A rare phenomenon, primary pulmonary smooth muscle tumor and its management.

Smooth muscle tumors of uncertain malignant potential, the borderline tumors arising from the smooth muscle cells, usually grow slowly and do not fulfill the diagnostic criteria of leiomyosarcoma and its variants, but may behave in a malignant manner. A 15-year-old female patient with an endobronchial mass in the left main bronchus on thoracic computed tomography underwent thoracotomy and tracheobronchoplasty with a wide and safe margin. Histopathological evaluation revealed a smooth muscle tumor of uncertain malignant potential. There were no complications related to the operation during the hospital stay. At six months of surgery, there were no symptoms or signs suggesting any recurrence in her follow-up. In conclusion, In conclusion, pulmonary leiomyomas may rarely present as an endobronchial mass and may mimic asthma by causing respiratory symptoms developing as attacks due to displacement of the mass within the lumen.

Comparative evaluation of the efficacy of ozone therapy and low level laser therapy on oral mucosal wound healing in rat experimental model.

OBJECTIVE: The aim of the present study was to evaluate and compare the effectiveness of ozone therapy and low-level laser therapy (LLLT) on healing of oral mucosal wounds in rats through histological assessment. METHODS: Thirty male Wistar rats were employed in this study. Following a 5-mm surgical wound created on the buccal mucosa, the rats were randomly distributed into 3 groups of 10: (1) ozone group (treated with topical gaseous ozone), (2) laser group (treated with LLLT), and (3) control group (received no treatment). Following the sacrifice of rats on day 21, samples were taken from rats' buccal mucosa for histological assay and scoring. The data were analyzed using Mann-Whitney test. RESULTS: Ozone and laser groups demonstrated reduced acute inflammation scores compared to control group (p=.01), while no significant differences were observed between the ozone and laser groups (p = 1.00). Similarly, ozone and laser groups showed higher histological tissue repair scores than the control group (p=.00), and no difference was found between ozone and laser groups (p=.76). On the other hand, no significant difference in expression of TNF-α (p=.33) and TGF-ß1 (p=.13) was identified between ozone, laser and control samples. CONCLUSION: The present study demonstrated that both adjunctive ozone therapy and LLLT with a 940 nm diode laser provided significant improvement in parameters of acute inflammation and tissue repair in surgical oral mucosal wounds in rats.

Noninvasive assessment of oral lesions using elastic light single-scattering spectroscopy: a pilot study.

PURPOSE: In the present study, we investigated the potential application of elastic light single-scattering spectroscopy (ELSSS) as a noninvasive, adjunctive tool to differentiate between malignant and benign oral lesions in vivo. METHODS: ELSSS spectra were acquired from 52 oral lesions of 47 patients prior to surgical biopsy using a single optical fiber probe. The sign of the spectral slope was used as a diagnostic parameter and was compared to the histopathology findings to obtain sensitivity and specificity of the ELSSS system in differentiating between benign and malignant tissues. RESULTS: The sign of the spectral slope was positive for the benign tissues and negative for the malignant tissues. Nine malignant lesions and one high-grade dysplasia were correctly classified as cancerous. Six out of the ten low-grade dysplasia were correctly classified as cancerous, and four of them were misclassified as benign. Thirty benign lesions were correctly classified as benign, and two were misclassified as malignant. Our results indicate that the sign of the spectral slope enables the differentiation between malignant and benign oral lesions with a sensitivity of 80% and specificity of 94%. CONCLUSIONS: ELSSS has the potential to be developed as an adjunctive screening tool in the noninvasive evaluation of oral lesions in vivo. This new diagnostic system may reduce the number of unnecessary biopsies.

Pediatric Tonsillar Synovial Sarcoma- Very Rare Localization: A Case Report and Review of the Literature.

Tonsillar synovial sarcoma is an extremely rare entity and only 9 adult patients have been reported up to now. Here, we describe the first pediatric tonsillar synovial sarcoma of the literature in a patient who presented with a 2-month history of dysphagia and snoring. Clinical and radiological examinations showed that the tumor arose from the right palatine tonsil and narrowed the parapharyngeal space. An incisional biopsy from the palatine tonsil revealed the diagnosis of synovial sarcoma. The patient has underwent total tonsillectomy and received radiotherapy and chemotherapy because of the positive surgical margins. The patient is clinically in good condition and free of tumor 30 months after the initial diagnosis. We achieved a long-term complete remission with a combination of surgery, radiotherapy and chemotherapy in our case. Tonsillar synovial sarcoma should be kept in mind while dealing with tonsillar masses. We can conclude that a multidisciplinary approach is warranted while treating synovial sarcoma with this localization.

