Low-grade intraductal carcinoma of the salivary gland with prominent oncocytic change: a newly described variant.

AIMS: Low-grade intraductal carcinoma (LG-IDC) is a clinically indolent malignant tumour of the salivary glands. Because of its rarity, the histological variants of LG-IDC have not been well characterised. Herein, we describe five LG-IDC cases with prominent oncocytic change in the major salivary glands. METHODS AND RESULTS: We examined five cases, three males and two females (mean age = 63 years), of LG-IDC with oncocytic change. The sites affected by LG-IDC were the parotid and submandibular glands. The lesions were macroscopically unilocular or multilocular cysts with a solid tumour arising from the cyst wall. Smaller tumour cell nests were also observed. As with classic LG-IDC, the cyst wall was surrounded by myoepithelial cells with no invasive component. The tumour cells had abundant oncocytic cytoplasm and proliferated in a low-papillary, tubular or cribriform pattern. Immunohistochemically, the tumour cells were diffusely positive for pan-cytokeratin, S100, mammaglobin and antimitochondria antibody, and were negative for androgen receptor and gross cystic disease fluid protein-15. Unlike classic LG-IDC, some of these cases demonstrated focal invagination of myoepithelial cells in the intraductal tumour. CONCLUSION: Oncocytic LG-IDC should be recognised as a histologically unique variant of LG-IDC. Awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment for histological mimics.

Comparative analysis of cytokine release from epithelial cell cultures of the upper airway.

INTRODUCTION: Upper airway epithelial cells show a multi-potential ability to produce a variety of cytokines/chemokines in the steady-state and under external stimuli. OBJECTIVE: To compare various cytokines/chemokines released from primary cultures of human nasal epithelial cells (HNECs) derived from healthy controls and subjects with allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNPs) in non- stimulated and IL-17A-stimulated conditions. METHODS: The supernatants derived from HNECs of healthy control, AR, CRSwNPs were used to measure 20 of cytokines/chemo- kines in the non-stimulated and IL-17A-stimulated conditions. RESULTS: AR and CRSwNPs showed significant up-regulation in the release of IL-6, IL-33, and thymic stromal lymphopoietin (TSLP), and the release of IL-6, TSLP, granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor α (TNFα) in comparison with normal controls, respectively. Secretion of GM-CSF and TNFα were enhanced in patients with nasal polyps as compared with AR. Stimulation with IL-17A enhanced the secretion of IL-8 and granulocyte-colony stimulating factor (G-CSF) in the normal control, IL-6 and IL-8 in AR, and IL-6, TSLP, G-CSF, GM-CSF and TNFα in nasal polyps. CONCLUSION: Epithelial cells derived from AR and CRSwNPs showed up-regulation of secretion of several cytokines/chemokines both in the steady state and after IL-17A stimulation, which may contribute to the inflammatory responses of AR and CRSwNPs.

Bacteriologic evaluation of sinus aspirates taken by balloon catheter devices in chronic rhinosinusitis: preliminary study.

PURPOSE: Chronic rhinosinusitis (CRS) is known to be a polymicrobial infection involving both aerobes and Gram-positive and Gram-negative anaerobes. Accurate bacterial evaluation by adequate culture methods can justify subsequent antimicrobial strategies. METHODS: Two specimens were obtained from each of 10 patients undergoing catheter-based Balloon Sinuplasty™, one from the middle meatus (endoscopic approach) and the other from the sinus (catheter-based approach). RESULTS: The bacterial culture from the middle meatus was positive in 9 of 10 patients, including 6 different aerobes without anaerobes. The bacterial culture of aspirates from the sinuses were positive in 8 out of 10 patients, with 4 different aerobic bacteria and 4 different anaerobic bacteria. Anaerobes were isolated in 0% of middle meatus samples, which was significantly lower than the 62.5% (5/8) detected in the sinus samples. CONCLUSIONS: Bacterial culture of sinus aspirates using a catheter-based technique improves the recovery of bacterial pathogens from CRS patients.

Postoperative Management of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps: Impact of High-Dose Corticosteroid Nasal Spray.

