Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix.

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor. In contrast to the modest parenchyma formed by native adult progenitors, Alx3-restored cells in decellularized scaffolds not only produced vascularized stroma that involved vascular endothelial growth factor signalling, but also parenchymal dentin via the Wnt/ß-catenin pathway. In an orthotopic large-animal model following parenchyma and stroma ablation, Wnt3a-recruited endogenous cells regenerated neurovascular stroma and differentiated into parenchymal odontoblast-like cells that extended the processes into newly formed dentin with a structure-mechanical equivalency to native dentin. Thus, the Alx3-Wnt3a axis enables postnatal progenitors with a modest innate regenerative capacity to regenerate adult tissues. Depleted signals in the decellularized matrix may be reinstated by a developmentally pivotal gene or corresponding protein.

Primary Ewing sarcoma of the anterior mandible localized to the midline.

Ewing sarcoma is a malignant, small, round blue-cell tumor of the bone that is usually located in the long bones and the pelvis. Fewer than 3% of all Ewing sarcomas originate in the head and neck region and these are mostly located in the posterior mandible. We report the case of a 17-year-old girl with a primary Ewing sarcoma localized at the midline of the anterior mandible.

Topical Application of Green Tea Polyphenol (-)-Epigallocatechin-3-gallate (EGCG) for Prevention of Recurrent Oral Neoplastic Lesions.

OBJECTIVE: A preliminary study was conducted to investigate feasibility of using an oral cancer chemopreventive agent (-)-epigallocatechin-3-gallate (EGCG), the most biologically active component in the green tea extract, in a form of 'swish-and-spit' mouthwash. Such application of EGCG is beneficial as it maximizes exposure of the oral mucosa to the agent but minimizes systemic side effect. STUDY DESIGN: The study was conducted on individuals suspected to have oral field cancerization who are at a high risk for developing recurrent oral precancerous and carcinomatous lesions. EGCG was used as a daily mouthwash for 7 days. EGCG's ability to modulate target molecules implicated in oral carcinogenesis was assessed by measuring the change in expression level of biomarkers. RESULTS: Immunohistochemical expression of phosphoactivated epidermal growth factor receptor (pEGFR), cyclooxygenase-2 (cox-2) and ki-67 were evaluated at baseline and at the endpoint (day 8). Although not statistically significant, overall decrease in expression levels of pEGFR (27.5%), cox-2 (15.9%) and ki-67 positive cells (51.8%) were observed following EGCG treatment. Moreover, a detectable level of EGCG was found in saliva but not in plasma after the one-week treatment regime, demonstrating local availability of EGCG in oral mucosa without significant systemic absorption. CONCLUSION: To best of our knowledge this is the first study to explore use of oral cancer chemopreventive agent in a form of mouthwash in patients with oral field cancerization. Although a definitive conclusion was not reached due to limited sample size, if proven effective, EGCG therapy may offer a non-invasive preventive modality for oral field cancerization.

Cartilage choristoma (soft tissue chondroma): a rare presentation in the lower lip.

Cartilage choristoma (soft tissue chondroma) is an ectopic cartilaginous tissue that is rarely found in oral mucosa. Awareness of such disease entity will guide proper diagnosis and treatment. A case of cartilage choristoma occurring in the lower lip of an 8-year-old child is reported. Potential pathogenetic mechanism and the histologic features of this unusual condition are further discussed.

Gingival squamous cell carcinoma in adolescence.

Squamous cell carcinoma (SCC) is a rare finding in the adolescent population, with most cases occurring in patients with underlying heritable diseases or immunologic conditions. Moreover, the incidence of oral SCC in this age group is extremely low. While isolated cases of adolescent oral SCC have been documented, most have been primary tongue or lip lesions. We report 4 cases of gingival SCC occurring in otherwise healthy adolescent patients. The preliminary clinical impressions ranged from factitial injury to inflammatory tissue. Microscopic similarities, including overlap with pseudoepitheliomatous hyperplasia and keratoacanthoma, were seen. Review of the literature indicates that adolescent gingival SCC is extremely rare and a challenging diagnosis for the clinician and pathologist alike. Diagnostic pitfalls, possible etiologic factors, and the prognostic outlook of this condition are discussed.

