Diffusion Reflection Method for Early Detection of Oral Squamous Cell Carcinoma Specifically Targeted by Circulating Gold-Nanorods Bio-Conjugated to Anti-Epidermal Growth Factor Receptor.

BACKGROUND: Translation of nanomedical developments into clinical application is receiving an increasing interest. However, its use for oral squamous cell carcinoma (OSCC) diagnosis remains limited. We present an advanced nanophotonic method for oral cancer detection, based on diffusion reflection (DR) measurements of gold-nanorods bio-conjugated to anti-epidermal growth factor receptor (C-GNRs) specifically attached to OSCC cells. OBJECTIVE: To investigate in a rat model of oral carcinogenesis the targeting potential of C-GNRs to OSCC by using the DR optical method. MATERIALS AND METHODS: OSCC was induced by the carcinogen 4-nitroquinoline-N-oxide (4NQO). C-GNRs were introduced locally and systemically and DR measurements were recorded from the surface of the rat tongue following illumination with red laser beam. Rats were divided into experimental and control groups. The results were compared with the histologic diagnosis. RESULTS: A total of 75 Wistar-derived rats were enrolled in the study. Local application did not reveal any statistical results. DR measurements following intravenous injection of C-GNRs revealed a significant increase in light absorption in rats with OSCC compare with rats without cancer (p<0.02, sensitivity 100%, specificity 89%). In addition, absorption of light increased significantly in cases of severe dysplasia and cancer (high risk) compared to rats without cancer and rats with mild dysplasia (low risk) (86% sensitivity and 89% specificity, AUC=0.79). CONCLUSION: Combining nanotechnology and nanophotonics for in vivo diagnosis of OSCC serves as additional tier in the translation of advanced nanomedical developments into clinical applications. The presented method shows a promising potential of nanophotonics for oral cancer identification, and provides support for the use of C-GNRs as a selective drug delivery.

Somatic NRAS mutation in patient with generalized lymphatic anomaly.

Generalized lymphatic anomaly (GLA or lymphangiomatosis) is a rare disease characterized by a diffuse proliferation of lymphatic vessels in skin and internal organs. It often leads to progressive respiratory failure and death, but its etiology is unknown. Here, we isolated lymphangiomatosis endothelial cells from GLA tissue. These cells were characterized by high proliferation and survival rates, but displayed impaired capacities for migration and tube formation. We employed whole exome sequencing to search for disease-causing genes and identified a somatic mutation in NRAS. We used mouse and zebrafish model systems to initially evaluate the role of this mutation in the development of the lymphatic system, and we studied the effect of drugs blocking the downstream effectors, mTOR and ERK, on this disease.

Gold nanorods reflectance discriminate benign from malignant oral lesions.

Nanoparticle-based contrast agents have been used as an imaging tool for selectively detecting cancerous processes. We aimed to evaluate the detection sensitivity of reflection measurements of gold nanorods (GNRs) bio-conjugated to anti-epidermal growth factor receptor (GNRs-EGFR) monoclonal antibodies in discriminating benign from premalignant and malignant human oral lesions. Tissue sections incubated with GNRs-EGFR and the reflectance spectrum was measured using hyperspectral microscopy. Reflectance intensity increased with the progression of the disease, lowest in the control group and increasing as the dysplastic changes increase (P<0.001 for linear trend of grade). Intensity was significantly higher in the moderate and severe dysplasias and cancer patients than in the controls and mild dysplasia (t test P=0.0003, Mann-Whitney P<0.0001). The GNRs reflection measurements can discriminate benign and mild dysplastic lesions from the more severe dysplasia and invasive cancer, suggesting an objective, not dependent on the qualification of a technician and with less interpretation errors.

