Squamous Cell Carcinoma of the Larynx Arising in Multifocal Pharyngolaryngeal Oncocytic Papillary Cystadenoma:A Case Report and Review of the Literature

We report on a rare case of a laryngeal carcinoma arising in a multifocal pharyngolaryngeal oncocytic papillary cystadenoma (OPC). The disease of a 63-year-old man is well documented by computed and positron emission tomography, histology, and electron microscopy. We could show that an OPC can even develop in the pharynx. The coexistence of both tumors makes this a challenging diagnosis for pathologists. Treated by surgery and radiotherapy, both lesions dissolved. Based on the literature available, we discuss the theory that the laryngeal carcinoma might be the result of a true metaplasia facilitated by chronic irritation and recommend a regular follow-up for OPC too. As in benign oncocytic lesions, we could show that the detection of numerous mitochondria is a diagnostic indicator for malignant variants as well

Residente endoneurale Makrophagen bei autoimmunen Entzündungen des peripheren Nervensystems

Makrophagen spielen eine Schlüsselrolle in der Pathogenese autoimmuner Neuropathien. Im PNS existiert eine Population residenter endoneuraler Makrophagen (REMph). Mangels identifizierender Marker war ihre Funktion bislang weitgehend unbekannt. REMph wurden bei der experimentellen autoimmunen Neuritis an knochenmarkchimären Ratten identifiziert, bei denen alle REMph ein funktionell stummes Transgen tragen, hämatogene Makrophagen jedoch nicht. In den Nn. ischiadici ließen sich im gesamten Krankheitsverlauf REMph nachweisen. REMph proliferierten sehr früh nach Krankheitsbeginn. Ihre Anzahl stieg stark an. Es fanden sich aktivierte REMph. Zahlreiche REMph phagozytierten Myelin und exprimierten MHC Klasse II-Antigen frühzeitig vor dem Einstrom hämatogener Makrophagen. Die Daten weisen darauf hin, dass identifizierte REMph durch frühe Phagozytose und MHC Klasse II-Expression als lokale Immunüberwachungszellen eine frühzeitige und potentiell wichtige regulatorische Rolle im Verlauf autoimmuner Entzündungen des PNS spielen

Adaption and validation of the nasal obstruction symptom evaluation scale in German language (D-NOSE)

BACKGROUND: Questionnaires have proven their worth in detecting changes in quality of life after medical interventions.The Nasal Obstruction Symptom Evaluation scale (NOSE) is a reliable and valid tool to identify restrictions of quality of life in patients with nasal problems. The aim of this prospective study was the validation of the German version of the NOSE scale (D-NOSE). METHODS: Adaption of the NOSE in German language was performed by forward and backward translation process.Patients undergoing functional septorhinoplasty were asked to complete the D-NOSE preoperatively, one, three or twelve months after surgery. Healthy volunteers served as controls. Reliability, validity and responsiveness of the D-NOSE were determined. RESULTS: The D-NOSE showed a good internal consistency as well as good inter-item, item-total correlation and a satisfactory test-retest reliability. The convincing validity of the adapted NOSE scale was approved by good construct validity and an excellent discriminant validity. Furthermore, a high sensitivity to identify clinical changes due to an intervention indicates a good responsiveness of the D-NOSE. CONCLUSIONS: The adapted German version of the NOSE questionnaire (D-NOSE) is an appropriate and validated tool to assess the influence of nasal obstruction in quality of life in German speaking patients

Potential of the Novel PTA Score to Identify Patients with Peritonsillar Inflammation Profiting from Medical Treatment

Peritonsillar inflammation is a common characteristic of both peritonsillar abscess (PTA) and peritonsillitis (PC). The aim of the present study was to apply the PTA score as an objective criterion to identify patients with peritonsillar inflammation (PI) who might profit from medical treatment. Hence, the recently developed PTA score was applied retrospectively on patients suffering from acute tonsillitis, peritonsillitis, and peritonsillar abscess. Analysis of the clinical data, the follow-up, and the initial PTA score was performed. Patients with peritonsillar inflammation show significant higher PTA score values compared to patients with acute tonsillitis without peritonsillar inflammation and healthy controls. Patients with a PTA score ≤ 2 profited from medical treatment consisting of antibiotics in 92.3% of the cases. In 89.2% of the patients with a PTA score > 2, pus was detected during abscess relief. Patients with peritonsillar inflammation who profited from medical treatment had significantly reduced PTA score values and a reduced duration of hospitalization compared to the patients with abscess relief. Thus, the PTA score has the potential as an objective criterion to identify patients with peritonsillar inflammation profiting from medical treatment. Hence, application of the PTA score helps to determine an optimal, individualized treatment approach and might reduce utilization of medical resources.</p

Increased Levels of S100A8/A9 in Patients with Peritonsillar Abscess: A New Promising Diagnostic Marker to Differentiate between Peritonsillar Abscess and Peritonsillitis

