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calcium‐binding protein Calretinin has been shown to be positive in up to 100% of ameloblastomas, including unicystic ameloblastoma. Odontogenic cysts including keratocysts are negative. Useful to differentiate cystic ameloblastoma from other cysts, especially in small biopsies from the posterior mandible region (Altini et al. 2000 ; Coleman et al. 2001 ; De Villiers et al. 2008; Jeyaraj 2019 ; Rudraraju et al. 2019 ; discussed in Chapters 5 and 7) Maspin Maspin, a member of the serine protease inhibitor superfamily May be useful in the differentiation of glandular odontogenic cyst from central mucoepidermoid carcinoma, especially in small biopsies where not all features may be apparent. Maspin is widely expressed, but studies have shown much greater expression in the mucous cells of mucoepidermoid carcinoma than in glandular odontogenic cyst. Note that the differences relate only to mucous cells – other epithelial cells of the cyst lining are positive (Vered et al. 2010 ; Chapter 10, Table 10.4) β‐catenin Cell surface protein important in cell adhesion, but also in the regulation of the WNT signalling pathway Intracellular expression of β‐catenin (cytoplasmic and nuclear) is characteristic of calcifying odontogenic cyst (and other ghost cell lesions – see CTNNB1 gene below) and is seen in all cases. However, it is not diagnostic, since it may also be seen in ameloblastomas p16 p16 is a cyclin‐dependent kinase inhibitor, involved in regulation of the cell cycle p16 antibodies are useful in the differentiation of branchial cleft cyst from a cystic metastasis in the lateral neck. p16 is activated by human papillomavirus (HPV) infection and strong expression, interpreted in context, is almost diagnostic of HPV‐associated oropharyngeal carcinoma. The majority of cystic metastases come from HPV‐associated squamous cell carcinomas and are p16 positive, but branchial cysts are negative. Note that positive staining must be carefully interpreted and the correct criteria must be used (Pai et al. 2009 ; Cao et al. 2010 ; Müller et al. 2015 ; Chapter 18, Figure 18.7) Molecular markers Gene Alterations Diagnostic utility PTCH Mutations or loss of heterozygosity (LOH) of PTCH gene Alteration or loss of PTCH gene is seen in up to 80% of odontogenic keratocysts, but is not diagnostic because altered PTCH may be seen in other cyst types. However, biallelic loss of PTCH has been recorded in keratocysts and not in other odontogenic cysts, and this may be diagnostic MAML2 Rearrangements of MAML2 gene, usually with CRCT1 or 3 MAML2 rearrangements are seen in mucoepidermoid carcinomas and their presence helps differentiate intraosseous mucoepidermoid carcinoma from glandular odontogenic cyst, which does not show the translocation (Bishop et al. 2014 ) CTNNB1 Mutations in the CTNNB1 (β‐catenin) gene CTNNB1 mutations are seen in a wide range of neoplasms, but within the jaws are almost unique to ghost cell lesions (calcifying odontogenic cyst and dentinogenic ghost cell tumour). However, molecular analysis has not been used for diagnostic purposes. CTNNB1 mutation results in aberrant intracellular (cytoplasmic and nuclear) expression of β‐catenin protein (see β‐catenin above) (Gomes et al. 2019 ; Chapter 11)

3 Radicular Cyst

      CHAPTER MENU

        Clinical Features Frequency Age Sex Site Clinical Presentation Radicular Cyst Residual Cyst

        Radiological Features

        Pathogenesis Pathology of Periapical Periodontitis Phase of Initiation Phase of Cyst Formation Growth and Enlargement of the Radicular Cyst Role of Hydrostatic Pressure Epithelial Proliferation Degradation of the Connective Tissues and Bone Resorption

        Histopathology Cellular and Metaplastic Changes Hyaline Bodies Accumulation of Cholesterol Residual Cyst Pocket Cyst (Bay Cyst)

        Malignant Change in Radicular Cysts

        Treatment

      The inflammatory odontogenic cysts arise as a result of epithelial proliferation within an inflammatory focus due to a number of causes. Radicular cyst is the most common inflammatory cyst and arises due to proliferation of epithelial remnants in the periodontal ligament as a result of periapical periodontitis following death and necrosis of the pulp. Radicular cysts are most commonly found at the apex of the involved tooth, but may arise on the lateral aspect of the root in relation to a lateral root canal. Quite often a radicular cyst remains behind in the jaws after removal of the offending tooth and this is referred to as a residual cyst (Speight and Soluk‐Tekkeşin 2022a ).

      Inflammatory cysts may also occur on the lateral aspect of a tooth as a consequence of an inflammatory

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