Clinical Implications of Incidental Sinonasal Positive FDG Uptake on PET-CT.

OBJECTIVES: Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) has been increasingly used in the past decade. Incidental FDG-avid findings are encountered in these studies, several of which with clinical significance. However, the significance of incidental FDG-avid sinonasal findings has not been studied to date. STUDY DESIGN: Retrospective cohort study. SETTING: A single tertiary medical center. MATERIALS AND METHODS: The medical records were reviewed of patients with incidental sinonasal positive FDG uptake between 2007 and 2016 who referred for further otolaryngological diagnostic workup. RESULTS: A total of 26 patients were identified, all of whom underwent a diagnostic surgical procedure. Histopathology revealed chronic inflammation (n = 12, 46.1%), malignancy (n = 7, 26.9%), inverted papilloma (n = 4, 15.5%), and fungal infections (n = 3, 11.5%). A unilateral maxillary sinus with FDG uptake was documented for 16 (61.5%) patients. CT evidence of bilateral disease and mucosal or sinus wall thickening correlated with inflammatory disease. CONCLUSIONS: Incidental lesions with positive FDG uptake in the sinonasal cavities are at a high risk (40%) of being neoplastic. A diagnostic biopsy is advocated in these cases.

Síndrome de la apnea-hipoapnea obstructiva del sueño en el niño: más allá de la hipertrofia adenoamigdalar / Obstructive sleep apnea-hypopnea syndrome in children: Beyond adenotonsillar hypertrophy

La prevalencia del síndrome de la apnea-hipoapnea obstructiva del sueño en la población infantil general es del 1-2% y su causa más frecuente es la hipertrofia adenoamigdalar. Las prevalencias en las otras causas de este síndrome, más allá de la hipertrofia adenoamigdalar, son elevadas. En muchas de estas enfermedades los motivos por los que se genera el síndrome de la apnea-hipoapnea obstructiva del sueño son multifactoriales (hipotonía muscular, alteraciones dentofaciales, hipertrofia de tejidos blandos de la vía aérea, alteraciones neurológicas). Es fundamental la colaboración entre las diferentes especialidades implicadas, dada la gran variabilidad de enfermedades, la frecuente participación de diferentes factores en su génesis y los diferentes tratamientos que deben aplicarse. Se ha procedido a una amplia revisión bibliográfica de estas otras causas de síndrome de la apnea-hipoapnea obstructiva del sueño infantil, que van más allá de la hipertrofia adenoamigdalar. Se han intentado ordenar de una forma coherente, a criterio del autor, revisando los aspectos más destacados con relación a la prevalencia de síndrome de la apnea-hipoapnea obstructiva del sueño en cada una de ellas, los motivos por los que provocan este síndrome, sus interacciones y manejo (AU)

The prevalence of obstructive sleep apnea-hypopnea syndrome in the general childhood population is 1-2% and the most common cause is adenotonsillar hypertrophy. However, beyond adenotonsillar hypertrophy, there are other highly prevalent causes of this syndrome in children. The causes are often multifactorial and include muscular hypotonia, dentofacial abnormalities, soft tissue hypertrophy of the airway, and neurological disorders). Collaboration between different specialties involved in the care of these children is essential, given the wide variability of conditions and how frequently different factors are involved in their genesis, as well as the different treatments to be applied. We carried out a wide literature review of other causes of obstructive sleep apnea-hypopnea syndrome in children, beyond adenotonsillar hypertrophy. We organised the prevalence of this syndrome in each pathology and the reasons that cause it, as well as their interactions and management, in a consistent manner (AU)

Does integration of various ion channel measurements improve diagnostic performance in cystic fibrosis?