Activated checkpoint kinase 2 expression and risk for oral squamous cell carcinoma.

BACKGROUND: Phosphoactivation of a DNA damage response molecule checkpoint kinase 2 (pChk2) may be a marker of oral epithelial cells that have entered the precancerous and squamous cell carcinoma (SCC) stages. We explored whether there was selective expression of pChk2 in precancerous lesions but not in nonneoplastic tissue of the oral mucosa. EXPERIMENTAL DESIGN: In a retrospective cohort design, 96 biopsied clinical leukoplakias and erythroplakias with known subsequent progression to SCC were identified from 48 subjects and assigned as the cases group. Expression status of pChk2 was compared with that of the 97 leukoplakias and erythroplakias that did not progress to SCC (control groups) by immunohistochemical analysis. Included in both groups were lesions with histologically confirmed dysplasia and those that lacked histologic evidence of atypia. RESULTS: Subjects with pChk2-positive but histology-negative (for atypia) lesions had an 8.6 times higher risk of developing SCC compared with those with pChk2-negative and histology-negative lesions. Overall, the presence of detectable pChk2 staining was able to identify lesions at risk of developing SCC within 3 years with a sensitivity of 85.2%, specificity of 74.2%, and predictive accuracy of 78.2% (odds ratio, 19.9; 95% confidence interval, 7.3-55.5). CONCLUSION: This is the first study to include histologically nonatypical cases in the analysis of a putative biomarker for oral precancerous lesions. Our data show that pChk2 merits further investigation as a promising biomarker that can discriminate those lesions at risk for developing SCC, regardless of histologic evidence for atypia.

Juvenile oral lichen planus: a report of 2 cases.

Lichen planus is a mucocutaneous disease that predominantly affects older patients and occurs much less frequently in the pediatric population. Furthermore, oral lichen planus is extremely rare in childhood with very few cases cited in the literature. The intention of this paper is to contribute two clinically and histologically documented cases of juvenile oral lichen planus cases to the literature. Although a rare occurrence, early recognition and diagnosis of this condition by dental practitioners can have a significant impact on the oral health of affected patients.

Bilateral canalicular adenomas of the upper lip.

An unusual case of canalicular adenomas appearing bilaterally and simultaneously as separate nodules of the right and left upper lip is described. Upon histological examination, both nodules revealed tumor islands within their respective capsules, as well as outside their capsules and extending into normal salivary gland tissues. The article describes this unusual case and reviews the significance of the extracapsular tumor islands. The immunohistochemical profiles of canalicular adenoma and other salivary gland neoplasms with similar histology are compared and discussed.

Myeloid sarcoma occurring concurrently with drug-induced gingival enlargement.

BACKGROUND: Myeloid sarcoma is an extramedullary malignancy of myeloblasts. An unusual case of myeloid sarcoma presenting in the gingiva and affected by drug-induced gingival enlargement is presented. METHODS: A 63-year-old male taking amlodipine for his hypertension presented with a 3-week gingival enlargement. Although the obvious clinical impression was that of drug-induced gingival enlargement, an incisional biopsy was performed to corroborate chemical enlargement while ruling out diseases such as lymphoma and leukemia. RESULTS: Microscopic examination of the thickened gingiva revealed surface stratified squamous epithelium having needle-like rete pegs characteristic of drug-induced gingival enlargement. Beneath the surface epithelium, the fibrous tissue was virtually replaced by a dense infiltrate of malignant cells. Immunohistochemical studies were performed with CD117 and myeloperoxidase identifying the malignant cell population as myeloblasts, leading to a diagnosis of myeloid sarcoma. CONCLUSION: Myeloid sarcoma and hematopoietic malignancies must be included in a differential diagnosis of gingival enlargement until the definitive diagnosis is reached by histologic/laboratory examination.