Fluorescence lifetime imaging of DAPI-stained nuclei as a novel diagnostic tool for the detection and classification of B-cell chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukaemia (B-CLL) and B-cell precursor acute lymphoblastic leukaemia (B-ALL) are the most common type of leukaemia in adults and children, respectively. Today, fluorescence in situ hybridization (FISH) is the standard for detecting chromosomal aberrations that reflect adverse and favorable outcome. This study revealed a new, simple, and fast diagnostic tool to detect pathological cells by measuring and imaging the fluorescence lifetime (FLT) using FLT imaging microscopy (FLIM) of the peripheral blood (PB) cells of B-CLL samples that were labeled with the DNA binder, DAPI. The FLT of DAPI in healthy individuals was found to be 2.66 ± 0.12 ns. In contrast, PB cells of B-CLL and BM cells of B-ALL patients were characterized by a specific group distribution of the FLT values. The FLT of DAPI was divided into four subgroups, relative to 2.66 ns: short+, normal, prolonged, and prolonged+. These alterations could be related to different chromatin arrangements of B-CLL and B-ALL interphase nuclei. Notably, extremely long FLT of nuclear DAPI correlate with the presence of extra chromosome 12, while moderate increases compared to normal characterize the deletion of p53. Such correlations potentially enable a FLT-based rapid automatic diagnosis and classification of B-CLL even when the frequency of genetic and chromosomal abnormalities is low. © 2016 International Society for Advancement of Cytometry.

Gold Nanorods Based Air Scanning Electron Microscopy and Diffusion Reflection Imaging for Mapping Tumor Margins in Squamous Cell Carcinoma.

A critical challenge arising during a surgical procedure for tumor removal is the determination of tumor margins. Gold nanorods (GNRs) conjugated to epidermal growth factor receptors (EGFR) (GNRs-EGFR) have long been used in the detection of cancerous cells as the expression of EGFR dramatically increases once the tissue becomes cancerous. Optical techniques for the identification of these GNRs-EGFR in tumor are intensively developed based on the unique scattering and absorption properties of the GNRs. In this study, we investigate the distribution of the GNRs in tissue sections presenting squamous cell carcinoma (SCC) to evaluate the SCC margins. Air scanning electron microscopy (airSEM), a novel, high resolution microscopy is used, enabling to localize and actually visualize nanoparticles on the tissue. The airSEM pictures presented a gradient of GNRs from the tumor to normal epithelium, spread in an area of 1 mm, suggesting tumor margins of 1 mm. Diffusion reflection (DR) measurements, performed in a resolution of 1 mm, of human oral SCC have shown a clear difference between the DR profiles of the healthy epithelium and the tumor itself.

Oral lichen planus patients exhibit consistent chromosomal numerical aberrations: A follow-up analysis.

BACKGROUND: Oral lichen planus (OLP) carries an increased risk for malignant transformation with aneuploid cells (ACs) being found in brush samples of a quarter of patients with OLP. METHODS: Patients with OLP were followed and repeated brush samples were simultaneously analyzed for morphology and fluorescent in situ hybridization (FISH) using centromeric probes for chromosomes 2 and 8. RESULTS: Three patients with a high proportion of ACs developed oral cancer. Fifteen patients had ≥1% ACs (13 in affected sites and 2 in nonaffected sites), whereas only 2 of the 15 patients with <1% ACs in the first sample had ≥1% ACs in the second sample. A strong positive correlation between the results of the initial and repeated samples was found. CONCLUSION: High proportion of ACs in brush samples from patients with OLP may imply an impending malignant transformation. As FISH analysis is consistent over time, it can be used to identify a subgroup of patients who would require close follow-up. © 2015 Wiley Periodicals, Inc. Head Neck 38: E741-E746, 2016.

Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis.

BACKGROUND: A study was designed to identify the source of fever in a patient with post-polycythemia myelofibrosis, associated with clonal Janus Kinase 2 (JAK2) mutation involving duplication of exon 12. The patient presented with 1-2 day long self-limited periodic episodes of high fever that became more frequent as the hematologic disease progressed. METHODS: After ruling out other causes for recurrent fever, analysis of the pyrin encoding Mediterranean fever gene (MEFV) was carried out by Sanger sequencing in peripheral blood DNA samples obtained 4 years apart, in buccal cells, laser dissected kidney tubular cells, and FACS-sorted CD3-positive or depleted mononucleated blood cells. Hematopoeitc cells results were validated by targeted deep sequencing. A Sanger sequence based screen for pathogenic variants of the autoinflammatory genes NLRP3, TNFRSF1A and MVK was also performed. RESULTS: A rare, c.1955G>A, p.Arg652His MEFV gene variant was identified at negligible levels in an early peripheral blood DNA sample, but affected 46 % of the MEFV alleles and was restricted to JAK2-positive, polymorphonuclear and CD3-depleted mononunuclear DNA samples obtained 4 years later, when the patient experienced fever bouts. The patient was also heterozygous for the germ line, non-pathogenic NLRP3 gene variant, p.Q705K. Upon the administration of colchicine, the gold standard treatment for familial Mediterranean fever (FMF), the fever attacks subsided. CONCLUSIONS: This is the first report of non-transmitted, acquired FMF, associated with a JAK2 driven clonal expansion of a somatic MEFV exon 10 mutation. The non-pathogenic germ line NLRP3 p.Q705K mutation possibly played a modifier role on the disease phenotype.

