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.

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.

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.

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.

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.

The influence of inflammation on the polarization colors of collagen fibers in the wall of odontogenic keratocyst.

Epithelial-mesenchymal interactions have been found to play a role in the pathogenesis of odontogenic keratocyst (OKC). In the present study we investigated the effect of inflammation in the OKC wall on the polarization colors of Picrosirius red-stained collagen fibers. 50 cases of OKC were selected and separated into two groups according to the inflammatory intensity: those with mild-to-moderate inflammation (Group A), and those with intense inflammation (Group B). The polarization colors of the collagen fibers were recorded separately for thick and thin fibers. Polarization colors of the thin fibers were in the green- to yellow spectrum, without significant differences between the groups. However, polarization colors of the thick fibers significantly differ between the groups. In Group B, the frequency of thick fibers with green birefringence decreased significantly, whereas fibers with red polarization colors increased in frequency (4.6% and 44%, respectively) compared with Group A (12.3% and 23.6%, respectively). It can than be concluded that inflammation has an impact on the packing of collagen fibers in the connective tissue wall of OKC as reflected by their birefringence colors under polarized light. In the presence of dense inflammation, the percentage of thick fibers with green birefringence decreases, with an increase in thick fibers with red birefringence which appeared more packed.

Identification of RNA editing sites in the SNP database.

The relationship between human inherited genomic variations and phenotypic differences has been the focus of much research effort in recent years. These studies benefit from millions of single-nucleotide polymorphism (SNP) records available in public databases, such as dbSNP. The importance of identifying false dbSNP records increases with the growing role played by SNPs in linkage analysis for disease traits. In particular, the emerging understanding of the abundance of DNA and RNA editing calls for a careful distinction between inherited SNPs and somatic DNA and RNA modifications. In order to demonstrate that some of the SNP database records are actually somatic modification, we focus on one type of these modifications, namely A-to-I RNA editing, and present evidence for hundreds of dbSNP records that are actually editing sites. We provide a list of 102 RNA editing sites previously annotated in dbSNP database as SNPs, and experimentally validate seven of these. Interestingly, we show how dbSNP can serve as a starting point to look for new editing sites. Our results, for this particular type of RNA editing, demonstrate the need for a careful analysis of SNP databases in light of the increasing recognition of the significance of somatic sequence modifications.

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.

Traumatic ulcerative granuloma with stromal eosinophilia: a reactive lesion of the oral mucosa.

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a benign lesion of the oral mucosa of an unclear pathogenesis. We analyzed the profile of the inflammatory infiltrate in 12 cases of TUGSE by using immunohistochemical analysis and polymerase chain reaction-based repertoire analysis to detect T- and B-cell receptor gene rearrangements. The inflammatory infiltrate consisted in most cases of B and T lymphocytes, macrophages, abundant eosinophils, and large atypical cells. In 5 cases, CD30+ cells were found. Spectratyping analysis displayed a polyclonal rearrangement of the T-cell receptor g gene in 6 cases and oligoclonality in 5 cases. Monoclonality was observed in 1 case that also fulfilled histologic criteria for lymphoma. Healing was uneventful in all cases, including the one suspected of being lymphoma, with no recurrences in more than 2 years'follow-up. TUGSE can be regarded reactive. Some cases, however, may harbor a dominant clonal T-cell population; in these cases, long-term follow-up is mandatory.

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.

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.

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.

The correlation between epithelial cell proliferation and inflammation in odontogenic keratocyst.

The objective of this study was to investigate the effect of inflammation on Ki-67 and PCNA labeling indices of odontogenic keratocysts. The study included 45 cases of OKC. From each case, three 5-microm sections were cut and stained with hematoxylin and eosin and with monoclonal antibodies for PCNA and Ki-67. In 10 high power fields (HPF), the type of epithelial lining was recorded separately for each field (metaplastic squamous or classic parakeratinized). Labeling indices for Ki-67 and PCNA and the inflammatory infiltrate density in the depth of 1 HPF adjacent to the basement membrane were recorded for each HPF. Parameters were compared between fields, and for each case the average inflammatory score and average labeling indices were calculated, and cases compared. No inflammation was observed in 24.5% of cases, mild in 30.5% and moderate to severe in 45%. Foci of metaplastic non-keratinizing epithelium were observed in 64% of cases, which were twice as common in inflamed cysts (90%) than in non-inflamed cysts (44%). The average labeling indices for PCNA and Ki-67 yielded no significant differences between inflamed and non-inflamed cysts. When compared between HPF's, there was an increase in the Ki-67 labeling index in metaplastic epithelium in areas with moderate to severe inflammation score (p=0.036). PCNA labeling index did not significantly change between areas with low and high inflammation. No differences in labeling indices were observed between areas of classic and metaplastic epithelium with equal inflammation density. A focal increase in Ki-67 expression adjacent to moderate to severe inflammation was found, with no significant effect on the overall proliferation activity of the cysts.

Histomorphologic and morphometric changes in minor salivary glands of the rat tongue during 4-nitroquinoline-1-oxide-induced carcinogenesis.