Hyalinizing Clear Cell Carcinoma of the Maxilla.

Hyalinizing clear cell carcinoma (HCCC) is a rare low-grade salivary gland tumor with distinctive clear cell morphology, accounting for < 1% of all salivary gland tumors. In the majority of cases, the tumor originates typically from the minor salivary glands in the oral cavity. A total of 155 cases of HCCCs from head and neck region have been reported in the literature until 2017, of which only 16 are of maxillary origin. Due to its low incidence, there is no clear consensus on prognostic factors and optimal treatment strategies yet. In this paper, a new case of HCCC of the maxilla is presented and its clinical and histopathological features are discussed.

Identification of novel mutations of Insulin Receptor Substrate 1 (IRS1) in tumor samples of non-small cell lung cancer (NSCLC): Implications for aberrant insulin signaling in development of cancer.

Lung cancer is the leading cause of cancer-related death, and NSCLC constitutes nearly 85%-90% of all cases. The IRS proteins function as adaptors and transmit signals from multiple receptors. Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. Therefore, we thought that gain of function mutantions of IRS1 could be related to development of lung cancer. In line with this, we wanted determine whether the IRS1 gene was mutated in the coding regions surrounding YXXM motifs. We sequenced the coding regions surrounding YXXM motifs of IRS1 using tumor samples of 42 NSCLC patients and 40 matching controls and found heterozygote p.S668T mutation in nine of 42 samples and four of nine also had the p.D674H mutation. We generated IRS1 expression vectors harboring p.S668T, p.D674H and double mutants. Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. Also, our mutants induced proliferation, glucose uptake, inhibited the migration of 293T cells and affected the responsiveness of the cells to cisplatin and radiation. Our results suggest that these novel mutations play a role in the phenotype of lung cancer.

Synchronous occurrence of multiple distinct jaw lesions in Simpson-Golabi-Behmel Syndrome: A case report.

Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked overgrowth syndrome characterized by pre- and post-natal overgrowth, typical facial appearance and multiple visceral, skeletal, and neurological anomalies. There is only few information in the current literature, on clinical and particularly dentofacial findings due to recent identification of the syndrome and its clinical overlap with other overgrowth syndromes. The aim of this case report is to present dentofacial findings in a 16-year-old boy who had been diagnosed with SGBS. Following comprehensive clinical, radiographic and histopathological examinations, six pathologically distinct lesions including odontogenic keratocyst, ameloblastoma, lateral periodontal cyst, dentigerous cyst and mucous retention cyst in both mandible and maxilla were identified. The clinical report is followed by a discussion aimed to clarify unique features of this condition and how practitioners should consider similar cases.

Coexisting sublingual dermoid cyst and heterotopic gastrointestinal cyst: Case report.

A heterotopic oral gastrointestinal cyst coexisting with a lingual dermoid cyst is a rare condition, with only 3 reported cases in the English-language literature. Clinically, both gastrointestinal and dermoid cysts tend to manifest as an asymptomatic swelling. Cysts above the mylohyoid often present with sublingual swelling, whereas those below the mylohyoid present with submental swelling. Increased salivation, altered speech, dyspnea and difficulties in eating, swallowing and respiration may be present, depending on the size of the cyst. This paper describes the case of a 4-year-old girl presenting with swelling of the tongue and floor of the mouth that interfered with normal speech. Two cystic lesions were surgically excised using an intraoral approach, and recovery was uneventful. Histopathological examination of the specimens taken during surgery revealed the first, anterior cyst to be a dermoid cyst and the second, posterior cyst to be a heterotopic oral gastrointestinal cyst (HGIC). Although this situation is very rare, it should be included in the differential diagnosis of swellings in the submandibular region in the pediatric population. Key words:Dermoid cyst, heterotopic gastrointestinal cyst, children, tongue.