Metastatic tumors to the jaws and mouth.

Metastatic dissemination to the oral cavity is rare and is usually the evidence of a wide spread disease with an average survival rate of 7 months. In almost a quarter of the cases, oral metastasis was found to be the first indication of an occult malignancy at a distant site. Metastatic lesions can be found anywhere in the oral cavity, however, the jaw bones with the molar area is the most frequently involved site. In the oral soft tissues, the gingiva is the most common site, suggesting the possible role of inflammation in the attraction of metastatic deposits. The most common primary malignancies presenting oral metastases were the lung, kidney, liver, and prostate for men, and breast, female genital organs, kidney, and colo-rectum for women. Most patients with jawbone metastasis complain of swelling, pain, and paresthesia. An exophytic lesion is the most common clinical presentation of metastatic lesions in the oral soft tissues. Early lesions, mainly those located in the gingiva, may resemble a hyperplastic or reactive lesion. Once a lesion is recognized as metastasis, the primary tumor site should be identified following clinical, radiological and histopathological investigations. If standardized diagnostic workup fails to detect the site of origin, then the term carcinoma of unknown primary is applied. Personalized medicine tools such as tissue-of-origin assays should be applied, either by immunohistochemical testing or by molecular-profiling methods as these may lead to a more favorable outcome.

Metallothionein, a marker of antiapoptosis, is associated with clinical forms of oral lichen planus.

OBJECTIVES: To investigate the expression of anti- and proapoptosis markers, metallothionein (MT), and caspase-2, in the epithelial and inflammatory cells of oral lichen planus (OLP) patients, and to investigate the association with clinical parameters. MATERIALS AND METHODS: Included were biopsies of 70 OLP patients. The clinical data were collected from patients' charts. The expression of MT and caspase-2 was immunomorphometrically analyzed in the epithelial and inflammatory cells, and the results were correlated with the clinical presentation. RESULTS: The epithelial and inflammatory cells expressed MT (10.2 ± 5.75 and 0.68 ± 0.86) and caspase-2 (1.54 ± 2.6 and 0.98 ± 1.15) which show a trend toward an inverse expression. The expression of MT in the epithelium was significantly higher in patients presenting with keratotic lichen planus than in patients with the atrophic and erosive forms (P = 0.0008). In the inflammatory cells, the expression of MT was inversely correlated with increasing age (R = 0.34, P = 0.0069). CONCLUSIONS: The pattern of expression of MT and caspase-2 in OLP suggests an extensive antiapoptotic response in the keratotic form of the disease. Symptomatic patients may benefit from therapy targeted to apoptosis in the future.

Metastatic tumors to the gingiva and the presence of teeth as a contributing factor: a literature analysis.

BACKGROUND: Gingiva that is prone to inflammation may serve as a pre-metastatic niche for the attraction of circulating malignant cells. The aim of this study is to analyze cases of metastatic lesions to the gingiva compared with cases metastasizing to other oral mucosal sites. The pathogenesis of gingival metastases is discussed, with emphasis on the role of inflammation. METHODS: The English-language literature between 1916 and 2011 was searched for cases of metastatic lesions to the oral mucosa; only cases metastasizing in the oral mucosa, gingiva, and periodontium were included. RESULTS: Two hundred seven cases were included. The gingiva was the most common site (60.4%), followed by tongue and tonsil. The most common primary sites were lung (24.2%), kidney (13.5%), skin (10.6%), and breast (8.7%). In 27%, the oral lesion was the first sign of a malignant disease. In most cases, the lesion appeared as an exophytic mass (96%) diagnosed clinically as a reactive gingival lesion. The presence of teeth was significantly associated with the development of gingival metastases: in 108 of 125 gingival metastases, the lesion was found adjacent to teeth (P <0.001; odds ratio = 8.2). The average life expectancy after diagnosis of the metastasis was 3.7 months. CONCLUSIONS: The gingiva is the most common site for metastases to oral soft tissues, with strong association with the presence of teeth. This finding may be related to the role of inflammation in the attraction of metastatic cells to chronically inflamed gingiva.

