Investigation of foreign materials in gingival lesions: a clinicopathologic, energy-dispersive microanalysis of the lesions and in vitro confirmation of pro-inflammatory effects of the foreign materials.

OBJECTIVES: This study aimed to evaluate the clinical and histopathologic features of gingival lesions containing foreign material (GLFMs). In parallel, the composition of the foreign material and its effects in primary human gingival fibroblasts (HGFs) were investigated. STUDY DESIGN: Eighty-six GLFMs were retrieved from an oral pathology biopsy service. Clinical and microscopic data were analyzed, and the composition of the particles was identified by using energy-dispersive X-ray spectroscopy (EDX). Furthermore, HGFs were stimulated with silica (SiO2) microparticles to investigate the production of collagen type 1 (COL-1), matrix metalloproteinase 2 (MMP2), and inflammatory cytokines. RESULTS: GLFMs were most commonly found in women (60.5%) and most frequently described as white plaques. Histopathologic examination identified verrucous hyperplasia in 59% and epithelial dysplasia in 28% of the cases. EDX microanalysis revealed that Si (94%) was the most frequently detected foreign element. SiO2 microparticles induced higher COL-1 expression; higher levels of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-8, and transforming growth factor-ß, and increased MMP-2 activity in HGFs. CONCLUSIONS: There was a strong association between the presence of foreign material in the gingiva and white verrucous clinical lesions. In addition, the most common element in the foreign material was Si, and our in vitro findings demonstrate the importance of silica-mediated effects on gingival fibroblasts.

Investigation of immune cell markers in feline oral squamous cell carcinoma.

Squamous cell carcinoma is the most common oral cancer in the cat and presents as a locally aggressive lesion for which an effective therapeutic protocol remains elusive. Feline oral squamous cell carcinoma (OSCC) shares many clinical characteristics with human head and neck squamous cell carcinoma (HNSCC). Accordingly, present studies were conducted to determine similarities for immune markers shared by feline OSCC and human HNSCC. Biopsies harvested from a feline patient cohort-1 (n = 12) were analyzed for lymphoid cell infiltrates by immunohistochemistry (IHC). Results revealed unique patterns of T cell infiltration involving both neoplastic epithelium and stroma that were detected in most patient tumor biopsies (92%) examined by IHC staining for CD3. Intratumoral B cell infiltrates were detected within tumor stroma only, based on IHC staining for CD79a and CD20 for all patients within the same cohort-1. Infiltration of tumors by a regulatory CD4 T cell subset (Tregs) defined by expression of the forkhead transcription factor FoxP3, was also detected in biopsies from 57% of patients and involved infiltration of neoplastic epithelium and stroma. Patient biopsies were also examined for expression of immunomodulator cyclooxygenase (COX)-2 and revealed positive but weak staining of neoplastic epithelium in a significant proportion of cases (75%). Interestingly, COX-2 expression was detected in both neoplastic epithelium and stroma. Blood collected from a second cohort of feline OSCC patients (n = 9) revealed an increased frequency of circulating CD4+FoxP3+ T cells when compared to healthy adult controls (n = 7) (P = 0.045), although frequencies of CD4+CD25+FoxP3+ T cells were comparable between patients and healthy pet cat controls. Lastly, biopsies from feline OSCC patients were characterized for histologic subtype using a classification scheme previously described for human HNSCC. This analysis revealed the conventional subtype as the predominant variant (75%) with conventional subtypes split evenly between well differentiated and moderately differentiated carcinomas. Two cases were classified as papillary and one case as basaloid subtypes. Correlations between subtype, immune marker scores or circulating Treg frequencies and clinical characteristics or outcome were not detected, most likely due to small patient numbers within patient cohorts. However, findings from these studies provide a preliminary step in the characterization of immune and histologic markers that will be critical to defining prognostic immune markers for feline OSCC and potential targets for testing of immunotherapeutics also relevant to human HNSCC in future studies.

The Oral Effects of Inhalation Corticosteroid Therapy: An Update.

Inhaled corticosteroids (IC) are commonly used for the treatment of respiratory diseases. Although these medications are generally considered safer when compared to oral systemic corticosteroids, there is evidence for potential systemic and local adverse effects with their use. Therefore, dentists should be aware of these adverse effects, especially the commonest local effects that can involve the oral mucosa. This article reviews the literature on the complications of IC therapy with emphasis on its potential oral effects.

Lymphangioma-like Kaposi sarcoma of the oral mucosa.