RATIONALE: The diagnosis of cystic fibrosis (CF) may remain inconclusive despite comprehensive evaluation. OBJECTIVES: Determine whether combined ion channel measurements (C-ICMs) obtained from different end-organ epithelia can help diagnose CF. METHODS: Prospective enrollment of (1) a training sample of 156 non-CF subjects and 107 patients with CF, and (2) a validation cohort of 202 patients with single-organ CF-like phenotypes. All subjects had genotyping, sweat test, and nasal potential difference (NPD). Principal components analysis was applied to derive various candidate C-ICMs by combining sweat chloride plus every one or two combination(s) of four NPD parameters (maximal potential difference [MaxPD], change in potential difference in response to perfusion with amiloride [ΔAmil], change after chloride-free and isoproterenol perfusion [ΔCl-free+Iso], and total change in potential difference [ΔAmil+Cl-free+Iso]). MEASUREMENTS AND MAIN RESULTS: The best of the 10 candidate C-ICMs, which combined sweat chloride and two NPD parameters (ΔCl-free+Iso and ΔAmil+Cl-free+Iso), diagnosed CF in the training sample with 100% sensitivity and specificity (CF cutoff > 0). In the validation cohort, C-ICM was normal in all subjects with normal sweat test and normal/borderline NPD, with the exception of one subject. C-ICM was abnormal in all subjects when the sweat test was abnormal and the NPD was abnormal/borderline, and when the sweat test was borderline and the NPD was abnormal. C-ICM was abnormal in 75 and 85.7% of subjects with normal sweat chloride plus abnormal NPD, and those with abnormal sweat test plus normal NPD, respectively. In borderline sweat test cases, 23.5, 90, and 100% of subjects had abnormal C-ICM with normal, borderline, and abnormal NPD, respectively. CONCLUSIONS: The concept of combining different measures of cystic fibrosis transmembrane conductance regulator function into a single composite score is feasible. The C-ICM may be useful for diagnostic determination of patients with questionable CF.

Inflammatory myofibroblastic tumor of the nose and paranasal sinuses masquerading as a malignancy.

Inflammatory myofibroblastic tumor (IMT) of the nose and paranasal sinuses is a rare entity that exhibits a diverse histologic pattern that can mimic malignant tumors clinically and radiologically. We present a case of IMT in an 88-year-old man who presented with an aggressive tumor-like lesion in the nose and paranasal sinuses that had a malignant appearance on radiology. We discuss this tumor's clinicoradiologic resemblance to a malignancy, and we review the treatment options following careful histologic and immunohistochemical analysis.

Nasal nitric oxide and sinonasal disease: a systematic review of published evidence.

OBJECTIVE: To critically and systematically review the data available on the sinonasal application of nasal nitric oxide measurement, particularly its use as a diagnostic, prognostic, or treatment effect indicator. DATA SOURCES: EMBASE 1980 to February 10, 2010; Medline 1950 to February 10, 2010; Cochrane Collaboration database; NHS Evidence Health Information Resources database. Review Methods. The databases were searched using a search strategy designed to include manuscripts relevant both to nitric oxide measurement and sinus or nasal problems. A title search was carried out on these manuscripts to select those relevant to clinical or basic science aspects of nitric oxide measurement. A subsequent abstract search selected those manuscripts concerning the application of nitric oxide measurement to sinonasal problems. The manuscripts selected were subject to a full-text review to extract data sets of nasal nitric oxide readings for different patient groups. RESULTS: Initially, 1088 manuscripts were selected. A title search found 335 manuscripts of basic scientific or clinical interest. An abstract search found 35 manuscripts directly relating to nitric oxide measurement in sinonasal disease. Full-text analysis produced 20 studies with extractable data on nasal nitric oxide levels in clearly defined patient groups. Studies did not show sufficient homogeneity to enable substantial meta-analysis of aggregated data. CONCLUSION: Current evidence shows that nasal nitric oxide is not a clinically useful measure for sinonasal disease. Although there is some evidence that sinus surgery is associated with lowered nasal nitric oxide levels, there is no evidence that this is associated with deterioration in sinus health.

Extensive juvenile xanthogranuloma involving the orbit, sinuses, brain, and subtemporal fossa in a newborn.

