Histological Evaluation of Alveolar Ridge Preservation Using Different Bone Grafts: Clinical Study Analysis Part II.

OBJECTIVE: To compare histologically the percentage of bone formation 12-20 weeks post-ridge augmentation using two different techniques. BACKGROUND: Tooth loss is associated with three-dimensional bone remodeling and ridge atrophy. Ridge preservation procedures can prevent alveolar bone volume loss. Different techniques and materials are used to preserve the alveolar ridge. MATERIALS & METHODS: Computer-generated randomization software was used to assign two ridge preservation techniques for 11 extraction sites. In group I (type I bovine Achilles tendon collagen plugs with bioactive resorbable calcium apatite crystals (CPCAC) and ingroup II, cortico-cancellous bone chips (CCBC) mix, and an expanded polytetrafluoroethylene (ePTFE) barrier membrane were placed. The histomorphometric studies were performed using a computer-based image analysis system (IMAGE-J 1.4, National Institute of Health, Bethesda, MD, USA) to calculate the pixel area of bone tissue and the remaining bone graft material. The histomorphometric data were analyzed using a Student's t-test to compare the measurements between the two experimental groups. This parametric statistical test was employed to determine if there were any statistically significant differences in the quantitative histological parameters between the groups. Results: The sockets that received CPCAC showed a lower (31.89%) percentage of native bone surface area compared to the CCBC group (43.87%). However, the difference was not statistically significant (P< 0.05). In addition, group CPCAC showed evidence of foreign body reaction. CONCLUSION: The CCBC graft covered with an ePTFE barrier may induce more bone formation with minimal inflammation in an extraction socket compared to a collagen plug with calcium apatite crystals. In addition, histological analysis of the CPCAC graft showed evidence of foreign body reaction, which indicates a negative clinical impact.

Tetraspanin CD82 Correlates with and May Regulate S100A7 Expression in Oral Cancer.

Many metastatic cancers with poor prognoses correlate to downregulated CD82, but exceptions exist. Understanding the context of this correlation is essential to CD82 as a prognostic biomarker and therapeutic target. Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancer. We aimed to uncover the function and mechanism of CD82 in OSCC. We investigated CD82 in human OSCC cell lines, tissues, and healthy controls using the CRISPR-Cas9 gene knockout, transcriptomics, proteomics, etc. CD82 expression is elevated in CAL 27 cells. Knockout CD82 altered over 300 genes and proteins and inhibited cell migration. Furthermore, CD82 expression correlates with S100 proteins in CAL 27, CD82KO, SCC-25, and S-G cells and some OSCC tissues. The 37-50 kDa CD82 protein in CAL 27 cells is upregulated, glycosylated, and truncated. CD82 correlates with S100 proteins and may regulate their expression and cell migration. The truncated CD82 explains the invasive metastasis and poor outcome of the CAL 27 donor. OSCC with upregulated truncated CD82 and S100A7 may represent a distinct subtype with a poor prognosis. Differing alternatives from wild-type CD82 may elucidate the contradictory functions and pave the way for CD82 as a prognostic biomarker and therapeutic target.

Evaluation of EWSR1/FUS rearrangements by FISH and NKX2.2 immunoexpression in simple bone cysts of the jaw.

OBJECTIVE: Recent studies have identified recurrent rearrangements of EWSR1 or FUS with NFATC2 in extragnathic simple bone cysts (SBCs). We investigated the presence of EWSR1 or FUS rearrangements and the immunophenotypic expression of NKX2.2 and CD99 in a series of SBCs of the jaw. STUDY DESIGN: We retrieved 10 cases of SBC of the jaw from the University of Pittsburgh archives. Of the 10 cases, we were able to evaluate 8 by immunohistochemistry for CD99 and NKX2.2 and 7 by fluorescence in situ hybridization (FISH) for EWSR1 and FUS rearrangement using EWSR1 and FUS break-apart probes. RESULTS: All 8 cases evaluated by immunohistochemistry expressed CD99 but were negative for NKX2.2, and all 7 cases assayed using FISH were negative for EWSR1 and FUS rearrangements. CONCLUSIONS: In contrast to the SBC of extragnathic sites, we found no presence of EWSR1 and FUS rearrangements by FISH in the SBC of the jaw, suggesting that this entity may be etiologically/molecularly distinct and reflects a non-neoplastic reactive process. However, as these lesions tend to be paucicellular, FISH may not be the appropriate technique for identifying EWSR1/FUS fusions. Other techniques should be used to evaluate them in future studies.

Cemento-Osseous Dysplasia of the Jaw: Demographic and Clinical Analysis of 191 New Cases.

