Dilemma in the Treatment of a Central Giant Cell Granuloma.

Management of central giant cell granuloma (CGCG) presents a clinical challenge. While eradicating a lesion known for its high recurrence rate calls for radical surgical approaches, these cause significant esthetic and functional impairment. We present an eight-year-old boy suffering from an extraordinarily large CGCG expanding into the mandible and base of the mouth in the whole anterior region. Combined treatment with surgical intervention and corticosteroid application was successfully applied, and all six attached dental germs could be preserved. Different approaches for clinical management in pediatric cases are discussed.

Ectomesenchymal chondromyxoid tumor: a comprehensive updated review of the literature and case report.

Prompted by a unique case of an ectomesenchymal chondromyxoid tumor (ECT) of the palate in a 54-year-old female, we reviewed the English and German literature on this entity until the end of 2016 using PubMed. The search produced 74 lingual cases with a nearly equal sex distribution and a mean age of 39.3 years, and two extra-lingual cases sharing histological and immunohistological features including nodular growth, round, fusiform or spindle-shaped cellular architecture, and chondromyxoid stroma. Immunophenotyping showed the majority of cases to be positive for glial fibrillary acidic protein (GFAP), S-100 protein, glycoprotein CD57, pancytokeratin (AE1/AE3), and smooth muscle actin (SMA); in isolated cases there was molecular-genetic rearrangement or gain of Ewing sarcoma breakpoint region 1 (EWSR1) but no rearrangement of pleomorphic adenoma gene 1 (PLAG1). At present, ectomesenchymal cells that migrate from the neural crest are considered to play a pivotal role in tumor origin. All cases had a benign course, although there were three recurrences. Because of the rarity of this tumor and the need for differential diagnostic differentiation from myoepithelioma and pleomorphic adenoma, both oral surgeons and pathologists should be aware of this entity.

Minimally Invasive Excision of Epulides with a CO2 Laser: A Retrospective Study of 90 Patients.

OBJECTIVE: It is the aim of this study to evaluate if the CO2 laser can beneficially be applied for excising epulides. BACKGROUND DATA: The standard procedure for treating epulides involves the excision of the hyperplastic tissue followed in most cases by the removal of parts of the underlying bone and the final closure of the wound by a flap. The use of the CO2 laser for the treatment of epulides has been documented only in isolated case reports and very few case series. PATIENTS AND METHODS: Ninety patients with different subtypes of epulides were treated with a CO2 laser (Lasram, model OPAL 25, 25 W, 10.600 nm, gas laser); power setting 4 W, continuous wave. The surgery was performed only after a pretreatment could remedy any gingivitis or occlusal trauma. A new surgical way of working using a special applicator that allowed tangential application of the laser beam was applied for all patients. Patients were followed up to 3 years. RESULTS: No perioperative complications or recurrences after 4 weeks could be found. Six patients were lost to further follow-up, whereas 84 patients were followed up to 36 months. In 71 cases there were no recurrences over the entire observation period. Thirteen patients developed a relapse, usually a fibroma/fibrosis according to histopathological evaluation. CONCLUSIONS: Overall CO2 laser seems to be an adequate tool for minimally invasive excision of epulides, although the respective histopathological entity could possibly influence the recurrence rate and so should be considered.

CO2 Laser Excision of a Pyogenic Granuloma Associated with Dental Implants: A Case Report and Review of the Literature.

OBJECTIVE: This article reports the CO2 laser excision of a pyogenic granuloma related to dental implants and reviews the current literature on this pathology in association with dental implants. BACKGROUND DATA: Five publications describe pyogenic granulomas related to dental implants, and a further one describes the removal of such a lesion with an Er:YAG laser; removal with a CO2 laser is not reported. PATIENTS AND METHODS: A 67-year-old male patient presented with a hyperplastic gingival lesion around two implants in the left lower jaw. The hyperplastic tissue was removed with a CO2 laser (Lasram; model OPAL 25, 25 W continuous wave, 10.600 nm, gas laser), and a vestibuloplasty was performed. The excised tissue was examined histopathologically. The patient was followed up after 4 weeks, 6 weeks, 6 months, and 1 year, and a panoramic X-ray was also made. RESULTS: There were no complications during surgery or follow-up. The panoramic X-ray taken 1 year after excision showed neither vertical bone loss nor impaired osseointegration of the implant. Histopathology reported a pyogenic granuloma. After vestibuloplasty, the height of the fixed mucosa was satisfactory. CONCLUSIONS: The CO2 laser seems to be a safe and appropriate tool for removal of a pyogenic granuloma in close proximity to dental implants. The laser parameters must, however, be chosen carefully and any additional irritants should be excluded to prevent a recurrence.