A 6-week-old-boy presented with a 3-week history of right axial proptosis. Vision, motility, anterior segment, and fundus examinations were normal in both eyes. Imaging revealed a multicystic right orbital lesion with extensive involvement of the infratemporal fossa and paranasal sinuses with intracranial extension. Systemic workup was negative, and he showed no functional deficits. Histopathology revealed a tumor rich in histiocytes, and immunohistochemistry indicated a juvenile xanthogranuloma. He did well with observation, and the tumor partially involuted after 18 months of follow-up.

Decreased production of human leukocyte antigen G molecules in sinonasal polyposis.

BACKGROUND: Sinonasal polyposis (SNP) is a chronic inflammatory pathology of nasal and paranasal cavities. Human leukocyte antigen (HLA) G molecules are nonclassic class I antigens with anti-inflammatory and tolerogenic properties. As most theories consider polyps to be the manifestation of chronic inflammation, there could be a possible implication of HLA-G molecules in SNP. The purpose of this study was to investigate the possible correlation between SNP and the production of soluble HLA-G (sHLA-G) by peripheral blood mononuclear cells (PBMCs). METHODS: The study involved 22 SNP patients (11 with no evidence of disease [NED] after surgery and 11 with relapse [RE]) and 20 healthy subjects. The presence of sHLA-G in PBMC lipopolysaccharide (LPS)-stimulated culture supernatants was analyzed. The levels of interleukin (IL) 10, one of the main up-regulators of sHLA-G production, were determined. Exogenous IL-10 was added to the SNP PBMC cultures to reconstitute the impairment in sHLA-G production. RESULTS: Increased IL-10 levels in LPS-activated PBMC culture supernatants were found in NED patients in comparison with healthy subjects (p = 0.0184). No sHLA-G production was observed in either of the patient subgroup supernatants (p < 0.0001). The addition of exogenous IL-10 showed the reconstitution of sHLA-G production in NED and in a lower amount in RE patients. CONCLUSION: The results show a defect in sHLA-G production in SNP patients mainly related to the IL-10/HLA-G pathway. Given the anti-inflammatory functions of HLA-G molecules, this impairment could increase the susceptibility to the disease. The different sHLA-G production after exogenous IL-10 addition between NED and RE SNP could represent a marker of disease severity.

Presence of cholesterol granuloma in the maxillary and ethmoid sinuses.

INTRODUCTION: Although cholesterol granuloma associated with chronic middle ear disease is shown to be common in the mastoid antrum and air cells of the temporal bone (Leon et al., Arch Pathol Lab Med 126:217-219, 2002), its presence in the maxillary and ethmoid sinuses is rarely encountered. There are few cases reported regarding the incidence of cholesterol granuloma in these sinuses (Ko et al., Am J Otoryngol 27:370-372, 2006). CASE: Here, we report a case of concomitant cholesterol granuloma in the maxillary and ethmoid sinuses of a 33-year-old man who underwent surgical excision. DISCUSSION: Histopathological examination of the removed specimen revealed fragments of respiratory mucosa with cholesterol clefts surrounded by multinucleated foreign-body giant cells.

[Unusual nasal clinical entities]. / Entidades clínicas nasales inusuales.

Three cases of rare entities in nasal pathology are reported. Two of them are high-grade lymphomas (T/NK type), with nasal blockage as the first symptom. Clinical course and treatment response are described. The third case refers to an infrequent benign nasal entity called angiocentric eosinophilic fibrosis. Its aetiology and management remains rather uncertain nowadays.

Expression of IL-12 and T helper cell 1 cytokines in the fluid of paranasal sinus mucoceles.