BRAF and GNAQ mutations in melanocytic tumors of the oral cavity.

OBJECTIVE: The genetic factors participating in oral melanoma evolution have not been studied extensively. We aimed to analyze the prevalence of BRAF and GNAQ mutations in a series of oral melanocytic tumors, nevi, and melanomas. STUDY DESIGN: The study group consisted of 4 melanomas and 10 nevi (6 intramucosal, 4 blue nevi). DNA was extracted from paraffin-embedded tissue sections, and mutations in GNAQ and BRAF were analyzed with the use of mass spectrometery. RESULTS: V600E point mutation was identified in the BRAF gene in 3 intramucosal nevi and in 2 melanomas. Only 1 blue nevus harbored the GNAQ209 mutation. None of the BRAF-positive samples harbored GNAQ mutations. CONCLUSIONS: The finding of BRAF mutations in oral benign and malignant melanocytic lesions points to a potential initiating role of BRAF in malignant transformation, which may have important therapeutic implications as those with BRAF mutations may benefit from specific treatment using RAF inhibitors.

Mutational analysis of PTEN/PIK3CA/AKT pathway in oral squamous cell carcinoma.

The phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma (AKT) viral oncogene pathway is involved in regulating the signaling of multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth. Mutations in the genes associated with the PI3K/AKT pathway including PI3K, AKT, RAS and PTEN, are infrequently found within head and neck squamous cell carcinoma and more specifically are rarely reported in oral squamous cell carcinoma (OSCC) cases. We aimed to investigate the frequency of mutations in AKT1, PTEN, PIK3CA, and RAS (K-RAS, N-RAS, H-RAS) genes in 37 cases of oral squamous cell carcinoma (OSCC). Mutational analysis of PTEN, RAS, PIK3CA and AKT genes was performed using chip-based matrix-assisted laser desorption time-of-flight (MALDI-TOF) mass spectrometry and by direct sequencing. The only gene mutated in our series was the PIK3CA. Missense mutations of the PIK3CA gene were found in 4 of our cases (10.8%); no correlation has been found with oral location, stage and survival. The absence of mutations in AKT1, PTEN, and RAS genes in the present study is in accordance with previous studies confirming that these genes are rarely mutated in OSCC. Our data confirm that PIK3CA is important to OSCC tumorigenesis and can contribute to oncogene activation of the PIK3CA/AKT pathway in OSCC. The knowledge of the PIK3CA's involvement in OSCC is important because a specific kinase inhibitor could be considered as a future therapeutic option for OSCC patients with PIK3CA mutations.

Noninvasive detection of aneuploid cells in laryngeal epithelial precursor lesions.

BACKGROUND: Most cases of laryngeal cancer are preceded by precursor lesions which, if left untreated, can progress toward an invasive cancer. The objective of this study was to investigate the presence of chromosomal numerical aberrations in cells that were collected by noninvasive brush sampling from laryngeal lesions. METHODS: Laryngeal brush samples from 52 patients were analyzed simultaneously for morphology and fluorescence in situ hybridization (FISH) using centromeric probes for chromosome 17, chromosome 8, and a locus-specific instability (LSI) v-myc avian myelocytomatosis viral oncogene homolog (myc) proto-oncogene protein (C-MYC) probe for the MYC gene. The patients were divided according to histopathologic diagnosis. Group 1 included patients with squamous cell carcinoma, carcinoma in situ, and severe dysplasia; Group 2 included patients with moderate dysplasia, mild dysplasia, and hyperplasia; and Group 3 included patients with benign nondysplastic lesions. RESULTS: The proportion of cells with MYC and chromosome 8 gains demonstrated significant trends toward being the highest in Group 1 and the lowest in Group 3 (P = .001 and P = .003, respectively). No significant trend was observed for chromosome 17. Mann-Whitney Bonferroni-corrected analyses revealed that the most significant contribution was the difference between Groups 1 and 3 (P = .0195 for MYC gains and P = .036 for chromosome 8 gains). When using a cutoff point of 4% aneuploid cells (ACs), both MYC and chromosome 8 differed significantly between groups (P = .030 and P = .037, respectively). CONCLUSIONS: The current results suggested that FISH analysis of brush samples obtained noninvasively from suspicious laryngeal lesions can augment the clinical examination in predicting the nature of the lesions and can aid clinicians in monitoring and follow-up of high-risk patients. Cancer (Cancer Cytopathol) 2011. © 2011 American Cancer Society.