Langerhans Cell Histiocytosis: A Diagnostic Challenge in the Oral Cavity.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder of the reticuloendothelial system with unknown etiology. This report aims to present a case of LCH with diffuse involvement of the oral cavity and to raise awareness of the distinguishing features of this diagnostically challenging entity. CASE REPORT: A 26-year-old male patient presented with complaints of teeth mobility, intense pain, and difficulty in chewing. Intraoral and radiological examinations revealed generalized gingival hyperplasia and severe teeth mobility with widespread alveolar bone loss. Periodontal therapy was performed with no significant improvement. An incisional biopsy revealed Langerhans cells and positive reaction to S-100 and CD1, and the patient was diagnosed with LCH. The patient underwent systemic chemotherapy with vinca alkaloids and corticosteroids. Regression of gingival lesions, as well as significant decrease in mobility of the remaining teeth and severity of pain, was achieved during 12 months of follow-up. CONCLUSION: The rarity and variable system involvement of LCH necessitate a multidisciplinary approach be carried out for accurate diagnosis, effective treatment, and an uneventful follow-up. Awareness of oral manifestations of LCH may aid clinicians greatly in reducing morbidity and mortality associated with this debilitating condition.

Changes in expressions of ADAM9, 10, and 17 as well as α-secretase activity in renal cell carcinoma.

BACKGROUND: ADAM9, 10, and 17 are a class of disintegrins and metallproteinases with α-secretase activity. There are conflicting results regarding the role(s) of ADAM9, 10, and 17 in carcinogenesis, and only a few studies have examined their levels and cellular localization in renal cell carcinoma (RCC). Studies examining changes in α-secretase activity in RCC compared to enzymatic activity of the uninvolved kidney are lacking. METHOD: A cross-sectional study was conducted in 56 patients undergoing radical nephrectomy after the diagnosis of RCC. α-Secretase activity was determined using flourogenic substrate in freshly frozen tumor tissues as well as similarly treated tissues from the neighboring kidney. Immunohistochemical analyses of ADAM9, 10, and 17 were also performed. RESULTS: α-Secretase activity decreased markedly in all types of RCC as compared to neighboring uninvolved kidney tissue having 5 to 10 times higher levels of α-secretase activity. Although type-dependent variations were observed, tumoral expressions of ADAMs, except for ADAM17, were lower in the tumors compared to that of neighboring tissues, but the changes in α-secretase activity were greater. In RCC tissue, ADAM9 expressions were localized in nuclear and cytoplasmic compartments, whereas ADAM10 and 17 were present predominately in the cytoplasm potentially explaining the markedly decreased enzyme activity. Membranous localization of ADAMs was noted in uninvolved kidney tissue. CONCLUSIONS: The loss of α-secretase activity observed here in conjunction with previous findings argue against tumorigenic effects of ADAM9, 10, and 17 supporting that increased nuclear and cytoplasmic expression may be an attempt to compensate for loss of function.

Chronic Invasive Nongranulomatous Fungal Rhinosinusitis in Immunocompetent Individuals.

Chronic invasive nongranulomatous fungal rhinosinusitis is a well-described but uncommon type of fungal rhinosinusitis (FRS). While the prevalence of chronic FRS is 0.11% in healthy individuals, only 1.3% of them are in nongranulomatous invasive nature. The majority of the cases in the literature have been reported from developing countries mostly located in the tropical regions, as typically occurring in the background of diabetes mellitus or corticosteroid treatment. The current paper reports four consecutive cases, who were diagnosed within a short period of six months at a single center of a country located outside the tropical climate zone. None of the patients had a comorbid disease that may cause immune suppression or a history of drug use. The only risk factor that may have a role in development of chronic invasive nongranulomatous FRS was that all of our patients were people working in greenhouse farming. Three cases underwent endoscopic sinus surgery, and one case underwent surgery with both endoscopic and external approaches. Systemic antifungal therapy was initiated in all cases in the postoperative period with voriconazole 200 mg orally twice a day. All patients achieved a complete clinical remission. Chronic invasive nongranulomatous FRS should be kept in mind in the presence of long-standing nonspecific sinonasal symptoms in immunocompetent individuals, particularly with a history of working in greenhouse farming.

Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma.

