Soft Tissue Biopsies Research Articles

Mycobacterium ahvazicum sp. nov., the nineteenth species of the Mycobacterium simiae complex

Four slowly growing mycobacteria isolates were isolated from the respiratory tract and soft tissue biopsies collected in four unrelated patients in Iran. Conventional phenotypic tests indicated that these four isolates were identical to Mycobacterium lentiflavum while 16S rRNA gene sequencing yielded a unique sequence separated from that of M. lentiflavum. One representative strain AFP-003T was characterized as comprising a 6,121,237-bp chromosome (66.24% guanosine-cytosine content) encoding for 5,758 protein-coding genes, 50 tRNA and one complete rRNA operon. A total of 2,876 proteins were found to be associated with the mobilome, including 195 phage proteins. A total of 1,235 proteins were found to be associated with virulence and 96 with toxin/antitoxin systems. The genome of AFP-003T has the genetic potential to produce secondary metabolites, with 39 genes found to be associated with polyketide synthases and non-ribosomal peptide syntases and 11 genes encoding for bacteriocins. Two regions encoding putative prophages and three OriC regions separated by the dnaA gene were predicted. Strain AFP-003T genome exhibits 86% average nucleotide identity with Mycobacterium genavense genome. Genetic and genomic data indicate that strain AFP-003T is representative of a novel Mycobacterium species that we named Mycobacterium ahvazicum, the nineteenth species of the expanding Mycobacterium simiae complex.

Prevalence of Propionibacterium acnes in the glenohumeral compared with the subacromial space in primary shoulder arthroscopies

We hypothesized that the prevalence of Propionibacterium acnes in patients undergoing primary shoulder arthroscopy is equal in the glenohumeral space compared with the subacromial space. Patients aged 18 years or older with shoulder arthroscopies were included. The exclusion criteria were prior shoulder operations, complete rotator cuff tears, systemic inflammatory diseases, tumors, shoulder injections within 6 months of surgery, and antibiotic therapy within 14 days preoperatively. After standardized skin disinfection with Kodan Tinktur Forte Gefärbt, a skin swab was taken at the posterior portal. Arthroscopy was performed without cannulas, prospectively randomized to start either in the glenohumeral space or in the subacromial space, with direct harvesting of a soft-tissue biopsy specimen. Sample cultivation was conducted according to standardized criteria for bone and joint aspirate samples and incubated for 14 days. Matrix-assisted laser desorption-ionization time-of-flight spectrometry was used for specimen identification in positive culture results. The study prospectively included 115 consecutive patients with normal C-reactive protein levels prior to surgery (54.8% men; mean age, 47.2 ± 14.6 years). P acnes was detected on the skin after disinfection in 36.5% of patients, in the glenohumeral space in 18.9%, and in the subacromial space in 3.5% (P = .016). The prevalence of P acnes is significantly higher in the glenohumeral space compared with the subacromial space in primary shoulder arthroscopies. The results do not confirm the contamination theory but also cannot clarify whether P acnes is a commensal or enters the joint hematologically or even lymphatically or via an unknown pathway. Despite standardized surgical skin disinfection, P acnes can be detected in skin swab samples in more than one-third of patients.

Clinical and histologic evaluation of different approaches to gain keratinized tissue prior to implant placement in fully edentulous patients.

This work aimed to investigate the effectiveness and predictability of different treatment modalities for gain of keratinized tissue (KT) in fully edentulous jaws prior to dental implant placement: apically positioned flap (APF), APF plus xenogeneic collagen matrix (XCM), and APF plus free gingival graft (FGG). In fully edentulous patients with insufficient zones of KT at the prospective implant positions, four treatment modalities were performed in the lower jaw: APF, XCM, FGG, and an untreated control group (control). APF and XCM were applied in the first molar positions, FGG and control in the canine positions. Assessed outcomes up to 3months post-surgery included changes in width of KT (over a 3-month period), histomorphometric analysis of harvested soft-tissue biopsies (at 3months postoperatively), and patient-reported outcomes measures (PROMs). For the primary outcome, changes in KT width demonstrated an increase of 1.93±1.6mm (APF), whereas XCM and FGG showed an increase of 4.63±1.25mm and 3.64±2.01, respectively. Histomorphometric analyses revealed a thickness of the epithelium ranging between 375 ± 122μm (APF), 410 ± 116μm (XCM), 336 ± 122μm (FGG), and 413 ± 109μm (control). All biopsies showed a regular muco-periosteal structure with a keratinized epithelium of comparable thickness in all groups. All three methods were suitable to increase the width of KT, although APF alone rendered roughly 50% less gain compared to XCM and FGG. The use of XCM in conjunction with an APF represents a valuable treatment option for the gain of keratinized tissue in edentulous sites.