With the epidemic of acquired immunodeficiency syndrome, the clinical and histopathological features of Kaposi sarcoma (KS) became routine for most practicing surgical pathologists. The histological spectrum of KS broadened significantly over time and today a wide variety of rare histological variants are reported, but not widely recognized. Lymphangioma-like KS (LLKS) is a rare histological variant of KS occurring in skin, with banal histological features that can lead to misdiagnosis and inappropriate therapy. We report a series of intra-oral cases of LLKS and review the literature regarding this lesion.

Rare diagnosis of IgG4-related systemic disease by lip biopsy in an international Sjögren syndrome registry.

IgG4-related disease has been recently defined as a distinct clinic-pathologic entity, characterized by dense IgG-4 plasmacytic infiltration of diverse organs, fibrosis, and tumefactive lesions. Salivary and lacrimal glands are a target of this disease and, when affected, may clinically resemble Küttner tumor, Mikulicz disease, or orbital inflammatory pseudotumor. In some patients, the disease is systemic, with metachronous involvement of multiple organs, including the pancreas, aorta, kidneys, and biliary tract. We report a 66-year-old man who presented with salivary gland enlargement and severe salivary hypofunction and was diagnosed with IgG4-related disease on the basis of a labial salivary gland biopsy. Additional features of his illness included a marked peripheral eosinophilia, obstructive pulmonary disease, and lymphoplasmacytic aortitis. He was evaluated in the context of a research registry for Sjögren syndrome and was the only 1 of 2594 registrants with minor salivary gland histopathologic findings supportive of this diagnosis.

p53 expression and mutation analysis of odontogenic cysts with and without dysplasia.

OBJECTIVE: Overexpression of p53 protein is well described in odontogenic cystic lesions (OCLs), including those with epithelial dysplasia; however, most p53 antibodies stain both wild-type and mutated p53 protein and may not reflect genotype. Direct sequencing of the p53 gene has not identified mutations in OCLs with dysplasia. The purpose of this study was to determine the molecular basis of p53 expression in several types of OCLs with and without dysplasia. METHODS: The study material comprised 13 OCLs: odontogenic keratocyst (n = 5), orthokeratinized odontogenic cyst (n = 5), dentigerous cyst (n = 2), lateral periodontal cyst (n = 1), and unspecified developmental odontogenic cyst (UDOC) (n = 1). Five of these had features of mild or moderate epithelial dysplasia. One intraosseous squamous cell carcinoma (SCC) that was believed to have arisen from an antecedent dysplastic orthokeratinized OC was also included. Immunohistochemistry was performed using the DO7 monoclonal antibody that recognizes wild-type and mutated p53. DNA was extracted from microdissected tissue for all samples and exons 4 to 8 of the p53 gene direct sequenced. RESULTS: In 4 of 5 OCLs with dysplasia there was strong nuclear staining of basal and suprabasal cells. In all cases without dysplasia, nuclear expression in basal cells was either negative or weak and was absent in suprabasal cell nuclei. A mutation in exon 6 of the p53 gene (E224D) was identified in both the dysplastic orthokeratinized OC and the subsequent intraosseous SCC. CONCLUSIONS: OCLs with features of dysplasia show increased expression of p53 protein that does not reflect p53 mutational status. One dysplastic OC shared the same p53 mutation with a subsequent intraosseous SCC, indicating that p53 mutation may be associated with malignant transformation in this case.

Clinical signs and histologic findings in dogs with odontogenic cysts: 41 cases (1995-2010).

OBJECTIVE: To characterize clinical signs and histologic findings in dogs with odontogenic cysts and determine whether histologic findings were associated with clinical features. DESIGN: Retrospective case series. ANIMALS: 41 dogs. PROCEDURES: Medical records were reviewed to obtain clinical data, including breed, age, sex, and lesion location. Microscopic sections and results of diagnostic imaging were reviewed. RESULTS: Odontogenic cysts were identified in 41 dogs between 1995 and 2010. There were 29 dogs with dentigerous cysts, 1 with a radicular cyst, 1 with a lateral periodontal cyst, and 1 with a gingival inclusion cyst. In addition, 9 dogs with odontogenic cysts that had clinical and histologic features suggestive of, but not diagnostic for, odontogenic keratocysts seen in people were identified. In all 9 dogs, these cysts were located in the maxilla and surrounded the roots of normally erupted teeth. Of the 29 dogs with dentigerous cysts, 23 had a single cyst, 5 had 2 cysts, and 1 had 3 cysts. Six cysts were associated with an unerupted canine tooth, and 30 were associated with an unerupted first premolar tooth (1 cyst was associated both with an unerupted canine tooth and with an unerupted first premolar tooth). Dentigerous cysts were identified in a variety of breeds, but several brachycephalic breeds were overrepresented, compared with the hospital population during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a variety of odontogenic cysts can occur in dogs. In addition, cysts that resembled odontogenic keratocysts reported in people were identified. We propose the term canine odontogenic parakeratinized cyst for this condition.