Introduction Eosinophilic chronic rhinosinusitis (ECRS) is characterized by an eosinophilic inflammation driven by Th2-type cytokines. Glucocorticosteroids are the most common first-line treatment for ECRS with nasal polyps. Objective We have evaluated the long-term treatment with double-dose intranasal corticosteroids in refractory ECRS nasal polyps resistant to the conventional dose and assessed the risk of adverse systemic effects Methods Sixteen subjects were enrolled in this study. All subjects had ECRS after endoscopic sinus surgery that resulted in recurrent mild and moderate nasal polyps and were undergoing a postoperative follow-up application of mometasone furoate at a dose of 2 sprays (100 µg) in each nostril once a day (200 µg). All the patients were prescribed mometasone furoate, administered at a dose of 2 sprays (100 µg) in each nostril twice a day (400 µg) for 6 months. Results The average scores of the symptoms during the regular dose of intranasal steroid treatment were 5.2 ± 2.2, but 6 months after the high-dose application, they had significantly decreased to 2.5 ± 1.4 ( p < 0.05). The polyp size showed an average score of 1.38 during the regular dose which was significantly reduced to 0.43 ( p < 0.01) by the double dose. Glycated hemoglobin (HbA1c) showed normal ranges in all the patients tested. The cortisol plasma concentration was also normal. Conclusion Doubling the dose of the nasal topical spray mometasone furoate might be recommended for the treatment of recurrent nasal polyps in the postoperative follow-up of intractable ECRS.

Endoscopic endonasal management of recurrent maxillary mucoceles using biliary T-tube stenting.

Mucoceles of the paranasal sinus can be managed endoscopically with an extremely low recurrence rate. Frontal sinus mucoceles can sometimes be prevented from closing and reforming by stenting, which to the best of our knowledge has not yet been reported in the maxillary sinus. We describe the cases of 5 patients-3 men and 2 women, aged 47 to 75 years (mean: 59.6)-with a recurrent and intractable maxillary sinus mucocele that was managed with biliary T-tube stenting. The indications for stenting included recurrent episodes of mucocele with or without a lateral location with a relatively thick bony wall. A latex rubber pediatric biliary T-tube was endoscopically inserted through a window opening into the marsupialized mucocele. The stent was removed 6 to 14 months postoperatively in 4 cases; in the other case, the stent remained adequately positioned for 35 months. None of the patients experienced signs or symptoms of recurrence. We conclude that a T-tube stent can be used successfully to maintain long-term patency in patients with a recurrent and intractable maxillary mucocele, with patency being maintained even after removal of the stent.

Fungal extracts detected in eosinophilic chronic rhinosinusitis induced cytokines from the nasal polyp cells.

OBJECTIVES/HYPOTHESIS: The role of fungi in chronic rhinosinusitis (CRS) is still controversial. The present study was conducted to detect and identify fungal species from the nasal polyp tissues of eosinophilic and noneosinophilic CRS, and to determine the role of fungal antigens in cytokine production. STUDY DESIGN: Prospective study. METHODS: Thirty-five specimens of nasal polyps were collected from patients with CRS and examined for fungus using culture, histology, and polymerase chain reaction analysis. The secretion of 14 cytokines stimulated by fungal extracts using dispersed nasal polyp cells (DNPCs) was determined by multiplex immunoassay. RESULTS: There was no microbiological growth (including fungus) in the cultures of homogenized nasal polyps. Furthermore, Grocott methanamine silver staining for all nasal polyps showed no fungal bodies. Sixteen of 35 samples of the nasal polyps showed amplification of fungal DNA. In none of the mucosa of the sphenoid sinus was fungal DNA detected. The number of eosinophils in the nasal polyps in which fungal DNA was detected was significantly higher than in the nasal polyps in which fungal DNA was not detected (P < .01). The extract of fungus enhanced the secretion of eosinophil-associated cytokines such as interleukine (IL)-5, IL-13, IL-17A, and RANTES (regulated on activation normal T-cell expressed and secreted), and proinflammatory cytokines such as IL-6, IL-8, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor from DNPCs. CONCLUSIONS: The present study offers direct evidence supporting that fungal elements modify the inflammatory response in the nasal polyps of eosinophilic CRS.