Percutaneous microwave ablation of renal cell carcinoma using a high power microwave system: focus upon safety and efficacy

Objectives: Percutaneous ablation is an expanding, minimally invasive approach for small- to medium-sized renal masses. The purpose of this study is to review safety, and mid-term efficacy of percutaneous microwave ablation (MWA) for Renal Cell Carcinoma (RCC) treatment using a high power microwave system.Methods and materials: Institutional database research identified 50 consecutive patients with a single lesion resembling renal cell carcinoma in CT and MRI who underwent percutaneous microwave ablation using a high power microwave system. All patients underwent biopsy on the same session with ablation using an 18G semi-automatic soft tissue biopsy needle. Contrast-enhanced computed tomography or magnetic resonance imaging was used for post-ablation follow-up. Patient and tumour characteristics, microwave technique, complications and pattern of recurrence were evaluated.Results: Mean patient age was 74 years (male–female: 31–19). Average lesion size was 3.1 cm (range 2.0–4.3 cm). Biopsy results report RCC (n = 48), inflammatory myofibroblastic tumour (n = 1), and non-diagnostic sample (n = 1). The 3-year overall survival was 95.8% (46/48). Two patients died during the 3-year follow-up period due to causes unrelated to the MW ablation and to the RCC. Minor complications including haematomas requiring nothing but observation occurred at 4% (2/50) of the cases. Local recurrence of 6.25% (3/48) was observed with 2/3 cases being re-treated achieving a total clinical success of 97.9% (47/48 lesions).Conclusions: Percutaneous microwave ablation of RCC using a high power microwave system is a safe and efficacious technique for the treatment of small- to medium-sized renal masses.

Tailored interactive sequences for continuous MR-image-guided freehand biopsies of different organs in an open system at 1.0 tesla (T) - Initial experience.

To assess the feasibility, image quality, and accuracy of freehand biopsies of liver, bone, muscle, vertebral disc, soft tissue, and other lesions using balanced steady-state free precession (SSFP, balanced fast field echo: bFFE), spoiled and nonspoiled gradient echo (FFE), and turbo spin echo (TSE) sequences for interactive continuous navigation in an open magnetic resonance imaging (MRI) system at 1.0 tesla (T). Twenty-six MR-guided biopsies (five liver, five bone, four muscle, four vertebral disc, one lung, one kidney, one suprarenal gland, and five soft or other tissue) were performed in 23 patients in a 1.0-T open magnetic resonance (MR) scanner (Panorama HFO, Philips Healthcare, Best, the Netherlands). A total of 42 samples were obtained. Depending on lesion size and location, 14-18-gauge MR-compatible biopsy sets with a length of 100 or 200 mm (Somatex Medical, Teltow, Germany), 14-18-gauge MR-compatible semiautomatic biopsy guns with a length of 100 or 150 mm (Invivo, Schwerin, Germany), or 11-gauge MR-compatible bone marrow biopsy needles with a length of 100 mm (Somatex Medical, Teltow, Germany) were employed. All lesions were visible with continuous interactive imaging. Our initial results indicate that bFFE is particularly suitable for fast-moving organs (pulmonary, paracardial); moving organs are targeted better with T1-weighted (T1W) TSE, T1W FFE (liver) or T2-weighted (T2W) TSE (complicated cysts, adrenal glands), and static organs are successfully approached with proton density (PD) (spine) or T1W TSE (peripheral bones, musculoskeletal system). No adverse events related to the use of MRI were obtained. No complications occurred according to the Society of Interventional Radiology (SIR) clinical practice guidelines. Applying tailored interactive dynamic imaging sequences for continuous navigation to liver, bone, muscle, vertebral disc, soft tissue, and other lesions can improve the feasibility, image quality, and interventional accuracy of freehand MR-guided biopsies and may hence reduce the risk of complications.