Calcitonin Gene-related Peptide (CGRP), Vasoactive Intestinal Peptide (VIP) and Substance P (SP) are sensory neuropeptides which may alter cancer growth through modulation of chronic inflammation. We recently reported that SP suppresses breast cancer growth and metastasis through neuroimmune modulation. These neuropeptides are hydrolyzed by Neprilysin (NEP) to bioactive fragments. Decreased activity of NEP was reported in clear cell and chromophobe type renal cell carcinoma (RCC). It is however not known how the levels of neuropeptides hydrolyzed with NEP changes in RCC. Decrease activity of SP and CGRP containing sensory nerve endings was previously reported to increase cancer metastasis in animal models. It is however not known how peptidergic nerve endings are altered in RCC. Hence we here evaluated the levels of neuronal and non-neuronal neuropeptides and NEP activity in RCC including papillary type as well as neighboring uninvolved kidney. A cross-sectional study was conducted in 57 patients undergoing radical nephrectomy and diagnosed with RCC. NEP activity, levels and expression were determined using flourogenic substrate, western blot and qPCR respectively in freshly-frozen tissues. Immunohistochemical analyses were also performed. Neuronal and non-neuronal levels of CGRP, SP and VIP levels were determined using two-step acetic acid extraction. Levels and activity of NEP were markedly decreased in RCC regardless of subtype. Similar levels of VIP were detected in first and second extractions. VIP levels were higher in clear cell and papillary RCC compared to nearby kidney tissue. VIP levels of neighboring kidney tissue of papillary type RCC was significantly lower compared to kidney samples from clear cell RCC. CGRP levels were higher in second extraction. Similar to VIP levels, CGRP levels of neighboring kidney tissue from clear cell and chromophobe type RCC was significantly lower compared to corresponding tumor samples, an effect observed in the second extraction. VIP and CGRP levels of nearby kidney tissue varied subtype dependently demonstrating that different subtypes of RCC alter their local environment differently. Furthermore NEP-induce hydrolysis of VIP creates selective VPAC-1 receptor agonist which has anti-proliferative and anti-inflammatory effects. Hence loss of NEP activity may prevent anti-tumoral effects of VIP on RCC.

Perinatal Diagnostic Approach to Fetal Skeletal Dysplasias: Six Years Experience of a Tertiary Center.

Skeletal dysplasias (SDs) constitute a group of heterogeneous disorders affecting growth morphology of the chondro-osseous tissues. Prenatal diagnosis of SD is a considerable clinical challenge due to phenotypic variability. We performed a retrospective analysis of the fetal autopsies series conducted between January 2006 and December 2012 at our center. SD was detected in 54 (10%) out of 542 fetal autopsy cases which included; 11.1% thanatophoric dysplasia (n = 6), 7.4% achondroplasia (n = 4), 3.7% osteogenesis imperfect (n = 2), 1.9% Jarcho-Levin Syndrome (n = 1), 1.9% arthrogryposis (n = 1), 1.9% Dyggve-Melchior-Clausen syndrome (n = 1), 72.1% of dysostosis cases (n = 39). All SD cases were diagnosed by ultrasonography. In 20 of the cases, amniocentesis was performed, 4 cases underwent molecular genetic analyses. Antenatal identification of dysplasia is important in the management of pregnancy and in genetic counseling. Our data analysis showed that SD is usually detected clinically after the 20th gestational week. Genetic analyses for SD may provide early diagnosis and management.

Rare congenital pulmonary malformation with diagnostic challenging: congenital pulmonary lymphangiectasia, report of four autopsy cases and review of literature.

Congenital pulmonary lymphangiectasia (CPL) is a rare congenital disorder that typically presents with intractable respiratory failure in the first few days of life. There is an association non-immun hydrops and CPL. In this study we reviewed four CPL cases between January 2006 and January 2014 among 684 fetal-pediatric autopsies. All cases were in the second trimester. In light microscopy there were marked dilatated channels in the subpleural -peribronchial-subseptal region of the lungs. The channels were lined with flattened cells which were expressing CD 31 and D2-40, negative for CD34. Although pulmonary interstitial emphysema (PIE) was considered an important differential diagnosis, a giant cell reaction surrounding the interstitial cystic lesions, a histological hallmark of PIE. CPL is characterized by dilatation of the pulmonary lymphatic vessels and occurs as a congenital anomaly. Noonan classified it into three groups. Primary developmental defect of pulmonary lymphatics is group 3. Group 3 is called also as CPL; normal regression of the connective tissue elements fails to occur after the 16th week of fetal life, associated with an aggressive clinical course, poor prognosis. In fetal autopsy examination CPL should be recognized if there is a fetus with pleural effusion, non-immune hydrops. There is no clinical evidence for CPL.

Effects of high-dose intravenous immunoglobulin on lipopolysaccharide-induced acute lung injury.