Cemento-osseous dysplasia (COD) is a form of benign fibro-osseous lesion of the jaw. We sought to evaluate the demographic and clinical presentations of COD by collecting and analyzing the demographic, clinical, radiographic, and pathologic data of COD diagnosed in our institution from 2017 to 2022. Over this six-year period, the records of 191 patients with COD were reviewed. Most patients were African American and female. Eighty-five patients were diagnosed with florid COD (FLCOD), 63 with periapical COD (PCOD), and 43 with focal COD (FCOD). Twenty-eight (14.7%) patients presented symptoms. The most common symptom was pain. All the symptomatic cases of COD that were histopathologically diagnosed were osteomyelitis in the setting of COD. Symptomatic patients were older (mean of 61.3 years) than the asymptomatic patients (mean of 51.2 years). Due to the radiographic appearance of a radiolucency or a mixture of radiolucency and radiopacity, forty-five asymptomatic patients were biopsied. Most of the asymptomatic patients biopsied were patients with FCOD (n = 19, 54.3%), followed by PCOD (n = 16, 25.8%), and FLCOD (n = 10, 15.2%). FLCOD is the most common form of COD to present with symptoms. Due to the significant overlap in clinical and radiographic presentation with other entities, FCOD and PCOD remain a diagnostic challenge to dentists. In conclusion, we analyzed the demographic and clinical features of 191 new cases of COD, which reaffirms that cemento-osseous dysplasia is a condition that primarily affects middle-aged females of African descent and occurs more frequently in the mandible.

Herpesvirus-Related Lesions of the Oral Mucosa.

The human herpesvirus (HHV) family is a group of enveloped DNA viruses containing 8 members known to produce oral mucosal lesions. Following initial exposure, which may result in symptomatic primary infection, the viruses establish latency within specific cells/tissues. After reactivation, herpesviruses can cause localized symptomatic or asymptomatic recurrent (secondary) infections or diseases. HHV may have a significant role in the cause of oral mucosal infectious diseases in immunocompromised patients. This article discusses the role of those herpesviruses that can induce oral mucosal lesions, with focus on the clinical features and treatment/management.

SATB2 Immunoexpression in Peripheral Ossifying Fibroma and Peripheral Odontogenic Fibroma.

Peripheral ossifying fibromas (POFs) and peripheral odontogenic fibromas (POdFs) appear clinically similar but of different histogenesis. The novel marker SATB2 is involved in regulation of osteoblastic differentiation and phenotype. However, SATB2 expression has not been previously explored in POFs and POdFs. Given the potential for mineralized tissue formation in POFs and POdFs, and to more clarify the phenotype of the lesional cells, this study was aimed to immunohistochemically investigate SATB2 expression in POFs and POdFs. Fourteen cases of POF and POdF (7 cases each) were selected, stained for SATB2 immunohistochemically, and scored according to the percentage of positive lesional cells (0, no staining; 1 +, < 5%; 2 +, 5-25%; 3 +, 26-50%; 4 +, 51-75%; and 5 +, 76-100%), and the intensity of staining was graded as weak, moderate, or strong. The control group included the inflammatory fibrous hyperplasia-like area present in two cases, 1 case fibroma, and 1 case giant cell fibroma. Moderate to strong, and diffuse SATB2 nuclear immunoreactivity was detected in the lesional cells of all cases of POFs and POdFs with variable scores; 3-5 + for the POFs and 3-4 + for the POdFs (P = 0.101). The distribution of staining was more prominent in those lesional cells associated with the osteoid/calcification in the cases of POFs. No staining was noted in the control group. The lesional cells in both POFs and POdFs express SATB2 and may exhibit the osteoblastic-like phenotype. SATB2 staining may be useful for diagnosis of subsets of POFs with minimal or absent calcification and some POdFs with unidentifiable odontogenic epithelium.

Oral cyst-like nodule caused by a long standing unusual embedded foreign object: Report of a case.

Traumatic implantation of foreign material in the oral mucosa is unusual and may occur. In this article, we report the presence of an unusual foreign object associated with a cyst-like inflammatory response in a 50-year-old male. The patient presented with a painless recurrent soft tissue swelling in the anterior vestibule of maxilla of at least 2-year duration. The lesion was surgically excised and a retained shrapnel-like object within a cyst-like and thick-walled structure was obtained. Histopathologically, the cyst-like structure exhibited a lymphohistiocytic infiltrate in the wall and a luminal synovial metaplasia-like change, predominantly composed of histiocytes. Immunohistochemical stain of CD163 highlighted the histiocytes. The patient stated a history of traumatic implantation of shrapnel fragments in the area that occurred 30 years ago due to an explosion in the Iran-Iraq war.

Myofibroma as a Rapidly Growing Gingival Mass in a 4-year-old Boy: a Case Report.

Solitary myofibroma is an uncommon benign soft tissue neoplasm of myofibroblastic origin exhibiting head and neck region predilection but its presence in the jaws is rare. Myofibroma presents as painless mass and may demonstrate rapid enlargement and growth that clinically mimic malignancies. This report presents a 4-year-old male patient with a rapidly growing mandibular gingival mass with some evidence of underlying alveolar bone destruction. Incisional biopsy was performed and the specimen was stained with hematoxylin and eosin and immunohistochemical antibodies for αSMA, CD34, S100 and desmin. The diagnosis of myofibroma was made and the lesion was completely excised. The knowledge about microscopic features of this rare neoplasm helps to have a proper diagnosis and avoid unnecessary treatment.

Reactive oral lesions associated with dental implants. A systematic review.