Perplexing Malignant Peritoneal Mesothelioma in a Young Woman Without Exposure

Introduction: Malignant mesothelioma is a rare disease that most often occurs in the pleura as a result of environmental exposure. Malignant peritoneal mesothelioma (MPM) is an even less common disease, accounting for approximately 10-15% of all cases of mesothelioma. Interestingly, MPM occurs more often in females than pleural mesotheliomas do for reasons that are not entirely understood. This higher proportion of females is thought to reflect their higher incidence of non-asbestos related disease. We report the case of a young woman with no known environmental exposure history who was diagnosed with MPM. Case Report: A healthy 20-year-old woman presented with dehydration and malnutrition. She reported a 2 month history of nausea, vomiting, diarrhea and abdominal pain. She also endorsed anorexia and an associated 20-30 pound weight loss over the same period. She had presented to her local emergency department 3 times with these complaints and had been found to have small pockets of ascites as well as hepatic sinusoidal dilatation on ultrasound. Additional workup including CT imaging, liver biopsy, paracentesis, colonoscopy and upper endoscopy had failed to identify any pathology. An MRI showed extensive soft tissue implants and omental caking in the abdomen and pelvis with abnormal peritoneal thickening and enhancement. The patient underwent a CT-guided biopsy of the omental soft tissue, which demonstrated a mesothelioma of epithelioid type. She was treated with peritonectomy, omentectomy, small bowel resection, total abdominal hysterectomy and installation and circulation of hyperthermic intraperitoneal chemotherapy. Biopsies of all sampled tissue showed extensive involvement by MPM. Of note, extensive imaging and evaluation did not capture any pleural involvement. Discussion: MPM is an exceedingly rare disease. Although previous studies have demonstrated an association between MPM and asbestos exposure in men, the same association has not been deduced in female populations. Other contributing exposures that have been described include radiation, chronic peritonitis, mica exposure and the simian virus-40. Both this patient's young age and lack of any such exposures reinforce the prevailing current wisdom that the risk factors for this rare, yet highly deadly disease have yet to be properly defined.Figure: A) Coronal MRI revealing broad sheet of omental caking along the left abdomen extending into the pelvis and diffuse peritoneal thickening and enhancement both along the abdominal wall and the bowel surfaces. Overall findings are suspicious for peritoneal malignancy. B) Coronal MRI revealing overall reduction in diffuse peritoneal disease burden with resolution of omental caking after therapy.

Fournier’s Gangrene: the Criteria for Diagnosis, Prognostic Factors, Complications and Mortality

The early diagnosis, prognosis, complications and mortality Fournier’s gangrene (FG) are discussed. The terms pre-hospital period with FG is amount of 8.0 ± 5.2 days. Cases of misdiagnosis are observed in 70% in the early stages of FG due to nonspecific clinical and laboratory picture, lack of awareness and alertness of doctors. Early diagnosis of FG is based on clinical and laboratory data of the picture. In order to timely diagnosis of FG is used scale laboratory indicators of necrotizing fasciitis (LRINEC), allowing suspect FG in doubtful cases. In diagnostically unclear cases FG used radiation methods. At the slightest suspicion on the FG made explorative operation, including express biopsy of soft tissues. The differential diagnosis is carried out in the early stages of FG with acute diseases anogenital region and is rarely used. As a prognostic criteria discussed the patient's age, the presence and nature of comorbid diseases, severity of the condition, the hospital admission dates, duration of preoperative period, necrosis area, metabolic parameters, the amount of remedial necrectomy, antibiotic regimen, hyperbaric oxygen therapy. For the systematic evaluation of the severity of the patient's condition and prognosis use different scoring systems. Many of the proposed prognostic criteria are controversial. The favorable prognosis in FG is entirely dependent on early diagnosis and timing of emergency surgery. Sepsis and its complications are the main causes of deaths. Mortality in the FG has been a steady downward trend, and is 22.3 ± 8.8%. Prevention of the FG is a timely treatment of infectious and inflammatory diseases of the urinary organs and their complications.

Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation

Perfluoroalkyl substances (PFAS), including two most commonly studied compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are widely distributed environmental pollutants, used extensively earlier. Due to their toxicological effects the use of PFAS is now regulated. Based on earlier studies on PFOA’s distribution in bone and bone marrow in mice, we investigated PFAS levels and their possible link to bone microarchitecture of human femoral bone samples (n = 18). Soft tissue and bone biopsies were also taken from a 49-year old female cadaver for PFAS analyses. We also studied how PFOA exposure affects differentiation of human osteoblasts and osteoclasts. PFAS were detectable from all dry bone and bone marrow samples, PFOS and PFOA being the most prominent. In cadaver biopsies, lungs and liver contained the highest concentrations of PFAS, whereas PFAS were absent in bone marrow. Perfluorononanoic acid (PFNA) was present in the bones, PFOA and PFOS were absent. In vitro results showed no disturbance in osteogenic differentiation after PFOA exposure, but in osteoclasts, lower concentrations led to increased resorption, which eventually dropped to zero after increase in PFOA concentration. In conclusion, PFAS are present in bone and have the potential to affect human bone cells partly at environmentally relevant concentrations.

The presence of neuroendocrine features generates a broad differential diagnosis in the fine-needle aspiration of bone and soft tissue neoplasms

Biopsy of bone and soft tissue (BST) lesions occasionally yields neoplasms with neuroendocrine (NE) features. We identify a differential diagnosis for neoplasms containing NE features when encountered on fine-needle aspiration (FNA) of BST masses. The cytopathology archives of the Johns Hopkins Hospital were searched for any BST FNA specimen diagnosed as a neoplasm with NE features or in which NE immunohistochemical (IHC) markers were ordered. Specimen diagnoses were reviewed and specimens were excluded if neuroendocrine features were not considered at the time of original diagnosis. A total of 179 specimens met the inclusion criteria. Of these, 64 (36%) and 115 (64%) neoplasms were primary and metastatic, respectively. A total of 29 distinct entities were identified. Sixteen were entities with established NE differentiation and 13 were entities not typically regarded as having an NE origin. The most commonly encountered neoplasms included small cell carcinoma of all primary locations (38), Ewing sarcoma (37), medullary thyroid carcinoma (24), Merkel cell carcinoma (23), and paraganglioma (10). NE IHC markers were ordered in 45% of cases; 86% were positive by at least one NE marker. Entities with established NE differentiation were more likely to be positive for NE IHC than those not typically regarded as having NE differentiation (100% and 59%, respectively). A variety of BST lesions-including neoplasms not typically thought to have neuroendocrine differentiation-can possess NE cytomorphologic features and/or NE IHC marker positivity. The patient's clinical presentation and history can help narrow the differential diagnosis.

The Potential Use of Ultrasound-Magnetic Resonance Imaging Fusion Applications in Musculoskeletal Intervention.

We sought to assess the potential use of an application allowing real-time ultrasound spatial registration with previously acquired magnetic resonance imaging in musculoskeletal procedures. The ultrasound fusion application was used to perform a range of outpatient procedures including piriformis, sacroiliac joint, pudendal and intercostal nerve perineurial injections, hamstring-origin calcific tendonopathy barbotage, and 2 soft tissue biopsies at our institution in 2015. The application was used in a total of 7 procedures in 7 patients, all of which were technically successful. The ages of patients ranged from 19 to 86 years. Particular use of the fusion application compared to sonography alone was noted in the biopsy of certain soft tissue lesions and in perineurial therapeutic injections.