4-Nitroqinoline-1-Oxide (4NQO)-induced tongue carcinogenesis in rats is considered to be a preferred model for study of oral squamous cell carcinoma. Aim of study was to investigate histomorphologic and morphometric 4NQO-induced changes in tongue minor salivary glands. Histopathological examinations of serous and mucous acini and ducts of tongue salivary glands of 26 Wistar-derived rats were performed after 14 (T(1)), 22 (T(2)) and 28 (T(3)) weeks of 0.001% 4NQO administration in drinking water and compared with nine controls. Histomorphological findings were recorded as normal/abnormal acini and as normal/dysplastic ducts. Morphometrical results were expressed as volume fraction (Vv%) of each of the components. Morphometric and histomorphologic changes in the salivary glands were evident only at T(3) and they included a significant (P=0.008) decrease in the Vv of the serous acini compared with the control group accompanied by abnormal acini (Vv=18%). In contrast, mucous acini and ducts did not demonstrate significant changes. In one case (3.8%), dysplastic ducts were found adjacent to islands of invasive squamous cell carcinoma of tongue mucosa origin. The change in saliva composition expected after considerable damage of the serous glands could create a microenvironment that makes entrapment of the carcinogen easier and prolongs exposure of tongue epithelium. Furthermore, the dysplastic changes in the ducts can serve as a reservoir of carcinoma cells. These observations should be considered in human patients diagnosed with oral dysplasia or carcinoma, especially involving the tongue and floor of mouth.

Peripheral giant cell granuloma associated with dental implants.

BACKGROUND: Peripheral giant cell granuloma (PGCG) is a well-circumscribed lesion confined to the alveolar and gingival mucosa. PGCG is considered a reactive lesion caused by local irritation or trauma. The objectives of the present study were to evaluate the incidence of PGCG in peri-implant lesions submitted for histologic examination, to establish its correlation with implant failure, and to discuss its pathogenesis. METHODS: The study was conducted on 25 periimplant biopsy specimens submitted for histological examination between 1999 and 2001. Sections (5 microm) of paraffin embedded tissues were cut and stained with hematoxylin and eosin. RESULTS: From the 25 specimens, three (two males and one female, ranging in age from 31 to 69 years) were identified as peripheral giant cell granuloma. The posterior mandible was affected in two cases and the anterior maxilla in one. The clinical appearance was an exophytic mass with a bleeding surface. The time interval between implantation and lesion development was from several months to 6 years. Recurrence following curettage was found in all cases. The implants were stable; however, two were removed either because of bone loss around the implant or because of several recurrences. In all cases healing was uneventful. CONCLUSIONS: Peripheral giant cell granuloma can develop in association with dental implants. Clinically, the lesions are similar to the classical PGCG. In the present study, the precise incidence could not be concluded because of the small number of selected cases. Due to the aggressive nature of the lesion and the high recurrence rate, implants can fail unless the lesion is detected early and proper surgical removal is performed. Tissue removed from the peri-implant area should always be submitted for histologic examination for accurate diagnosis.

Periapical actinomycosis: a clinicopathologic study.

OBJECTIVE: We sought to evaluate the incidence and clinical outcome of an accidental finding of actinomycotic colonies in periapical lesions submitted for histologic examination. STUDY DESIGN: The study included all periapical biopsy specimens submitted for histologic examination between 1997 and 2000. Sections of paraffin-embedded tissues, 5 microm, were cut and stained by using hematoxylin and eosin, periodic acid-Schiff, and the Gram stain. The presence of typical branching colonies of filamentous bacteria staining positive for periodic acid-Schiff and Gram stain was indicative of Actinomyces. RESULTS: Typical actinomycotic colonies were identified in 17 of 963 (1.8%) periapical biopsy specimens. The mean patient age was 42, and males were predominant (65%). The maxilla was the most frequently involved site (65%), with equal distribution in the anterior and posterior areas. Radiographically, most cases presented as well-demarcated radiolucent lesions. Malignancy was suspected in 3 cases. Of the periapical lesions, 15 were epithelialized, and in 4 cases, a true epithelial-lined lumen was found, which was diagnosed as a radicular cyst. A residual cyst was diagnosed in 1 case, and in 1 case, an epithelial lining was not identified. Treatment included surgical curettage and a short course of antibiotic therapy. Healing was uneventful in all cases. CONCLUSIONS: Periapical actinomycosis is not common. Its outcome is favorable after surgical curettage supplemented by short-term antibiotic treatment. The relationship of periapical actinomycosis with the more serious cervicofacial actinomycosis should be evaluated.

Temporomandibular joint involvement in malignant external otitis.

OBJECTIVE: The purpose of this study was to present 6 patients with malignant external otitis (MEO) that resulted in temporomandibular joint (TMJ) involvement and to discuss the incidence, clinical presentation, and treatment modalities. STUDY DESIGN: All patients diagnosed with MEO between 1994 and 2002 were reviewed for cases in which the TMJ was invaded by the infectious process. Only patients in whom TMJ involvement was documented radiographically and in whom the clinical course was well documented were included in this study. RESULTS: MEO was diagnosed in 42 patients over an 8-year period; TMJ involvement was recorded in 6 patients (14%). The medical history revealed controlled type 2 diabetes mellitus in 4 of the 6 patients. All patients reported early ear symptoms, mainly otalgia and otorrhea. Local signs included an ear canal filled with granulation material, edematous overlying skin, and sensitivity to palpation. Cultures taken from the external ear were positive for either Pseudomonas aeruginosa, Staphylococcus epidermidis, Aspergillus, or Proteus mirabilis. TMJ symptoms developed between 1 and 5 months after admission and included painful periauricular swelling and trismus. In 3 patients, healing was uneventful; 3 also died of the disease. CONCLUSIONS: TMJ involvement in MEO is associated with a resistant disease process, often with several recurrences. Prolonged administration of antibiotics is the treatment of choice. Surgical debridement of the TMJ is necessary for the positive identification of the pathogenic organism, in cases of abscess formation, or when osteomyelitic bone destruction of the condyle and glenoid fossa develop.