Peritonsillar abscess (PTA) is a very frequent reason for urgent outpatient consultation and otolaryngological hospital admission. Early, correct diagnosis and therapy of peritonsillar abscess are important to prevent possible life-threatening complications. Based on physical examinations, a reliable differentiation between peritonsillar cellulitis and peritonsillar abscess is restricted. A heterodimeric complex called calprotectin consists of the S100 proteins A8 and A9 (S100A8/A9) and is predominantly expressed not only in monocytes and neutrophils but also in epithelial cells. Due to its release by activated phagocytes at local sites of inflammation, we assumed S100A8/A9 to be a potential biomarker for peritonsillar abscess. We examined serum and saliva of patients with peritonsillitis, acute tonsillitis, peritonsillar abscess, and healthy controls and found significantly increased levels of S100A8/A9 in patients with PTA. Furthermore, we could identify halitosis, trismus, uvula edema, and unilateral swelling of the arched palate to be characteristic symptoms for PTA. Using a combination of these characteristic symptoms and S100A8/A9 levels, we developed a PTA score as an objective and appropriate tool to differentiate between peritonsillitis and peritonsillar abscess with a sensitivity of 92% and specificity of 93%

IL-8 and IFN-γ as Preoperative Predictors of the Outcome of Tonsillectomy

Objectives: Tonsillectomy (TE) and tonsillotomy (TO) due to recurrent episodes of acute tonsillitis (RAT) belong to the most frequent surgical procedures. However, an adequate objective marker predicting the outcome of TE/TO preoperatively is missing. Methods: Patients with RAT who underwent TE/TO (n = 31) were included in this pilot study. A panel of cytokines and chemokines in serum and saliva were determined preoperatively. Health-related quality of life was assessed pre- and postoperatively by the Tonsillectomy Outcome Inventory-14. Results: Health-related quality of life improved significantly after surgery. Increased serum levels of interleukin-8 (IL-8) and interferon gamma (IFN-γ) are associated with a less successful outcome. No correlation between the number of acute tonsillitis episodes and the health-related quality of life after TE or TO could be observed. Conclusions: Tonsillectomy and TO improve health-related quality of life independently from the number of past acute tonsillitis episodes. Interleukin-8 and IFN-γ in serum may serve as promising markers, predicting the benefit of TE or TO for patients preoperatively

Nuclear translocation of beta-catenin and decreased expression of epithelial cadherin in human papillomavirus-positive tonsillar cancer: an early event in human papillomavirus-related tumour progression?

International audienceAims: High-risk human papillomaviruses (HPV) seem to be an important risk factor for tonsillar cancer. However, only few data exist concerning molecular changes during metastasis. Methods and Results: We examined 48 primary tonsillar carcinoma samples (25 HPV-16 DNA positive, 23 HPV-16 DNA negative) and their respective lymph node metastases for their HPV status and for the expression of p16, E-cadherin, β-catenin and vimentin. A positive HPV-specific PCR correlated significantly with p16 overexpression in both the primary tumor and metastasis (p<0.0001 both). In HPV-unrelated patients the expression of E-cadherin was significantly less abundant in metastases than in primary tumors (p<0.001). The expression of nuclear β-catenin was contrariwise significantly higher in metastases than in primary tumors (p=0.016). Compared to HPV-unrelated patients, in HPV-related ones the nuclear localisation of β-catenin expression was already apparent in primary tumors (p=0.030). The expression of vimentin significantly correlated with the grading of the primary tumor (p=0.021). Conclusions: Our data newly indicate that the downregulation of E-cadherin together with an upregulation of nuclear β-catenin might be crucial steps during tumor progression of tonsillar cancer being already present in primary tumors in HPV driven cancers but become apparent in HPV-unrelated tumors later during the process of metastasizing

Integration of HPV6 and Downregulation of AKR1C3 Expression Mark Malignant Transformation in a Patient with Juvenile-Onset Laryngeal Papillomatosis

Juvenile-onset recurrent respiratory papillomatosis (RRP) is associated with low risk human papillomavirus (HPV) types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2-4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR) or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16(INK4A), p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH) revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR) showed integration in the aldo-keto reductase 1C3 gene (AKR1C3) on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related) malignancies

Efficacy of selective digestive decontamination in patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell transplantation

Selective digestive decontamination (SDD) with the oral, non-absorbable antimicrobial substances gentamicin, vancomycin and amphotericin B was optionally used at our institution to reduce the risk of gastrointestinal tract derived infections in multiple myeloma (MM) patients undergoing high-dose chemotherapy with subsequent autologous stem cell transplantation (HDCT/ASCT). The majority of patients received sulfamethoxazole-trimethoprim as pneumocystis pneumonia prophylaxis. From 203 patients receiving their first HDCT/ASCT between 2009 and 2015, we compared retrospectively 90 patients receiving SDD to 113 patients not receiving SDD. The administration of SDD was associated with a reduction of bacterial infections after HDCT/ASCT (overall: 8% versus 24%, p = .002; gram-negative pathogens: 1% versus 11%, p = .006) and less use of systemic antibiotics (62% versus 77%, p = .022). Omission of SDD was an independent risk factor for developing neutropenic fever and bloodstream infections. SDD could be an option to reduce bacterial infections in patients undergoing HDCT/ASCT that needs to be tested in prospective trials