Postoperative Management of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps: Impact of High-Dose Corticosteroid Nasal Spray

Abstract Introduction Eosinophilic chronic rhinosinusitis (ECRS) is characterized by an eosinophilic inflammation driven by Th2-type cytokines. Glucocorticosteroids are the most common first-line treatment for ECRS with nasal polyps. Objective We have evaluated the long-term treatment with double-dose intranasal corticosteroids in refractory ECRS nasal polyps resistant to the conventional dose and assessed the risk of adverse systemic effects Methods Sixteen subjects were enrolled in this study. All subjects had ECRS after endoscopic sinus surgery that resulted in recurrentmild andmoderate nasal polyps and were undergoing a postoperative follow-up application of mometasone furoate at a dose of 2 sprays (100 μg) in each nostril once a day (200 μg). All the patients were prescribed mometasone furoate, administered at a dose of 2 sprays (100 μg) in each nostril twice a day (400 μg) for 6 months. Results The average scores of the symptoms during the regular dose of intranasal steroid treatment were 5.2 ± 2.2, but 6 months after the high-dose application, they had significantly decreased to 2.5 ± 1.4 (p < 0.05). The polyp size showed an average score of 1.38 during the regular dose which was significantly reduced to 0.43 (p < 0.01) by the double dose. Glycated hemoglobin (HbA1c) showed normal ranges in all the patients tested. The cortisol plasma concentration was also normal. Conclusion Doubling the dose of the nasal topical spray mometasone furoate might be recommended for the treatment of recurrent nasal polyps in the postoperative follow-up of intractable ECRS. (AU)

Subclassification of chronic rhinosinusitis with nasal polyp based on eosinophil and neutrophil.

OBJECTIVES/HYPOTHESIS: Japanese patients with chronic rhinosinusitis with nasal polyps (CRSwNP), differing from European and U.S. patients, are suggested to show two distinct phenotypes: Th2-polarized and Th1-shifted immunity. The purpose of this study was to conduct clinical subgrouping of CRSwNP based on inflammatory cell infiltration, which was evaluated and supported by clinical backgrounds and immunological characteristics. STUDY DESIGN: A cross-sectional study. METHODS: One hundred thirty Japanese patients with CRSwNP were classified by the infiltration of eosinophils and neutrophils in nasal polyps. Immunohistochemical analysis was performed in 42 patients. RESULTS: The patients were classified into three groups: 1) 42 patients with eosinophilic type, 2) 27 patients with neutrophilic type, and 3) 61 patients with noneosinophilic nonneutrophilic type. Both the number of serum eosinophils and the recurrence rates were significantly higher in the eosinophilic group compared to the other two groups. The IgE value was significantly higher in the eosinophilic group, followed by the noneosinophilic nonneutrophilic and neutrophilic groups. Both the symptomatic and CT scores were significantly greater in the eosinophilic group than in the neutrophilic group. The expressions of eotaxin, IL-17A, MUC5AC, and CD68 were greater in the eosinophilic group than in the other two groups. CONCLUSION: The eosinophilic CRSwNP phenotype is clinically characterized by serum eosinophilia, atopy, extensive disease, and poor prognosis compared to the neutrophilic and the noneosinophilic nonneutrophilic groups. We clearly demonstrated that all three subgroups of CRSwNP had characteristic differences in those inflammatory markers, which allows for pathophysiologically meaningful differentiations with likely therapeutic consequences.

Relationships between IL-17A and macrophages or MUC5AC in eosinophilic chronic rhinosinusitis and proposed pathological significance.

Recently, some researchers have reported that macrophages and neutrophils were related to severe asthma. Mucus hypersecretion and persistent airway inflammation result from increased expression of mucin gene (MUC5AC). Eosinophilic chronic rhinosinusitis (ECRS) is considered as intractable rhinosinusitis. From the viewpoint of "one way one disease," we examined whether ECRS is associated with infiltrating macrophages, neutrophils, their promotive factors, and MUC5AC. We examined 21 nasal polyps with CRS. Each specimen was fixed in 10% phosphate-buffered formalin, embedded in paraffin, processed routinely, and then prepared as semithin sections (3.5 µm). We immunohistochemically observed the macrophages by using CD68, neutrophils by using neutrophil elastase and the promotive factors, monocyte chemotactic protein (MCP) 1, IL-17A, and IL-8, in both ECRS and non-ECRS. The number of macrophages (CD68(+) cells), IL-17A, and MUC5AC(+) cells in ECRS were significantly greater than in non-ECRS. The mean number of MCP-1(+) cells in ECRS was greater than that in non-ECRS, but not significantly. There was a significant correlation in all cases between IL-17A and macrophages or MUC5AC(+) cells. Neither the numbers of neutrophils (positive cells for neutrophil elastase) nor the IL-8(+) cells showed any significant differences between ECRS and non-ECRS. Our study suggested that infiltrating macrophages, IL-17A and MUC5AC, as well as eosinophils could have roles in the development of ECRS.