Clinicopathologic characterization of odontogenic tumors and focal fibrous hyperplasia in dogs: 152 cases (1995-2005).

OBJECTIVE: To characterize clinicopathologic features of the most common odontogenic tumors and focal fibrous hyperplasia (FFH) in dogs. DESIGN: Retrospective case series. ANIMALS: 152 dogs evaluated for oral tumors of possible odontogenic origin at the William R. Pritchard Veterinary Medical Teaching Hospital of the University of California-Davis between 1995 and 2005. PROCEDURES: Information was collected from records, including dog breed, age, reproductive status, and location of lesion in the oral cavity. Histologic slides pertaining to each dog were reviewed by 3 investigators. Data regarding clinicopathologic features of the 3 most common lesions (canine acanthomatous ameloblastoma [CAA], peripheral odontogenic fibroma [POF], and FFH) were summarized. RESULTS: 152 dogs with odontogenic tumors or FFH were identified. Sixty-eight (45%) dogs had CAA, 47 (31 %) had POF, 24 (16%) had FFH, and 13 (9%) had other odontogenic tumors. Canine acanthomatous ameloblastoma was present most commonly in the rostral aspect of the mandible, with POF and FFH more common in the rostral aspect of the maxilla. Males and females were equally represented among dogs with CAA and FFH. Castrated males were overrepresented among dogs with POF. Golden Retrievers, Akitas, Cocker Spaniels, and Shetland Sheepdogs were overrepresented among dogs with CAA. No breed predisposition was detected for FFH or POF. Dogs with FFH had a greater mean age at initial evaluation than did dogs with CAA or POF. CONCLUSIONS AND CLINICAL RELEVANCE: CAA, POF, and FFH have distinct clinical patterns that may help clinicians and pathologists identify such lesions more readily.

Mutations in the c-Kit gene disrupt mitogen-activated protein kinase signaling during tumor development in adenoid cystic carcinoma of the salivary glands.

The Ras/mitogen-activated protein kinase (MAPK) pathway is considered to be a positive regulator of tumor initiation, progression, and maintenance. This study reports an opposite finding: we have found strong evidence that the MAPK pathway is inhibited in a subset of adenoid cystic carcinomas (ACCs) of the salivary glands. ACC tumors consistently overexpress the receptor tyrosine kinase (RTK) c-Kit, which has been considered a therapeutic target. We performed mutational analysis of the c-Kit gene (KIT in 17 cases of ACC and found that 2 cases of ACC had distinct missense mutations in KIT at both the genomic DNA and messenger RNA levels. These mutations caused G664R and R796G amino acid substitutions in the kinase domains. Surprisingly, the mutations were functionally inactive in cultured cells. We observed a significant reduction of MAPK (ERK1/2) activity in tumor cells, as assessed by immunohistochemistry. We performed further mutational analysis of the downstream effectors in the c-Kit pathway in the genes HRAS, KRAS, NRAS, BRAF, PIK3CA, and PTEN. This analysis revealed that two ACC tumors without KIT mutations had missense mutations in either KRAS or BRAF, causing S17N K-Ras and V590I B-Raf mutants, respectively. Our functional analysis showed that proteins with these mutations were also inactive in cultured cells. This is the first time that MAPK activity from the RTK signaling has been shown to be inhibited by gene mutations during tumor development. Because ACC seems to proliferate despite inactivation of the c-Kit signaling pathway, we suggest that selective inhibition of c-Kit is probably not a suitable treatment strategy for ACC.

Solitary fibrous tumor of the head and neck.

OBJECTIVE: The aim of this study was to review the reported cases of solitary fibrous tumor (SFT) in the head and neck and to evaluate this tumor regarding histologic features, treatment, and recurrence. SFT has been described in many extrapleural sites, including the head and neck. Uniform overexpression of CD34 differentiates SFT from other spindle cell neoplasms. SFT is a slow-growing neoplasm that can be successfully treated by complete excision. A rare malignant counterpart has also been described. STUDY DESIGN: In this case series and review of published cases from English-language journals in the National Library of Medicine, we reviewed 142 cases of SFT reported in English-language literature and add 11 new cases. We compared the features reported in the previous publications of SFT from the head and neck with our series, including cases described as malignant or atypical SFT. RESULTS: Four out of 9 cases with positive margins recurred, whereas only 1 out of 10 cases with atypical or malignant features recurred. CONCLUSIONS: An important finding in SFT of the head and neck is that recurrence appears more related to incomplete excision than to microscopic grade.