Reactive lesion formation around dental implants a complication that has been given much consideration. These lesions can lead to marginal bone loss, and consequently, implant failure. In the present systematic review, all reported reactive lesions associated with dental implants in the literature were assessed. An electronic search was performed using PubMed Central, Scopus, Google Scholar, and Science Direct. The search strategy was limited to human studies (case reports and case series), full-text English language articles, published until May 2017. A total of 19 articles reporting 27 lesions in 25 cases were included. Peripheral giant cell granuloma and pyogenic granuloma were the most reactive lesions found around dental implants. The mean age of the patients was 51.28 ± 14.48 years, with a slight female predilection. Posterior mandibular gingiva was the most common location for these lesions. The recurrence rate of lesions was 33.33%, and the chance of implant removal was 29.62%. Due to the clinical significance of these lesions, early histopathologic examination is recommended to exclude the presence of such pathological lesions.

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.

Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas.

Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family members. The role of NRPs in neurons and endothelial cells has been investigated, but the expression and role of NRPs in epithelial cells is much less clear. Herein, the expression and localization of NRP1 was investigated in human and mouse skin and squamous cell carcinomas (SCCs). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of the skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did co-localize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or epidermal growth factor-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity.

Granulomatous foreign body reaction to dermal cosmetic fillers with intraoral migration.

OBJECTIVE: We report intraoral granulomatous foreign body reactions in patients treated with calcium hydroxylapatite (CHA) or poly-l-lactic acid (PLA). STUDY DESIGN: Clinical and histopathologic data were obtained from 25 patients who developed orofacial nodules or swelling after dermal filler injections. RESULTS: All 25 patients were women aged 35 to 78 years (median, 55 years). All had a history of injection of CHA (n = 13) or PLA (n = 12) to the lips, nasolabial area, or mental area. Two patients developed cutaneous nodules at the sites of injections; all others presented with intraoral nodules (labial/buccal or vestibular mucosa) distant from the site of injections, suggestive of filler migration. Five of 21 cases presented with pain. Histopathologically, CHA presented as a diffuse mass of mauve-gray or beige, nonrefractile spherules, and PLA as rice- or spindle-shaped, geometric, refractile bodies within circumscribed nodules. CONCLUSIONS: Cutaneous injections of CHA and PLA fillers may induce granulomatous reactions presenting as intraoral nodules distant from the injection sites.

Lip nodules caused by hyaluronic acid filler injection: report of three cases.

Many dermal fillers have been used for reducing facial skin lines and for providing lip augmentation, and hyaluronic acid (HA) is one of the most widely used agents. One of the main commercial forms of HA is Restylane (Q Med, Sweden) produced by microbiological engineering techniques. Although HA is non-immunogenic, hypersensitivity and Granulomatous foreign body reactions have been reported. Herein, we report three female patients (average age 56 years) who presented with firm nodular lesions of the lip and a history of injection with HA (Restylane, Q Med, Sweden). Histopathologically, all cases showed pools of amorphous hematoxyphilic material surrounded by bands of densely collagenized connective tissue with no inflammation or foreign body reaction. Histochemical stains confirmed the presence of acid mucopolysaccharides such as hyaluronic acid. We conclude HA (Restylane, Q Med, Sweden) is an inert filler that may persist at an injection site, resulting in a tumor-like nodule.

Oral verruciform xanthoma associated with chronic graft-versus-host disease: a report of five cases and a review of the literature.

Verruciform xanthoma (VX) is an uncommon benign inflammatory mucocutaneous condition that chiefly occurs in the oral cavity. It is often associated with pre-existing epithelial and/or inflammatory disorder and is characterized histopathologically by papillary epithelial hyperplasia and the presence of foamy macrophages in connective tissue papillae. We report of a series of five cases with VX who concurrently had chronic oral graft-versus-host disease following hematopoietic stem cell transplantation.

A pigmented dentigerous cyst in a patient with multiple dentigerous cysts of the jaws: a case report.

AIM: The aim of this article is to report an unusual and interesting case of non-syndromic multiple dentigerous cysts of the maxilla and mandible associated with melanin pigment and melanocytes in the epithelial lining in one of the cysts. In addition, embryologic aspect and origin of melanocytes are briefly discussed. BACKGROUND: Dentigerous cysts are the second most common odontogenic cysts after radicular cysts. They are usually solitary with multiple cysts reported on occasion in association with syndromes. While melanocytes and melanin-pigment are widely distributed in the skin, the nervous system, certain types of mucosa, uveal tract, and other areas, they are not normally present within bone in mammals. REPORT: A 37-year-old Iranian male was referred to an oral surgeon by his dentist for evaluation and treatment of multiple cyst-like radiolucent lesions around the crowns of some unerupted permanent teeth in both maxillary and mandibular anterior areas. The biopsy revealed numerous granules of melanin-pigment distributed throughout the epithelial lining of one of these cysts in addition to the characteristic histopathologic features of adentigerous cyst. Histochemical analysis confirmed the pigment was melanin, and many of the cells containing melanin were immunohistochemically positive for s-100 protein. SUMMARY: Although the specific origin and pathologic significance of the melanocytes described here cannot be explained, it may be of interest for future investigations.