A PUBMED search of case reports on PCOCs published between the years 1962 and 2023 was completed using the keyword: Peripheral Calcifying Odontogenic Cyst. A total of 52 publications were identified. All cases reviewed were published in English. Publications originally reported in a different language were excluded from our review. Review articles and meta-analysis were excluded due to the potential for subjects being accounted for multiple times and over-estimating the incidence of PCOC. Histological analysis and diagnosis of the lesions as PCOC using unique hallmarks of the lesion were required to be included in this study. 22 articles with total of 40 cases of PCOC were reviewed and the descriptive information from these cases and the current case are summarized in Table 2.

PCOC commonly presents as a uniform, painless, firm to soft gingival swelling without unique or distinguishing characteristics that would differentiate itself from other gingival pathologies commonly found in the oral environment. These lesions usually do not involve the underlying bone with very few rare cases reported with absorption of the adjacent alveolar bone, adjacent tooth root resorption, and potential for tooth displacement (1–3, 6, 7). PCOC lesions usually have no distinct radiographical characteristics, except in some case where sporadic calcifications in the lesions may appear on radiographs as radiopaque specks (6, 8). Histological analysis is often required for appropriate classification of these lesions. The most common histopathological findings of PCOC include a cystic lesion lined by epithelium with a well-defined ameloblastic-like basal layer of columnar cells in a palisaded fashion, an overlying layer with cells resembling stellate reticulum, and ghost cells that may be in the epithelial cyst lining or in the fibrous capsule (29). Presence of eosinophilic ghost cells is a characteristic microscopic feature of PCOC, however, may also be seen in other lesions, such as ghost cell odontogenic carcinoma, odontomas, and ameloblastic fibro-odontoma (29). Basophilic calcifications and calcifications of ghost cells can also be noted microscopically in PCOC lesions (29). The function of these ghost cells is currently debated but have been determined to not have a negative impact on the patient or with treatment outcomes (2).

Similar to previous study, our review found the most common site of occurrence for PCOC is the mandibular area, with a predilection for the anterior area of the jaw (2, 6). Previous studies found either similar distribution between genders or a higher percentage of occurrence in females while the present review noted a slightly higher percentage of occurrence in males (51.3%) (2, 6). The size of the PCOC lesions reviewed had a mean of 1.38 cm with standard deviation of 1.1 cm and a range of 0.5 cm to 4.3 cm.

Due to their non-aggressive behavior, and low risk of recurrence, PCOC lesions are often treated with enucleation or excisional removal with favorable prognosis. Recurrence of PCOC after treatment has not yet been reported in literature. Excision can be done via conventional surgical blade, laser, or electrosurgery devices. PCOC is often limited in the peripheral oral soft tissue without bony involvement and has an average size of 1.38 cm, therefore complete removal of the lesion if often reported in literature. Alternative management methods of decompression, marsupialization may be considered in lesion of large size. The patient in the present case reported slow growth of the lesion over the span of six month. Due to the limited number of cases available in literature it cannot be concluded if left alone without treatment if PCOC would continue to slowly expand in size or self-arrest at some point. In addition to microscopic examination, it has been suggested that utilization of immunohistochemical investigations on cell proliferation activity may also aid in diagnosis of PCOC and may further contribute to further understanding on debate of its cystic or neoplastic nature (4).

In 1962, Gorlin first described the calcifying ghost cell odontogenic cyst (CGCOC) under the term calcifying odontogenic cyst (COC) (11). Since its introduction, its classification and terminology continue to change through time due to a continued debate on whether there are two variants of the lesion—cystic and the neoplastic forms (4, 5). The “monistic” concept believes that all COCs are neoplastic in nature. However, majority of COC are cystic in architecture and appear to be non-neoplastic. Hence, the “dualistic” concept believes that COCs exist as two entities: a cyst or a neoplasm (4, 5). A chorological timeline of the various classification and terminology systems are presented in Table 1 (4, 5).