Epulis: a study of 92 cases with special emphasis on histopathological diagnosis and associated clinical data.

OBJECTIVES: Aim of the present study was clinical and histopathological evaluation of a series of epulides to provide clinicians data to frequency distribution and biological behaviour of different underlying entities. MATERIALS AND METHODS: Ninety-two cases of epulides removed by CO2-laser at the Department of Oral Surgery and Radiology, Medical University of Graz from 2000 to 2014 were studied retrospectively for clinical data and histopathological diagnosis. RESULTS: In the presented study, histopathological examination revealed peripheral ossifying fibroma (32.6 %), fibroma/fibrosis (29.3 %), giant cell lesion (13.1 %) and granuloma pyogenicum (8.7 %) as the most frequent underlying entities. For the first time, hyperplastic squamous epithelium (7.6 %), granulation tissue (5.4 %) and peripheral odontogenic fibromas (3.3 %) were detected to clinically appear as epulides. Irrespective of the histological diagnosis, the mean age in our patients was 43.8 years. The majority of the lesions were found in the frontal region of both jaws. In all cases, the patients showed poor oral hygiene, local gingivitis and some of them an occlusal trauma. CONCLUSIONS: To identify different entities with different biological behaviour, to exclude malignant tumours and to identify new entities among epulides, histopathological examination is required. Poor oral hygiene and occlusal trauma seem to play an important role in the pathogenesis and could be risk factors for recurrences. CLINICAL RELEVANCE: Frequency distribution of different entities in epulides is provided to clinicians, and new histopathological entities were detected to clinically appear as epulides.

Is wide resection obsolete for desmoid tumors in children and adolescents? Evaluation of histological margins, immunohistochemical markers, and review of literature.

Desmoid fibromatosis is a benign fibroblastic neoplasm with high recurrence rates predominantly observed in pediatric and adolescent patients. The use of wide resection margins has been discussed controversially in literature. In addition, data on non-surgical treatment is limited as phase III studies are still missing. Nineteen patients under the age of 18 years were identified. Tumor location, surgical treatment for primary or recurrent tumors, resection margins, medical neo-/adjuvant treatment, time to recurrence as well as immunohistochemical markers (estrogen receptor, ER α and ß, progesterone and androgen receptors, somatostatin, Ki-67, c-kit, platelet-derived growth factor receptors, PDGFRs, α and ß, ß-catenin) were evaluated. The mean age at diagnosis was 6.6 years, with a mean follow-up of 114 months. Recurrences were detected in four out of nineteen patients. Surprisingly, the recurrence rate was not influenced by type of resection used (R0, R1/2). All samples were tested negative for ER α, somatostatin, and progesterone receptor. In contrast, a majority of tumors showed positive results for PDGFR α and ß and ß-catenin. No correlation between positive immunohistochemical markers and tumor recurrences was detectable. In conclusion, recurrence rates are not depending on resection type and immunohistochemical markers seem to behave differently in children and adolescents in contrast to adult patients.

The sensitivity of biomarkers for genotoxicity and acute cytotoxicity in nasal and buccal cells of welders.