Nerve growth factor and tyrosine kinase A receptor in oral squamous cell carcinoma: is there an association with perineural invasion?

PURPOSE: Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is recognized as a significant predictor of outcome. PNI is associated with locoregional recurrence and decreased survival of patients with head and neck SCC. Nerve growth factor (NGF) has been shown to be involved in PNI in several malignancies, including breast, prostate, and pancreatic cancers. We investigated the hypothesis that NGF and its high-affinity receptor tyrosine kinase A (TrkA) are highly expressed in cases of oral SCC that have histologic evidence of PNI. MATERIALS AND METHODS: We performed immunohistochemistry on archived oral tongue SCC specimens from the established oral and general pathology databases at the University of California, San Francisco. The following groups were evaluated: 1) 21 T1/T2 oral tongue SCC cases with PNI and 2) 21 T1/T2 oral tongue SCC cases without histologic evidence of PNI. RESULTS: Strong homogeneous cytoplasmic staining for NGF and TrkA was detected in the malignant cells in the PNI-positive group of tumors. In group II (PNI negative) NGF and TrkA were detected in the stroma cells or were very weakly expressed by the malignant cells. We were able to show the presence of NGF and TrkA in the cytoplasm of malignant squamous cells in tumors with histologic evidence of PNI. Immunostaining for NGF (P = .0001) and TrkA (P = .039) was significantly higher in the PNI-positive oral SCC group than in the PNI-negative oral SCC group. CONCLUSION: This study shows that oral SCC with evidence of PNI shows increased expression of NGF and TrkA and suggests that NGF and TrkA are involved with the mechanism leading to PNI. Further investigations are warranted to determine the potential for use of NGF and TrkA as candidate biomarkers to predict progression and outcome.

Presence and quantification of mast cells in the gingiva of cats with tooth resorption, periodontitis and chronic stomatitis.

OBJECTIVE: Mast cells are tissue-dwelling granule-containing immune cells that play a pivotal role in the pathogenesis of inflammation and other processes. The three most common orodental disorders in cats are periodontitis, feline resorptive lesions (FRL), and chronic gingivostomatitis (FCGS). The presence and density of mast cells in the gingiva has been established in healthy cats but not in cats affected by FRL, FCGS or periodontitis. The aim of the present study was to document and quantify the presence of mast cells in the gingiva adjacent to teeth affected by FRL, FCGS or chronic periodontitis. METHODS: Samples from the gingiva of 32 cats affected by FRL, FCGS or periodontitis were obtained and compared to samples obtained from 7 specific pathogen-free (SPF) cats. Evaluation of mast cells and the inflammatory infiltrate were performed on hematoxylin and eosin, and toluidine blue stained sections. RESULTS: Mast cells densities were significantly increased in gingival tissues adjacent to teeth affected by FRL, FCGS or periodontitis in comparison to SPF samples. There were no significant differences between gingival tissues of the FRL, FCGS and periodontitis groups. However, the relative inflammatory score in the FRL group was significantly lower as compared to the FCGS or periodontitis groups, yet with similar density of mast cells. CONCLUSION: In the gingiva of cats affected with FRL, FCGS or periodontitis, there is an increase in the number of mast cells. The high number of mast cells in the FRL group and concurrent mild inflammatory reaction suggests the notion that mast cells may potentially play role in the pathogenesis of FRL.

Pulpal effects of enamel ablation with a microsecond pulsed lambda = 9.3-microm CO2 laser.

