type II neutral/basic hard a-keratins. Immunohistochemical examination revealed that all 3 antibodies reacted only with the hair shaft in sections of normal skin and dermoid cyst. In all pilomatrixoma cases, 3 antibodies reacted with the cytoplasm of transitional and shadow cells but not with that of basophilic cells. Positive reactions were found only in shadow cells of all 13 adamantinomatous craniopharyngiomas. In all COCs, the antibodies reacted only with ghost cells, not with other epithelial components. Immunoreactivity for phosphothreonine, detected in hard a-keratins, also was found in transitional, shadow, and ghost cells. The appearance of shadow or ghost cells might represent differentiation into hair in these 3 kinds of tumors.
ODONTOGENIC KERATOCYSTS
Molecular analysis to demonstrate that odontogenic keratocysts are neoplastic. Agaram NP, Collins BM, Barnes L, Lomago D, Aldeeb D, Swalsky P, Finkelstein S, Hunt JL. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pa 15213, USA.	Arch Pathol Lab Med. 2004 Mar;128(3):313-7. Abstract quote   CONTEXT: Odontogenic keratocysts (OKCs) are unique odontogenic lesions that have the potential to behave aggressively, that can recur, and that can be associated with the nevoid basal cell carcinoma syndrome. Whether they are developmental or neoplastic continues to be debated. OBJECTIVES: To identify loss of heterozygosity of tumor suppressor genes in OKCs and to suggest a pathogenetic origin for these lesions. DESIGN: We examined 10 OKCs for loss of heterozygosity of tumor suppressor genes, using a microdissection and semiquantitative genotyping analysis. The genes analyzed included 10 common tumor suppressor genes, as well as the PTCH gene, which is mutated in nevoid basal cell carcinoma syndrome. RESULTS: Loss of heterozygosity was seen in 7 of 10 cases, with a frequency between 11% and 80% of the genes studied. The genes that exhibited the most frequent allelic losses were p16, p53, PTCH, and MCC (75%, 66%, 60%, and 60%, respectively). Daughter cysts were associated with a higher frequency of allelic loss (P =.02), but epithelial budding was not. CONCLUSIONS: Our study indicates that a significant number of OKCs show clonal loss of heterozygosity of common tumor suppressor genes. The finding of clonal deletion mutations of genomic DNA in these cysts supports the hypothesis that they are neoplastic rather than developmental in origin.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Clinicopathologic spectrum of the so-called calcifying odontogenic cysts: a study of 21 intraosseous cases with reconsideration of the terminology and classification. Li TJ, Yu SF.	Am J Surg Pathol 2003 Mar;27(3):372-84 Abstract quote The so-called calcifying odontogenic cyst (COC) represents a heterogeneous group of lesions that exhibit a variety of clinicopathologic and behavioral features. Because of this diversity, there has been confusion and disagreement on the terminology and classification of these lesions. We reviewed the clinicopathologic features of 21 intraosseous cases that were previously diagnosed as COC or under related diagnostic terms. Based on the biologic behavior, the lesions of the present series were divided into three subgroups: cyst, benign tumor, and malignant tumor. Sixteen cases (nine men and seven women) proved to be unicystic lesions with (five cases) or without associated odontoma. The lining epithelium of the cystic lesions fulfilled the histologic criteria for COC proposed by the World Health Organization, and their overall clinicopathologic features were consistent with that of developmental odontogenic cysts. The age of patients from the cyst group peaked at the second decade. The maxilla was affected more often (69%) than the mandible, with a predilection for the canine-premolar region (62.5%). Thirteen patients with follow-up information revealed no recurrence following enucleation. The four cases in the benign tumor group had variable clinicopathologic features. Two cases were solid tumors consisting of ameloblastoma-like sheets of odontogenic epithelium that contained ghost cells/calcification foci and juxtaepithelial dentinoid. Both patients experienced multiple recurrences following conservative surgeries. The other two lesions contained typical areas of COC and other types of odontogenic tumors (one ameloblastoma and one odontogenic myxofibroma). All four lesions occurred in the mandible and were relatively large. In the present series one case identified as malignant tumor arose from a previously benign COC. The tumor shared some features of COC (ghost cell foci and dystrophic calcification) but also had prominent mitotic activity, nuclear and cytoplasmic pleomorphism, areas of tumor necrosis, and infiltrative/destructive growth. Recognizing the extreme diversity in clinicopathologic features and biologic behavior among the so-called COCs, we suggest that the term COC should be used to specifically designate the unicystic lesions with or without an associated odontoma, i.e., lesions of the cyst group, and other related lesions identified as benign tumor and malignant tumor should be termed and classified separately. A tentative scheme with respect to the terminology and classification for this group of disparately behaving lesions was herein proposed to reflect the likely difference of their nature.
INFLAMMATORY
PERIAPICAL CYST	Also known as radicular cyst, apical periodontal cyst, or lateral radicular cyst Trauma or dental caries causes necrosis of the dental pulp allowing inflammatory mediators to exit through the apical foramen leading to granulation tissue in the apical periodontal connective tissue Causes proliferation of epithelial rests of Malassez and cyst formation
PARADENTAL CYST	Also known as inflammatory paradental cysts, mandibular infected buccal cyst, or buccal bifurcation cyst Occurs buccal and distal to a mandibular molar within 2 years after eruption of the tooth Inflammation induces odontogenic epithelium
DEVELOPMENTAL
DENTIGEROUS	AKA follicular cyst Should never diagnose unless there is an associated impacted tooth
ODONTOGENIC KERATOCYST	AKA primordial cysts, parakeratinized odontogenic cyst, or OKC May be associated with basal cell nevoid syndrome Unilocular cyst occurring between or apical to teeth Multilocular cyst frequently in posterior mandible Little jaw expansion Radiographs reveal edge effect with scalloped periphery with incomplete septation
CALCIFYING ODONTOGENIC CYST	AKA Gorlin cyst, COC Most are intraosseous but occasional extraosseous (peripheral or gingival) lesions occur
LATERAL PERIODONTAL CYST	AKA LPC 0.5-1 cm unilocular cyst between tooth roots in the premolar/canine region of the mandible Associated teeth are vital Extraosseous analogue is gingival cyst of the adult occurring in the buccal gingiva of the premolar area of the mandible Multicystic intraosseous LPCs are botryoid odontogenic cysts and may recur following currettage
GLANDULAR ODONTOGENIC CYST	AKA sialo-odontogenic syst, GOC Large multilocular cyst in anterior mandible