Oncogene Induced Senescence As a Potential Breakpoint Mechanism Against Malignant Transformation in Plasma Cell Disorders

Background: Cellular senescence has been recognized as a failsafe mechanism against hyperproliferation and might thus be induced by DNA replicative stress and oncogenic signaling, commonly termed oncogene-induced senescence (OIS). OIS has been described in several premalignant conditions such as colon adenomas and melanocytic nevi, with impaired OIS capabilities found in their malignant counterparts. Here, we analyze the possible impact of cellular senescence on malignant transformation in plasma cell disorders.Methods: Bone marrow and soft tissue biopsies from 125 patients with different stages of plasma cell disorders (16 monoclonal gammopathy of undetermined significance (MGUS), 32 smoldering multiple myeloma (SMM), 56 symptomatic multiple myeloma (MM), 21 extramedullary MM) as well as from 10 healthy donors were analyzed. Expression of OIS associated proteins p16INK4A, p21Cip1/Waf1, p27Kip1, phospho-Chk2, the DNA double-strand break marker γH2AX, as well as the proliferation marker Ki67 were assessed on plasma cells by immunohistochemistry. Additionally, double staining experiments for p21 and Ki67 were performed applying immunofluorescence confocal microscopy. Levels of protein expression were compared between different disease stages using the Kruskal-Wallis test.Results: A differential expression pattern was found for p21 in various stages of plasma cell disorders with peak expression of p21 in SMM compared to both healthy controls (p<0.001) and MGUS (p=0.02), as well as compared to symptomatic multiple myeloma (MM) (p=0.007) (see Figure 1a). Median p21 expression was 0.63% of plasma cells from healthy subjects, 6.67% in MGUS, 13.81% in SMM, 2.37% in MM, and 0% in EMM. Plasma cells of SMM patients expressing p21 were negative for Ki67 consistent with a potentially senescent phenotype. In contrast, p27 was highly expressed in healthy controls, MGUS and SMM but decreased significantly in MM patients (p=0.02) (see Figure 1b). p16 showed no nuclear expression in healthy controls, MGUS or SMM and was expressed only in few patients with MM. In addition, we found low expression of p21, p27 and phospho-Chk2 in extramedullary MM compared to medullary MM samples, accompanied by increased expression of γH2AX and high levels of proliferation (Ki67 58%).Conclusions: We found indication of induction of OIS in SMM compared to symptomatic MM, mainly mediated by increased expression of p21. Further disease progression to extramedullary MM was characterized by almost complete absence of OIS markers and increased signs of DNA damage and proliferation. These observations are consistent with the hypothesis of OIS as a breakpoint mechanism against malignant transformation in plasma cell disorders and should be further explored mechanistically and as a possible therapeutic target. [Display omitted] DisclosuresGoldschmidt:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Raab:Novartis: Consultancy, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy.

Histopathology of vascular anomalies: update based on the revised 2014 ISSVA classification.

Precise diagnosis of childhood vascular anomalies is challenging, and requires careful correlation of clinical findings, diagnostic imaging, histopathology and genetic analysis. Skin and soft tissue biopsies remain an important element in the complete evaluation of many vascular anomalies included in the revised 2014 International Society for the Study of Vascular Anomalies (ISSVA) classification. Here we present an overview of the light microscopic and immunohistochemical features of the entities in this updated classification scheme, with emphasis on newly-included diagnoses such as PTEN hamartoma of soft tissue.

Primary Soft Tissue Lymphomas: Description of Seven Cases and Review of the Literature.

The present study describes a series of primary soft tissue lymphomas, including immunohistochemical characterization by tissue microarray and cytogenetic profiling. Formalin-fixed, paraffin-embedded tissue samples were collected from patients who underwent soft tissue biopsy. Cases were selected according to the definition of primary soft tissue lymphoma as a lymphoid malignancy arising in soft tissues without evidence of other nodal or extranodal localization for a period of at least 6months. Our series comprised seven patients with a mean age of 72years. There were three diffuse large B-cell lymphomas (DLBCLs); one B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma; one DLBCL derived from follicular lymphoma; one ALK-negative anaplastic large cell lymphoma; and one follicular lymphoma. Immunohistochemical and molecular profiles were consistent with the histological diagnoses. The present study contributes to our knowledge about uncommon presentation of lymphoid neoplasms and confirms previously published clinical-pathological data. We present, for the first time, the complete immunohistochemical profile and molecular cytogenetic studies of these lymphoid neoplasms. A rare case of a primary soft tissue ALK-negative anaplastic large cell lymphoma is described in detail.