BACKGROUND AND OBJECTIVES: In vitro studies have shown that CO2 lasers operating at the highly absorbed 9.3 and 9.6-microm wavelengths with a pulse duration in the range of 10-20-microsecond are well suited for the efficient ablation of enamel and dentin with minimal peripheral thermal damage. Even though these CO2 lasers are highly promising, they have yet to receive FDA approval. Clinical studies are necessary to determine if excessive heat deposition in the tooth may have any detrimental pulpal effects, particularly at higher ablative fluencies. The purpose of this study was to evaluate the pulpal safety of laser irradiation of tooth occlusal surfaces under the conditions required for small conservative preparations confined to enamel. STUDY DESIGN/MATERIALS AND METHODS: Test subjects requiring removal of third molar teeth were recruited and teeth scheduled for extraction were irradiated using a pulsed CO2 laser at a wavelength of 9.3 microm operating at 25 or 50 Hz using a incident fluence of 20 J/cm(2) for a total of 3,000 laser pulses (36 J) for both rates with water cooling. Two control groups were used, one with no treatment and one with a small cut made with a conventional high-speed hand-piece. No anesthetic was used for any of the procedures and tooth vitality was evaluated prior to treatment by heat, cold and electrical testing. Short term effects were observed on teeth extracted within 72 hours after treatment and long term effects were observed on teeth extracted 90 days after treatment. The pulps of the teeth were fixed with formalin immediately after extraction and subjected to histological examination. Additionally, micro-thermocouple measurements were used to estimate the potential temperature rise in the pulp chamber of extracted teeth employing the same irradiation conditions used in vivo. RESULTS: Pulpal thermocouple measurements showed the internal temperature rise in the tooth was within safe limits, 3.3+/-1.4 degrees C without water cooling versus 1.7+/-1.6 degrees C with water-cooling, n = 25, P<0.05. None of the control or treatment groups showed any deleterious effects on pulpal tissues and none of the 29 test-subjects felt pain or discomfort after the procedure. Only two test-subjects felt discomfort from "cold sensitivity" during the procedure caused by the water-spray. CONCLUSION: It appears that this CO2 laser can ablate enamel safely without harming the pulp under the rate of energy deposition employed in this study.

Leukocyte adhesion deficiency type 1: an important consideration in the clinical differential diagnosis of prepubertal periodontitis. A case report and review of the literature.

Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects 1 in 1 million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. Features of this disease result from mutations in the region of the CD18 gene, which is encoded on chromosome 21q22.3. This gene codes for the common subunit of the leukocyte integrins LFA-1, Mac 1, and p150,95. Failure to produce a functional subunit results in the defective expression of all 3 leukocyte integrins, and the leukocytes of LAD have subnormal adhesion properties. We present a case of the moderate-to-severe form of LAD in a 3-year-old girl who initially presented with generalized swelling and erythema of the gingiva, with slight tooth mobility and a nonhealing labial ulceration. Her medical history was significant for recurrent urinary tract infections. Periodontal pathogens, including Capnocytophaga, Eikenella corrodens, and Candida albicans, were cultured. The patient had a significantly elevated white blood cell count and absolute neutrophil count. The diagnosis of LAD was confirmed with flow cytometry, which revealed significantly decreased subunits. Twenty-four months after the diagnosis was made and after a series of granulocyte transfusions and bone marrow transplantations, she expired as the result of respiratory failure.

Rare oral cavity presentation of a B-cell lymphoblastic lymphoma. A case report and review of the literature.

Lymphoblastic lymphoma is an uncommon malignancy, with most cases showing a T-cell phenotype and presenting as a mediastinal mass. By contrast, B-cell lymphoblastic lymphoma/leukemia is a rare high-grade malignancy that comprises approximately 10% of all lymphoblastic lymphomas. Lymphomas of the oral cavity are rare and typically present as intraosseous lesions that are most commonly diffuse large B-cell type. Here we present what we believe is the first B-cell lymphoblastic lymphoma initially presenting in the oral cavity. The case involves a 46-year-old white woman who presented with a mass in the right mandible. This report discusses this rare malignancy, including clinical presentation, histopathologic features, immunologic profile, treatment, and prognosis. This case emphasizes the importance of recognizing rare entities that may present in the oral cavity and the impact of the disease and its management.

Myopericytoma of the thoracic spine: a case report.

STUDY DESIGN: A case of myopericytoma of the thoracic spine is reported. OBJECTIVE: To report a recently described and extremely rare soft tissue neoplasm in the previously unreported location of the thoracic spine. SUMMARY OF BACKGROUND DATA: Myopericytoma is a recently described soft tissue neoplasm with perivascular myoid differentiation. All cases have been reported in the subcutaneous and superficial soft tissues of the extremities. This represents the first reported case of this unusual lesion in the spine. METHODS: A patient with a 3-month history of progressive weakness of the arms and legs was found to have a lytic lesion of T3. The lesion was surgically treated by curettage followed by a course of radiation. Presenting symptoms, imaging studies, histologic findings, and related literature are reviewed in this study. RESULTS: Histologic evaluation of sections of the surgically removed lesion revealed a concentric, periluminal proliferation of cells with prominent positive smooth muscle actin immunoreactivity. These findings are consistent with the diagnosis of a myopericytoma, a lesion not previously reported in the spine. CONCLUSIONS: This study shows the presence of a lesion in the thoracic spine only previously described in the soft tissue of the extremities. The diagnosis of myopericytoma should be included, along with hemangiopericytoma, in the differential diagnosis of lytic lesions of the spine.