Clinicopathological Analysis of Orthokeratinized Odontogenic Cyst Aided by a Pilot Molecular Characterization Using...

To assess the prevalence and detailed clinicopathological features of orthokeratinized odontogenic cysts (OOC) with special emphasis on molecular profiling using next-generation sequencing (NGS). To assess the prevalence and detailed clinicopathological features of orthokeratinized odontogenic cysts (OOC) with special emphasis on molecular profiling using next-generation sequencing (NGS). For radiographic analysis and evaluation of clinicopathological features, we included thirty-nine histologically proven cases of OOC, after obtaining clearance from the institutional ethical clearance board. Furthermore, cases of histopathologically proven OKC were selected for comparison of the radiographic mean surface area. ImageJ software, version 1.53, was used to measure the radiographic mean surface area. The molecular profiling of OKC was performed on formalin-fixed paraffin-embedded tissue from three available cases of OOC and analyzed using a 50-gene NGS panel. The estimated prevalence of OOCs over the past 20 years was 0.55% with a male-to-female ratio of 2:1. The mean age at diagnosis was 33.33 10.74 years (median 33 years). The mandibular molar and ramus region was most frequently affected. OOC had a mean surface area of 113.86 mm2, whereas in OKCs it was found to be 114.87 mm2; the mean difference was not statistically significant. OOC showed a missense mutation in TP53 at exon 6 with loss of function [variant- chr17:7578226 (T>A)] and another NRAS missense mutation at exon 3 [variant- chr1:115256529 (T>C)]. Both mutations were depicted as likely pathogenic. Radiographs were found to be ineffective in differentiating OOC and OKC. In a pioneer study, we genetically analyzed OOC using NGS and found a potential role of TP53 and NRAS mutations in its pathogenesis.