Welders are inhalatively exposed to fumes which contain genotoxic carcinogens and it was found in epidemiological studies that they have increased cancer rates which may be causally related to DNA damage. In order to assess their health risks and to find out which chemicals cause the adverse effects, bioassays can be performed which enable the detection of genetic damage. The aim of the present study was a comparative investigation with exfoliated buccal and nasal cells in regard to induction of chromosomal alterations and acute cytotoxicity in welders and unexposed controls (n=22 per group). To elucidate the factors which account for genotoxic and cytotoxic effects, additional biochemical parameters were monitored reflecting the redox status as well as concentrations of different metals and 1-hydroxypyrene (1-OHP) in body fluids. We found in the nasal cells significant induction of alterations which are indicative for DNA damage, i.e. of micronuclei (MNi) and nuclear buds, while elevated rates of nuclear anomalies reflecting cytotoxic effects (condensed chromatin, karyorrhexis, karyolylsis) were detected in cells from both organs. The levels of certain metals (Cr, Cu, Mn, Mo, Ni), but not markers of oxidative damage were significantly higher in the body fluids of the welders. Multivariate Poisson regression analyses indicate that exposure to Mo (15% MNi increase by one standard deviation increase of Mo in serum), Ni (9% increase) and Mn (14% increase) are positively associated with the induction of MNi in nasal cells while Ni was associated with cytotoxic effects in both types of cells (12 and 16% increase). Taken together, our findings indicate that epithelial cells from the respiratory tract are suitable for the detection of DNA-damaging and cytotoxic effects in welders and can be used to assess health risks associated with genomic instability.

Histone deacetylase inhibitors as potential therapeutic approaches for chordoma: an immunohistochemical and functional analysis.

Chordomas are rare malignancies of the axial skeleton. Therapy is mainly restricted to surgery. This study investigates histone deacetylase (HDAC) inhibitors as potential therapeutics for chordomas. Immunohistochemistry (IHC) was performed using the HDAC 1-6 antibodies on 50 chordoma samples (34 primary tumors, 16 recurrences) from 44 patients (27 male, 17 female). Pan-HDAC-inhibitors Vorinostat (SAHA), Panobinostat (LBH-589), and Belinostat (PXD101) were tested for their efficacy in the chordoma cell line MUG-Chor1 via Western blot, cell cycle analysis, caspase 3/7 activity (MUG-Chor1, UCh-1), cleaved caspase-3, and PARP cleavage. p-Values below 0.05 were considered significant. IHC was negative for HDAC1, positive for HDAC2 in most (n = 36; 72%), and for HDACs 3-6 in all specimens available (n = 43; 86%). HDAC6 expression was strongest. SAHA and LBH-589, but not PXD101 caused a significant increase of G2/M phase cells and of cleaved caspase-3 (p = 0.0003, and p = 0.0014 after 72 h, respectively), and a peak of caspase 3/7 activity. PARP cleavage confirmed apoptosis. The presented chordoma series expressed HDACs 2-6 with strongest expression of HDAC6. SAHA and LBH-589 significantly increased apoptosis and changed cell cycle distribution in vitro. HDAC-inhibitors should be further evaluated as therapeutic options for chordoma.

Clusterin expression in elastofibroma dorsi.

BACKGROUND: Elastofibroma dorsi is a benign soft tissue lesion composed of abnormal elastic fibers. Degenerated elastic fibers in skin and liver are associated with clusterin, an apoprotein that shares functional properties with small heat shock proteins. We evaluated the staining pattern and possible role of clusterin in elastofibroma dorsi. MATERIAL AND METHODS: Twenty-one subcutaneous elastofibromas from the scapular region were evaluated with Elastica van Gieson and Orcein stains, immunohistochemically with antibodies to clusterin, smooth muscle actin, S-100, vimentin and CD34 and correlated with clinical data with respect to physical trauma. RESULTS: Clusterin correlated with the staining pattern of Elastica van Gieson and labelled abnormal broad coarse fibrillar and globular elastic fibers in all elastofibromas. Orcein stains additionally identified fine oxytalan fibers which were not stained by clusterin. Clusterin staining was observed only on the outside of the elastin fibers, while the cores of fibers and globules were unstained. 4/21 elastofibromas showed cellular nodules with a myxoid/collagenous stroma. The round to oval cells showed cytoplasmic staining with vimentin and clusterin; CD34 labelled mostly cell membranes. The cells lacked SMA and S-100 expression. The central areas of the nodules were devoid of elastic fibers, but the periphery contained coarse fibers and globules. 9/ 11 patients, for whom clinical data were available, reported trauma to the scapular region. CONCLUSION: Many investigated ED were associated with trauma, which supports a reactive/degenerative etiology of ED. The abnormal large elastic fibers in all ED were enveloped by clusterin. Clusterin deposition may protect elastic fibers from degradation and thus contribute indirectly to the tumor-like presentation of ED.

