Orthokeratinized Odontogenic Cyst with an Associated Keratocystic Odontogenic Tumor Component and Ghost Cell Keratinization and Calcifications in a Patient with Gardner Syndrome

Abstract

Gardner syndrome (GS) is caused by mutations in the APC and besides adenomatous colorectal polyps includes such manifestations as osteomas, epidermoid cysts (ECs) and occasionally multiple pilomatricomas. More than 50 % of ECs in patients with GS exhibit pilomatricoma-like ghost cell keratinization. The latter may be explained by the fact that the development of both GS and pilomatricoma is driven by activation of the Wnt/β-catenin signaling pathway. A 62-year-old, Caucasian male with history of GS presented with a unilocular, mixed radiopaque/radiolucent mandibular lesion causing divergence and external root resorption of involved teeth. Histopathologically, the lesion was composed of two cystic components, an orthokeratinized odontogenic cyst (OOC) and a smaller one with characteristics of keratocystic odontogenic tumor (KCOT) featuring, focally, ghost cells and an epithelial morule-like structure. Dystrophic calcifications essentially similar to those seen in pilomatricomas were observed in the fibrous connective tissue wall. The KCOT and OOC epithelia revealed strong and diffuse cytokeratin (AE1/AE3) and β-catenin immunoreactivity. CD10 positive immunostaining was seen in the keratin and superficial spinous cell layers in both OOC and KCOT. The intraepithelial and mural ghost cells showed a cytokeratin (+), β-catenin and CD10 (-) immunophenotype. The diagnosis of OOC with ghost cell calcifications in association with KCOT was rendered. The patient was lost to follow-up. Although a coincidental co-existence cannot be excluded, ghost cell calcifications mimicking pilomatricoma-like changes in an unusual odontogenic cyst combining OOC and KCOT features as seen in this patient with GS may be explained by the common molecular mechanisms underlying the pathogenesis of cutaneous pilomatricomas and GS.

Keywords: Gardner syndrome; Ghost cells; Keratocystic odontogenic tumor; Orthokeratinized odontogenic cyst; Pilomatricoma; β-catenin.

Fig. 1

a Bluish discoloration of the overlying oral mucosa between the right lateral incisor (tooth #26) and right mandibular canine (tooth #27). b Periapical radiograph showing a unilocular, generally circumscribed, mixed radiopaque/radiolucent lesion of the right anterior mandible, along with divergence and external root resorption of involved teeth

Fig. 2

a Low-magnification photomicrograph revealing a fragmented cystic lining. Labels were added to show the location of the three components of the lesion; OOC orthokeratined odontogenic cyst, KCOT keratocystic odontogenic tumor, GCs ghost cells. b The epithelial lining showed areas of hyperorthokeratinization. c Medium-magnification photomicrograph highlighting the thick, verrucoid, orthokeratin layer as well as the pronounced granular cell layer. d Fragments of the hyperorthokeratinized cystic lining juxtaposed to non-keratinized areas (H&E; original magnification a: ×10, b: ×40, c: ×200, d: ×180)

Fig. 3

a Low-magnification photomicrograph of the keratocystic odontogenic tumor (KCOT). b High-magnification photomicrograph demonstrating an epithelial lining of 5–7 cells in thickness with fine parakeratinization, a slightly corrugated surface, nuclear hyperchromatism and palisading of the basal cell layer. c and d High-magnification photomicrographs showing the presence of large pale epidermoid cells some of which with faint eosinophilic cytoplasm and empty nucleus (ghost cells) in the KCOT. The location of ghost cells is indicated with asterisks (H&E; original magnification a: ×180, b: ×420, c: ×420, d: ×460)

Fig. 4

a The epithelial whorl or morule-like structure (asterisk) observed in the KCOT lining. b Low-magnification photomicrograph depicting aggregates of ghost cells and multiple dystrophic calcifications in the fibrous connective tissue wall. c Calcified ghost cell deposits resembling those of cutaneous pilomatricomas. d This singular calcifying cystic odontogenic tumor (CCOT)-like nest was present in the initial preparation only (H&E; original magnification a: ×400, b: ×150, c: ×260, d: ×420)

Fig. 5

Immunohistochemical findings. Strong and diffuse immunopositivity for cytokeratin AE1/AE3 throughout the OOC (a) and the KCOT (b), as well as the intraepithelial (c) and mural ghost cells (inset). The asterisks highlight the ghost cells. Strong and diffuse expression of β-catenin in the OOC (d) and KCOT (e). The ghost cells (asterisks) were β-catenin negative (f). CD10 immunoreactivity was seen in the keratin and superficial spinous cell layers in both OOC (g) and KCOT (h). The intraepithelial (i) and mural ghost cells (inset), indicated with asterisks, were uniformly CD10 negative (immunoperoxidase stain; original magnification a: ×50, b: ×150, c: ×300 (inset: ×280), d: ×40, e: ×180, f: ×280, g: ×60, h: ×160, i: ×280 (inset: ×260)

Fig. 6

Panoramic X-ray revealing the presence of multiple circumscribed radiopacities consistent with osteomas