 

HISTOLOGICAL TYPES	CHARACTERIZATION
INFLAMMATORY
PERIAPICAL CYST	Thin nonkeratinized stratified squamous epithelium with slender interconnecting rete processes, exocytosis of neutrophils, and granulation tissue Lining may have mucous cells and Rushton bodies (intraepithelial curvilinear eosinophilic hyaline bodies) and occasional keratinization
PARADENTAL CYST	Histologically identical to periapical cyst
DEVELOPMENTAL
DENTIGEROUS
ODONTOGENIC KERATOCYST	Resembles steatocystoma simplex with corrugated surface Basal layer with palisaded columnar cells with hyperchromatic nuclei Parakeratotic cells present on luminal surface
Orthokeratinized odontogenic cyst	Identical to epidermal inclusion cyst with orthokeratin and a granular layer
CALCIFYING ODONTOGENIC CYST	Ghost cell keratinization in lining epithelium and may be found in connective tissue wall with foreign body giant cell reaction
LATERAL PERIODONTAL CYST	Thin nonkeratinized epithelium with polygonal to flattened squamous cells May have intraepithelial nodular aggregations of polygonal cells with clear cytoplasm Connective tissue may have islands of clear cells or nests of squamous odontogenic epithelium (dental lamina or rests of Serres)
GLANDULAR ODONTOGENIC CYST	Surface columnar to cuboidal cells with eosinophilic cytoplasm with rounded apices and intraepithelial lumina Mucous cells and ciliated cells Intraepithelial spherules of concentrically whorled keratinocytes

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Hyperplastic dental follicle	Thickness of the membranous connective tissue wall is >3mm Thickened normal dental follicular tisssue
Dental papilla	0.7 cm translucent white button-like nodule of myxoid tissue associated with an incompletely developed third molar with little or no evidence of root formation
Pericoronitis	Inflammation in soft tissue around the crown of an impacted or erupting mandibular third molar

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
RECURRENCE	If a cyst recurs, it is one of these three cysts It is always advisable to review the histology of the original cyst For these three entities, curettage is inadequate
Odontogenic keratocyst	43% recurrence following currettage
Unicystic ameloblastoma	Look for palisaded columnar cells in the basal layer with hyperchromatic nuclei polarized from the basement membrane
Glandular odontogenic cyst
TREATMENT	Depends upon type of cyst

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated March 15, 2005

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