Does insulin-like growth factor 1 receptor (IGF-1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study.

AIMS: The overall prognosis of chordoma is poor, and current treatment options are limited. The insulin-like growth factor 1 receptor (IGF-1R) pathway is important for cell signalling, and attractive for selective inhibition. We investigated the expression of IGF-1R and its ligands, IGF-1 and IGF-2, in a series of 50 chordomas, in order to assess whether IGF-1R-signalling could be a potential target for specific inhibition in chordomas. METHODS AND RESULTS: Fifty chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated immunohistochemically for the expression of IGF-1R, IGF-1 and IGF-2. Thirty-eight chordomas (76%) expressed IGF-1R, 46 (92%) expressed IGF-1 and 25 (50%) expressed IGF-2. Semi-quantitative analyses revealed a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R, IGF-1 and IGF-2 in 18 (36%), 32 (64%) and eight (16%) chordomas, respectively. Tumour volume correlated significantly with IGF-1R-staining intensity in primary chordomas (P = 0.042). CONCLUSIONS: IGF-1R and IGF-1 are expressed in the majority of chordomas. IGF-1 expression is much stronger than IGF-2 expression. Patients whose chordomas show a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R (36%) might benefit most from IGF-1R targeting, particularly if they suffer from large and surgically non-resectable chordomas.

Expression of ezrin, MMP-9, and COX-2 in 50 chordoma specimens: a clinical and immunohistochemical analysis.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the immunohistochemical expression profile of ezrin, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX)-2 in chordomas. SUMMARY OF BACKGROUND DATA: Ezrin, MMP-9, and COX-2 are expressed in different solid tumors, including chordomas. This study investigates the immunohistochemical expression of the aforementioned biomarkers and the clinical outcome in regard to immunohistochemistry, tumor volume, and localization. METHODS: Fifty brachyury-verified chordoma specimens of 34 primary and 16 recurrent tumors of 44 patients were tested for ezrin, MMP-9, and COX-2 as possible therapeutical targets by immunohistochemistry. The clinical evaluation concentrated on tumor location, volume, and age-related data. RESULTS: Ezrin expression was detected in 33 of 34 primary chordomas and in 16 of 16 recurrent cases. The primary chordomas located in the sacrum and the spine demonstrated a significantly higher percentage of positively stained tumor cells (P = 0.034) than the skull-based chordomas. An expression of MMP-9 and COX-2 was observed in 33 of 34 primary chordomas and in 16 of 16 recurrences, and in 13 of 34 primary chordomas and in 11 of 16 recurrences, respectively. Patients' survival was significantly influenced by age (P = 0.01), tumor location (P = 0.029), and tumor volume (P = 0.002). A significant positive correlation between tumor volume and the anatomic distance of the chordoma from the skull was calculated (P = 0.00002). CONCLUSION: En bloc resection with tumor-free margins is seldom feasible, particularly in the sacrum. Intralesional excisions mostly end in early local recurrence; therefore, the demand for further treatment options is frequently posed. The marked trend of the investigated biomarkers of this study may build a starting point for further investigations as molecular targets for future adjuvant therapies in chordomas. Future multicenter studies on larger patients' series are necessary to elucidate these preliminary data and to test new treatment options for patients with chordomas.

Solitary paralysis of the flexor pollicis longus muscle after minimally invasive elbow procedures: anatomical and clinical study of the anterior interosseous nerve.

