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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.

SUBMITTER: Argyris PP

PROVIDER: S-EPMC5429271 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Project description:PurposeChildren with Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disease, exhibit extraskeletal calcifications detected by radiographic analysis and on physical examination. The aim of this study was to describe the natural history and pathophysiology of these abnormal calcifications in HGPS, and to determine whether medications and/or supplements tested in clinical trials alter their development.MethodsChildren from two successive clinical trials administering 1) lonafarnib (n = 26) and 2) lonafarnib + pravastatin + zoledronic acid (n = 37) were studied at baseline (pre-therapy), one year on therapy, and at end-of-therapy (3.3-4.3 years after the baseline visit). Calcium supplementation (oral calcium carbonate) was administered during the first year of the second trial and was subsequently discontinued. Information on calcifications was obtained from physical examinations, radiographs, and serum and urinary biochemical measures. The mineral content of two skin-derived calcifications was determined by x-ray diffraction.ResultsExtraskeletal calcifications were detected radiographically in 12/39 (31%) patients at baseline. The odds of exhibiting calcifications increased with age (p = 0.045). The odds were unaffected by receipt of lonafarnib, pravastatin, and zoledronate therapies. However, administration of calcium carbonate supplementation, in conjunction with all three therapeutic agents, significantly increased the odds of developing calcifications (p = 0.009), with the odds plateauing after the supplement's discontinuation. Composition analysis of calcinosis cutis showed hydroxyapatite similar to bone. Although serum calcium, phosphorus, and parathyroid hormone (PTH) were within normal limits at baseline and on-therapy, PTH increased significantly after lonafarnib initiation (p < 0.001). Both the urinary calcium/creatinine ratio and tubular reabsorption of phosphate (TRP) were elevated at baseline in 22/39 (56%) and 31/37 (84%) evaluable patients, respectively, with no significant changes while on-therapy. The mean calcium × phosphorus product (Ca × Pi) was within normal limits, but plasma magnesium decreased over both clinical trials. Fibroblast growth factor 23 (FGF23) was lower compared to age-matched controls (p = 0.03).ConclusionsExtraskeletal calcifications increased with age in children with HGPS and were composed of hydroxyapatite. The urinary calcium/creatinine ratio and TRP were elevated for age while FGF23 was decreased. Magnesium decreased and PTH increased after lonafarnib therapy which may alter the ability to mobilize calcium. These findings demonstrate that children with HGPS with normal renal function and an unremarkable Ca × Pi develop extraskeletal calcifications by an unidentified mechanism that may involve decreased plasma magnesium and FGF23. Calcium carbonate accelerated their development and is, therefore, not recommended for routine supplementation in these children.

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

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