OBJECTIVE: The objective of this study was to assess the expression of regulatory cytokines and T helper cell (Th)1/Th2 cytokines in paranasal sinus mucoceles. MATERIALS AND METHODS: Fluid samples of 12 paranasal sinus mucoceles were assessed by enzyme-linked immunosorbent assay for concentrations of regulatory cytokines (interleukin [IL]-10 and IL-12), Th1 cytokines (IL-2 and interferon gamma), and Th2 cytokines (IL-4 and IL-5). RESULTS: IL-12 was detected in all samples, whereas IL-10 was detected in only one case. The concentration of IL-12 tended to correlate with that of interferon gamma and was significantly and positively correlated with that of IL-2. CONCLUSIONS: Th1 cytokines and the Th1 regulatory cytokine IL-12, but not IL-10, potentially play a key role in the pathogenesis of paranasal sinus mucoceles. Together with our recent report showing that lipopolysaccharide is highly detected in mucocele fluid, the data from this study suggest that the Th1 response induced by lipopolysaccharide may affect the immunological inflammation in the epithelium of paranasal sinus mucoceles.

MR spectroscopy in sinus mucocele: N-acetyl mimics of brain N-acetylaspartate.

We describe MR spectroscopy in 2 patients with frontal sinus mucoceles that showed a dominant metabolite peak at 2.0-ppm chemical shift, simulating N-acetylaspartate (NAA) of normal neuronal tissue. In vitro analysis of postsurgical mucocele samples confirmed that the signal at 2.0 ppm was arising from the methyl moiety of an N-acetyl compound. This is probably caused by N-acetylgalactosamine or N-acetylglucosamine, which are glycoproteins found in normal respiratory mucus produced by the paranasal sinus epithelium.

Voriconazole brain tissue levels in rhinocerebral aspergillosis in a successfully treated young woman.

Invasive aspergillosis of the central nervous system has a mortality rate exceeding 90%. We describe a 29-year-old woman with a medical history of chronic polyarthritis who developed a proven rhinocerebral Aspergillus fumigatus infection refractory to first-line treatment with liposomal amphotericin B. The patient responded successfully to salvage combination treatment with voriconazole and caspofungin. Furthermore, for the first time, voriconazole levels in an intracerebral abscess were measured in this patient undergoing voriconazole oral therapy.

Characterization of oxidative pathways in chronic rhinosinusitis and sinonasal polyposis.

BACKGROUND: Eosinophils are a characteristic inflammatory cell infiltrate in both chronic rhinosinusitis (CRS) and sinonasal polyposis (SNP). The posttranslational modifications, 3-bromo-tyrosine (Br-Tyr) and 3-chloro-tyrosine (Cl-Tyr), serve as specific molecular markers for production of brominating and chlorinating oxidants, respectively, by the eosinophil peroxidase and myeloperoxidase systems of leukocytes. The aim of this study was to identify mechanisms of oxidative protein modifications in sinonasal mucosa of CRS and SNP patients by measuring Br-Tyr, Cl-Tyr, and alternative molecular markers of distinct oxidative pathways. METHODS: Levels of Br-Tyr; Cl-Tyr; di-Tyrosine (di-Tyr), a specific oxidative cross-link; ortho-tyrosine (o-Tyr) and meta-tyrosine (m-Tyr), markers for protein modification by hydroxyl radical-like oxidants; and nitro-tyrosine (NO2-Tyr), a stable product of nitric oxide (NO)-derived oxidants, were measured in anterior ethmoid mucosa tissue from CRS and SNP patients, as well as in middle turbinate mucosa from normal volunteers, using tandem mass spectrometry. RESULTS: Tissue levels of Br-Tyr were significantly higher in the CRS group compared with the control group (797 micromol/mol versus 515 micromol/mol tyrosine, p < 0.015), but no differences were detected for Cl-Tyr, di-Tyr, m-Tyr, o-Tyr, and NO2-Tyr. Tissue levels of both Br-Tyr and di-Tyr were significantly higher in the SNP group compared with the control group (879 micromol/mol versus 515 micromol/mol, p < 0.005; 5090 micromol/mol versus 1700 micromol/mol, p < 0.024, respectively), but no differences were detected for Cl-Tyr, m-Tyr, o-Tyr, and NO2-Tyr. CONCLUSION: Br-Tyr, a molecular footprint predominantly formed by eosinophil peroxidase-catalyzed tissue damage, may serve as an objective index of CRS and SNP disease activity.