BACKGROUND: The origin of the flexor pollicis longus muscle can vary, causing compression of the anterior interosseous nerve in the forearm. The topographic relationship of the flexor pollicis longus to the median and anterior interosseous nerves must be considered when these nerves are decompressed. The anterior interosseous nerve is a motor nerve supplying the flexor pollicis longus, the flexor digitorum profundus, and the pronator quadratus. Unusual etiologic conditions can occasionally cause isolated neuropathy of the flexor pollicis longus branch from the anterior interosseous nerve. METHODS: Six patients presented with isolated paralysis of the flexor pollicis longus, four following venipuncture in the cubital fossa and two following arthroscopy of the elbow joint. Cadaveric dissections were performed to examine any anatomy clinically relevant to the above techniques. The structure of the flexor pollicis longus nerve branch at different levels was examined with macroscopic and microscopic dissections and immunohistochemistry. RESULTS: In each case, clinical symptoms resolved completely with conservative treatment. Dissection of cadaver arms showed that the nerve branch to the flexor pollicis longus joins the anterior interosseous nerve in the proximal third of the forearm and shares a common epineurium, but has its own fascicle up to the proximal aspect of the elbow. The branch to the flexor pollicis longus has no proximal interneural cross-connections up to the main trunk of the median nerve. CONCLUSION: The variable relationship of the superficial cubital veins to the underlying muscles and minimally invasive approaches to the elbow joint may cause an isolated neuropathy in the motor branch to the flexor pollicis longus, with a resultant solitary paralysis of the muscle.

Microcystic/reticular schwannoma of the pancreas: a potential diagnostic pitfall.

Schwannomas occurring in the pancreatic head are rare benign non-recurring mesenchymal neoplasms and are reported to show classic morphologic features. Herein we report a case of a 62 year old male presenting with a 5 cm mass in the pancreatic head encasing the portal vein and the truncus coeliacus. Preoperative fine needle aspiration revealed malignant tumour cells consistent with a moderately differentiated adenocarcinoma. A Whipple surgery was performed after palliative chemotherapy. Histological evaluation revealed a multinodular unencapsulated tumour with focal infiltration into pancreas parenchyma and a striking microcystic/reticular growth pattern. Anastomosing and intersecting strands of spindle cells with eosinophilic cytoplasm set in a myxoid partly collagenous stroma were observed. The tumour cell nuclei were round oval and tapered and showed inconspicuous small nucleoli. Degenerative nuclear atypia was seen. Mitotic activity was sparse (1/50 HPF). Pleomorphism or necrosis was absent. The tumour cells showed strong nuclear and cytoplasmic positivity for S-100 protein, and focal positivity for glial fibrillary acidic protein. The diagnosis of a microcystic/reticular schwannoma was made. The awareness of and, to some extent, the knowledge about this rare tumour are needed to achieve the correct diagnosis and to avoid confusion, especially with malignant pancreatic neoplasms.

Chlamydia psittaci Infection in nongastrointestinal extranodal MALT lymphomas and their precursor lesions.

Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) are associated with various infectious pathogens. We analyzed the presence of Chlamydia psittaci, Chlamydia pneumoniae, and Chlamydia trachomatis DNA in 47 nongastrointestinal and 14 gastrointestinal MALT lymphomas, 37 nonmalignant control samples, and 27 autoimmune precursor lesions by polymerase chain reaction amplification and direct sequencing. In 47 nongastrointestinal MALT lymphomas, 13 (28%) were positive for C psittaci DNA compared with 4 (11%) of 37 nonmalignant control samples (P = .09). C psittaci was detected at variable frequencies in MALT lymphomas of different sites: lung, 100% (5/5; P < .01); thyroid gland, 30% (3/10; P > .05); salivary gland, 13% (2/15; P > .05); ocular adnexa, 15% (2/13); and skin, 25% (1/4). Of 27 autoimmune precursor lesions (11 Hashimoto thyroiditis and 16 Sjögren syndrome), 11 (41%) contained C psittaci DNA. Only 1 (7%) of 14 gastrointestinal MALT lymphomas was positive for C psittaci. All specimens were negative for C trachomatis and C pneumoniae. Besides ocular adnexal lymphomas, C psittaci infection is associated with nongastrointestinal MALT lymphomas and autoimmune precursor lesions, suggesting possible involvement of C psittaci-induced antigenic-driven MALT lymphomagenesis.