Differential diagnosis of exophytic oral lesion with soft tissue enlargement can include various etiologies from reactive, viral, neoplastic, to developmental. Reactive lesions such as peripheral giant cell granuloma (PGCG) or pyogenic granuloma (PG) are inflammatory response to localized irritation or trauma with association to hormonal changes, or certain medications (30). PGCG often presents as a soft tissue purplish-red nodule consisting of multinucleated giant cells in a background of mononuclear stromal cells and extravasated red blood cells (30). PG often presents as smooth or lobulated exophytic lesion that is red-bluish in coloration and histologically noted for mass of angiomatous tissue with proliferation of capillary vessels and infiltrations of plasma cells, lymphocytes and neutrophils (31). Peripheral ossifying fibroma (POF) is a smooth surfaced reactive gingival enlargement to local irritant. POF often has normal squamous surface epithelium with proliferation of fibroblasts, endothelial proliferation, mineralized osteoids or calcifications, and inflammatory cells (34). Mucocele is a mucus retention lesion due to alteration to excretory duct of the salivary gland (35). It has smooth surface with normal coloration to bluish tint (35). Histologically, mucocele usually has hyperplastic parakeratinized stratified squamous epithelium and cystic space containing mucin and mucus-filled cells (35). Presence of salivary gland tissue and sialomucin is a diagnostic histological feature of mucocele (35). Traumatic fibroma usually presents as smooth-surfaced, normal-colored mucosa with sessile or pedunculated base as a reactive hyperplastic lesion to localized trauma (36). Histologically, irritation fibroma usually is noted as non-encapsulated nodular mass composed of fibrous connective tissue with collagen bundles interspersed with fibroblasts, blood vessels and scattered chronic inflammatory cells (36). The overlying squamous epithelium can be hyperkeratotic (36). Viral lesions such as condyloma acuminatum, verruca vulgaris, papilloma are associated with human papilloma virus (HPV) and have rough verrucous surface (32). Histologically theses lesions are noted for acanthosis with overlying hyperkeratosis and distinctive cells termed koilocytes (32). Koilocytes are large keratinocytes with abundant cytoplasm and small pyknotic nuclei often present in the upper layers of the epidermis (32). In addition to microscopic examination, in-situ hybridization, immunohistochemical studies for papillomavirus common antigen, or polymerase chain reaction may be used to confirm presence of HPV or further identify the HPV type (32). Developmental lesions may include PCOC as in this case or adult gingival cyst. The distinctive histological finding of PCOC is presence of ghost cells. Ghost cells are enlarged epithelial cells with eosinophilic cytoplasm and no nucleus which can be found in the lining epithelium and in the cyst lumen (1). Adult gingival cyst is a developmental odontogenic cyst that has mucosal surface lined by stratified squamous epithelium and a fibrous connective tissue capsule containing a cystic lumen lined by flat to cuboidal cells and mild chronic inflammatory cell infiltrates (33). Additional differential diagnosis of peripheral oral soft tissue enlargement may also include benign and malignant neoplasm. Differential diagnoses for oral soft tissue as exophytic lesion are listed in Figure 4 (12, 13, 36). Definitive diagnosis of peripheral oral exophytic lesions can be challenging and histological examination along with clinical correlation often is needed to aid in proper diagnosis.

Literature on PCOC is limited to case reports and case series, which is considered lowest level of evidence in evidence-based research. Case reports and series can provide clinicians a useful narrative observational trend of the characteristic, incidence, location, and biological behavior of PCOC and gender, ethnicities, and age of patients. However, meaningful statistical analysis often is difficult with case reports/series due to limited number of case available in the literature and/or missing data. Data reported in case reports may not always be comprehensive and missing data can lead to missed observational trend. Ethnicity, gender, age of the patient, size, and location of the lesion were missing in some of the case reports reviewed. Incidence of PCOC may also be underreported due to the various terminologies and changing classification systems used throughout the years. This case report and review of literature presented a narrative description of the general characteristics on PCOC solely based on 41 case reports available in PubMed utilizing the key term PCOC. Systemic analysis of larger number of cases and inclusion of all available terminologies related to PCOC throughout the years in literature search key terms will provide a higher level of evidence of results.