PURPOSE: Intravenous immunoglobulin (IVIG) therapy is used in inflammatory diseases but the use of immunoglobulin as a treatment for acute lung injury (ALI) has not been previously studied. Transforming growth factor beta (TGF-ß) plays a critical role in the pathogenesis of of ALI. Therefore we examined the levels of TGF-ß and lung inflammation scores in IVIG treated ALI models. METHODS: Intratracheal lipopolysacccharide was given to rats. Groups 1 and 3 received saline, whereas group 2 received IVIG. 24h later saline was given to groups 1 and 2 and IVIG to group 3. Blood samples and bronchoalveolar lavage (BAL) fluids were obtained from each group and sacrificed for pathological evaluation. RESULTS: BAL TGF-ß levels of groups 2 and 3 on day 30, were lower compared to their levels of day 2 (p=0.01, p=0.01). BAL TGF-ß levels of groups 2 and 3 were lower than the levels of group 1 on day 30 (p=0.002, p=0.001). Pathological examination revealed that the inflammation scores of groups 2 and 3 on day 30, were lower than the scores of day 2 (p=0.02, p=0.01). Inflammation scores of group 2 were lower than group 1 on day 30 (p=0.02). Moderate fibrosis was seen in half of the rats from group 1 and one rat from group 2. CONCLUSION: High-dose IVIG decreased lung inflammation scores and BAL TGF-ß1 levels and this therapy would give even better results if it is given earlier.

Differential expression and activation of epidermal growth factor receptor 1 (EGFR1), ERK, AKT, STAT3, and TWIST1 in nonsmall cell lung cancer (NSCLC).

Lung cancer is the leading cause of death of both men and women across the world. Overexpression and activating mutations of the epidermal growth factor receptor-1 (EGFR1) are frequently observed and associated with poor prognosis. To inhibit the function of EGFR1, multiple antibodies and small-molecule tyrosine kinase inhibitors (TKI) that target EGFR1 have been developed. Even though some patients respond to these TKI, subsequent studies reveal that this is not the case for all nonsmall cell lung cancer (NSCLC) patients. In this study, we determine whether activation and expression levels of EGFR1, ERK, AKT, STAT3, and TWIST1 are dependent on the activating mutations of EGFR1. Protein lysates and DNA have been isolated from tumor and corresponding normal tissues of 16 NSCLC patients. Genomic-DNA is used to sequence the exons 18, 19, and 21 of EGFR1, and exon 2 of k-RAS. Protein lysates were used to determine the expression or phosphorylation levels of EGFR, STAT3, ERK, AKT, and TWIST1. Our results revealed that 16 tumor samples of NSCLC patients showed no mutation in any of the indicated exons of EGFR1 and k-RAS albeit significant levels of activation or expression of the above-mentined oncogenes. In NSCLC patients, the tumor micro-environment can be as important as the activating mutations of EGFR1. TK therapy may also be considered for patients who show high levels of activation of EGFR1 even in the absence of activating mutations.

Clinical and pathologic prognostic factors that are influential in the survival and prognosis of lung adenocarcinomas and invasive predominant subtypes.

Therapeutic approaches to lung adenocarcinomas differ because of their heterogeneous morphologies, prognoses, and clinical features. For this reason, new histopathologic classifications for lung adenocarcinomas were done by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society to form subtypes with homogeneous prognoses. There are limited clinical data in the literature on the prognosis of the subgroups formed according to the new classification. A total of 86 patients with adenocarcinoma who had undergone pathologic stages I and II curative resection and mediastinal lymph node dissection were retrospectively analyzed according to the seventh TNM staging system revised by the Union for International Cancer Control/American Joint Committee on Cancer. Histologic subtyping was reassessed according to the dominant histopathologic morphology. When survival rates of lung adenocarcinomas were compared according to their localizations, it was observed that adenocarcinomas localized to the right hemithorax had a longer survival than the ones with left hemithorax localization (P = 0.026). When necrosis was taken into account, it was seen that necrosis rate was higher in solid predominant type compared with other types, whereas it was lower in acinary type (P = 0.046). When peritumoral lymphovascular invasion data were assessed, it was observed that disease-free survival was influenced in a negative fashion (P = 0.018). New histopathologic classification of adenocarcinomas has been a step forward to attaining homogeneous groups, but when the biologic heterogeneity of the adenocarcinomas is taken into account, the authors believe that considering the peritumoral lymphatic vascular invasion, left hemithorax localization, and tumoral necrosis entities in the upcoming TNM classification will contribute to evaluating the prognosis.