First report of intralaminar tumorlike lipomatous lesions of the thyroid cartilage.

INTRODUCTION: We present two cases of tumorlike lipomatous lesions in the thyroid cartilage. Both presented as circumscribed tumors by ultrasonography and were identified accidentally. METHODS: Two tumorlike lesions were identified in two different patients. Additionally, computed tomography and magnetic resonance imaging scans of the laryngeal skeleton were performed. Surgery was performed in one patient, and the lesion was excised. Histopathology revealed fatty tissue with several foci of hematopoietic cells. CONCLUSION: This is the first report of intralaminar tumorlike lipomatous lesions in the thyroid cartilage. These should be included in the differential diagnoses of primary cartilaginous lesions of the laryngeal skeleton.

Aggressive inverted papilloma with intracranial invasion and short malignization time.

Inverted papillomas (IP) are considered benign lesions with a prevalence up to 4% among all sinunasal tumors; however, invasive growth and varying tendency for malignization are reported in literature. We report the case of a 69-year-old woman suffering from a large, aggressively growing IP invading the orbit, skull base, and frontal lobe of the brain. Within only 3 months' time the papilloma showed transformation into an invasive carcinoma, leaving surgical therapy in vain due to explosive recurrence. Intracranial and intraorbital expansion by IP is possible despite histology not showing signs of malignancy initially. In "regular" IP close endoscopic follow-up is mandatory to not overlook recurrence harboring malignancy.

European position paper on endoscopic management of tumours of the nose, paranasal sinuses and skull base.

Tumours affecting the nose, paranasal sinuses and adjacent skull base are fortunately rare. However, they pose significant problems of management due their late presentation and juxtaposition to important anatomical structures such eye and brain. The increasing application of endonasal endoscopic techniques to their excision offers potentially similar scales of resection but with reduced morbidity. The present document is intended to be a state-of-the art review for any specialist with an interest in this area 1. to update their knowledge of neoplasia affecting the nose, paranasal sinuses and adjacent skull base; 2. to provide an evidence-based review of the diagnostic methods; 3. to provide an evidence-based review of endoscopic techniques in the context of other available treatments; 4. to propose algorithms for the management of the disease; 5. to propose guidance for outcome measurements for research and encourage prospective collection of data. The importance of a multidisciplinary approach, adherence to oncologic principles with intent to cure and need for long-term follow-up is emphasised.

Desmoid tumor treated with polychemotherapy followed by imatinib: a case report and review of the literature.

Desmoid tumors, also known as aggressive fibromatosis, are tumors of intermediate dignity, which grow slowly but are locally aggressive. These tumors do not metastasize but can be potentially life threatening when infiltrating vital structures. The therapy strategy consists of surgery, radiation and systemic therapy with non-steroidal anti-inflammatory drugs, antiestrogen compounds and cytotoxic chemotherapy. We report on a 40-year-old male patient with advanced fibromatosis of the neck who has been treated with 7 cycles of polychemotherapy (adriablastin, ifosfamide and dacarbazine) followed by targeted therapy with imatinib. Tumor response was evaluated clinically and by magnetic resonance imaging. The tumor decreased significantly after the first cycle of chemotherapy and tumor-related symptoms declined. The response continued after switching to targeted therapy with imatinib, which is currently ongoing. The best treatment for this rare tumor remains under discussion. Doxorubicin and dacarbazine are frequently used agents. We included ifosfamide in our therapy, which is standard in the treatment of soft tissue tumors. The tyrosine kinase inhibitor imatinib seems to offer new possibilities and is currently investigated in randomized trials. We conclude that combination chemotherapy including doxorubicin, ifosfamide and dacarbazine in the treatment of aggressive fibromatosis should be considered for patients suffering from unresectable, advanced disease and clinical symptoms which require a rapid response to therapy.