[Cholesterol granuloma in paranasal sinus. An unfrequent pseudotumor in maxillary sinuses]. / Granuloma de colesterol en senos paranasales. Un pseudotumor infrequente.

The cholesterol granuloma is well known in the middle ear, in the mastoid antrum and the air cells of temporal bone, mostly related to a chronic infectious process. There are other localizations such as the pleura, lung, pericardium, kidneys, arterial wall, nerves, brain, testicles, lymphatic ganglion and in the paranasals sinuses. Its localization in the mediofacial area is very unfrequent, having only been described 44 cases up to the year 2002. We present a 42 year-old patient, who required surgical treatment because of a increase in the volume of area her left facial of one month's old. It resulted to be secundary to an expansion of the maxilar sinus, such as seen on the computerized tomography carried out on the patient. The diagnosis was cholesterol granuloma, performed, through the anatomo-pathology study. We review the litterature on this subject and analyse the possible etiologic cause of this lesion, its clinic, diagnostic methodology and treatment.

Nasal chondromesenchymal hamartoma: report of a case and review of the literature.

The sinonasal region is the site of several hamartomatous lesions, the majority of which are mesenchymal, with vascular hamartomas predominating. The occurrence of hamartomas in the nasal cavity of infants and children is especially rare. Nasal chondromesenchymal hamartoma (NCMH) is a rare lesion of the intranasal sinuses generally diagnosed in the newborn period, with the eldest reported patient presenting at 16 years of age. This neoplasm is composed of mesenchymal-stromal and chondroid tissue in varying proportions. It is felt to be analogous to the mesenchymal hamartoma of the chest wall, a lesion of similar histology generally involving the ribs and chest wall of neonates. To the best of our knowledge, only 14 cases of NCMH have been reported to date. We report a case of NCMH in an 11-year-old boy.

Partial removal of orbital tumor in Rosai-Dorfman disease.

BACKGROUND: Rosai-Dorfman disease is a rare idiopathic histiocytic proliferation disorder that typically presents with painless cervical lymphadenopathy. We report our experience with the management of a case of Rosai-Dorfman disease with compressive optic neuropathy. CASE: Rosai-Dorfman disease involving the bilateral orbital and paranasal sinuses was diagnosed in a 14-year-old boy. Diagnosis was based on the characteristic histopathologic features of sinus histiocytosis, composed of large, round S-100 protein-positive histiocytes with striking emperipolesis. The boy received chemotherapy to resolve the bilateral proptosis and compressive optic neuropathy in the right eye, but this treatment failed. Orbital debulking surgery using the Lynch approach was performed. OBSERVATIONS: Corneal exposure was resolved and visual acuity recovered from 14/20 to 20/20 after partial removal of the tumor mass. There were no complications after surgery. During the 22 months of follow-up, orbital tumor masses redeveloped to cause lagophthalmos again, but did not cause visual impairment. CONCLUSIONS: Rosai-Dorfman disease is a rare disorder, especially in Asia. The disease is usually chronic with spontaneous remission and is refractory to treatment. Partial removal of tumor masses is a workable way to improve visual acuity and correct corneal exposure. Before carrying out this procedure, we discussed with the parents of the patient the potential complications that might follow surgery and secured their permission before proceeding further.

Effect of clarithromycin on nuclear factor-kappa B and transforming growth factor-beta in chronic rhinosinusitis.