Abstract 2283: Molecular signaling in multiple myeloma: association of RAS/RAF mutation status and MAPK pathway activation in primary myeloma patient biopsies

Abstract Multiple myeloma (MM) is an incurable plasma cell malignancy. Recent studies have identified a dominant mutation cluster in RAS/BRAF genes, highlighting the MEK/ERK signaling pathway as a potentially promising therapeutic target. However, treatment of RAS/RAF mutant MM with the MEK inhibitor, trametinib, resulted in moderate response rates. There were, however, durable remissions in those patients (pts) who responded. This suggests a variable degree of dependency on MEK/ERK signaling in RAS/RAF mutant MM. To address this issue, we correlated RAS/RAF mutations with the RAF/MEK/ERK cascade activation in primary MM patient biopsies. Primary material consisted of bone marrow or soft tissue biopsies from 179 pts, including 102 pts with newly diagnosed myeloma (NDMM) and 77 pts with relapsed/refractory myeloma (rrMM). Activation of the RAF/MEK/ERK cascade was assessed using an immunohistochemical (IHC) assay for phospho-ERK. In parallel, KRAS, NRAS, HRAS and BRAF mutation status was assessed by targeted re-sequencing using the Ion Torrent NGS technology. The mutation frequencies found were KRAS (25%), NRAS (24%), and BRAF (8%) while no HRAS was detected, consistent with previous studies. Overall, RAS/RAF mutations were significantly more frequent in rrMM (p = 0.010), mainly driven by an increase in NRAS mutations (p = 0.017), proving the importance of RAS/RAF-mediated signaling in MM and indicating a potential role for NRAS mutations in drug resistance development. The top nine recurrently detected individual mutations were KRAS Q61H (n = 11), NRAS Q61R (11), NRAS Q61K (10), KRAS G12D/G12V (6 each), BRAF V600E (6), NRAS G13D (5), NRAS G13R/Q61H (4 each). When correlated with ERK activation status, KRAS but not NRAS mutations were associated with pathway activation compared to RAS/RAF-wild type (wt) (p = 0.003). However, these were not mutually exclusive, suggesting that ERK activation is dependent on the type of mutation rather than the fact that the RAS/RAF gene is mutated. Therefore, each recurrent RAS/RAF mutation was tested against all RAS/RAF-wt samples: Only KRAS G12D and BRAF V600E were consistently associated with ERK activation (p&amp;lt; 0.001 each). In summary, we found that RAS/RAF mutations are not generally associated with RAF/MEK/ERK pathway activation in MM. However, we did identify specific amino acid changes in KRAS and BRAF which are more likely to be associated with pathway activation and two mutations which were consistently associated with MEK/ERK signaling. These findings indicate that confirmation of protein-level pathway activation is needed when considering targeted therapy. In this regard, IHC is a cost-effective and reliable method to assess pathway activation and should therefore be considered in future. The clinical relevance of RAS/RAF mutations in MM should be further elucidated in prospective cohort studies. Citation Format: Jing Xu, Nicole Pfarr, Volker Endris, Elias K. Mai, Nur Hafzan Md Hanafiah, Nicola Lehners, Roland Penzel, Wilko Weichert, Anthony D. Ho, Peter Schirmacher, Hartmut Goldschmidt, Mindaugas Andrulis, Marc S. Raab. Molecular signaling in multiple myeloma: association of RAS/RAF mutation status and MAPK pathway activation in primary myeloma patient biopsies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2283.

Guided bone regeneration using individualized ceramic sheets

Guided bone regeneration (GBR) describes the use of membranes to regenerate bony defects. A membrane for GBR needs to be biocompatible, cell-occlusive, non-toxic, and mouldable, and possess space-maintaining properties including stability. The purpose of this pilot study was to describe a new method of GBR using individualized ceramic sheets to perfect bone regeneration prior to implant placement; bone regeneration was assessed using traditional histology and three-dimensional (3D) volumetric changes in the bone and soft tissue. Three patients were included. After full-thickness flap reflection, the individualized ceramic sheets were fixed. The sites were left to heal for 7 months. All patients were evaluated preoperatively and at 7 months postoperative using cone beam computed tomography and 3D optical equipment. Samples of the regenerated bone and soft tissue were collected and analyzed. The bone regenerated in the entire interior volume of all sheets. Bone biopsies revealed newly formed trabecular bone with a lamellar structure. Soft tissue biopsies showed connective tissue with no signs of an inflammatory response. This was considered to be newly formed periosteum. Thus ceramic individualized sheets can be used to regenerate large volumes of bone in both vertical and horizontal directions independent of the bone defect and with good biological acceptance of the material.