Chromosomal numerical aberrations in apparently normal oral mucosa of heavy smokers affected by lung cancer.

Cigarette smoke creates a field of injury in the epithelial lining of the entire respiratory tract causing an increased risk for the development of malignant lesions. It is conceivable, therefore, that early genetic alterations, can be detected in oral mucosa of heavy smokers mainly those affected by lung cancer. As aneuploidy was shown to be an early event in oral carcinogenesis, we aimed to investigate the prevalence of aneuploid cells (ACs) in samples obtained from apparently normal looking oral mucosa of heavy smokers affected by lung cancer (LC). Two brush samples were collected from the oral mucosa of 152 subjects; 31 heavy smokers with LC, 59 heavy smokers without LC and 62 never-smokers. The samples were simultaneously analyzed for morphology and fluorescent in situ hybridization (FISH) using chromosomes 2 and 8 centromeric probes. Over 2% ACs were found in 23% of heavy smokers with LC compared to 12% in heavy smokers without LC and 5% of the never-smokers group (P=0.015). A trend was also noticed when comparing the group of heavy smokers without LC with the never-smokers (P=0.198). We conclude that heavy smokers harbour detectable chromosomal numerical aberrations in oral epithelial cells of normal looking mucosa. These aberrations are more frequently found in heavy smokers affected by LC.

Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

Metastatic tumours to the oral cavity - pathogenesis and analysis of 673 cases.

The oral region is an uncommon site for metastatic tumour cell colonization and is usually evidence of a wide spread disease. In 25% of cases, oral metastases were found to be the first sign of the metastatic spread and in 23% it was the first indication of an undiscovered malignancy at a distant site. The jawbones, particularly the mandible, were more frequently affected than the oral soft tissues (2:1). In the oral soft tissues, the attached gingiva was the most commonly affected site (54%). The major primary sites presenting oral metastases were the lung, kidney, liver, and prostate for men, breast, female genital organs (FGO), kidney, and colo-rectum for women. The primary site differs according to oral site colonization, in men the lung was the most common primary site affecting both the jawbones and oral mucosa (22% and 31.3%, respectively) followed by the prostate gland in the jawbones (11%) and kidney in the oral soft tissues (14%). In women, the breast was the most common primary tumour affecting the jawbones and soft tissues (41% and 24.3%, respectively), followed by the adrenal and female genital organs (FGO) in the jawbones (7.7%) and FGO in the soft tissues (14.8%). The clinical presentation of the metastatic lesions differ between the various sites in the oral region. In the jawbones most patients complain of swelling, pain and paresthesia which developed in a relative short period. Early manifestation of the gingival metastases resembled a hyperplastic or reactive lesion, such as pyogenic granuloma, peripheral giant cell granuloma, or fibrous epulis. Because of its rarity, the diagnosis of a metastatic lesion in the oral region is challenging, both to the clinician and to the pathologist, in recognizing that a lesion is metastatic and in determining the site of origin. The clinical presentation of a metastatic lesion in the oral cavity can be deceiving leading to a misdiagnosis of a benign process, therefore, in any case where the clinical presentation is unusual especially in patients with a known malignant disease a biopsy is mandatory.

Lingual perimandibular vessels associated with life-threatening bleeding: an anatomic study.