OBJECTIVES: Long-term, low-dose macrolide therapy is effective in the treatment of chronic rhinosinusitis. It is believed that macrolide antibiotics produce this benefit through an anti-inflammatory effect. In this study, the effect of clarithromycin treatment on the expression of transforming growth factor (TGF)-beta and the key pro-inflammatory nuclear transcription factor, NF-kappa B, was examined in vitro and in vivo. STUDY DESIGN AND METHODS: In vitro: nasal mucosa was obtained from 10 patients with chronic sinusitis and was cultured for 24 hours in the presence of clarithromycin or control. Cellular expression of TGF-beta and NF-kappa B was determined by immunohistochemistry. In vivo: 10 patients with chronic rhinosinusitis were treated for 3 months with clarithromycin. Nasal mucosal biopsies were taken pre- and posttreatment. Cellular expression of TGF-beta and NF-kappa B was again determined by immunohistochemistry. RESULTS: Clarithromycin, when applied to nasal biopsies in vitro, reduced cellular expression of TGF-beta and NF-kappa B. Nasal biopsies taken before and after clarithromycin treatment showed no differences in cellular expression of NF-kappa B or TGF-beta. CONCLUSION: Clarithromycin can reduce cellular expression of TGF-beta and NF-kappa B when applied in vitro, but its action during clinical therapy is less clear. Clarithromycin is capable of inhibiting pro-inflammatory cytokines in vitro, and reductions of TGF-beta and NF-kappa B may represent additional mechanisms by which macrolides reduce inflammation in chronic airway disease. Discrepancies between the actions of clarithromycin on nasal biopsies in vitro and after clinical therapy warrant further investigation.

Current value of nasal nitric oxide measurement in rhinology.

PURPOSE OF REVIEW: Since the first description of nitric oxide in the exhaled breath of humans by Gustafsson et al., there has been enormous interest in the study of nitric oxide and its role in the nose and paranasal sinuses. The aim of this review is to present the current knowledge about nasal NO: its physiology, novel methods of detection and measurement, and implications in sinonasal disease, focusing on the recent data from the literature. RECENT FINDINGS: Nitric oxide production is known to be produced in the nose at the apical tip of the ciliated respiratory mucosa. A new study has localized nitric oxide production in the pericytes and osteocytes of nasal turbinates. Studies have also discovered the efficacy of offline measurement techniques showing high correlation between standard online measurements with offline techniques. In an interesting study examining the influence of maxillary ostium size and nasal nitric oxide levels, decreased nitric oxide levels found with larger size ostia may eventually influence our approach to sinus surgery. SUMMARY: Nasal nitric oxide has been an ever-increasing topic of interest to both the allergist and the head and neck surgeon. The recent advances in the study of nasal nitric oxide as it relates to sinonasal disease and nasal physiology are discussed and important new findings are highlighted.

Sinonasal adenocarcinoma: evidence for histogenetic divergence of the enteric and nonenteric phenotypes.

Adenocarcinomas of nonsalivary origin represent approximately 10% to 20% of all sinonasal malignancies and are characterized by varying histopathologic features and uncertain histogenesis. To better understand the histogenesis and phenotypic heterogeneity of these tumors, we performed immunohistochemical analyses for cytokeratin (CK) 7 and CK20 on 12 primary sinonasal adenocarcinomas (SNACs) representing the histopathologic spectrum of these tumors, adjacent normal mucosa, and 2 metastatic adenocarcinomas from colonic primaries. The demographic and clinicopathologic characteristics of our cohort were similar to those in previously published series. Our results indicate that histologically normal respiratory-type epithelium and submucosal seromucous glands show restricted reactivity to CK7. Epithelial metaplasia of surface epithelium associated with enteric SNACs was accompanied by a conversion from CK7 positivity to CK20 positivity. All primary enteric-type carcinomas and the 2 colonic metastases were reactive to CK20, but all nonenteric-type tumors were negative for CK20 (P=0.003) and positive for CK7. In some of the enteric types, coexpression of CK7 and CK20 was noted. We conclude that (1) nonenteric-type (seromucinous) adenocarcinoma may originate directly from surface respiratory-type epithelium or from seromucous glands, (2) metaplastic transformation of surface respiratory to enteric-type epithelium precedes the development of enteric adenocarcinoma, and (3) coordinate analyses of CK7 and CK20 reactivity may aid the differential diagnosis of adenocarcinoma in the sinonasal tract.