PNR-20PRIMARY METASTATIC LEIOMYOSARCOMA OF THE SKULL

PNR-20. PRIMARY METASTATIC LEIOMYOSARCOMA OF THE SKULL Alexandra Paul1, Olinda Rebelo2, and Alice Carvalho1; Pediatric Oncology Department, Centro Hospitalar e Universitario de Coimbra-EPE, Coimbra, Portugal; Neuropathology Department, CentroHospitalar e Universitario de Coimbra-EPE, Coimbra, Portugal We report the case of a previous healthy 11 yearold-boy, with a one month history of worsening headache which appeared apparently in the context of trauma. He had an x-ray of the skull that showed a right fronto-parietal lytic lesion with 10 cm in size and with ill-defined borders. CT scan and MRI of the skull revealed a soft tissue mass invading the cranial cavity just beyond the lytic lesion, compressing the brain parenchyma, the upper sagittal sinus and the right ventricle. Skeletal scintigraphy with technetium 99m showed a positive uptake of the proximal left femur and the distal right femur. Chest CT scan detected multiple bilateral lesions of the lung. Blood tests were normal, HIV 1 and 2 were negative. Histopathological results of the soft tissue biopsy were compatible with an unspecified high-grade sarcoma and a second opinion was requested to Prof. Christopher Fletcher Harvard Medical School, USA. His examination was compatible with a high-grade spindle cell malignant neoplasm with extensive necrosis. Immunohistochemistry showed multifocal positivity for smoth muscle actin, numerous scattered cells were positive fordesmin andalsowith quiteextensivekeratinpositivity,while caldesmon, CD34 and epithelial membrane antigen were negative, suggesting a high grade leiomyosarcoma. A high complex karyotype was detected by genetic analysis. Despite chemotherapy and radiotherapy, the disease progressed and he died five months after the diagnosis. Neuro-Oncology 18:iii7–iii15, 2016. doi:10.1093/neuonc/now067.17 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fungal skin and soft tissue infections.

Cutaneous and subcutaneous mycoses are a source of significant morbidity both in immunocompetent and immunocompromised patients. We here review the latest findings in terms of genetic predisposition, epidemiology, clinical manifestations, and therapeutic strategies in these diseases. A growing number of fungal skin and soft tissue infections are reported worldwide. In immunocompromised patients, these infections are often associated with disseminated disease. Skin and soft tissue biopsies usually allow mycological identification. Although tissue culture remains the gold standard, molecular biology is increasingly used and sometimes mandatory for accurate diagnosis. Advances in therapeutics have improved outcome and lowered dissemination risk in patients. Cutaneous and subcutaneous mycoses are an evolving field. Clinicians all over the world should be aware of the common manifestations of these diseases - infectious diseases - as they are increasingly reported and may lead to or be associated with dissemination.

The range of diagnoses for oral soft-tissue biopsies of geriatric patients in a Saudi Arabian teaching hospital.

IntroductionThe increased life expectancy being observed worldwide necessitates careful planning for future geriatric oral health care needs, which should be based on epidemiologic surveys to identify these needs. We aimed to survey the range of lesions diagnosed in soft-tissue biopsies of patients over age 60 over a 30-year period in a Saudi Arabian teaching hospital.MethodsThe histopathology records of geriatric patients with complete demographic data who were diagnosed between 1984 and 2013 at the College of Dentistry, King Saud University, were reviewed. The lesions were then classified into eight broad categories. Associations between variables were evaluated using Pearson’s Chi square test.ResultsThere were 231 soft-tissue biopsies obtained from geriatric patients whose complete records were available. The male to female ratio was 1.1:1, and the mean age was 66.7 years. Most lesions (69%) occurred in patents aged 60–69 years. Although reactive lesions were generally the most common, the most common lesions were squamous cell carcinoma and fibroma. Lesions were most commonly located on the buccal mucosa and the alveolar ridge/gingivae.ConclusionsThe range of lesions seen in Saudi geriatric patients were similar to those reported for other parts of the world, although the lesions were more similar to those reported from developing countries. The very high rate of oral cancer, however, is expected to take the majority of the resources allocated to geriatric oral health care, except if a strong, population-based prevention program is initiated immediately.