A case of retropharyngeal abscess with spondylitis causing tetraplegia.

We report a case of retropharyngeal abscess with spondylitis causing tetraplegia. At a previous hospital, administration of antibiotics improved the inflammation findings. However, magnetic resonace imaging showed a remaining retropharyngeal abscess. This patient showed a disturbance of consciousness under this therapy. Therefore, he was admitted to our hospital and underwent a drainage operation. At 1 day after this operation, he recovered from the disturbance of consciousness.

Heme oxygenase-1 expression in chronic rhinosinusitis with eosinophilic infiltration.

OBJECTIVES: Chronic rhinosinusitis (CRS) with eosinophilic infiltration is a type of intractable rhinosinusitis often associated with asthma. The oxidants are well known to induce aggravate asthma. Heme oxygenase-1 (HO-1), a cytoprotective enzyme against oxidant, has been extensively studied in airway diseases. However, no study that observed HO-1 in both epithelial and subepithelial tissues of CRS has been reported. METHODS: Part of each specimen derived from the nasal polyps of CRS with and without eosinophilic infiltration was promptly fixed for hematoxylin-eosin staining and immunohistochemical analysis for HO-1 and macrophages. RESULTS: We found that the expression of HO-1 in the epithelial layers of CRS without eosinophilic infiltration was significantly enhanced as compared with that of CRS with eosinophilic infiltration. On the other hand, the number of macrophages with HO-1 positive reactions was significantly greater in CRS with eosinophilic infiltration compared with CRS without eosinophilic infiltration. CONCLUSIONS: Our study suggests that both a reduction of HO-1 expression in epithelial cells and an increase of infiltration of macrophages positive for HO-1 are related to the epithelial damage of CRS with eosinophilic infiltration.

Comparison of bacterial examinations between eosinophilic and neutrophilic chronic rhinosinusitis with nasal polyps.

CONCLUSION: We found no significant differences in the bacterial features of the maxillary sinuses between eosinophilic and neutrophilic chronic rhinosinusitis (CRS) with nasal polyps. OBJECTIVES: Since neutrophilic CRS is often influenced by a predisposition to bacterial infection, and eosinophilic CRS is likely to be developed by allergic antigens, differences in the microbiology between the two pathologies of CRS can be expected. The present study was designed to investigate the bacterial findings from the maxillary sinus in eosinophilic and neutrophilic CRS. METHODS: Seventy patients with CRS with nasal polyps were divided into eosinophilic and neutrophilic types based on histopathological observations of the nasal polyps. The specimens for bacterial culture were obtained from the maxillary sinus during endoscopic sinus surgery. RESULTS: In all, 29 and 41 patients were classified as having eosinophilic and neutrophilic CRS with nasal polyps, respectively. The isolation rate of bacteria showed no significant difference between eosinophilic (90%) and neutrophilic CRS (98%). Aerobic bacteria were found in 25 patients (86%) with eosinophilic CRS, which was not significantly different from that in neutrophilic CRS (40 patients, 98%). The isolation rate for aerobic and anaerobic bacteria showed no significant differences.

Maxillary sinus infundibulum narrowing influences sinus abnormalities in spite of the presence or absence of allergy.

CONCLUSION: Maxillary sinus abnormalities were demonstrated to be associated with maxillary sinus infundibulum narrowing as well as nasal airflow resistance secondary to nonspecific nasal inflammation. OBJECTIVES: There is no consensus regarding the pathogenetic roles of allergy and anatomic variations in sinus mucosa abnormalities. We investigated the correlation between allergy and anatomic variations in sinus abnormalities in chronic rhinitis patients in the presence or absence of allergy. METHODS: In all, 148 adult patients with allergic rhinitis (AR) and non-allergic rhinitis (NAR) were enrolled. Opacification of sinuses, the size of the maxillary sinus infundibulum, Haller cells, and concha bullosa were evaluated based on computed tomography (CT) images. Simultaneously, nasal airflow resistance was measured. RESULTS: The AR group comprising 105 patients showed maxillary sinus opacification in 45 patients. In the NAR group including 43 patients, soft tissue opacification was observed in 13 patients. There was no significant difference in the incidence of sinus opacification between the AR and NAR groups. Both nasal resistance and the infundibulum size in both the AR and NAR groups with sinus opacification showed significant differences from those without sinus abnormalities. The presence of concha bullosa influenced the sinus opacification in both the AR and NAR groups.