PURPOSE: To describe the anatomy of the lingual perimandibular vessels and emphasize the distance to the bone. MATERIALS AND METHODS: The hemifacial lower third was dissected in 12 human cadavers. The blood vessels in the floor of the mouth were exposed using sagittal incisions at the canine, mental foramen, and second molar areas. RESULTS: The diameter of the dissected vessels ranged from 0.5 to 3 mm (mean, 1.5 mm). Most vessels were found superior to the mylohyoid muscle in the canine area and beneath the muscle in the mental and second molar areas. The smallest median vertical distance from blood vessel to bone was in the canine area (14.5 mm), followed by the mental foramen area (15.5 mm) and the second premolar area (19 mm). The median horizontal distance of the vessels from the lingual plate was 2 mm at the canine and second molar areas and 4 mm at the mental area. DISCUSSION: Lingual plate perforation, especially anterior to the canine area, can easily injure blood vessels in the floor of the mouth and cause life-threatening hemorrhage following implant placement. Bleeding can occur when the mandibular lingual plate is perforated. Care should be taken to recognize situations where this complication may occur. CONCLUSIONS: Based on the study of human cadavers, it appears that vessels in the floor of the mouth are sometimes in close proximity to the site of implant placement. Caution should be exercised when placing implants in this area.

Detection of non-diploid cells in premalignant and malignant oral lesions using combined morphological and FISH analysis - a new method for early detection of suspicious oral lesions.

Alteration in DNA content is an early event in oral carcinogenesis. We have examined oral brush samples to detect non-diploid cells (NDC) using simultaneous morphological and cytogenetic analysis. The study included 8 oral squamous cell carcinomas (OSCC), 22 premalignant lesions (OPLs), and 25 control individuals. Slides stained with Giemsa followed by FISH using chromosome 2 centromeric DNA probe, were scanned and fluorescent signals were simultaneously analyzed in parallel with the morphology. The proportion of NDC increased with the severity of the diagnosis. In two control subjects, 1-1.5% of the examined cells were NDC. Over 2% NDC were present in all OSCC cases and in 11 of the OPLs, of which, in 8 the histologic diagnosis was either epithelial hyperplasia or mild dysplasia. A significant number of NDC had normal morphology when cytomorphology and FISH were compared. Two patients with OPLs developed OSCC these patients had a significant proportion of NDC. We suggest that the combined morphological and cytogenetic analysis of cells collected by a non-invasive brush sampling can enhance early detection of potentially malignant cells.

Central giant cell granuloma associated with central ossifying fibroma of the jaws: a clinicopathologic study.

OBJECTIVE: To investigate the prevalence of clinical, radiographic, and histopathologic characteristics of combined central giant cell granuloma (CGCG) and central ossifying fibroma (COF). STUDY DESIGN: Retrospective clinical and histomorphometric analysis of all cases diagnosed as CGCG or COF between 1994 and 2002. RESULTS: A total of 51 cases were included in the study: CGCG (n = 23), COF (n = 25), and combined COF-CGCG (n = 3). All 3 lesions presented expansile, well-defined unilocular radiolucencies, with radiopacities (66%), root resorption (66%) and tooth displacement (33%). Microscopically, areas of classical CGCG and COF were separated by a transition zone of nonvascularized densely packed spindle cells. Surgical procedure resulted in recurrence within 1 year in 1 of 2 patients, calcitonin nasal spray treatment resulted in growth arrest in 1 case. CONCLUSIONS: Because of the small number of the combined cases, the biologic behavior of the lesions is uncertain. The CGCG component may drive the clinical behavior toward a more aggressive behavior than classical COF; therefore, close follow-up is recommended.

Maxillary sinus augmentation in the presence of antral pseudocyst: a clinical approach.

OBJECTIVE: The objective of this study is to present patients with sinus augmentation in the presence of an antral pseudocyst and the surgical procedure, complications, and outcome. STUDY DESIGN: From 2002 to 2005, 109 patients were scheduled for 1- or 2-stage maxillary sinus floor augmentation (n = 129) because of inadequate alveolar bone height for implant placement. Radiographically, a significant antral pseudocyst was shown. RESULTS: In 8 (7.3%) patients, an antral pseudocyst was diagnosed, and in 2 a history of inactive sinusitis was found preoperatively. A faint dome-shaped radiopacity was found at the lower border of the maxillary sinus. Average lesion size was 5.09 cm2. All implants functioned well at follow-up (mean 20 months). CONCLUSION: A pseudocyst of the maxillary sinus is not a contraindication for sinus augmentation. The low frequency of sinus membrane perforation and postsurgery sinusitis make the operation safe. In large lesions and in cases with an unclear diagnosis, further evaluation is needed before sinus augmentation.