Randomized controlled clinical pilot study of all-ceramic single-tooth implant reconstructions: clinical and microbiological outcomes at one year of loading.

To test whether or not pink veneering of the submucosal part of zirconia abutments influences clinical, microbiological and histological outcomes of cemented implant-supported single crowns (ISSC). A total of 20 patients with one single-tooth implant in the esthetic zone were included. Implants were randomly restored with either pink-veneered zirconia abutments (test group; n=10) or non-veneered white zirconia abutments (control group; n=10) and with adhesively cemented all-ceramic crowns. At the 6-month follow-up, soft tissue biopsies were prepared for histological evaluation and microbiological samples were collected around abutments and the respective contra-lateral teeth (in 10 of 20 patients). One year after the initiation of loading, clinical parameters were assessed. Robust linear mixed model and cumulative linked mixed model analyses were performed to investigate the effect of group and time-point on clinical and biological outcomes. Clinical evaluations revealed stable peri-implant soft tissues in terms of probing pocket depth, but a high BOP index (87.5% control; 80.0% test). No statistically significant differences were observed between the test and control group for any outcome measure (P>0.05). No major biological complications occurred during the observation period. Histological samples revealed a remarkable degree of inflammation in both groups without clear differences in qualitative histological features. Microbiological evaluation demonstrated a slightly higher bacterial count at implants compared to natural teeth at one year of loading without marked differences between groups. Limited by a small sample size and a relatively short observation period, pink-veneered zirconia abutments exhibited similar clinical, histological and microbiological outcomes as non-veneered zirconia abutments supporting cemented single crowns.

Clinical Management Protocol for Dental Implants Inserted in Patients with Active Lichen Planus.

To propose a treatment protocol for management of implant candidates suffering from active lichen planus. Twenty-three patients who were diagnosed with active lichen planus were referred to a dental practice seeking dental implants. Patients received dental implants using open flap technique and sequential osteotomy. After a healing time of 6 weeks, implants were put into occlusal contact using interim prostheses. Of the 55 inserted implants, 42 failed after a short clinical service time (7 to 11 weeks). Failed implants were surgically removed, and osteotomy sites were carefully cleaned using manual curettes and scrubbing of osteotomy walls. CD4/CD8 cell count and gingival biopsies were collected from the surgical sites. Patients were put on an ascending dose (5 mg/10 days) of oral corticosteroids until a daily dose of 20 mg/day was achieved and maintained for 2 weeks. All patients received ten sessions of low-energy soft tissue laser irradiation at the implant insertion sites to assess soft tissue healing through improving blood circulation, reduction of inflammation, and sterilization of the osteotomy region. After approximately 8 weeks, a new set of 42 implants was placed, and definitive restorations were cemented using early loading technique. Marginal bone levels around inserted implants were periodically evaluated every 3 months using digital periapical radiographs (α = 0.05). Primary blood tests revealed a high CD8 cell count, while soft tissue biopsies revealed infiltration of inflammatory cells at the epithelium soft tissue interface of the examined tissue. Repetition of immunological investigations after administration of the oral corticosteroids and soft tissue laser irradiation revealed reduction of CD8 cell counts and disappearance of inflammatory cell infiltration of the examined soft tissue biopsy. Patients reported marked improvement of the oral mucosa after treatment. All implants (n = 42) were functional after 3 years of clinical observation. There was an initial reduction in marginal bone level after 3 months from insertion time, after which it remained constant during the following observation periods. Active lichen planus should be managed with oral corticosteroids and soft tissue laser irradiation before insertion of dental implants.